FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Wiener, L
Viola, A
Koretski, J
Perper, ED
Patenaude, AF
AF Wiener, Lori
Viola, Adrienne
Koretski, Julia
Perper, Emily Diana
Patenaude, Andrea Farkas
TI Pediatric psycho-oncology care: standards, guidelines, and consensus
reports
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE pediatric; psychosocial; standards; guidelines; consensus reports
ID SIOP WORKING COMMITTEE; QUALITY CANCER CARE; CHILDHOOD-CANCER; ISSUES;
CHILDREN; ADOLESCENT; DIAGNOSIS; SURVIVORS; SUPPORT; ASSISTANCE
AB ObjectiveThe aim of this study was to identify existing guidelines, standards, or consensus-based reports for psychosocial care of children with cancer and their families.
PurposePsychosocial standards of care for children with cancer can systematize the approach to care and create a replicable model that can be utilized in pediatric hospitals around the world. Determining gaps in existing standards in pediatric psycho-oncology can guide development of useful evidence-based and consensus-based standards.
MethodsThe MEDLINE and PubMed databases were searched by investigators at two major pediatric oncology centers for existing guidelines, consensus-based reports, or standards for psychosocial care of patients with pediatric cancer and their families published in peer-reviewed journals in English between 1980 and 2013.
ResultsWe located 27 articles about psychosocial care that met inclusion criteria: 5 set forth standards, 19 were guidelines, and 3 were consensus-based reports. None was sufficiently up to date, comprehensive, specific enough, or evidence- or consensus-based to serve as a current standard for psychosocial care for children with cancer and their families.
ConclusionDespite calls by a number of international pediatric oncology and psycho-oncology professional organizations about the urgency of addressing the psychosocial needs of the child with cancer to reduce suffering, there remains a need for development of a widely acceptable, evidence-based and consensus-based, comprehensive standard of care to guide provision of essential psychosocial services to all patients with pediatric cancer. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Wiener, Lori] NCI, NIH, Bethesda, MD 20892 USA.
[Viola, Adrienne] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Koretski, Julia; Patenaude, Andrea Farkas] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Perper, Emily Diana] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Patenaude, Andrea Farkas] Childrens Hosp, Boston, MA 02115 USA.
[Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Wiener, L (reprint author), NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 47
TC 7
Z9 7
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD FEB
PY 2015
VL 24
IS 2
BP 204
EP 211
DI 10.1002/pon.3589
PG 8
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA CA2TN
UT WOS:000348760800012
PM 24906202
ER
PT J
AU Shinagare, AB
Ip, IK
Lacson, R
Ramaiya, NH
George, S
Khorasani, R
AF Shinagare, Atul B.
Ip, Ivan K.
Lacson, Ronilda
Ramaiya, Nikhil H.
George, Suzanne
Khorasani, Ramin
TI Gastrointestinal Stromal Tumor: Optimizing the Use of Cross-sectional
Chest Imaging during Follow-up
SO RADIOLOGY
LA English
DT Article
ID FEATURES; METASTASIS; SURVIVAL
AB Purpose: To identify the frequency of and variables associated with thoracic metastasis in patients with gastrointestinal stromal tumor (GIST) to help optimize the use of cross-sectional chest imaging.
Materials and Methods: This retrospective institutional review board-approved study included 631 patients (343 men; mean age, 55 years; range, 19-94 years) with pathologically confirmed GIST who were identified with a natural language processing algorithm in a review of radiologic reports from January 2004 through October 2012, followed by manual confirmation. The requirement for informed consent was waived. Available imaging, pathologic, and clinical records were reviewed to confirm the presence of abdominal and thoracic metastases. The association of age; sex; size, location, mitotic count, and risk stratification of the primary tumor; initial treatment; presence of abdominal metastases; and bulky abdominal metastases (more than 10 lesions larger than 1 cm, or more than five lesions with at least one larger than 5 cm) with development of thoracic metastases, the primary outcome measure, was studied by using logistic regression.
Results: During median follow-up of 61.4 months (interquartile range, 37.8-93 months), 401 of 631 (63.5%) patients developed metastatic disease (median interval, 6.9 months; interquartile range, 0-25.6 months), all with peritoneal (n = 324) and/or hepatic metastases (n = 303). Bulky abdominal metastases were found in 218 (34.5%) patients. Although 579 (91.8%) patients underwent chest imaging, only 64 of 631 (10.1%) developed thoracic metastases (median, 51.4 months; interquartile range, 36-78.7 months); all had bulky abdominal metastases except one patient who presented with symptomatic scapular metastasis. Only bulky abdominal metastasis was significantly associated with the development of thoracic metastasis (P < .0001; odds ratio, 42.6; range, 8.6-211.5).
Conclusion: Thoracic metastases are relatively uncommon in patients with GIST and are significantly associated only with presence of bulky abdominal metastases. (C) RSNA, 2014
C1 [Shinagare, Atul B.; Ip, Ivan K.; Lacson, Ronilda; Khorasani, Ramin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Shinagare, Atul B.; Ip, Ivan K.; Lacson, Ronilda; Khorasani, Ramin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Evidence Based Imaging, Boston, MA 02115 USA.
[Shinagare, Atul B.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
[George, Suzanne] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
RP Shinagare, AB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
EM ashinagare@partners.org
NR 24
TC 4
Z9 4
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD FEB
PY 2015
VL 274
IS 2
BP 395
EP 404
DI 10.1148/radiol.14132456
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CA1WS
UT WOS:000348700300011
PM 25203129
ER
PT J
AU Honda, JR
Wallace, RJ
Chan, ED
AF Honda, Jennifer R.
Wallace, Richard J., Jr.
Chan, Edward D.
TI First you have to row a little boat
SO RESPIROLOGY
LA English
DT Editorial Material
DE infection and inflammation; pneumonia; respiratory infection
(non-tuberculous)
ID COMPLEX LUNG-DISEASE; NONTUBERCULOUS MYCOBACTERIAL DISEASES;
AVIUM-INTRACELLULARE; ETHAMBUTOL; RIFAMPICIN; MACROLIDE; THERAPY
C1 [Honda, Jennifer R.; Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA.
[Honda, Jennifer R.; Chan, Edward D.] Natl Jewish Hlth, Dept Med & Acad Affairs, Denver, CO USA.
[Honda, Jennifer R.; Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO USA.
[Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr Tyler, Dept Med, Tyler, TX USA.
[Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr Tyler, Mycobacteria Nocardia Res Lab, Tyler, TX USA.
RP Honda, JR (reprint author), Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA.
NR 15
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1323-7799
EI 1440-1843
J9 RESPIROLOGY
JI Respirology
PD FEB
PY 2015
VL 20
IS 2
BP 181
EP 182
DI 10.1111/resp.12465
PG 2
WC Respiratory System
SC Respiratory System
GA AZ3EK
UT WOS:000348110300003
PM 25581353
ER
PT J
AU Liu, QY
Hu, YJ
Yu, HH
Yuan, L
Hu, J
Atik, A
Guan, M
Li, DL
Li, X
Tang, SB
AF Liu, Qingyun
Hu, Yijun
Yu, Honghua
Yuan, Ling
Hu, Jie
Atik, Alp
Guan, Meng
Li, Dongli
Li, Xin
Tang, Shibo
TI COMPARISON OF INTRAVITREAL TRIAMCINOLONE ACETONIDE VERSUS INTRAVITREAL
BEVACIZUMAB AS THE PRIMARY TREATMENT OF CLINICALLY SIGNIFICANT MACULAR
EDEMA
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE CSME; DME; bevacizumab; triamcinolone acitonide; OCT
ID OPTICAL COHERENCE TOMOGRAPHY; DIABETIC-RETINOPATHY; AQUEOUS-HUMOR;
INJECTION; PATTERNS; EFFICACY; THERAPY
AB Objectives: To evaluate the short-term efficacy of triamcinolone acetonide versus bevacizumab for the treatment of diabetic, clinically significant, macular edema with different optical coherence tomography findings.
Methods: Fifty eyes of 45 consecutive patients with diabetic, clinically significant, macular edema were incorporated in this prospective interventional case series. Patients were divided into 3 groups according to findings on optical coherence tomography: 1) macular edema combined with serous retinal detachment (Group 1), 2) diffused macular thickening (Group 2), and 3) cystoid macular edema (Group 3). Patients from each group were treated with a single intravitreal injection of triamcinolone (IVTA) or 2 intravitreal injections of bevacizumab (IVB) with an interval of 6 weeks. Patients were observed at 6, 12, and 24 weeks after IVTA or the first IVB injection. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were examined at each visit. Repeated-measures analysis of variance was used to compare the efficacy of the treatment groups.
Results: In Group 1, IVTA showed more favorable effects on CRT reduction and BCVA improvement compared with IVB at 6, 12, and 24 weeks (P = 0.002, 0.001, 0.027 and P = 0.036, 0.001, 0.027), respectively. In Group 2, IVB had more CRT reduction than IVTA at 6 and 12 weeks (P = 0.013 and 0.036), although there was no significant difference in BCVA improvement between the 2 groups (p > 0.05). In Group 3, IVTA and IVB did not have significant effects on CRT reduction and BCVA improvement (p > 0.05).
Conclusion: The short-term efficacy of IVTA and IVB on treating clinically significant macular edema varied with different optical coherence tomography findings. In clinically significant macular edema combined with serous retinal detachment, IVTA may be more favorable than IVB in CRT reduction and BCVA improvement. In patients with diffused macular thickening, IVB may be better than IVTA in macular thickness reduction, although this does not translate to a significant improvement in BCVA.
C1 [Liu, Qingyun] Tongliao City Hosp, Dept Ophthalmol, Tongliao, Peoples R China.
[Hu, Yijun; Hu, Jie] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
[Hu, Yijun; Atik, Alp] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA.
[Yu, Honghua] Gen Hosp Guangzhou Mil Command PLA, Dept Ophthalmol, Guangzhou, Guangdong, Peoples R China.
[Yuan, Ling; Guan, Meng; Li, Dongli] Kunming Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Kunming, Peoples R China.
[Tang, Shibo] Cent S Univ, Aier Sch Ophthalmol, Changsha 410015, Hunan, Peoples R China.
RP Tang, SB (reprint author), Cent S Univ, Aier Sch Ophthalmol, Fourth Floor,198 Middle Furong Rd, Changsha 410015, Hunan, Peoples R China.
EM tangshibo@vip.163.com
FU National Natural Science Foundation of China [81260151]; Applied Basic
Research Foundation of the Department of Science and Technology of
Yunnan Province [2011FB062]; Science and Technology Foundation of the
Department of Health of Yunnan Province [2011WS0041]
FX Supported by grant 81260151 from the National Natural Science Foundation
of China (L. Yuan), grant 2011FB062 from the Applied Basic Research
Foundation of the Department of Science and Technology of Yunnan
Province (L. Yuan), and grant 2011WS0041 from the Science and Technology
Foundation of the Department of Health of Yunnan Province (L. Yuan).
NR 30
TC 4
Z9 4
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0275-004X
EI 1539-2864
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD FEB
PY 2015
VL 35
IS 2
BP 272
EP 279
PG 8
WC Ophthalmology
SC Ophthalmology
GA CA2UU
UT WOS:000348764200016
PM 25105313
ER
PT J
AU Abou Zahr, Z
Spiegelman, A
Cantu, M
Ng, B
AF Abou Zahr, Zaki
Spiegelman, Andrew
Cantu, Maria
Ng, Bernard
TI Perioperative use of anti-rheumatic agents does not increase early
postoperative infection risks: a Veteran Affairs' administrative
database study
SO RHEUMATOLOGY INTERNATIONAL
LA English
DT Article
DE Anti-TNF drugs; Rheumatoid arthritis; Disease-modifying anti-rheumatic
drugs (DMARD); Infection; Surgery
ID RHEUMATOID-ARTHRITIS PATIENTS; FACTOR-ALPHA BLOCKERS; NECROSIS-FACTOR;
METHOTREXATE; COMPLICATIONS; SURGERY; DRUGS; HAND
AB The aim of this study was to validate a novel technique that predicts stopping of disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents (BA) from the Veterans Affairs (VA) database and compare infection risks of rheumatoid arthritis patients who stopped versus continued DMARDs/BA perioperatively. We identified 6,024 patients on 1 DMARD or BA in the perioperative period between 1999 and 2009. Time gap between medication stop date and the next start date predicted drug stoppage (X). Time gap between surgery date and stop date predicted whether stoppage was before surgery (Y). Chart review from Houston VA was used for validation. ROC analyses were performed on chart review data to obtain X and Y cutoffs. The primary endpoints were wound infections and other infections within 30 days. ROC analyses found X a parts per thousand yen 33 (AUC = 0.954) and Y a parts per thousand yen -11 (AUC = 0.846). Risk of postoperative infections was not different when stopping and continuing DMARDs/BA preoperatively. Stopping BA after surgery was associated with higher odds of postoperative wound (OR 14.15, 95 % CI 1.76-113.76) and general infection (OR 9.2, 95 % CI 1.99-42.60) compared to not stopping. Stopping DMARDs after surgery was associated with increased risk of postoperative general infection (OR 1.84, 95 % CI 1.07-3.16) compared with not stopping. There was positive association between stopping DMARDs after surgery and postoperative wound infection but failed to achieve statistical significance (OR 1.67, 95 % CI 0.96-2.91). There was no significant difference in postoperative infection risk when stopping or continuing DMARD/BA. Our new validated method can be utilized in the VA and other databases to predict drug stoppage.
C1 [Abou Zahr, Zaki] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Spiegelman, Andrew] Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA.
[Cantu, Maria] Baylor Coll Med, Houston, TX 77030 USA.
[Ng, Bernard] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
RP Ng, B (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM dr_zaki_abouzahr@yahoo.com; bernardng1@gmail.com
FU Department of Veteran Affairs, Veterans Health Administration, Health
Services Research and Development Service [VA.SCV.1010./000-00.B_N];
Veterans Affairs Health Services Research and Development Service
Houston Center of Excellence [HFP90-020]; South Central VA Health Care
Network Research Pilot Grant Award
FX The research reported here was supported by the Department of Veteran
Affairs, Veterans Health Administration, Health Services Research and
Development Service, (VA.SCV.1010./000-00.B_N). This work was also
partly supported by the Veterans Affairs Health Services Research and
Development Service Houston Center of Excellence (HFP90-020). Dr.
Bernard Ng held a South Central VA Health Care Network Research Pilot
Grant Award and was a consultant to UCB Pharmaceuticals. The rest of the
authors have no conflicts of interest to declare. The funding sources
had no role in the study design, conduct and analysis or in the decision
to submit the manuscript for publication.
NR 25
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0172-8172
EI 1437-160X
J9 RHEUMATOL INT
JI Rheumatol. Int.
PD FEB
PY 2015
VL 35
IS 2
BP 265
EP 272
DI 10.1007/s00296-014-3121-0
PG 8
WC Rheumatology
SC Rheumatology
GA CA5YB
UT WOS:000348983300006
PM 25187198
ER
PT J
AU Hazlett, EA
Rothstein, EG
Ferreira, R
Silverman, JM
Siever, LJ
Olincy, A
AF Hazlett, Erin A.
Rothstein, Ethan G.
Ferreira, Rui
Silverman, Jeremy M.
Siever, Larry J.
Olincy, Ann
TI Sensory gating disturbances in the spectrum: Similarities and
differences in schizotypal personality disorder and schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizotypal personality disorder; Schizophrenia; Event-related
potential; Evoked potential; P50; Psychophysiology; Sensory gating
ID REPEATED AUDITORY-STIMULI; DEFICIENT ATTENTIONAL MODULATION; P50
SUPPRESSION; BIPOLAR DISORDER; EVOKED-RESPONSE; POTENTIAL ABNORMALITIES;
COGNITIVE IMPAIRMENT; NICOTINIC RECEPTORS; STARTLE RESPONSE;
WORKING-MEMORY
AB Background: DSM-5 places schizophrenia on a continuum from severe, chronic schizophrenia to the attenuated schizophrenia-like traits of schizotypal personality disorder (SPD), the prototypic schizophrenia-related personality disorder. SPD shares common genetic and neurobiological substrates with schizophrenia, including information processing abnormalities, although they are less marked. This is the first study to directly compare the P50 evoked electroencephalographic response-a measure of sensory gating and a neurophysiological endophenotype-between schizophrenia-spectrum groups. Two hypotheses were tested: (1) Compared with healthy controls (HCs), schizophrenia patients show reduced P50 suppression and SPD patients resemble schizophrenia but exhibit less marked deficits; and (2) Deficient P50 suppression in SPD is associated with greater clinical symptom severity.
Methods: P50 was assessed in 32 schizophrenia-spectrum disorder patients (12 SPD, 20 schizophrenia patients) and 25 demographically-matched HCs. The standard conditioning (C)-testing (T) paradigm was used and P50 suppression was quantified using the T-C difference and the T/C ratio.
Results: All P50 measures showed a linear, stepwise pattern with the SPD group intermediate between the HC and schizophrenia groups. Compared with HCs, both patient groups had lower conditioning and T-C difference values. Among the SPD group, greater clinical symptom severity was associated with greater conditioning-response amplitude deficits.
Conclusion: These findings: (1) are novel in showing that P50 deficits in SPD resemble those observed in schizophrenia, albeit less marked; (2) support the concept that the phenomenological link between SPD and schizophrenia lies in shared neurocognitive/neurophysiological pathologies; and (3) provide evidence that P50 is a neurophysiological endophenotype for schizophrenia-spectrum disorders. Published by Elsevier B.V.
C1 [Hazlett, Erin A.; Rothstein, Ethan G.; Ferreira, Rui; Silverman, Jeremy M.; Siever, Larry J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Hazlett, Erin A.; Silverman, Jeremy M.; Siever, Larry J.] James J Peters VA Med Ctr, Res & Dev, Bronx, NY 10468 USA.
[Hazlett, Erin A.; Siever, Larry J.] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, Bronx, NY 10468 USA.
[Olincy, Ann] Univ Colorado, Dept Psychiat, Denver, CO 80202 USA.
RP Hazlett, EA (reprint author), James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN3, 130 West Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA.
EM erin.hazlett@mssm.edu
FU VA MERIT Award [I01CX000261]; NIMH Collaborative R01 grant [R01MH065554,
R01MH056140]; National Center for Advancing Translational Sciences
(NCATS), a component of the National Institutes of Health (NIH)
[UL1TR000067]
FX Support for this work came from a VA MERIT Award I01CX000261 to E. A.
H., NIMH Collaborative R01 grants to each of the seven Consortia on
Genetics of Schizophrenia (COGS) sites including R01MH065554 to L.J.S,
R01MH056140 to L.J.S., and grant no. UL1TR000067 from the National
Center for Advancing Translational Sciences (NCATS), a component of the
National Institutes of Health (NIH).
NR 87
TC 3
Z9 3
U1 3
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD FEB
PY 2015
VL 161
IS 2-3
BP 283
EP 290
DI 10.1016/j.schres.2014.11.020
PG 8
WC Psychiatry
SC Psychiatry
GA AZ8GB
UT WOS:000348452100021
PM 25482574
ER
PT J
AU Trockel, M
Karlin, BE
Taylor, CB
Brown, GK
Manber, R
AF Trockel, Mickey
Karlin, Bradley E.
Taylor, C. Barr
Brown, Gregory K.
Manber, Rachel
TI Effects of Cognitive Behavioral Therapy for Insomnia on Suicidal
Ideation in Veterans
SO SLEEP
LA English
DT Article
DE cognitive behavioral therapy; insomnia; suicidal ideation;
dissemination; Veterans
ID RANDOMIZED CONTROLLED-TRIAL; SLEEP DISTURBANCE; NATIONAL-DISSEMINATION;
PERSISTENT INSOMNIA; DEPRESSIVE SYMPTOMS; FOLLOW-UP; ADULTS; SYSTEM;
PHARMACOTHERAPY; METAANALYSIS
AB Objective: To examine the effects of cognitive behavioral therapy for insomnia (CBT-I) on suicidal ideation among Veterans with insomnia.
Design: Longitudinal data collected in the course of an uncontrolled evaluation of a large-scale CBT-I training program.
Setting: Outpatient and residential treatment facilities.
Participants: Four hundred five Veterans presenting for treatment of insomnia.
Interventions: Cognitive behavioral therapy for insomnia.
Measurement and Results: At baseline, 32% of patients, compared with 21% at final assessment, endorsed some level of suicidal ideation [chi(2)(df = 1) = 125; P < 0.001]. After adjusting for demographic variables and baseline insomnia severity, each 7-point decrease in Insomnia Severity Index score achieved during CBT-I treatment was associated with a 65% (odds ratio = 0.35; 95% confidence intervals = 0.24 to 0.52) reduction in odds of suicidal ideation. The effect of change in insomnia severity on change in depression severity was also significant. After controlling for change in depression severity and other variables in the model, the effect of change in insomnia severity on change in suicidal ideation remained significant.
Conclusion: This evaluation of the largest dissemination of cognitive behavioral therapy for insomnia (CBT-I) in the United States found a clinically meaningful reduction in suicidal ideation among Veterans receiving CBT-I. The mechanisms by which effective treatment of insomnia with CBT-I reduces suicide risk are unknown and warrant investigation. The current results may have significant public health implications for preventing suicide among Veterans.
C1 [Trockel, Mickey; Manber, Rachel] Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA.
[Trockel, Mickey; Taylor, C. Barr; Manber, Rachel] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Karlin, Bradley E.] US Dept Vet Affairs, Cent Off, Mental Hlth Serv, Washington, DC USA.
[Karlin, Bradley E.] Educ Dev Ctr Inc, New York, NY 10014 USA.
[Karlin, Bradley E.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Brown, Gregory K.] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA.
[Brown, Gregory K.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Karlin, BE (reprint author), Educ Dev Ctr Inc, Mental Hlth & Aging, 96 Morton St,7th Floor, New York, NY 10014 USA.
EM bradkarlin@gmail.com
FU Mental Health Services, U.S. Department of Veterans Affairs Central
Office
FX This was not an industry supported study. This project was supported by
Mental Health Services, U.S. Department of Veterans Affairs Central
Office. Dr. Karlin is currently affiliated with the Education
Development Center, Inc., and the Department of Mental Health, Bloomberg
School of Public Health, Johns Hopkins University. Dr. Manber is a
co-author of a workbook related to the treatment described in this paper
from which she receives royalties. The other authors have indicated no
financial conflicts of interest.
NR 47
TC 17
Z9 17
U1 1
U2 12
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
EI 1550-9109
J9 SLEEP
JI Sleep
PD FEB 1
PY 2015
VL 38
IS 2
BP 259
EP 265
DI 10.5665/sleep.4410
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CA2SO
UT WOS:000348757800014
PM 25515115
ER
PT J
AU Manconi, M
Zavalko, I
Fanfulla, F
Winkelman, JW
Fulda, S
AF Manconi, Mauro
Zavalko, Irina
Fanfulla, Francesco
Winkelman, John W.
Fulda, Stephany
TI An Evidence-Based Recommendation for a New Definition of
Respiratory-Related Leg Movements
SO SLEEP
LA English
DT Article
DE respiratory-related leg movements; periodic leg movements; sleep apnea
ID OBSTRUCTIVE SLEEP-APNEA; POSITIVE AIRWAY PRESSURE; PERIODIC LIMB
MOVEMENTS; HEART-FAILURE; PREVALENCE; MORTALITY; WAKEFULNESS; DISORDER;
THERAPY; PLMS
AB Study Objectives: Current sleep scoring rules exclude leg movements that occur near respiratory events from being scored as periodic leg movements during sleep (PLMS) but differ in whether they exclude leg movements occurring at the end (WASM/IRLSSG) or during a respiratory event (AASM). The aim of the present study was to describe the distribution of leg movements in relation to respiratory events and to contribute to an evidence-based rule for the identification and scoring of respiratory-related leg movements (RRLMs).
Design: Retrospective chart review and analysis of polysomnographic recordings.
Setting: Clinical sleep laboratory.
Participants: 64 patients with polysomnographic recordings between January 2010 and July 2011, aged 18 to 75 years, with AHI > 20, ODI > 10, more than 50% of apneas being obstructive, > 15 leg movements of any type per hour of sleep, no more than 20% of total sleep time with artifacts and no medical condition or medication that could influence leg movements or respiratory disturbances.
Interventions: None.
Measurements and Results: Back-averaging of leg movement activity (LMA) with respect to respiratory events revealed that LMA was present shortly before the end of the respiratory events, but occurred mostly following respiratory events with peak onset of LMA 2.5 s after respiratory event termination. Increased LMA before the beginning of the respiratory event consisted mainly of the tail of LMA after the end of the previous respiratory event. Change-point analysis indicated that LMA was increased over an interval of -2.0 s to +10.25 s around the end of respiratory events. Changing the definition of RRLMs had a significant influence on PLMS counts. The number of patients with obstructive sleep apnea with PLMS index > 15 was 80% when considering the WASM/IRLSSG definition, 67% for the AASM criteria, and 41% when based on the interval identified by change-point analysis (-2.0 to 10.25 s).
Conclusions: Leg movements are not augmented at the beginning or middle of respiratory events but are increased around the end of respiratory events over a period significantly longer than specified in the AASM and the WASM/IRLSSG rules. Both rules underestimate the number of respiratory-related leg movements and thus overestimate the number of periodic leg movements during sleep in patients with obstructive sleep apnea.
C1 [Manconi, Mauro; Zavalko, Irina; Fulda, Stephany] Civ Hosp EOC Lugano, Sleep & Epilepsy Ctr, Neuroctr Southern Switzerland, CH-6900 Lugano, Switzerland.
[Zavalko, Irina] Russian Acad Sci, Inst Biomed Problems, Moscow, Russia.
[Fanfulla, Francesco] Salvatore Maugeri Fdn IRCCS, Sci Inst Pavia, Sleep Ctr, Pavia, Italy.
[Winkelman, John W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Sleep Disorders Clin Res Program, Boston, MA USA.
RP Fulda, S (reprint author), Civ Hosp EOC Lugano, Sleep & Epilepsy Ctr, Neuroctr Southern Switzerland, Via Tesserete 46, CH-6900 Lugano, Switzerland.
EM stephany.fulda@gmail.com
OI Fanfulla, Francesco/0000-0002-8601-423X
NR 29
TC 10
Z9 10
U1 0
U2 4
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
EI 1550-9109
J9 SLEEP
JI Sleep
PD FEB 1
PY 2015
VL 38
IS 2
BP 295
EP 304
DI 10.5665/sleep.4418
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CA2SO
UT WOS:000348757800018
PM 25325500
ER
PT J
AU Tanabe, KK
AF Tanabe, Kenneth K.
TI Commentary on "Can we improve the morbidity and mortality associated
with the associating liver partition with portal vein ligation for
staged hepatectomy (ALPPS) procedure in the management of colorectal
liver metastases?"
SO SURGERY
LA English
DT Editorial Material
ID RESECTION
C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA.
RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA.
EM ktanabe@partners.org
NR 10
TC 3
Z9 3
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD FEB
PY 2015
VL 157
IS 2
BP 204
EP 206
DI 10.1016/j.surg.2014.08.053
PG 3
WC Surgery
SC Surgery
GA CA5TX
UT WOS:000348971800004
PM 25433729
ER
PT J
AU Valsangkar, NP
Ingkakul, T
Correa-Gallego, C
Mino-Kenudson, M
Masia, R
Lillemoe, KD
Fernandez-del Castillo, C
Warshaw, AL
Liss, AS
Thayer, SP
AF Valsangkar, Nakul P.
Ingkakul, Thun
Correa-Gallego, Camilo
Mino-Kenudson, Mari
Masia, Ricard
Lillemoe, Keith D.
Fernandez-del Castillo, Carlos
Warshaw, Andrew L.
Liss, Andrew S.
Thayer, Sarah P.
TI Survival in ampullary cancer: Potential role of different KRAS mutations
SO SURGERY
LA English
DT Article
ID K-RAS MUTATION; ADJUVANT CHEMORADIATION THERAPY; COLORECTAL-CANCER;
PROGNOSTIC VALUE; LUNG ADENOCARCINOMAS; CARCINOMA; VATER; PREDICTORS;
PANCREATICODUODENECTOMY; NODES
AB Objective. The prognosis of ampullary adenocarcinoma (AA) usually is favorable; however a subset of AA have poor biology and outcomes similar to pancreatic cancer Patients in this subset will have early recurrence and death usually within 2 years. To date, there are no genetic markers to identify these patients. This study identifies the high-risk subset of AA and evaluates the mutational status of KRAS in predicting poor outcome.
Methods. The tumor registry of an academic center was reviewed for data on patients managed operatively with AA. KRAS genotypes were determined for these patients using a polymerase chain reaction-based assay on clinical specimens. Analysis of variance and chi(2) tests was used to categorize continuous and categorical variables. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox methods, respectively.
Results. A total of 146 patients were identified with AA between 1982 and 2008. After stringent pathologic review, 97 patients were confirmed with AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed 67% were wild-type (KRAS(wT)), and 33% were mutant for KRAS. Patients with KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median survival (62 months) compared with those with KRAS(non-G12D) mutants (median survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P = .05). Patients with survival 30 months were labeled "high-risk." Of the 9 patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with KRAS(G12D) also were more likely to present with advanced T stage.
Conclusion. The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses and may be used to identifiy patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy.
C1 [Valsangkar, Nakul P.; Ingkakul, Thun; Correa-Gallego, Camilo; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Liss, Andrew S.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Mino-Kenudson, Mari; Masia, Ricard] Massachusetts Gen Hosp, Dept Pathol, MD Inst Pancreat Canc Res, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Thayer, SP (reprint author), Univ Nebraska Med Ctr, Div Surg Oncol, Fred & Pamela Buffett Canc Ctr, 986345 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM sarah.thayer@unmc.edu
FU National Cancer Institute [CA117969, GA127003]
FX Supported by the Andrew L. Warshaw, M.D. Institute for Pancreatic Cancer
Research (to N.P.V.) and the grants CA117969, GA127003 from the National
Cancer Institute (to S.P.T.).
NR 36
TC 8
Z9 8
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD FEB
PY 2015
VL 157
IS 2
BP 260
EP 268
DI 10.1016/j.surg.2014.08.092
PG 9
WC Surgery
SC Surgery
GA CA5TX
UT WOS:000348971800011
PM 25616942
ER
PT J
AU Stey, AM
Russell, MM
Ko, CY
Sacks, GD
Dawes, AJ
Gibbons, MM
AF Stey, Anne M.
Russell, Marcia M.
Ko, Clifford Y.
Sacks, Greg D.
Dawes, Aaron J.
Gibbons, Melinda M.
TI Clinical registries and quality measurement in surgery: A systematic
review
SO SURGERY
LA English
DT Review
ID OUTCOMES LONGITUDINAL DATABASE; SURGICAL-SITE-INFECTION; RISK-ADJUSTED
OUTCOMES; ARTERY-BYPASS-SURGERY; OF-VETERANS-AFFAIRS; ABDOMINAL
AORTIC-ANEURYSM; NORTHERN NEW-ENGLAND; VENA-CAVA FILTERS; TRAUMA
DATA-BANK; BARIATRIC-SURGERY
AB Background. Surgical clinical registries provide clinical information with the intent of measuring and improving quality. This study aimed to describe how surgical clinical registries have been used to measure surgical quality, the reported findings, and the limitations of registry measurements.
Methods. Medline, CINAHL, and Cochrane were queried for English articles with the terms: "registry AND surgery AND quality. "Eligibility criteria were studies explicitly assessing quality measurement with registries as the primary data source. Studies were abstracted to identify registries, define registry structure, uses for quality measurement, and limitations of the measurements used.
Results. A total of 111 studies of 18 registries were identified for data abstraction. Two registries were financed privately, and 5 registries were financed by a governmental organization. Across registries, the most common uses of process measures were for monitoring providers and as platforms for quality improvement initiatives. The most common uses of outcome measures were to improve quality modeling and to identify preoperative risk factors for poor outcomes. Eight studies noted improvements in risk-adjusted mortality with registry participation; one found no change. A major limitation is bias from context and means of data collection threatening internal validity of registry quality measurement. Conversely, the other major limitation is the cost of participation, which threatens the external validity of registry quality measurement.
Conclusion. Clinical registries have advanced surgical quality definition, measurement, and modeling as well as having served as platforms for local initiatives for quality improvement. The implication of this finding is that subsidizing registry participation may improve data validity as well as engage providers in quality improvement.
C1 [Stey, Anne M.] Mt Sinai Med Ctr, Icahn Sch Med, Los Angeles, CA 90024 USA.
[Stey, Anne M.; Russell, Marcia M.; Ko, Clifford Y.; Sacks, Greg D.; Dawes, Aaron J.; Gibbons, Melinda M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Russell, Marcia M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
[Ko, Clifford Y.] Amer Coll Surg, Chicago, IL USA.
RP Stey, AM (reprint author), Mt Sinai Med Ctr, Icahn Sch Med, 10940 Wilshire Blvd,Suite 710, Los Angeles, CA 90024 USA.
EM astey@mednet.ucla.edu
OI Stey, Anne/0000-0002-8334-0304; Dawes, Aaron/0000-0003-4574-6765
FU Robert Wood Johnson Foundation Clinical Scholars program; U.S.
Department of Veterans Affairs [70039]
FX A.M.S., A.D., G.D.S. time was supported for this publication by The
Robert Wood Johnson Foundation Clinical Scholars program and the U.S.
Department of Veterans Affairs Grant number 70039.
NR 140
TC 11
Z9 11
U1 3
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD FEB
PY 2015
VL 157
IS 2
BP 381
EP 395
DI 10.1016/j.surg.2014.08.097
PG 15
WC Surgery
SC Surgery
GA CA5TX
UT WOS:000348971800025
PM 25616951
ER
PT J
AU Mehra, S
Tuttle, RM
Milas, M
Orloff, L
Bergman, D
Bernet, V
Brett, E
Cobin, R
Doherty, G
Judson, BL
Klopper, J
Lee, S
Lupo, M
Machac, J
Mechanick, JI
Randolph, G
Ross, DS
Smallridge, R
Terris, D
Tufano, R
Alon, E
Clain, J
DosReis, L
Scherl, S
Urken, ML
AF Mehra, Saral
Tuttle, R. Michael
Milas, Mira
Orloff, Lisa
Bergman, Donald
Bernet, Victor
Brett, Elise
Cobin, Rhoda
Doherty, Gerard
Judson, Benjamin L.
Klopper, Joshua
Lee, Stephanie
Lupo, Mark
Machac, Josef
Mechanick, Jeffrey I.
Randolph, Gregory
Ross, Douglas S.
Smallridge, Robert
Terris, David
Tufano, Ralph
Alon, Eran
Clain, Jason
DosReis, Laura
Scherl, Sophie
Urken, Mark L.
TI Database and Registry Research in Thyroid Cancer: Striving for a New and
Improved National Thyroid Cancer Database
SO THYROID
LA English
DT Review
ID PROGNOSTIC SCORING SYSTEM; UNITED-STATES; DATA-BASE; PERIOPERATIVE
INFORMATION; RISK-GROUP; CARCINOMA; SURVIVAL; PAPILLARY; WELL;
COMMUNICATION
AB Background: Health registries have become extremely powerful tools for cancer research. Unfortunately, certain details and the ability to adapt to new information are necessarily limited in current registries, and they cannot address many controversial issues in cancer management. This is of particular concern in differentiated thyroid cancer, which is rapidly increasing in incidence and has many unknowns related to optimal treatment and surveillance recommendations.
Summary: In this study, we review different types of health registries used in cancer research in the United States, with a focus on their advantages and disadvantages as related to the study of thyroid cancer. This analysis includes population-based cancer registries, health systems-based cancer registries, and patient-based disease registries. It is important that clinicians understand the way data are collected in, as well as the composition of, these different registries in order to more critically interpret the clinical research that is conducted using that data. In an attempt to address shortcoming of current databases for thyroid cancer, we present the potential of an innovative web-based disease management tool for thyroid cancer called the Thyroid Cancer Care Collaborative (TCCC) to become a patient-based registry that can be used to evaluate and improve the quality of care delivered to patients with thyroid cancer as well as to answer questions that we have not been able to address with current databases and registries.
Conclusion: A cancer registry that follows a specific patient, is integrated into physician workflow, and collects data across different treatment sites and different payers does not exist in the current fragmented system of healthcare in the United States. The TCCC offers physicians who treat thyroid cancer numerous time-saving and quality improvement services, and could significantly improve patient care. With rapid adoption across the nation, the TCCC could become a new paradigm for database research in thyroid cancer to improve our understanding of thyroid cancer management.
C1 [Mehra, Saral; Judson, Benjamin L.] Yale Univ, Sch Med, Dept Surg Otolaryngol, New Haven, CT 06520 USA.
[Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Milas, Mira] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Orloff, Lisa] Stanford Otolaryngol Head & Neck Surg, Stanford, CA USA.
[Bergman, Donald; Brett, Elise] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA.
[Bernet, Victor; Smallridge, Robert] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA.
[Cobin, Rhoda] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, Ridgewood, NJ USA.
[Doherty, Gerard] Boston Univ, Med Ctr, Dept Surg, Boston, MA USA.
[Klopper, Joshua] Univ Colorado Denver, Aurora, CO USA.
[Lee, Stephanie] Boston Med Ctr, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA USA.
[Lupo, Mark] Florida State Univ, Coll Med, Sarasota, FL USA.
[Lupo, Mark] Florida State Univ, Thyroid & Endocrine Ctr Florida, Sarasota, FL USA.
[Machac, Josef; Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Randolph, Gregory] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Terris, David] Med Coll Georgia, Augusta, GA 30912 USA.
[Tufano, Ralph] Johns Hopkins Sch Med, Baltimore, MD USA.
[Alon, Eran] Tel Aviv Univ, Sackler Sch Med, Tel Hashomer, Israel.
[Clain, Jason; DosReis, Laura; Scherl, Sophie] THANC Fdn, New York, NY USA.
[Urken, Mark L.] Mt Sinai Beth Israel Med Ctr, New York, NY USA.
RP Mehra, S (reprint author), Yale Univ, Sch Med, 333 Cedar St,Box 208041, New Haven, CT 06520 USA.
EM saral.mehra@yale.edu
FU Mount Sinai Health System; Thyroid Head and Neck Cancer (THANC)
Foundation
FX The preparation of this article was supported by a generous grant from
the Mount Sinai Health System and the Thyroid Head and Neck Cancer
(THANC) Foundation.
NR 37
TC 7
Z9 8
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD FEB 1
PY 2015
VL 25
IS 2
BP 157
EP 168
DI 10.1089/thy.2014.0270
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CA6HQ
UT WOS:000349012300003
PM 25517683
ER
PT J
AU Sammon, JD
McKay, RR
Kim, SP
Sood, A
Sukumar, S
Hayn, MH
Hu, JC
Kibel, AS
Nguyen, PL
Peabody, JO
Saad, F
Sun, M
Varda, B
Menon, M
Choueiri, TK
Trinh, QD
AF Sammon, Jesse D.
McKay, Rana R.
Kim, Simon P.
Sood, Akshay
Sukumar, Shyam
Hayn, Matthew H.
Hu, Jim C.
Kibel, Adam S.
Nguyen, Paul L.
Peabody, James O.
Saad, Fred
Sun, Maxine
Varda, Briony
Menon, Mani
Choueiri, Toni K.
Quoc-Dien Trinh
TI Burden of Hospital Admissions and Utilization of Hospice Care in
Metastatic Prostate Cancer Patients
SO UROLOGY
LA English
DT Article
ID UNITED-STATES; INCREASED SURVIVAL; ZOLEDRONIC ACID; CHEMOTHERAPY; COST;
ABIRATERONE; CARCINOMA; ANTIGEN
AB OBJECTIVE To examine the rates of hospitalization in patients with metastatic prostate cancer (mCaP), as well as the effect of hospice utilization on the cost patterns of mCaP. Over the past decade, dramatic changes in the management of advanced prostate cancer have proceeded alongside changes in end-of-life care. But, the impact of these contemporary advances in management of mCaP and its implications on US health care expenditure remains unknown.
METHODS Patients hospitalized with mCaP from 1998 to 2010 were extracted from the Nationwide Inpatient Sample (n = 100,220). Temporal trends in incidence and charges were assessed by linear regression. Complex samples logistic regression models were used to identify the predictors of in-hospital mortality, elevated hospital charges beyond the 75th percentile and hospice utilization.
RESULTS Between 1998 and 2010, admissions for mCaP decreased at a rate of -5.95% per year (P<.001), whereas per-incident charges increased at the rate of 6.1% (P<.001) annually; the national economic burden of care was stable. Over the study period, hospice use increased 488.0% per year (P<.001) but was significantly lower among black (odds ratio [OR], 0.73; P = .01) and Hispanic (OR, 0.65; P = .03) patients. In multivariable analyses, hospice utilization was associated with decreased odds of elevated hospital charges beyond the 75th percentile (OR, 0.84; P = .02).
CONCLUSION Despite a decline in hospitalizations for mCaP, the economic burden of care has remained stable. Increasing use of hospice services has moderated the effect of rising per-incident hospital charges, highlighting the importance of promoting access to hospice in the right clinical setting. These findings have important policy implications, particularly as advances in treatment are expected to further increase expenditures related the inpatient management of mCaP. (C) 2015 Elsevier Inc.
C1 Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA.
Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
Yale Univ, Dept Urol, New Haven, CT USA.
Harvard Univ, Dana Farber Canc Inst, Sch Med, Div Urol Oncol, Boston, MA 02115 USA.
Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
Univ Minnesota, Dept Urol, Minneapolis, MN USA.
Maine Med Ctr, Dept Urol, Portland, ME 04102 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA.
Univ Montreal, Ctr Hosp, Div Urol, Montreal, PQ, Canada.
Univ Montreal, Ctr Hosp, Div Urol, Montreal, PQ, Canada.
Univ Montreal, Ctr Hosp, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada.
RP Trinh, QD (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 45 Francis St,ASB II-3, Boston, MA 02115 USA.
EM trinh.qd@gmail.com
NR 28
TC 4
Z9 4
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD FEB
PY 2015
VL 85
IS 2
BP 343
EP 349
DI 10.1016/j.urology.2014.09.053
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AZ9UN
UT WOS:000348562200020
PM 25623683
ER
PT J
AU Hshieh, TT
Petrone, AB
Gaziano, JM
Djousse, L
AF Hshieh, Tammy T.
Petrone, Andrew B.
Gaziano, J. Michael
Djousse, Luc
TI Nut consumption and risk of mortality in the Physicians' Health Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE cardiovascular disease; coronary artery disease; mortality; nut
consumption; nuts
ID POLYUNSATURATED FATTY-ACIDS; CORONARY-HEART-DISEASE; FOOD FREQUENCY
QUESTIONNAIRE; MEDITERRANEAN DIET; CARDIOVASCULAR-DISEASE;
BLOOD-PRESSURE; INFLAMMATORY MARKERS; ALZHEIMERS-DISEASE; COGNITIVE
FUNCTION; PRIMARY PREVENTION
AB Background: Previous studies have suggested that nut consumption is associated with beneficial cardiovascular outcomes. However, limited data are available on the association between nut intake and all-cause mortality.
Objective: Our aim was to test the hypothesis that nut consumption is inversely associated with the risk of all-cause mortality.
Design: In this prospective cohort study in 20,742 male physicians, we assessed nut intake between 1999 and 2002 via a food-frequency questionnaire and ascertained deaths through an endpoint committee. We used Cox regression to estimate multivariable-adjusted HRs for death according to nut consumption. In secondary analyses, we evaluated associations of nut consumption with cause-specific mortality.
Results: During a mean follow-up of 9.6 y, there were 2732 deaths. The mean (+/- SD) age at baseline was 66.6 +/- 9.3 y. Median nut consumption was 1 serving/wk. Multivariable-adjusted HRs (95% CIs) were 1.0 (reference), 0.92 (0.83, 1.01), 0.85 (0.76, 0.96), 0.86 (0.75, 0.98), and 0.74 (0.63, 0.87) for nut consumption of never or <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and >= 5 servings/wk, respectively (P-linear trend < 0.0001), after adjustment for age, body mass index, alcohol use, smoking, exercise, prevalent diabetes and hypertension, and intakes of energy, saturated fat, fruit and vegetables, and red meat. In a secondary analysis, results were consistent for cardiovascular disease mortality but only suggestive and non-statistically significant for coronary artery disease and cancer mortality.
Conclusion: Our data are consistent with an inverse association between nut consumption and the risk of all-cause and cardiovascular disease mortality in US male physicians.
C1 [Hshieh, Tammy T.; Petrone, Andrew B.; Gaziano, J. Michael; Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA.
[Hshieh, Tammy T.] Inst Aging Res, Aging Brain Ctr, Boston, MA USA.
[Gaziano, J. Michael; Djousse, Luc] Geriatr Res GRECC, Massachusetts Vet Epidemiol, Boston, MA USA.
[Gaziano, J. Michael; Djousse, Luc] Geriatr Res GRECC, Res Informat Ctr MAVERIC, Boston, MA USA.
[Gaziano, J. Michael; Djousse, Luc] VA Boston Healthcare Syst, Boston, MA USA.
RP Djousse, L (reprint author), Brigham & Womens Hosp, Div Aging, One Brigham Circle,1620 Tremont St,3rd Floor, Boston, MA 02120 USA.
EM ldjousse@rics.bwh.harvard.edu
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD [R21
HL088081]; National Cancer Institute [CA-34944, CA-40360, CA-097193];
NHLBI [HL-26490, HL-34595]; NTH-funded T32 training grant [AG000158]
FX Supported by grant R21 HL088081 from the National Heart, Lung, and Blood
Institute (NHLBI), Bethesda, MD (to LD). The Physicians' Health Study is
supported by grants CA-34944, CA-40360, and CA-097193 from the National
Cancer Institute and grants HL-26490 and HL-34595 from the NHLBI. TTH is
supported by an NTH-funded T32 training grant (AG000158).
NR 60
TC 8
Z9 8
U1 0
U2 15
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD FEB
PY 2015
VL 101
IS 2
BP 407
EP 412
DI 10.3945/ajcn.114.099846
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CA5US
UT WOS:000348973900021
PM 25646339
ER
PT J
AU Berkowitz, SA
Meigs, JB
DeWalt, D
Seligman, HK
Barnard, LS
Bright, OJM
Schow, M
Atlas, SJ
Wexler, DJ
AF Berkowitz, Seth A.
Meigs, James B.
DeWalt, Darren
Seligman, Hilary K.
Barnard, Lily S.
Bright, Oliver-John M.
Schow, Marie
Atlas, Steven J.
Wexler, Deborah J.
TI Material Need Insecurities, Control of Diabetes Mellitus, and Use of
Health Care Resources Results of the Measuring Economic Insecurity in
Diabetes Study
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; FOOD INSECURITY; LOW-INCOME;
SENSITIVE-CONDITIONS; SOCIOECONOMIC DISPARITIES; CARDIOVASCULAR-DISEASE;
SOCIAL DETERMINANTS; HOUSING INSTABILITY; SELF-MANAGEMENT; ADULTS
AB IMPORTANCE Increasing access to care may be insufficient to improve the health of patients with diabetes mellitus and unmet basic needs (hereinafter referred to as material need insecurities). How specific material need insecurities relate to clinical outcomes and the use of health care resources in a setting of near-universal access to health care is unclear.
OBJECTIVE To determine the association of food insecurity, cost-related medication underuse, housing instability, and energy insecurity with control of diabetes mellitus and the use of health care resources.
DESIGN, SETTING, AND PARTICIPANTS Cross-sectional data were collected from June 1, 2012, through October 31, 2013, at 1 academic primary care clinic, 2 community health centers, and 1 specialty center for the treatment of diabetes mellitus in Massachusetts. A random sample of 411 patients, stratified by clinic, consisted of adults (aged >= 21 years) with diabetes mellitus (response rate, 62.3%).
MAIN OUTCOMES AND MEASURES The prespecified primary outcome was a composite indicator of poor diabetes control (hemoglobin A(1c) level, >9.0%; low-density lipoprotein cholesterol level, >100mg/dL; or blood pressure, >140/90 mm Hg). Prespecified secondary outcomes included outpatient visits and a composite of emergency department (ED) visits and acute care hospitalizations (ED/inpatient visits). RESULTS Overall, 19.1% of respondents reported food insecurity; 27.6%, cost-related medication underuse; 10.7%, housing instability; 14.1%, energy insecurity; and 39.1%, at least 1 material need insecurity. Poor diabetes control was observed in 46.0% of respondents. In multivariable models, food insecurity was associated with a greater odds of poor diabetes control (adjusted odds ratio [OR], 1.97 [95% CI, 1.58-2.47]) and increased outpatient visits (adjusted incident rate ratio [IRR], 1.19 [95% CI, 1.05-1.36]) but not increased ED/inpatient visits (IRR, 1.00 [95% CI, 0.51-1.97]). Cost-related medication underuse was associated with poor diabetes control (OR, 1.91 [95% CI, 1.35-2.70]) and increased ED/inpatient visits (IRR, 1.68 [95% CI, 1.21-2.34]) but not outpatient visits (IRR, 1.07 [95% CI, 0.95-1.21]). Housing instability (IRR, 1.31 [95% CI, 1.14-1.51]) and energy insecurity (IRR, 1.12 [95% CI, 1.00-1.25]) were associated with increased outpatient visits but not with diabetes control (OR, 1.10 [95% CI, 0.60-2.02] and OR, 1.27 [95% CI, 0.96-1.69], respectively) or with ED/inpatient visits (IRR, 1.49 [95% CI, 0.81-2.73] and IRR, 1.31 [95% CI, 0.80-2.13], respectively). An increasing number of insecurities was associated with poor diabetes control (OR for each additional need, 1.39 [95% CI, 1.18-1.63]) and increased use of health care resources (IRR for outpatient visits, 1.09 [95% CI, 1.03-1.15]; IRR for ED/inpatient visits, 1.22 [95% CI, 0.99-1.51]).
CONCLUSIONS AND RELEVANCE Material need insecurities were common among patients with diabetes mellitus and had varying but generally adverse associations with diabetes control and the use of health care resources. Material need insecurities may be important targets for improving care of diabetes mellitus.
C1 [Berkowitz, Seth A.; Meigs, James B.; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02141 USA.
[Berkowitz, Seth A.; Wexler, Deborah J.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02141 USA.
[Berkowitz, Seth A.; Meigs, James B.; Atlas, Steven J.; Wexler, Deborah J.] Harvard Univ, Sch Med, Boston, MA USA.
[DeWalt, Darren] Univ N Carolina, Sch Med, Div Gen Med & Clin Epidemiol, Chapel Hill, NC USA.
[Seligman, Hilary K.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Seligman, Hilary K.] San Francisco Gen Hosp & Trauma Ctr, Ctr Vulnerable Populat, San Francisco, CA USA.
RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,Ninth Floor, Boston, MA 02141 USA.
EM saberkowitz@partners.org
OI Berkowitz, Seth/0000-0003-1030-4297; DeWalt, Darren/0000-0003-2270-751X
FU Institutional National Research Service award [T32HP10251]; Ryoichi
Sasakawa Fellowship Fund; Division of General Internal Medicine,
Massachusetts General Hospital; National Institutes of Health
[R03DK090196-01A1, U01DK098246, K24DK080140]
FX This study was supported by Institutional National Research Service
award T32HP10251 (Dr Berkowitz), by the Ryoichi Sasakawa Fellowship Fund
(Dr Berkowitz), by the Division of General Internal Medicine,
Massachusetts General Hospital (Dr Berkowitz), by awards
R03DK090196-01A1 and U01DK098246 from the National Institutes of Health
(DrWexler), and in part by award K24DK080140 from the National
Institutes of Health (Dr Meigs).
NR 53
TC 15
Z9 15
U1 4
U2 16
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD FEB
PY 2015
VL 175
IS 2
BP 257
EP 265
DI 10.1001/jamainternmed.2014.6888
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7TL
UT WOS:000349120100026
PM 25545780
ER
PT J
AU Sebro, R
Aslam, R
Muglia, VF
Wang, ZJ
Westphalen, AC
AF Sebro, Ronnie
Aslam, Rizwan
Muglia, Valdair Francisco
Wang, Z. Jane
Westphalen, Antonio Carlos
TI Low yield of chemical shift MRI for characterization of adrenal lesions
with high attenuation density on unenhanced CT
SO ABDOMINAL IMAGING
LA English
DT Article
DE Adrenal adenoma; Adrenal lesion; Adrenal nodule; Adrenal mass; Chemical
shift; Magnetic resonance imaging (MRI); Computed tomography (CT)
ID DELAYED ENHANCED CT; INITIAL-EXPERIENCE; F-18-FDG PET/CT; IN-PHASE;
MASSES; PHEOCHROMOCYTOMA; ADENOMAS; BENIGN; DIFFERENTIATION; METASTASES
AB Purpose: To investigate the threshold unenhanced CT density of adrenal nodules at which further evaluation with chemical shift MRI is unlikely to be definitive and therefore not helpful in further characterizing some indeterminate adrenal lesions.
Methods: Retrospective evaluation of 44 adrenal lesions imaged with unenhanced CT and chemical shift MRI and followed for at least 1 year. Qualitative and quantitative assessment of signal loss on chemical shift MRI was performed. Adenomas were diagnosed if the lesion measured equal or less than 10 HU on unenhanced CT; on MRI a SI index greater than 16.5% or adrenal: spleen chemical shift ratio less than 0.71 was considered diagnostic of adenoma.
Results: 31.8% (14/44), 47.7% (21/44), and 20.5% (9/44) of the adrenal lesions had an unenhanced CT attenuation density <= 10, 10-30, and > 30 HU. Adrenal lesions with an unenhanced CT density 10-30 and > 30 HU had a 76.2% (16/21) and a 33.3% (3/9) chance of being categorized as an adenoma using MRI SI index, respectively.
Conclusions: Adrenal lesions with unenhanced attenuation CT density > 30 HU had a 66.6% of remaining indeterminate even after evaluation with chemical shift MRI. Advances in knowledge: Chemical shift MRI is reasonable for evaluating adrenal lesions with an unenhanced CT attenuation density less than 30 HU. The likelihood of chemical shift MRI detecting signal loss in lesions CT density greater than 30 HU, however, is low.
C1 [Sebro, Ronnie] Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA.
[Aslam, Rizwan; Wang, Z. Jane; Westphalen, Antonio Carlos] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Aslam, Rizwan; Wang, Z. Jane; Westphalen, Antonio Carlos] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA.
[Muglia, Valdair Francisco] Univ Sao Paulo, Ribeirao Preto Sch Med, BR-14048900 Ribeirao Preto, SP, Brazil.
RP Westphalen, AC (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave, San Francisco, CA 94143 USA.
EM antonio.west-phalen@ucsf.edu
RI Muglia, Valdair/H-5208-2012
OI Muglia, Valdair/0000-0002-4700-0599
NR 35
TC 2
Z9 2
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-8925
EI 1432-0509
J9 ABDOM IMAGING
JI Abdom. Imaging
PD FEB
PY 2015
VL 40
IS 2
BP 318
EP 326
DI 10.1007/s00261-014-0208-8
PG 9
WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
GA AZ6AC
UT WOS:000348298800012
PM 25095753
ER
PT J
AU Suh, CH
Baheti, AD
Tirumani, SH
Rosenthal, MH
Kim, KW
Ramaiya, NH
Shinagare, AB
AF Suh, Chong Hyun
Baheti, Akshay D.
Tirumani, Sree Harsha
Rosenthal, Michael H.
Kim, Kyung Won
Ramaiya, Nikhil H.
Shinagare, Atul B.
TI Multimodality imaging of penile cancer: what radiologists need to know
SO ABDOMINAL IMAGING
LA English
DT Article
DE Penile cancer; 2010 AJCC TNM staging; Role of imaging; Management
ID SQUAMOUS-CELL CARCINOMA; METASTASIS CLASSIFICATION-SYSTEM; LYMPH-NODE
METASTASIS; HUMAN-PAPILLOMAVIRUS; ASPIRATION-CYTOLOGY;
PROGNOSTIC-FACTORS; SURGICAL-TREATMENT; GROIN DISSECTION; PHASE-II;
LYMPHADENECTOMY
AB The purpose of this article is to provide a comprehensive update on the role of imaging in the diagnosis and management of penile cancer. Imaging plays a major role in the initial assessment, treatment planning, and follow-up of patients with penile carcinoma. MRI helps in assessing the T staging of the primary and in detecting local recurrence. PET/CT and CT are useful for detecting regional nodal and distant metastases.
C1 [Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul 138736, South Korea.
[Suh, Chong Hyun; Kim, Kyung Won] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, Seoul 138736, South Korea.
[Baheti, Akshay D.; Tirumani, Sree Harsha; Rosenthal, Michael H.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA.
[Baheti, Akshay D.; Tirumani, Sree Harsha; Rosenthal, Michael H.; Ramaiya, Nikhil H.; Shinagare, Atul B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
RP Suh, CH (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, 88 Olymp Ro 43 Gil, Seoul 138736, South Korea.
EM jhsuh04@gmail.com
RI Rosenthal, Michael/D-4080-2015
NR 58
TC 2
Z9 2
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-8925
EI 1432-0509
J9 ABDOM IMAGING
JI Abdom. Imaging
PD FEB
PY 2015
VL 40
IS 2
BP 424
EP 435
DI 10.1007/s00261-014-0218-6
PG 12
WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
GA AZ6AC
UT WOS:000348298800021
PM 25117563
ER
PT J
AU Malchau, H
Graves, SE
Porter, M
Harris, WH
Troelsen, A
AF Malchau, Henrik
Graves, Stephen E.
Porter, Martyn
Harris, William H.
Troelsen, Anders
TI The next critical role of orthopedic registries
SO ACTA ORTHOPAEDICA
LA English
DT Editorial Material
C1 [Malchau, Henrik; Harris, William H.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Dept Orthoped, Boston, MA 02114 USA.
[Malchau, Henrik] Sahlgrens Univ Hosp, Dept Orthoped, Molndal, Sweden.
[Graves, Stephen E.] Australian Orthopaed Assoc Natl Joint Replacement, Adelaide, SA, Australia.
[Graves, Stephen E.] Flinders Univ S Australia, Dept Surg, Adelaide, SA 5001, Australia.
[Porter, Martyn] Wrightington Hosp, Wigan, Lancs, England.
[Troelsen, Anders] Copenhagen Univ Hosp Hvidovre, Clin Orthopaed Res Hvidovre CORH, Dept Orthopaed Surg, Copenhagen, Denmark.
RP Malchau, H (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Dept Orthoped, Boston, MA 02114 USA.
EM hmalchau@mgh.harvard.edu
RI Graves, Stephen/A-9463-2016
OI Graves, Stephen/0000-0002-1629-319X
NR 3
TC 3
Z9 3
U1 0
U2 0
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 1745-3674
EI 1745-3682
J9 ACTA ORTHOP
JI Acta Orthop.
PD FEB
PY 2015
VL 86
IS 1
BP 3
EP 4
DI 10.3109/17453674.2014.1002184
PG 2
WC Orthopedics
SC Orthopedics
GA AZ6ZD
UT WOS:000348367000002
PM 25583041
ER
PT J
AU Goy, ER
Bohlig, A
Carter, J
Ganzini, L
AF Goy, Elizabeth R.
Bohlig, Amanda
Carter, Julie
Ganzini, Linda
TI Identifying Predictors of Hospice Eligibility in Patients With Parkinson
Disease
SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE
LA English
DT Article
DE Parkinson disease; hospice; palliative
ID BODY-WEIGHT; PROGRESSION; MORTALITY; LIFE; CARE; END
AB This study aims to improve recognition of hospice eligibility for patients with Parkinson disease (PD) by ascertaining which variables have a higher probability of occurring uniquely in 6 to 12 months before death when compared to 18 to 24 months before death. Participants were 339 patients who died who were diagnosed with PD or Parkinsonism and treated with dopaminergic prescriptions for at least 3 years in northwestern US Veterans Affairs medical centers. A range of indicators were compared across 3 time periods (30-36 months, 24-18 months, and 12-6 months before death) using within-subjects repeated measures design. Results indicate that body mass index less than 18, alone or combined with a shift in prescribing (when benefits of dopaminergic medications no longer outweigh their risk of side effects), may signal appropriate timing for hospice referral.
C1 [Goy, Elizabeth R.; Bohlig, Amanda; Ganzini, Linda] Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97239 USA.
[Carter, Julie] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
RP Goy, ER (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd P3MHDC, Portland, OR 97239 USA.
EM Elizabeth.Goy@va.gov
FU Health Services Research and Development (HSR&D) Career Development
Award [RCD 04326]; HSR&D Portland Center for the Study of Chronic,
Comorbid Mental and Physical Disorders, at the Portland VA Medical
Center [REA 06-174]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research is funded in part by a Health Services Research and Development
(HSR&D) Career Development Award for Dr. Goy (RCD 04326), and the HSR&D
Portland Center for the Study of Chronic, Comorbid Mental and Physical
Disorders (REA 06-174), at the Portland VA Medical Center.
NR 18
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-9091
EI 1938-2715
J9 AM J HOSP PALLIAT ME
JI Am. J. Hosp. Palliat. Med.
PD FEB
PY 2015
VL 32
IS 1
BP 29
EP 33
DI 10.1177/1049909113502119
PG 5
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AZ4MQ
UT WOS:000348196000004
PM 23975684
ER
PT J
AU Clark, JK
Fasciano, K
AF Clark, Jennifer K.
Fasciano, Karen
TI Young Adult Palliative Care: Challenges and Opportunities
SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE
LA English
DT Review
DE young adult; emerging adult; adolescents and young adults; palliative
care; hospice; end-of-life care
ID OF-LIFE CARE; CYSTIC-FIBROSIS; DYING ADOLESCENT; SELF-MANAGEMENT;
CANCER-PATIENTS; CHRONIC ILLNESS; TRANSITION; CHILDREN; DISEASE; PEOPLE
AB Young adulthood is a time of immense growth and possibilities. As a result, it is also a time when serious illness can have profound effects. This review examines the current data pertinent to young adult palliative care and discusses the challenges and opportunities where palliative medicine can enhance the care provided to this growing and vulnerable population. From the data, 2 primary themes emerged (1) ongoing young adult development not only generates unique biologic disease burdens and clinical treatment options but also requires frequent assessment and promotion and (2) binary health care systems often leave young adults without access to developmentally appropriate health care. Given its interdisciplinary approach, palliative care is uniquely poised to address the challenges known to caring for the seriously ill young adult.
C1 [Clark, Jennifer K.] Univ Oklahoma, Dept Internal Med, Sch Community Med Tulsa, OU Ctr Palliat Care, Tulsa, OK 74135 USA.
[Clark, Jennifer K.] Univ Oklahoma, Dept Pediat, Sch Community Med Tulsa, OU Ctr Palliat Care, Tulsa, OK 74135 USA.
[Fasciano, Karen] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
RP Clark, JK (reprint author), Univ Oklahoma, Dept Internal Med, Sch Community Med Tulsa, OU Ctr Palliat Care, 4502 E 41st St, Tulsa, OK 74135 USA.
EM jennifer-k-clark@ouhsc.edu
NR 80
TC 2
Z9 2
U1 2
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-9091
EI 1938-2715
J9 AM J HOSP PALLIAT ME
JI Am. J. Hosp. Palliat. Med.
PD FEB
PY 2015
VL 32
IS 1
BP 101
EP 111
DI 10.1177/1049909113510394
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AZ4MQ
UT WOS:000348196000013
PM 24198063
ER
PT J
AU Simon, HB
AF Simon, Harvey B.
TI Music as Medicine
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID BRAIN; INTERVENTION; METAANALYSIS; DEPRESSION; RECOVERY; CANCER; MOOD;
GAIT; PAIN
C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA.
[Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Simon, HB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA.
EM hsimon@partners.org
NR 32
TC 0
Z9 0
U1 3
U2 22
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD FEB
PY 2015
VL 128
IS 2
BP 208
EP 210
DI 10.1016/j.amjmed.2014.10.023
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AZ5YG
UT WOS:000348293800027
PM 25448175
ER
PT J
AU Wosu, AC
Gelaye, B
Valdimarsdottir, U
Kirschbaum, C
Stalder, T
Shields, AE
Williams, MA
AF Wosu, Adaeze C.
Gelaye, Bizu
Valdimarsdottir, Unnur
Kirschbaum, Clemens
Stalder, Tobias
Shields, Alexandra E.
Williams, Michelle A.
TI Hair cortisol in relation to sociodemographic and lifestyle
characteristics in a multiethnic US sample
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Correlates; Race; Ethnicity; Chronic stress; Biomarker; Community
ID INDIVIDUALS
AB Purpose: We investigated the feasibility of obtaining hair samples from men and women at community-based barbershops and hair salons for analysis of cortisol and assessed sociodemographic and lifestyle correlates of hair cortisol concentrations (HCCs). A total of 102 participants completed the study.
Methods: Research staff interviewed participants using a structured questionnaire, and samples of hair were collected. HCCs were determined using liquid chromatography-tandem mass spectrometry. Age- and sex-adjusted linear regression models were used to evaluate the association of HCC with covariates.
Results:: Analyses by race/ethnicity showed highest median HCC in blacks (12.5 [6.9-29.31) pg/mg) followed by Hispanics (10.7 15.8-14.91 pg/mg), whites (5.0 [3.8-10.8] pg/mg), and other participants (4.2 [3.3-15.71 pg/mg), P < .01. Current smokers had significantly higher median HCC (11.7 [8.8-18.91 pg/mg) compared with former smokers (4.6 [3.5-14.6] pg/mg) and those who had never smoked (6.9 [4.7-12.81 pg/mg), P = .04. After adjustment for age and sex, geometric mean HCC was 0.72 pg/mg lower in dyed hair compared with hair that was not dyed (beta = 0.72, standard error = 0.30, 95% confidence interval, -1.29 to -0.15, P = .02).
Conclusions: HCC can be assessed in community-based studies. Future HCC studies should consider cosmetic hair treatment, cigarette smoking, and the potential role of psychosocial stressors in the association between race/ethnicity and HCC. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Wosu, Adaeze C.; Gelaye, Bizu; Valdimarsdottir, Unnur; Williams, Michelle A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Valdimarsdottir, Unnur] Univ Iceland, Fac Med, Ctr Publ Hlth Sci, Reykjavik, Iceland.
[Kirschbaum, Clemens; Stalder, Tobias] Tech Univ Dresden, Dept Psychol, D-01062 Dresden, Germany.
[Shields, Alexandra E.] Harvard Univ, Sch Med, Harvard Massachusetts Gen Hosp,Dept Med, Ctr Genom Vulnerable Populat & Hlth Dispar,Mongan, Boston, MA USA.
RP Wosu, AC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Room 500, Boston, MA 02115 USA.
EM awosu@hsph.harvard.edu
OI Gelaye, Bizu/0000-0001-7934-548X
FU National Institutes of Health; National Center for Research Resources
(NCRR); National Center for Advancing Translational Sciences (NCATS)
[8UL1TR000170-05]
FX This research was supported, in part, by an award from the National
Institutes of Health, National Center for Research Resources (NCRR) and
the National Center for Advancing Translational Sciences (NCATS):
8UL1TR000170-05. The National Institutes of Health had no further role
in the study design, in the collection, analysis and interpretation of
data, in the writing of the report, or in the decision to submit the
article for publication. The authors would like to thank the study
participants, owners, managers, and staff of the barbershops and hair
salons for granting access to conduct the study and the laboratory staff
at the Department of Biopsychology, Technical University of Dresden,
Dresden, Germany, for completing all laboratory analyses. The authors
also wish to thank Ms. Kristin Roynesdal for her assistance with data
collection.
NR 20
TC 12
Z9 12
U1 0
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD FEB
PY 2015
VL 25
IS 2
BP 90
EP 95
DI 10.1016/j.annepidem.2014.11.022
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CA2QE
UT WOS:000348751700005
PM 25534254
ER
PT J
AU Balch, C
Arias-Pulido, H
Banerjee, S
Lancaster, AK
Clark, KB
Perilstein, M
Hawkins, B
Rhodes, J
Sliz, P
Wilkins, J
Chittenden, TW
AF Balch, Curt
Arias-Pulido, Hugo
Banerjee, Soumya
Lancaster, Alex K.
Clark, Kevin B.
Perilstein, Michael
Hawkins, Brian
Rhodes, John
Sliz, Piotr
Wilkins, Jon
Chittenden, Thomas W.
TI Science and technology consortia in US biomedical research: A paradigm
shift in response to unsustainable academic growth
SO BIOESSAYS
LA English
DT Editorial Material
C1 [Balch, Curt; Arias-Pulido, Hugo; Banerjee, Soumya; Lancaster, Alex K.; Clark, Kevin B.; Perilstein, Michael; Hawkins, Brian; Rhodes, John; Sliz, Piotr; Wilkins, Jon; Chittenden, Thomas W.] Complex Biol Syst Alliance, N Andover, MA 01845 USA.
[Balch, Curt; Arias-Pulido, Hugo; Banerjee, Soumya; Lancaster, Alex K.; Wilkins, Jon; Chittenden, Thomas W.] Ronin Inst, Montclair, NJ USA.
[Banerjee, Soumya] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Banerjee, Soumya] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Lancaster, Alex K.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Clark, Kevin B.] Vet Affairs Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA USA.
[Clark, Kevin B.] Univ Illinois, Natl Ctr Supercomp Applicat, Urbana, IL USA.
[Hawkins, Brian] Univ Washington, Sch Med, Mitochondria & Metab Ctr, Seattle, WA USA.
[Rhodes, John] Yale Univ, Sch Med, Yale Cardiovasc Res Ctr, New Haven, CT USA.
[Sliz, Piotr] Harvard Univ, Sch Med, SBGrid Consortium, Boston, MA USA.
[Wilkins, Jon] Santa Fe Inst, Santa Fe, NM 87501 USA.
[Chittenden, Thomas W.] Harvard Univ, Sch Med, Res Comp Grp, Boston, MA USA.
RP Chittenden, TW (reprint author), Complex Biol Syst Alliance, N Andover, MA 01845 USA.
EM tom_chittenden@hms.harvard.edu
RI Lancaster, Alexander/K-2855-2013;
OI Wilkins, Jon/0000-0001-6405-6538; Lancaster,
Alexander/0000-0002-0002-9263; Sliz, Piotr/0000-0002-6522-0835
NR 10
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD FEB
PY 2015
VL 37
IS 2
BP 119
EP 122
DI 10.1002/bies.201400167
PG 4
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA AZ9AQ
UT WOS:000348504100004
PM 25387399
ER
PT J
AU Appelbaum, FR
Anasetti, C
Antin, JH
Atkins, H
Davies, S
Devine, S
Giralt, S
Heslop, H
Laport, G
Lee, SJ
Loganw, B
Pasquini, M
Pulsipher, M
Stadtmauer, E
Wingard, JR
Horowitz, MM
AF Appelbaum, Frederick R.
Anasetti, Claudio
Antin, Joseph H.
Atkins, Harold
Davies, Stella
Devine, Steven
Giralt, Sergio
Heslop, Helen
Laport, Ginna
Lee, Stephanie J.
Loganw, Brent
Pasquini, Marcelo
Pulsipher, Michael
Stadtmauer, Edward
Wingard, John R.
Horowitz, Mary M.
TI Blood and Marrow Transplant Clinical Trials Network State of the Science
Symposium 2014
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Hematopoietic cell; transplantation; Leukemia; Lymphoma; Myeloma
ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; BRONCHIOLITIS OBLITERANS
SYNDROME; IDIOPATHIC PNEUMONIA SYNDROME; ACUTE MYELOID-LEUKEMIA; SEVERE
APLASTIC-ANEMIA; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; UNRELATED DONOR
TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; SIALIDASE FUSION PROTEIN
C1 [Appelbaum, Frederick R.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Atkins, Harold] Ottawa Hosp, Res Inst, Canc Therapeut Program, Ottawa, ON, Canada.
[Davies, Stella] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Devine, Steven] Ohio State Univ, Blood & Marrow Transplant Program, Columbus, OH 43210 USA.
[Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Bone Marrow Transplant Serv, New York, NY 10021 USA.
[Heslop, Helen] Baylor Coll Med, Adult Bone Marrow & Stem Cell Transplant Program, Houston, TX 77030 USA.
[Laport, Ginna] Stanford Hosp & Clin, Stanford, CA USA.
[Loganw, Brent; Pasquini, Marcelo; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Div Clin Res, Milwaukee, WI 53226 USA.
[Pulsipher, Michael] Univ Utah, Sch Med, Primary Childrens Hosp, Salt Lake City, UT USA.
[Stadtmauer, Edward] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA.
[Wingard, John R.] Univ Florida, Dept Internal Med, Div Hematol, Gainesville, FL USA.
RP Appelbaum, FR (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,D5-310, Seattle, WA 98109 USA.
EM fappelba@fhcrc.org
FU National Heart, Lung, and Blood Institute [U10HL069294]; National Cancer
Institute [U10HL069294]; Be The Match Foundation [U10HL069294]
FX Support was provided by grant #U10HL069294 from the National Heart,
Lung, and Blood Institute and the National Cancer Institute (Grant #
U10HL069294) and by the Be The Match Foundation (Grant # U10HL069294).
NR 140
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
BP 202
EP 224
DI 10.1016/j.bbmt.2014.10.003
PG 23
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UW
UT WOS:000348632700003
PM 25445636
ER
PT J
AU Arai, S
Arora, M
Wang, T
Spellman, SR
He, W
Courie, DR
Urbano-Ispizua, A
Cutler, CS
Bacigalupo, AA
Battiwallaw, M
Flowers, ME
Juckett, MB
Lee, SJ
Loren, AW
Klumpp, TR
Prockup, SE
Ringden, OETH
Savani, BN
Socie, G
Schultz, KR
Spitzer, T
Teshima, T
Bredeson, CN
Jacobsohn, DA
Hayashi, RJ
Drobyski, WR
Frangoul, HA
Akpek, G
Ho, VT
Lewis, VA
Gale, RP
Koreth, J
Chao, NJ
Aljurf, MD
Cooper, BW
Laughlin, MJ
Hsu, JW
Hematti, P
Verdonck, LF
Solh, MM
Norkin, M
Reddy, V
Perez-Simon, JA
Khera, N
Lewis, ID
Atsuta, Y
Olsson, RF
Saber, W
Waller, EK
Blaise, D
Pidala, JA
Martin, PJ
Satwani, P
Bornhauser, M
Inamoto, Y
Weisdorf, DJ
Horowitz, MM
Pavletic, SZ
AF Arai, Sally
Arora, Mukta
Wang, Tao
Spellman, Stephen R.
He, Wensheng
Courie, Daniel R.
Urbano-Ispizua, Alvaro
Cutler, Corey S.
Bacigalupo, Andrea A.
Battiwallaw, Minoo
Flowers, Mary E.
Juckett, Mark B.
Lee, Stephanie J.
Loren, Alison W.
Klumpp, Thomas R.
Prockup, Susan E.
Ringden, Olle E. T. H.
Savani, Bipin N.
Socie, Gerard
Schultz, Kirk R.
Spitzer, Thomas
Teshima, Takanori
Bredeson, Christopher N.
Jacobsohn, David A.
Hayashi, Robert J.
Drobyski, William R.
Frangoul, Haydar A.
Akpek, Gorgiin
Ho, Vincent T.
Lewis, Victor A.
Gale, Robert Peter
Koreth, John
Chao, Nelson J.
Aljurf, Mahmoud D.
Cooper, Brenda W.
Laughlin, Mary J.
Hsu, Jack W.
Hematti, Peiman
Verdonck, Leo F.
Solh, Melhelm M.
Norkin, Maxim
Reddy, Vijay
Perez-Simon, Jose A.
Khera, Nandita
Lewis, Ian D.
Atsuta, Yoshiko
Olsson, Richard F.
Saber, Wael
Waller, Edmund K.
Blaise, Didier
Pidala, Joseph A.
Martin, Paul J.
Satwani, Prakash
Bornhauser, Martin
Inamoto, Yoshihiro
Weisdorf, Daniel J.
Horowitz, Mary M.
Pavletic, Steven Z.
CA Graft-Vs-Host Dis Working Comm CIB
TI Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic
Transplantation: A Report from the Center for International Blood and
Marrow Transplant Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Incidence; cGVHD; Allogeneic transplant; Nonrelapse mortality
ID HEMATOPOIETIC-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT;
WORKING GROUP-REPORT; BONE-MARROW; UNRELATED DONORS; STEM-CELL;
REDUCED-INTENSITY; CLINICAL-TRIALS; COMPETING RISKS; SINGLE-CENTER
AB Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P <.0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Arai, Sally; Arora, Mukta; Wang, Tao] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Arora, Mukta] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA.
[Wang, Tao] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA.
[Wang, Tao] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA.
[Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN USA.
[He, Wensheng; Loren, Alison W.] Univ Michigan, Div Hematol Oncol, Ann Arbor, MI USA.
[Loren, Alison W.; Spitzer, Thomas] Hosp Clin Barcelona, Div Hematol Oncol, Barcelona, Spain.
[Socie, Gerard; Bredeson, Christopher N.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Teshima, Takanori; Waller, Edmund K.] IRCCS AOU San Martino IST, Dept Hematol, Genoa, Italy.
[Loren, Alison W.; Hematti, Peiman; Satwani, Prakash] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Koreth, John; Norkin, Maxim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Koreth, John; Perez-Simon, Jose A.] Univ Washington, Seattle, WA 98195 USA.
[Aljurf, Mahmoud D.; Cooper, Brenda W.; Laughlin, Mary J.] Univ Wisconsin, Hosp & Clin, Dept Med, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI 53792 USA.
[Hematti, Peiman; Verdonck, Leo F.; Solh, Melhelm M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Hematti, Peiman; Solh, Melhelm M.; Norkin, Maxim] Univ Penn, Med Ctr, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Reddy, Vijay; Perez-Simon, Jose A.; Khera, Nandita] Temple Bone Marrow Transplant Program, Div Bone Marrow Transplantat, Philadelphia, PA USA.
[Lewis, Ian D.; Atsuta, Yoshiko; Olsson, Richard F.] Mem Sloan Kettering Canc Ctr, Dept Pediat, Div Bone Marrow Transplant, New York, NY 10021 USA.
[Saber, Wael; Waller, Edmund K.; Blaise, Didier] Karolinska Univ Hosp, Div Clin Immunol, Stockholm, Sweden.
[Saber, Wael; Waller, Edmund K.; Blaise, Didier] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
[Pidala, Joseph A.; Martin, Paul J.; Satwani, Prakash] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN 37235 USA.
[Martin, Paul J.] Hop St Louis, Div Hematol, Paris, France.
[Satwani, Prakash; Bornhauser, Martin] Univ British Columbia, British Columbias Childrens Hosp, Dept Pediat Hematol Oncol BMT, Vancouver, BC V5Z 1M9, Canada.
[Bornhauser, Martin; Inamoto, Yoshihiro] Massachusetts Gen Hosp, Dept Bone Marrow Transplant Oncol, Boston, MA 02114 USA.
[Inamoto, Yoshihiro; Weisdorf, Daniel J.] Kyushu Univ Hosp, Fukuoka 812, Japan.
[Horowitz, Mary M.] Ottawa Hosp, Dept Med, Ottawa, ON, Canada.
[Horowitz, Mary M.; Pavletic, Steven Z.] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC USA.
[Pavletic, Steven Z.; Graft-Vs-Host Dis Working Comm CIB] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO USA.
RP Pavletic, SZ (reprint author), NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10 CRC,Room 3E-3330, Bethesda, MD 20892 USA.
EM pavletis@mail.nih.gov
RI IBIS, ONCOHEMATOLOGI/P-3457-2015;
OI Olsson, Richard/0000-0001-5970-2128
FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and
Blood Institute (NHLBI) [U24-CA76518]; National Institute of Allergy and
Infectious Diseases (NIAID) [U24-CA76518]; NHLBI [5U01HL069294]; NCI;
Health Resources and Services Administration [HHSH234200637015C]; Office
of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.;
Amgen, Inc.; Angioblast; Anonymous donation to the Medical College of
Wisconsin; Ariad; Be The Match Foundation; Blue Cross and Blue Shield
Association; Buchanan Family Foundation; CaridianBCT; Celgene
Corporation; CellGenix, GmbH; Fresenius-Biotech North America, Inc.;
Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme
Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma;
Medical College of Wisconsin; Merck 82 Co, Inc.; Millennium: The Takeda
Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow
Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics,
Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle
Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global
Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan
Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; Therakos;
WellPoint The views expressed in this article do not reflect the
official policy or position of the NIH; Department of the Navy;
Department of Defense, or any other agency of the U.S. Government
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA76518 from the National Cancer Institute (NCI), the
National Heart, Lung, and Blood Institute (NHLBI) (U24-CA76518), and the
National Institute of Allergy and Infectious Diseases (NIAID)
(U24-CA76518); Grant/Cooperative Agreement 5U01HL069294 from the NHLBI
and NCI; contract HHSH234200637015C with Health Resources and Services
Administration; 2 grants (N00014-06-1-0704 and N00014-08-1-0058) from
the Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.;
Angioblast; Anonymous donation to the Medical College of Wisconsin;
Ariad; Be The Match Foundation; Blue Cross and Blue Shield Association;
Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix,
GmbH; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint
Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline;
HistoGenetics, Inc.; Kiadis Pharma; The Medical College of Wisconsin;
Merck 82 Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA,
Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum
Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau
Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood
Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum;
Tarix Pharmaceuticals; Teva Neuroscience, Inc.; Therakos; and WellPoint
The views expressed in this article do not reflect the official policy
or position of the NIH, the Department of the Navy, the Department of
Defense, or any other agency of the U.S. Government.
NR 32
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U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
BP 266
EP 274
DI 10.1016/j.bbmt.2014.10.021
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UW
UT WOS:000348632700009
PM 25445023
ER
PT J
AU Bona, K
London, WB
Guo, DJ
Abel, G
Lehmann, L
Wolfe, J
AF Bona, Kira
London, Wendy B.
Guo, Dongjing
Abel, Gregory
Lehmann, Leslie
Wolfe, Joanne
TI Prevalence and Impact of Financial Hardship among New England Pediatric
Stem Cell Transplantation Families
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Pediatric; Hematopoietic stem cell transplantation; Financial hardship;
Graft-versus-host disease; Poverty
ID QUALITY-OF-LIFE; LOW-INCOME; CHILD HEALTH; MULTISITE SURVEILLANCE;
SOCIOECONOMIC-STATUS; CANCER-TREATMENT; CYSTIC-FIBROSIS;
ECONOMIC-IMPACT; FOOD SECURITY; COSTS
AB Poverty is correlated with negative health outcomes in pediatric primary care and subspecialties; its association with childhood hematopoietic stem cell transplantation (HSCT) patterns of care and clinical outcomes is not known. We describe family-reported financial hardship at a primary referral center in New England and explore the relationship between measures of poverty and patterns of care and clinical outcomes. Forty-five English-speaking parents of children after allogeneic HSCT in the prior 12 months completed a 1-time survey (response rate 88%). Low-income families, defined as <= 200% federal poverty level (FPL), were compared with all others. Eighteen (40%) families reported pre-HSCT incomes <= 200% FPL. Material hardship, including food, housing, or energy insecurity was reported by 17 (38%) families in the cohort. Low-income families reported disproportionate transplantation-related income losses, with 7 (39%) reporting annual income losses of >40% compared with 2 (18%) wealthier families (P = .02). In univariate analyses, 11(61%) low-income children experienced graft-versus-host disease (GVHD) of any grade in the first 180 days after HSCT compared with 2 (7%) wealthier children (P = .004). We conclude that low income and, in particular, material hardship, are prevalent in a New England pediatric HSCT population and represent targets for improvement in quality of life. The role of poverty in mediating GVHD deserves further investigation in larger studies that can control for known risk factors and may provide a targetable source of transplantation-associated morbidity. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Bona, Kira; London, Wendy B.; Guo, Dongjing; Lehmann, Leslie; Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA.
[Bona, Kira; London, Wendy B.; Guo, Dongjing; Lehmann, Leslie; Wolfe, Joanne] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA USA.
[Bona, Kira; London, Wendy B.; Abel, Gregory; Lehmann, Leslie; Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MA USA.
[Bona, Kira; Abel, Gregory; Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Populat Res, Boston, MA 02115 USA.
[Abel, Gregory] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Oncol, Boston, MA 02115 USA.
[Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
RP Bona, K (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM kira.bona@childrens.harvard.edu
FU Family Reach Foundation; Pedals for Pediatrics; St. Baldrick's
Foundation; National Palliative Care Research Center; American Society
of Clinical Oncology
FX The authors thank our families for sharing their time and stories with
us. The authors additionally thank Dr. Deborah Frank and colleagues for
sharing their research experience and measurement instruments. This
study was funded in part by grants from the Family Reach Foundation and
Pedals for Pediatrics. Dr. Bona is supported by grants from the St.
Baldrick's Foundation, the National Palliative Care Research Center, and
the American Society of Clinical Oncology.
NR 48
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U1 4
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
BP 312
EP 318
DI 10.1016/j.bbmt.2014.10.016
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UW
UT WOS:000348632700016
PM 25445021
ER
PT J
AU Vij, R
Kumar, S
Zhang, MJ
Zhong, XB
Huang, JX
Dispenzieri, A
Abidi, MH
Bird, JM
Freytes, CO
Gale, RP
Kindwall-Keller, TL
Kyle, RA
Landsburg, DJ
Lazarus, HM
Munker, R
Roy, V
Sharma, M
Vogl, DT
Wirk, B
Hari, PN
AF Vij, Ravi
Kumar, Shaji
Zhang, Mei-Jie
Zhong, Xiaobo
Huang, Jiaxing
Dispenzieri, Angela
Abidi, Muneer H.
Bird, Jennifer M.
Freytes, Cesar O.
Gale, Robert Peter
Kindwall-Keller, Tamila L.
Kyle, Robert A.
Landsburg, Daniel J.
Lazarus, Hillard M.
Munker, Reinhold
Roy, Vivek
Sharma, Manish
Vogl, Dan T.
Wirk, Baldeep
Hari, Parameswaran N.
TI Impact of Pretransplant Therapy and Depth of Disease Response before
Autologous Transplantation for Multiple Myeloma
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Myeloma; Primary refractory; Autologous transplant
ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; COMPLETE REMISSION;
INTENSIVE THERAPY; CHEMOTHERAPY; SURVIVAL; INDUCTION; OUTCOMES; BENEFIT
AB Patients with multiple myeloma (MM) who are eligible for autologous stem cell transplantation (ASCT) typically receive a finite period of initial therapy before ASCT. It is not clear if patients with suboptimal (less than a partial) response to initial therapy benefit from additional alternative therapy with intent to maximize pretransplant response. We identified 539 patients with MM who had an ASCT after having achieved less than a partial response (PR) to first-line induction chemotherapy between 1995 and 2010. These patients were then divided into 2 groups: those who received additional salvage chemotherapy before ASCT (n = 324) and those who had no additional salvage chemotherapy immediately before ASCT (n = 215). Additional pretransplant chemotherapy resulted in deepening responses in 68% (complete response in 8% and PR in 60%). On multivariate analysis there was no impact of pretransplant salvage chemotherapy on treatment-related mortality, risk for relapse, progression-free survival, or overall survival. In conclusion, for patients achieving less than a PR to initial induction therapy, including with novel agent combinations, additional pre-ASCT salvage chemotherapy improved the depth of response and pre-ASCT disease status but was not associated with survival benefit. (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Vij, Ravi] Washington Univ, Sch Med, Div Hematol & Oncol, St Louis, MO USA.
[Kumar, Shaji; Dispenzieri, Angela; Kyle, Robert A.] Mayo Clin, Dept Hematol, Rochester, MN USA.
[Zhang, Mei-Jie; Zhong, Xiaobo; Huang, Jiaxing; Hari, Parameswaran N.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Div Hematol & Oncol, Milwaukee, WI 53226 USA.
[Zhang, Mei-Jie] Inst Hlth & Soc, Div Biostat, Milwaukee, WI USA.
[Abidi, Muneer H.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Div BMT, Detroit, MI USA.
[Bird, Jennifer M.] Univ Hosp Bristol NHS, Dept Haematol, Bristol, Avon, England.
[Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, Div Expt Med, London, England.
[Kindwall-Keller, Tamila L.] Univ Virginia Hlth Syst, Div Hematol Oncol, Charlottesville, VA USA.
[Landsburg, Daniel J.; Vogl, Dan T.] Univ Penn, Abramson Canc Ctr, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA.
[Munker, Reinhold] Louisiana State Univ Hlth Shreveport, Dept Internal Med, Div Hematol Oncol, Shreveport, LA USA.
[Roy, Vivek] Mayo Clin, Blood & Marrow Transplant Program, Jacksonville, FL 32224 USA.
[Sharma, Manish] Thomas Jefferson Univ, Dept Internal Med, Philadelphia, PA 19107 USA.
[Wirk, Baldeep] SUNY Stony Brook, Med Ctr, Dept Internal Med, Stony Brook, NY 11794 USA.
RP Hari, PN (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Div Hematol & Oncol, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA.
EM phari@mcw.edu
RI Kumar, Shaji/A-9853-2008;
OI Kumar, Shaji/0000-0001-5392-9284; Abidi, Muneer/0000-0002-9936-6031;
Hari, Parameswaran/0000-0002-8800-297X; Dispenzieri,
Angela/0000-0001-8780-9512
FU National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung,
and Blood Institute (NHLBI); National Institute of Allergy and
Infectious Diseases (NIAID); NHLBI and NCI [5U10HL069294]; Health
Resources and Services Administration [HHSH250201200016C]; Office of
Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Office of Naval
Research; *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen,
Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be
The Match Foundation; *Blue Cross and Blue Shield Association; *Celgene
Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center;
Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture
Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation;
GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute;
HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's
Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH;
Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda
Oncology Co.; Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National
Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions,
Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.;
Perkin Elmer, Inc.; *Remedy Informatics; Sanofi US; Seattle Genetics;
Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation;
StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.;
Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *Terumo BCT; *Teva
Neuroscience, Inc.; *Therakos; University of Minnesota; University of
Utah; WellPoint
FX Financial disclosure: The CIBMTR is supported by Public Health Service
Grant/Cooperative Agreement U24-CA076518 from the National Cancer
Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI),
and the National Institute of Allergy and Infectious Diseases (NIAID);
Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; contract
HHSH250201200016C with the Health Resources and Services Administration;
2 grants (N00014-12-1-0142 and N00014-13-1-0039) from the Office of
Naval Research; and grants from *Actinium Pharmaceuticals; Allos
Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical
College of Wisconsin; Ariad; Be The Match Foundation; *Blue Cross and
Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred
Hutchinson Cancer Research Center; Fresenius-Biotech North America,
Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium
SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell
Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff
Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma
Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.;
Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi
Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum
Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi
US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St.
Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.;
Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix
Pharmaceuticals; *Terumo BCT; *Teva Neuroscience, Inc.; *Therakos;
University of Minnesota; University of Utah; and *WellPoint The views
expressed in this article do not reflect the official policy or position
of the National Institutes of Health, the Department of the Navy, the
Department of Defense, Health Resources and Services Administration; or
any other agency of the U.S. Government. Asterisk (*) indicates
corporate members.
NR 19
TC 14
Z9 14
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
BP 335
EP 341
DI 10.1016/j.bbmt.2014.10.023
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UW
UT WOS:000348632700019
PM 25445028
ER
PT J
AU Billen, A
Madrigal, JA
Strydom, A
Szydlo, RM
Switzer, GE
Shaw, BE
AF Billen, Annelies
Madrigal, J. Alejandro
Strydom, Andre
Szydlo, Richard M.
Switzer, Galen E.
Shaw, Bronwen E.
TI Predonation Health-Related Quality of Life Scores Predict Time to
Recovery in Hematopoietic Stem Cell Donors
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Peripheral blood stem cells; Bone marrow; Donation experience;
Health-related quality of life
ID COLONY-STIMULATING FACTOR; UNRELATED BONE-MARROW; ADVERSE EVENTS;
PROSPECTIVE TRIAL; FOLLOW-UP; BLOOD; DONATION; PAIN; DEPRESSION;
EXPERIENCE
AB The physical reactions to hematopoietic stem cell donation have been extensively studied, but less is known about factors that predict poorer donation experiences. The aim of this prospective study was to examine demographic and health-related quality of life (HRQOL) factors that might be associated with recovery and side effects. We also described the changes in HRQOL during the donation process. In total, 275 peripheral blood stem cell (PBSC) and 37 bone marrow (BM) consecutive donors completed the SF-36 questionnaire predonation and 4 weeks, and 3 months postdonation. Predonation HRQOL markers were the strongest predictors of time to recovery. Poorer predonation physical health was associated with longer recovery (P = .017) and certain side effects in PBSC donors. Poorer predonation mental health was associated with longer recovery in BM donors (P = .03) and pain after PBSC donation (P = .003). Physical HRQOL scores declined significantly from predonation to 4 weeks postdonation. This was shown both for PBSC and BM donors (P < .001 and P = .009, respectively), but the decline was much greater for BM donors. There was a return to predonation HRQOL values 3 months after donation in both groups with values well above the mean of the general population (P < .001). (C) 2015 American Society for Blood and Marrow Transplantation.
C1 [Billen, Annelies; Madrigal, J. Alejandro; Shaw, Bronwen E.] UCL, Inst Canc, London, England.
[Billen, Annelies; Madrigal, J. Alejandro; Shaw, Bronwen E.] Anthony Nolan Res Inst, London, England.
[Strydom, Andre] UCL, Mental Hlth Sci Unit, London, England.
[Szydlo, Richard M.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England.
[Switzer, Galen E.] Univ Pittsburgh, Dept Gen Internal Med, Pittsburgh, PA USA.
[Switzer, Galen E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
[Shaw, Bronwen E.] Royal Marsden Hosp, Dept Haematol, London SW3 6JJ, England.
RP Billen, A (reprint author), Anthony Nolan,2 Heathgate Pl,75-87 Agincourt Rd, London NW3 2N, England.
EM Annelies.billen@anthonynolan.org
RI Szydlo, Richard/C-6678-2012
OI Szydlo, Richard/0000-0003-1102-8298
NR 36
TC 3
Z9 4
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
BP 350
EP 356
DI 10.1016/j.bbmt.2014.10.028
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UW
UT WOS:000348632700021
PM 25452034
ER
PT J
AU Bedair, H
Yang, J
Dwyer, MK
McCarthy, JC
AF Bedair, Hany
Yang, Judy
Dwyer, Maureen K.
McCarthy, Joseph C.
TI Preoperative Erythropoietin Alpha Reduces Postoperative Transfusions in
THA and TKA but May Not Be Cost-effective
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID TOTAL KNEE ARTHROPLASTY; PRIMARY TOTAL HIP; AUTOLOGOUS BLOOD-DONATION;
TOTAL JOINT ARTHROPLASTY; RECOMBINANT-HUMAN-ERYTHROPOIETIN; TRANEXAMIC
ACID; ORTHOPEDIC-SURGERY; EPOETIN-ALPHA; REPLACEMENT; TRIAL
AB Preoperative erythropoietin alpha (EPO) has been shown to be effective at reducing postoperative blood transfusions in total hip arthroplasty (THA) and total knee arthroplasty (TKA); however, treatment with EPO is associated with additional costs, and it is not known whether these costs can be justified when weighed against the transfusion reductions achieved in patients who receive the drug.
The purpose of this study is to investigate (1) efficacy of preoperative EPO in reducing postoperative transfusions in TKA and THA; (2) whether patients treated with EPO have reduced length of stay or a different discharge disposition; and (3) whether EPO use reduces overall blood management costs.
Patients undergoing primary THA or TKA over a 10-month period with preoperative hemoglobin < 13 g/dL were recommended to be treated preoperatively with EPO. During that time, 80 of 286 (28%) patients met that inclusion criterion and the treating team recommended EPO to all of them; of that group, 24 (30%) opted to take EPO and 56 (70%) opted not to. Patients receiving at least one dose of EPO and those not receiving EPO were compared in terms of transfusion frequency, length of stay and discharge disposition, and overall blood management costs. Demographics, preoperative hemoglobin, and operative blood loss for both groups were similar (p > 0.05). No transfusion triggers were used; rather, patients with postoperative hemoglobin < 10 mg/dL and who were symptomatic despite fluid boluses were transfused. The clinician responsible for transfusing symptomatic patients was blinded to the patient's EPO treatment status. Costs were defined as direct costs paid or incurred by our institution for EPO, allogeneic blood, and variable costs associated with patient care after THA/TKA. A decision-tree cost analysis was performed using the collected clinical data and cost data collected from our institution; the analysis considered total associated blood management cost for an EPO and a non-EPO strategy with sensitivity analysis of key cost variables.
The proportion of patients receiving transfusions was lower in patients who received EPO than in patients who did not (0% [zero of 24] versus 41% [23 of 56]; p < 0.001). The mean length of inpatient hospital stay (EPO: 3.0 +/- A 0.4 versus control: 3.3 +/- A 0.8 days, p = 0.77) and discharge disposition also was not different between the groups. The cost analysis demonstrated that the EPO strategy was more costly compared with no EPO (USD 2632 versus USD 2284) and its cost would need to be less than USD 225/dose for this to change.
EPO reduced the need for postoperative transfusions in high-risk patients undergoing THA and TKA; however, it was not found to be cost-effective in our model. Our model could not consider relatively rare complications of blood transfusions, including disease transmission, deep periprosthetic infections, and transfusion reactions, but if surgeons or patients value avoiding these potential but rare factors highly, this could reasonably influence the decision of whether to use EPO despite our findings that it was not cost-effective.
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
C1 [Bedair, Hany; Dwyer, Maureen K.; McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA.
[Bedair, Hany; Yang, Judy; Dwyer, Maureen K.; McCarthy, Joseph C.] Newton Wellesley Hosp, Kaplan Ctr Joint Reconstruct Surg, Newton, MA 02462 USA.
RP Bedair, H (reprint author), Newton Wellesley Hosp, Kaplan Ctr Joint Reconstruct Surg, 2014 Washington St,Green Bldg,Suite 361, Newton, MA 02462 USA.
EM hbedair@partners.org
NR 39
TC 15
Z9 16
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2015
VL 473
IS 2
BP 590
EP 596
DI 10.1007/s11999-014-3819-z
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AZ6QY
UT WOS:000348344900035
PM 25106796
ER
PT J
AU Hansen, VJ
Gromov, K
Lebrun, LM
Rubash, HE
Malchau, H
Freiberg, AA
AF Hansen, Viktor J.
Gromov, Kirill
Lebrun, Lauren M.
Rubash, Harry E.
Malchau, Henrik
Freiberg, Andrew A.
TI Does the Risk Assessment and Prediction Tool Predict Discharge
Disposition After Joint Replacement?
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID TOTAL KNEE REPLACEMENT; TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE;
RESOURCE UTILIZATION; COST-EFFECTIVENESS
AB Payers of health services and policymakers place a major focus on cost containment in health care. Studies have shown that early planning of discharge is essential in reducing length of stay and achieving financial benefit; tools that can help predict discharge disposition would therefore be of use. The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA). The RAPT was developed and tested on a population of Australian patients undergoing joint replacement, but its validity in other populations is unknown. A low RAPT score is reported to indicate a high risk of needing any form of inpatient rehabilitation after TJA, including short-term nursing facilities.
This study attempts (1) to assess predictive accuracy of the RAPT on US patients undergoing total hip and knee arthroplasty (THA/TKA); and (2) to determine predictive accuracy of each individual score (1-12).
Between June 2006 and December 2011, RAPT scores of 3213 patients (1449 THAs; 1764 TKAs) were prospectively captured during the preoperative clinical visit. Scores were stored along with other clinical data, including discharge disposition, in a dedicated database on a secure server. The database was queried by the nursing case manager to retrieve the RAPT scores of all patients captured during this time period. Binary logistic regression was used to analyze the scores and determine predictive accuracy.
Overall predictive accuracy was 78%. RAPT scores < 6 and > 10 (of 12) predicted with > 90% accuracy discharge to inpatient rehabilitation and home, respectively. Predictive accuracy was lowest for scores between 7 and 10 at 65.2% and almost 50% of patients received scores in this range. Based on our findings, the risk categories in our populations should be high risk < 7, intermediate risk 7 to 10, and low risk > 10.
The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort. Based on our data, intermediate-risk patients should be defined as those with scores of 7 to 10. Predictive accuracy for these patients could potentially be improved through the identification and addition of other factors correlated to discharge disposition. The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care. Additionally, it identifies intermediate-risk patients and could be used to implement targeted interventions to facilitate discharge home in this group of patients.
Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.
C1 [Hansen, Viktor J.; Gromov, Kirill; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Lebrun, Lauren M.; Rubash, Harry E.; Malchau, Henrik; Freiberg, Andrew A.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Gromov, Kirill] Copenhagen Univ Hosp, Dept Orthopaed Surg, Copenhagen, Denmark.
RP Freiberg, AA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,Yawkey Suite 3B, Boston, MA 02114 USA.
EM afreiberg@mgh.harvard.edu
NR 16
TC 9
Z9 9
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2015
VL 473
IS 2
BP 597
EP 601
DI 10.1007/s11999-014-3851-z
PG 5
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AZ6QY
UT WOS:000348344900036
PM 25106801
ER
PT J
AU Dwyer, MK
Jones, HL
Field, RE
McCarthy, JC
Noble, PC
AF Dwyer, Maureen K.
Jones, Hugh L.
Field, Richard E.
McCarthy, Joseph C.
Noble, Philip C.
TI Femoroacetabular Impingement Negates the Acetabular Labral Seal During
Pivoting Maneuvers but Not Gait
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID FINITE-ELEMENT MODEL; HIP-JOINT; OSTEOARTHRITIS; MECHANICS; FEATURES;
ANATOMY; DAMAGE; TEARS; MRI
AB Experimental disruption of the labrum has been shown to compromise its sealing function and alter cartilage lubrication. However, it is not known whether pathological changes to the labrum secondary to femoroacetabular impingement (FAI) have a similar impact on labral function.
Does damage to the labrum occurring in association with abnormal femoral morphology affect the labral seal?
Using 10 fresh cadaveric specimens (mean age 50 years, +/- A 8), we measured the capacity of the central compartment of the hip (the iliofemoral joint) to maintain a seal during fluid infusion, which may help elucidate the function of the labrum during weightbearing. Specimens with and without abnormal femoral morphology (six normal-appearing specimens and four whose geometry suggested cam-type FAI) were tested in postures observed during functional activities, including simulations of normal gait, stooping, and pivoting. Each specimen with FAI morphology exhibited secondary damage of the labrum and the adjacent chondral surface, whereas specimens of normal morphology were undamaged.
Average peak central compartment pressure was reduced during pivoting for specimens with the presence of labral damage secondary to FAI. When placed in pivoting positions, hips with FAI maintained lower fluid pressures within the central compartment compared with intact specimens (15 +/- A 3 versus 42 +/- A 8 kPa, respectively; effect size: 1.08 [-0.36 to 2.31]; p = 0.007). No differences in peak pressure were observed between groups (FAI versus normal) for postures simulating either gait (21 +/- A 6 versus 22 +/- A 4 kPa; p = 0.902) or stooping (9 +/- A 2 versus 8 +/- A 3 kPa; p = 0.775) with the numbers available.
The acetabular seal, quantified by the maximum intraarticular pressure, was reduced during pivoting; however, the seal was maintained during simulated gait and stooping.
Because degeneration is progressive with repetitive impingement, loss of the labral seal starts to be seen during pivoting and may progress from there, but in this small-sample cadaver study that evaluated specimens in middle adulthood, the seal remains intact during simulated gait and stooping. Our study suggests that labral damage secondary to cam-type FAI may reduce the ability of the labral to provide an adequate seal of the central compartment of the hip during loading; however, the extent to which this is affected requires further investigation.
C1 [Dwyer, Maureen K.; McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA.
[Dwyer, Maureen K.; McCarthy, Joseph C.] Newton Wellesley Hosp, Kaplan Joint Ctr, Newton, MA 02462 USA.
[Jones, Hugh L.; Noble, Philip C.] Inst Orthoped Res & Educ, Houston, TX USA.
[Field, Richard E.] St Anthony Hosp, Sutton, Surrey, England.
[Noble, Philip C.] Baylor Coll Med, Houston, TX 77030 USA.
RP Dwyer, MK (reprint author), Newton Wellesley Hosp, Kaplan Joint Ctr, 2000 Washington St,Green Bldg,Suite 361, Newton, MA 02462 USA.
EM mkdwyer@partners.org
NR 22
TC 3
Z9 3
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2015
VL 473
IS 2
BP 602
EP 607
DI 10.1007/s11999-014-3760-1
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AZ6QY
UT WOS:000348344900037
PM 24989124
ER
PT J
AU Hageman, MGJS
Briet, JP
Bossen, JK
Blok, RD
Ring, DC
Vranceanu, AM
AF Hageman, Michiel G. J. S.
Briet, Jan Paul
Bossen, Jeroen K.
Blok, Robin D.
Ring, David C.
Vranceanu, Ana-Maria
TI Do Previsit Expectations Correlate With Satisfaction of New Patients
Presenting for Evaluation With an Orthopaedic Surgical Practice?
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID TOTAL HIP-ARTHROPLASTY; PRIMARY-CARE; HEALTH-CARE; PREOPERATIVE
EXPECTATIONS; GENERAL-PRACTICE; DETERMINANTS; CONSULTATIONS; POPULATION;
PREDICTORS; SURGERY
AB Patient satisfaction is associated with increased compliance, improved treatment outcomes, and decreased risk of litigation. Factors such as patient understanding and psychological well-being are recognized influences on satisfaction. Less is known about the relationship between previsit expectations and satisfaction.
(1) Are there correlations among previsit expectations, met expectations, and patient satisfaction? (2) What are the categories of expectations, and which one(s) correlate with satisfaction?
Eighty-six new patients presenting to a hand surgery practice of a tertiary referral hospital with 70% direct primary care referrals, mostly with elective concerns, indicated their previsit expectations (Patient Intention Questionnaire [PIQ]). Immediately after the visit, the same patients rated the degree to which their previsit expectations were met (Expectation Met Questionnaire [EMQ]) and their satisfaction level (Medical Interview Satisfaction Scale). These tools have been used in primary care office settings and claim good psychometric properties, and although they have not been strictly validated for responsiveness and other test parameters, they have good face validity. We then conducted a multivariable backward linear regression to determine whether (1) scores on the PIQ; and (2) scores on the EMQ are associated with satisfaction.
Satisfaction correlated with met expectations (r = 0.36; p < 0.001) but not with previsit expectations (r = -0.01, p = 0.94). We identified five primary categories of previsit expectations that accounted for 50% of the variance in PIQ: (1) "Information and Explanation"; (2) "Emotional and Understanding"; (3) "Emotional Problems"; (4) "Diagnostics"; and (5) "Comforting". The only category of met expectations that correlated with satisfaction was Information and Explanation (r = 0.43; p < 0.001).
Among patients seeing a hand surgeon, met expectations correlate with satisfaction. In particular, patients with met expectations regarding information and explanation were more satisfied with their visit. Efforts to determine the most effective methods for conveying unexpected information warrant investigation.
Level II, prognostic study.
C1 [Hageman, Michiel G. J. S.; Briet, Jan Paul; Bossen, Jeroen K.; Blok, Robin D.; Ring, David C.; Vranceanu, Ana-Maria] Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Boston, MA 02114 USA.
RP Ring, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM d.ring@mgh.harvard.edu
OI Blok, Robin/0000-0002-5291-546X
FU "Marti kuning Eckhardt fonds"; "Spinoza fonds"; "AnnaFonds Travel grant"
(Dutch orthopaedic travel grant)
FX One of the authors (MGJSH) was supported by "Marti kuning Eckhardt
fonds," a nonmedical study grant, "Spinoza fonds," a nonmedical study
grant, and a "AnnaFonds Travel grant" (Dutch orthopaedic travel grant).
One of the authors (RDB) was supported by "Spinza fonds," a nonmedical
study grant.
NR 27
TC 4
Z9 4
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2015
VL 473
IS 2
BP 716
EP 721
DI 10.1007/s11999-014-3970-6
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AZ6QY
UT WOS:000348344900053
PM 25269531
ER
PT J
AU Teunis, T
Nota, SPFT
Schwab, JH
AF Teunis, Teun
Nota, Sjoerd P. F. T.
Schwab, Joseph H.
TI Do Corresponding Authors Take Responsibility for Their Work? A Covert
Survey
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID AVAILABILITY; METAANALYSIS; SCIENCE; TRIALS
AB Publication of a manuscript does not end an author's responsibilities. Reasons to contact an author after publication include clarification, access to raw data, and collaboration. However, legitimate questions have been raised regarding whether these responsibilities generally are being met by corresponding authors of biomedical publications.
This study aims to establish (1) what proportion of corresponding authors accept the responsibility of correspondence; (2) identify characteristics of responders; and (3) assess email address decay with time. We hypothesize that the response rate is unrelated to journal impact factor.
We contacted 450 corresponding authors throughout various fields of biomedical research regarding the availability of additional data from their study, under the pretense of needing these data for a related review article. Authors were randomly selected from 45 journals whose impact factors ranged from 52 to 0; the source articles were published between May 2003 and May 2013. The proportion of corresponding authors who replied, along with author characteristics were recorded, as was the proportion of emails that were returned for inactive addresses; 446 authors were available for final analysis.
Fifty-three percent (190/357) of the authors with working email addresses responded to our request. Clinical researchers were more likely to reply than basic/translational scientists (51% [114/225] versus 34% [76/221]; p < 0.001). Impact factor and other author characteristics did not differ. Logistic regression analysis showed that the odds of replying decreased by 15% per year (odds ratio [OR], 0.85; 95% CI, 0.79-0.91; p < 0.001), and showed a positive relationship between clinical research and response (OR, 2.0; 95% CI, 1.3-2.9; p = 0.001). In 2013 all email addresses (45/45) were reachable, but within 10 years, 49% (21/43) had become invalid.
Our results suggest that contacting corresponding authors is problematic throughout the field of biomedical research. Defining the responsibilities of corresponding authors by journals more explicitly-particularly after publication of their manuscript-may increase the response rate on data requests. Possible other ways to improve communication after research publication are: (1) listing more than one email address per corresponding author, eg, an institutional and personal address; (2) specifying all authors' email addresses; (3) when an author leaves an institution, send an automated reply offering alternative ways to get in touch; and (4) linking published manuscripts to research platforms.
C1 [Teunis, Teun; Nota, Sjoerd P. F. T.] Harvard Univ, Dept Orthopaed Surg, Musculoskeletal Oncol Serv, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
[Schwab, Joseph H.] Harvard Univ, Dept Orthopaed Surg, Musculoskeletal Oncol Serv, Massachusetts Gen Hosp,Med Sch,Spine Surg Serv, Boston, MA 02114 USA.
RP Teunis, T (reprint author), Harvard Univ, Dept Orthopaed Surg, Musculoskeletal Oncol Serv, Massachusetts Gen Hosp,Med Sch, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA.
EM teunteunis@gmail.com
FU Prince Bernhard Culture Fund; Kuitse Fung (Amsterdam, The Netherlands);
Fundatie van de Vrijvrouwe van Renswoude te's-Gravenhage (The Hague, The
Netherlands); Stryker (Kalamazoo, MI, USA); Biom'up (Saint-Priest,
France)
FX One of the authors (TT) received research grants from the Prince
Bernhard Culture Fund & Kuitse Fung (Amsterdam, The Netherlands) (less
than USD 10,000), and Fundatie van de Vrijvrouwe van Renswoude
te's-Gravenhage (The Hague, The Netherlands) (less than USD 10,000).;
One of the authors (JS) certifies that he, or a member of his immediate
family, has or may receive payments or benefits, during the study period
from Stryker (Kalamazoo, MI, USA) (less than USD 10,000), and Biom'up
(Saint-Priest, France) (less than USD 10,000).
NR 18
TC 4
Z9 4
U1 3
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2015
VL 473
IS 2
BP 729
EP 735
DI 10.1007/s11999-014-3868-3
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AZ6QY
UT WOS:000348344900055
PM 25123243
ER
PT J
AU Dzhala, V
Staley, KJ
AF Dzhala, Volodymyr
Staley, Kevin J.
TI Acute and Chronic Efficacy of Bumetanide in an in vitro Model of
Posttraumatic Epileptogenesis
SO CNS Neuroscience & Therapeutics
LA English
DT Article
DE Bumetanide; NKCC1; phenobarbital; posttraumatic seizures; Trauma
ID CATION-CHLORIDE COTRANSPORTERS; TEMPORAL-LOBE EPILEPSY; K-CL
COTRANSPORTER; NEONATAL SEIZURES; RAT HIPPOCAMPUS; NEURONAL
COMMUNICATION; SYNAPTIC PLASTICITY; EXCITATORY ACTIONS; INTERICTAL
SPIKES; DEVELOPING BRAIN
AB BackgroundSeizures triggered by acute injuries to the developing brain respond poorly to first-line medications that target the inhibitory chloride-permeable GABA(A) receptor. Neuronal injury is associated with profound increases in cytoplasmic chloride ([Cl-](i)) resulting in depolarizing GABA signaling, higher seizure propensity and limited efficacy of GABAergic anticonvulsants. The Na+-K+-2Cl(-) (NKCC1) cotransporter blocker bumetanide reduces [Cl-](i) and causes more negative GABA equilibrium potential in injured neurons. We therefore tested both the acute and chronic efficacy of bumetanide on early posttraumatic ictal-like epileptiform discharges and epileptogenesis.
MethodsAcute hippocampal slices were used as a model of severe traumatic brain injury and posttraumatic epileptogenesis. Hippocampal slices were then incubated for 3weeks. After a 1-week latent period, slice cultures developed chronic spontaneous ictal-like discharges. The anticonvulsant and anti-epileptogenic efficacy of bumetanide, phenobarbital, and the combination of these drugs was studied.
ResultsBumetanide reduced the frequency and power of early posttraumatic ictal-like discharges in vitro and enhanced the anticonvulsant efficacy of phenobarbital. Continuous 2-3weeks administration of bumetanide as well as phenobarbital in combination with bumetanide failed to prevent posttraumatic ictal-like discharges and epileptogenesis.
ConclusionsOur data demonstrate a persistent contribution of NKCC1 cotransport in posttraumatic ictal-like activity, presumably as a consequence of chronic alterations in neuronal chloride homeostasis and GABA-mediated inhibition. New strategies for more effective reduction in posttraumatic and seizure-induced [Cl-](i) accumulation could provide the basis for effective treatments for posttraumatic epileptogenesis and the resultant seizures.
C1 [Dzhala, Volodymyr; Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Staley, KJ (reprint author), MGH Neurol, CNY 114,Room 2600,114 16th St, Charlestown, MA 02129 USA.
EM staley.kevin@mgh.harvard.edu
FU NIH (NINDS) [RO1 NS 40109-13]
FX This study was supported by NIH grant RO1 NS 40109-13 (NINDS). We thank
Michelle Mail for technical assistance.
NR 55
TC 4
Z9 4
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-5930
EI 1755-5949
J9 CNS NEUROSCI THER
JI CNS Neurosci. Ther.
PD FEB
PY 2015
VL 21
IS 2
SI SI
BP 173
EP 180
DI 10.1111/cns.12369
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA CA3YL
UT WOS:000348841000011
PM 25495911
ER
PT J
AU Barnard, LS
Wexler, DJ
DeWalt, D
Berkowitz, SA
AF Barnard, Lily S.
Wexler, Deborah J.
DeWalt, Darren
Berkowitz, Seth A.
TI Material Need Support Interventions for Diabetes Prevention and Control:
a Systematic Review
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Diabetes mellitus; Social determinants of health; Food insecurity;
Poverty; Housing instability; Diabetes mellitus/therapy; Socioeconomic
status
ID NUTRITION EXAMINATION SURVEY; FOOD INSECURITY; SOCIAL DETERMINANTS;
CARDIOVASCULAR-DISEASE; MEDICATION UNDERUSE; SOCIOECONOMIC DISPARITIES;
FINANCIAL INCENTIVES; AFRICAN-AMERICAN; GLYCEMIC CONTROL;
SELF-MANAGEMENT
AB Unmet material needs, such as food insecurity and housing instability, are associated with increased risk of diabetes and worse outcomes among diabetes patients. Healthcare delivery organizations are increasingly held accountable for health outcomes that may be related to these "social determinants," which are outside the scope of traditional medical intervention. This review summarizes the current literature regarding interventions that provide material support for income, food, housing, and other basic needs. In addition, we propose a conceptual model of the relationship between unmet needs and diabetes outcomes and provide recommendations for future interventional research.
C1 [Barnard, Lily S.] Tufts Univ, Biol Program, Medford, MA 02155 USA.
[Barnard, Lily S.] Tufts Univ, Community Hlth Program, Medford, MA 02155 USA.
[Wexler, Deborah J.; Berkowitz, Seth A.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Wexler, Deborah J.; Berkowitz, Seth A.] Harvard Univ, Sch Med, Boston, MA USA.
[DeWalt, Darren] Univ N Carolina, Div Gen Internal Med & Clin Epidemiol, Chapel Hill, NC USA.
[Berkowitz, Seth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
RP Berkowitz, SA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM SABerkowitz@partners.org
OI Berkowitz, Seth/0000-0003-1030-4297; DeWalt, Darren/0000-0003-2270-751X
NR 70
TC 2
Z9 2
U1 4
U2 23
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
EI 1539-0829
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD FEB
PY 2015
VL 15
IS 2
AR 2
DI 10.1007/s11892-014-0574-1
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CA3EJ
UT WOS:000348788800006
ER
PT J
AU Buschur, E
Brown, F
Wyckoff, J
AF Buschur, Elizabeth
Brown, Florence
Wyckoff, Jennifer
TI Using Oral Agents to Manage Gestational Diabetes: What Have We Learned?
SO CURRENT DIABETES REPORTS
LA English
DT Article
DE Glyburide; Metformin; Pregnancy; Gestational diabetes; Oral agents
ID HYPOGLYCEMIC AGENTS; CLINICAL-PRACTICE; PERINATAL OUTCOMES; PREGNANCY
OUTCOMES; HUMAN PLACENTA; FETAL SAFETY; GLYBURIDE; INSULIN; METFORMIN;
MELLITUS
AB Insulin has been the mainstay of treatment of diabetes during pregnancy for decades. Although glyburide and metformin are classified as category B during pregnancy, recent research has suggested that these oral agents alone or in conjunction with insulin may be safe for the treatment of gestational diabetes (GDM). This paper summarizes the data on the use of glyburide and metformin for treatment of GDM.
C1 [Buschur, Elizabeth; Wyckoff, Jennifer] Univ Michigan, Ann Arbor, MI 48105 USA.
[Brown, Florence] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Wyckoff, J (reprint author), Univ Michigan, 24 Frank Lloyd Wright Dr, Ann Arbor, MI 48105 USA.
EM eliosbor@med.umich.edu; Florence.brown@joslin.harvard.edu;
jwyckoff@med.umich.edu
NR 66
TC 0
Z9 0
U1 1
U2 5
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
EI 1539-0829
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD FEB
PY 2015
VL 15
IS 2
AR 4
DI 10.1007/s11892-014-0570-5
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CA3EJ
UT WOS:000348788800002
ER
PT J
AU Satterthwaite, TD
Baker, JT
AF Satterthwaite, Theodore D.
Baker, Justin T.
TI How can studies of resting-state functional connectivity help us
understand psychosis as a disorder of brain development?
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID BIPOLAR DISORDER; DEFAULT NETWORK; SCHIZOPHRENIA; ORGANIZATION; MOTION;
DYSCONNECTIVITY; ARCHITECTURE; DYNAMICS; IMPACT; CORTEX
AB Psychosis is increasingly being understood as a neurodevelopmental 'dysconnection' syndrome, in which neural connectivity at both microscopic and macroscopic levels of brain organization becomes disrupted during late adolescence and early adulthood. Tools to quantify normative brain development and identify individuals at risk are urgently needed to tailor appropriate strategies for prevention and intervention, and could substantially improve clinical outcomes. Resting-state functional connectivity magnetic resonance imaging (rsfc-MRI) provides a rich, functional description of the brain's macroscopic connectivity structure. Over the past several years, rsfc-MRI has evolved to be a powerful tool for studying both normal brain development and abnormalities associated with psychosis. Several recent advances highlight intriguing and potentially significant parallels between these two lines of research. For instance, rsfc-MRI work suggests that psychosis is accompanied by loss of segregation between large-scale brain association networks, a pattern that is normal in early life but typically matures into more segregated systems by young adulthood. Coupled with data sharing across large-scale neuroimaging studies, longitudinal assessments using rsfc-MRI in patients and those at risk will be essential for improving our biological understanding of psychosis and will help inform diagnosis, prognosis, and clinical decision-making.
C1 [Satterthwaite, Theodore D.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Baker, Justin T.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA.
[Baker, Justin T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Satterthwaite, TD (reprint author), Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM sattertt@upenn.edu
FU NIMH [K23MH098130, K23MH104515-01]; Marc Rapport Family Investigator
grant through the Brain and Behavior Foundation; Maria Lorenz Pope
Fellowship; [KL2 TR001100]
FX TDS was supported by NIMH K23MH098130 and the Marc Rapport Family
Investigator grant through the Brain and Behavior Foundation. JTB was
supported by KL2 TR001100 (Harvard Catalyst), the Maria Lorenz Pope
Fellowship, and NIMH K23MH104515-01.
NR 50
TC 11
Z9 11
U1 3
U2 12
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
EI 1873-6882
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD FEB
PY 2015
VL 30
BP 85
EP 91
DI 10.1016/j.conb.2014.10.005
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA AZ6OA
UT WOS:000348337600013
PM 25464373
ER
PT J
AU Neale, BM
Sklar, P
AF Neale, Benjamin M.
Sklar, Pamela
TI Genetic analysis of schizophrenia and bipolar disorder reveals
polygenicity but also suggests new directions for molecular
interrogation
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; RARE
CHROMOSOMAL DELETIONS; SCAN METAANALYSIS; HYPERACTIVITY DISORDER;
ATTENTION-DEFICIT; HAPLOTYPE MAP; DUPLICATIONS; LOCI
AB Over the last few years, genetics research has made significant strides in identifying many risk factors for schizophrenia and bipolar disorder. These risk factors include inherited common single nucleotide polymorphisms, copy number variants, and rare single nucleotide variants, as well as rare de novo variants. For all variants, the common theme has been that of polygenicity, meaning that many small genetic risk factors influence risk in the population and that no gene or variant on its own has been shown to be fully deterministic of schizophrenia or bipolar. When taken together, biological themes that have emerged including the importance of synaptic function and calcium signaling. This has implications for our understanding of the biological underpinnings of these diseases.
C1 [Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Neale, Benjamin M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Neale, Benjamin M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Sklar, Pamela] Icahn Sch Med Mt Sinai, Div Psychiat Genom, Dept Psychiat, New York, NY 10029 USA.
RP Neale, BM (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
EM bneale@broadinstitute.org; pamela.sklar@mssm.edu
NR 62
TC 23
Z9 23
U1 5
U2 18
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
EI 1873-6882
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD FEB
PY 2015
VL 30
BP 131
EP 138
DI 10.1016/j.conb.2014.12.001
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AZ6OA
UT WOS:000348337600019
PM 25544106
ER
PT J
AU Sosenko, JM
Skyler, JS
DiMeglio, LA
Beam, CA
Krischer, JP
Greenbaum, CJ
Boulware, D
Rafkin, LE
Matheson, D
Herold, KC
Mahon, J
Palmer, JP
AF Sosenko, Jay M.
Skyler, Jay S.
DiMeglio, Linda A.
Beam, Craig A.
Krischer, Jeffrey P.
Greenbaum, Carla J.
Boulware, David
Rafkin, Lisa E.
Matheson, Della
Herold, Kevan C.
Mahon, Jeffrey
Palmer, Jerry P.
CA Type 1 Diabet TrialNet
Diabet Prevention Trial-Type 1
TI A New Approach for Diagnosing Type 1 Diabetes in Autoantibody-Positive
Individuals Based on Prediction and Natural History
SO DIABETES CARE
LA English
DT Article
ID TRIAL-TYPE 1; IMPAIRED GLUCOSE-TOLERANCE; RISK SCORE; PREVENTION
TRIAL-TYPE-1; INSULIN-RESISTANCE; MELLITUS; PARTICIPANTS; PROGRESSION;
CHILDREN; PUBERTY
AB OBJECTIVEWe assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals.RESEARCH DESIGN AND METHODSDiabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participants were studied. A metabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 2.00 and 2-h glucose <200 mg/dL (Ind60+Only) were compared with Index60 <2.00 and 2-h glucose 200 mg/dL (2hglu+Only) OGTTs as criteria for T1D. Individuals were assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis.RESULTSAreas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range -22 to -34% in DPT-1 and -14 to -27% in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs.CONCLUSIONSAn approach based on prediction and natural history appears to have utility for diagnosing T1D.
C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.; Matheson, Della] Univ Miami, Div Endocrinol, Miami, FL 33132 USA.
[DiMeglio, Linda A.] Indiana Univ, Sect Pediat Endocrinol Diabetol, Indianapolis, IN 46204 USA.
[Beam, Craig A.] Western Michigan Univ, Sch Med, Div Epidemiol & Biostat, Kalamazoo, MI 49008 USA.
[Krischer, Jeffrey P.; Boulware, David] Univ S Florida, Div Informat & Biostat, Tampa, FL USA.
[Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA.
[Herold, Kevan C.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA.
[Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada.
[Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Endocrinol Metab & Nutr, Seattle, WA 98195 USA.
RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33132 USA.
EM jsosenko@med.miami.edu
RI Skyler, Jay/F-4211-2016;
OI DiMeglio, Linda/0000-0002-8033-6078
FU National Institutes of Health through the National Institute of Diabetes
and Digestive and Kidney Diseases; National Institute of Allergy and
Infectious Diseases; Eunice Kennedy Shriver National Institute of Child
Health and Human Development; National Center for Research Resources;
JDRF; American Diabetes Association
FX This work was funded by the National Institutes of Health through the
National Institute of Diabetes and Digestive and Kidney Diseases, the
National Institute of Allergy and Infectious Diseases, the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, and the National Center for Research Resources, JDRF, and
the American Diabetes Association.
NR 16
TC 8
Z9 8
U1 0
U2 8
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD FEB
PY 2015
VL 38
IS 2
BP 271
EP 276
DI 10.2337/dc14-1813
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AZ8JK
UT WOS:000348461400027
PM 25519451
ER
PT J
AU Rasbach, L
Jenkins, C
Laffel, L
AF Rasbach, Lisa
Jenkins, Carolyn
Laffel, Lori
TI An Integrative Review of Self-efficacy Measurement Instruments in Youth
With Type 1 Diabetes
SO DIABETES EDUCATOR
LA English
DT Article
ID SCHOOL-AGE-CHILDREN; GLYCEMIC CONTROL; HEALTH-PROMOTION; EMERGING
ADULTS; ADOLESCENTS; MANAGEMENT; MELLITUS; OUTCOMES; BEHAVIORS;
ADHERENCE
AB Purpose The purpose of this study is to assess the extant literature on instruments used to measure self-efficacy in youth with type 1 diabetes (T1DM) and their caregivers and to critically evaluate these measurements.
Methods An integrative review (2003-2013) was conducted searching PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and US National Library of Medicine PubMed service (PubMed) databases using key words diabetes, type 1 diabetes, and self-efficacy. The authors reviewed the resulting 294 references for inclusion criteria of (a) sample of youth with T1DM or sample of caregivers of youth with T1DM, (b) description of the self-efficacy instrument as primary research, and (c) the instrument measured self-efficacy specifically related to diabetes management. Forty-five articles out of the initial 294 met criteria.
Results Of the 45 articles, 10 different self-efficacy instruments were identified. The primary theoretical framework used was Bandura's social cognitive theory and model of self-efficacy. Most participants were white middle-class T1DM youth. Evaluations to assess validity often were not reported; however, a majority of studies reported high internal consistency of the instruments.
Conclusions Sample homogeneity could limit the applicability of results to certain patient populations. Further psychometric analysis, including validity assessments, should be conducted in more diverse samples. Development of valid and reliable instruments for measuring self-efficacy that are sensitive to change across a wider caregiver base over time is necessary. While this review examined reliable and valid instruments used in research, future opportunities include evaluation of measuring self-efficacy in T1DM youth exposed to recent advances in diabetes management technologies.
C1 [Rasbach, Lisa; Jenkins, Carolyn] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA.
[Rasbach, Lisa; Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Rasbach, L (reprint author), Med Univ S Carolina, Coll Nursing, 99 Jonathan Lucas St,MSC 160, Charleston, SC 29425 USA.
EM greenli@musc.edu
FU NIH [P30DK036836]
FX This research was supported by the NIH grant P30DK036836. The content is
solely the responsibility of the authors and does not represent the
official view of this organization.
NR 75
TC 3
Z9 3
U1 3
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0145-7217
EI 1554-6063
J9 DIABETES EDUCATOR
JI Diabetes Educ.
PD FEB
PY 2015
VL 41
IS 1
BP 43
EP 58
DI 10.1177/0145721714550254
PG 16
WC Endocrinology & Metabolism; Public, Environmental & Occupational Health
SC Endocrinology & Metabolism; Public, Environmental & Occupational Health
GA AZ9IL
UT WOS:000348527000004
PM 25216655
ER
PT J
AU Ananthakrishnan, AN
AF Ananthakrishnan, Ashwin N.
TI Environmental Risk Factors for Inflammatory Bowel Diseases: A Review
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Review
DE Crohn's disease; Ulcerative colitis; Environment; Smoking; Diet; Vitamin
D
ID ARYL-HYDROCARBON RECEPTOR; AMBIENT AIR-POLLUTION; 25-HYDROXY VITAMIN-D;
CROHNS-DISEASE; ULCERATIVE-COLITIS; CLOSTRIDIUM-DIFFICILE; PSYCHOLOGICAL
STRESS; CIGARETTE-SMOKING; REDUCED RISK; DIETARY-FAT
AB Inflammatory bowel diseases comprising Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases. The key mechanism underlying the pathogenesis of these diseases is a dysregulated immune response to commensal flora in a genetically susceptible host. Thus intestinal microbial dysbiosis, host genetics, and the external environment all play an important role in the development of incident disease and in determining subsequent disease behavior and outcomes. There are several well-defined or putative environmental risk factors including cigarette smoking, appendectomy, diet, stress and depression, vitamin D as well as hormonal influence. The effect of some of the risk factors appears to differ between CD and UC suggesting that despite shared genetic and immunologic mechanisms, distinct pathways of pathogenesis exist. There is a growing body of literature identifying risk factors for incident disease. There is less rigorous literature defining triggers of relapse, and few controlled clinical trials examining if modification of such risk factors results in an improvement in patient outcomes. This is an area of considerable patient, physician, and scientific interest, and there is an important unmet need for rigorous studies of the external environment in disease pathogenesis and subsequent course.
C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@partners.org
FU US National Institutes of Health [K23 DK097142]
FX A.N.A is supported by funding from the US National Institutes of Health
(K23 DK097142).
NR 112
TC 19
Z9 20
U1 5
U2 37
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
EI 1573-2568
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD FEB
PY 2015
VL 60
IS 2
BP 290
EP 298
DI 10.1007/s10620-014-3350-9
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AZ7SP
UT WOS:000348418400004
PM 25204669
ER
PT J
AU Wright, AP
Desai, AP
Bajpai, S
King, LY
Sahani, DV
Corey, KE
AF Wright, Andrew P.
Desai, Amit P.
Bajpai, Surabhi
King, Lindsay Y.
Sahani, Dushyant V.
Corey, Kathleen E.
TI Gaps in Recognition and Evaluation of Incidentally Identified Hepatic
Steatosis
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Fatty liver; Primary care; Nonalcoholic steatohepatitis; CT scan;
Imaging; Steatosis
ID FATTY LIVER-DISEASE; FIBROSIS; SYSTEMS
AB Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease, is frequently diagnosed incidentally on imaging. The goal of the present study was to characterize rates of documentation and evaluation of incidentally identified steatosis.
Adults who underwent abdominal computed tomography with incidentally reported steatosis from January 2008 to October 2011 and with a parts per thousand yen1 primary care appointment within 14 months following imaging were included.
One hundred twenty-seven individuals with newly identified steatosis on imaging were included. Medical record documentation of newly identified steatosis occurred in only 29 individuals (22.8 %). Mention of steatosis within the "impression" section of radiology reports in addition to the report body was associated with significantly higher likelihood of primary care documentation (p = 0.007). Primary care documentation of steatosis was associated higher rates of evaluation for the etiology of steatosis include testing of aminotransferase levels (96.5 vs. 77.5 %, p = 0.025), alcohol use screening (89.6 vs. 66.3 %, p = 0.02), and hepatitis C screening (20.6 vs. 2.0 %, p = 0.002). No patient had documentation of the NAFLD fibrosis score and none were referred for specialist evaluation or for liver biopsy. However, when calculated, the NAFLD fibrosis score identified 14 patients (11 %) as high risk for advanced hepatic fibrosis.
Documentation of incidentally identified steatosis is infrequent but was improved when steatosis was mentioned in the "impression" of radiographic reports. Documentation of steatosis was associated with increased rates of aminotransferase testing and alcohol use and hepatitis C screening. An important proportion of individuals with incidentally identified steatosis are at high risk of fibrosis and may benefit from additional evaluation.
C1 [Wright, Andrew P.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
[Wright, Andrew P.; Bajpai, Surabhi; King, Lindsay Y.; Sahani, Dushyant V.; Corey, Kathleen E.] Harvard Univ, Sch Med, Boston, MA USA.
[Desai, Amit P.] New York Presbyterian Hosp, Dept Gastroenterol & Hepatol, New York, NY USA.
[Bajpai, Surabhi; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[King, Lindsay Y.; Corey, Kathleen E.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
RP Corey, KE (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 55 Fruit St, Boston, MA 02114 USA.
EM apwright@partners.org; apd9006@nyp.org; sbajpai@partners.org;
lyking@partners.org; dsahani@partners.org; kcorey@partners.org
FU NIK [K23DK 099422-0]
FX K.E.C. receives funding from NIK K23DK 099422-0.
NR 8
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
EI 1573-2568
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD FEB
PY 2015
VL 60
IS 2
BP 333
EP 338
DI 10.1007/s10620-014-3346-5
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AZ7SP
UT WOS:000348418400009
PM 25190263
ER
PT J
AU Ananthakrishnan, AN
Cheng, A
Cagan, A
Cai, TX
Gainer, VS
Shaw, SY
Churchill, S
Karlson, EW
Murphy, SN
Kohane, I
Liao, KP
AF Ananthakrishnan, Ashwin N.
Cheng, Alice
Cagan, Andrew
Cai, Tianxi
Gainer, Vivian S.
Shaw, Stanley Y.
Churchill, Susanne
Karlson, Elizabeth W.
Murphy, Shawn N.
Kohane, Isaac
Liao, Katherine P.
TI Mode of Childbirth and Long-Term Outcomes in Women with Inflammatory
Bowel Diseases
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE Crohn's disease; Ulcerative colitis; Pregnancy; Delivery; Caesarean
section
ID PREGNANCY-RELATED ISSUES; PERIANAL CROHNS-DISEASE; 25-HYDROXY VITAMIN-D;
INCREASED RISK; DELIVERY; SAFETY; COHORT; IMPACT; EPIDEMIOLOGY; SURGERY
AB Inflammatory bowel diseases [IBD; Crohn's disease (CD), ulcerative colitis] often affect women in their reproductive years. Few studies have analyzed the impact of mode of childbirth on long-term IBD outcomes.
We used a multi-institutional IBD cohort to identify all women in the reproductive age-group with a diagnosis of IBD prior to pregnancy. We identified the occurrence of a new diagnosis code for perianal complications, IBD-related hospitalization and surgery, and initiation of medical therapy after either a vaginal delivery or caesarean section (CS). Cox proportional hazards models adjusting for potential confounders were used to estimate independent effect of mode of childbirth on IBD outcomes.
Our cohort included 360 women with IBD (161 CS). Women in the CS group were likely to be older and more likely to have complicated disease behavior prior to pregnancy. During follow-up, there was no difference in the likelihood of IBD-related surgery (multivariate hazard ratio 1.75, 95 % confidence interval (CI) 0.40-7.75), IBD-related hospitalization (HR 1.39), initiation of immunomodulator therapy (HR 1.45), or anti-TNF therapy (HR 1.11). Among the 133 CD pregnancies with no prior perianal disease, we found no excess risk of subsequent new diagnosis perianal fistulae with vaginal delivery compared to CS (HR 0.19, 95 % CI 0.04-1.05).
Mode of delivery did not influence natural history of IBD. In our cohort, vaginal delivery was not associated with increased risk of subsequent perianal disease in women with CD.
C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Karlson, Elizabeth W.; Murphy, Shawn N.; Kohane, Isaac; Liao, Katherine P.] Harvard Univ, Sch Med, Boston, MA USA.
[Cheng, Alice; Shaw, Stanley Y.; Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Cagan, Andrew; Gainer, Vivian S.] Partners HealthCare, Res IS & Comp, Charlestown, MA USA.
[Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Churchill, Susanne; Murphy, Shawn N.; Kohane, Isaac] Brigham & Womens Hosp, Natl Ctr Biomed Comp I2b2, Boston, MA 02115 USA.
[Karlson, Elizabeth W.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Kohane, Isaac] Childrens Hosp, Boston, MA 02115 USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@mgh.harvard.edu
FU NIH [U54LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01
AR049880]; American Gastroenterological Association; US National
Institutes of Health [K23 DK097142]; Harold and Duval Bowen Fund
FX The study was supported by NIH U54LM008748. A.N.A is supported by
funding from the American Gastroenterological Association and from the
US National Institutes of Health (K23 DK097142). K.P.L. is supported by
NIH K08 AR060257 and the Harold and Duval Bowen Fund. E.W.K is supported
by grants from the NIH (K24 AR052403, P60 AR047782, R01 AR049880).
NR 35
TC 4
Z9 4
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
EI 1573-2568
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD FEB
PY 2015
VL 60
IS 2
BP 471
EP 477
DI 10.1007/s10620-014-3353-6
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AZ7SP
UT WOS:000348418400026
PM 25213079
ER
PT J
AU Borck, G
Hog, F
Dentici, ML
Tan, PL
Sowada, N
Medeira, A
Gueneau, L
Thiele, H
Kousi, M
Lepri, F
Wenzeck, L
Blumenthal, I
Radicioni, A
Schwarzenberg, TL
Mandriani, B
Fischetto, R
Morris-Rosendahl, DJ
Altmuller, J
Reymond, A
Nurnberg, P
Merla, G
Dallapiccola, B
Katsanis, N
Cramer, P
Kubisch, C
AF Borck, Guntram
Hog, Friederike
Dentici, Maria Lisa
Tan, Perciliz L.
Sowada, Nadine
Medeira, Ana
Gueneau, Lucie
Thiele, Holger
Kousi, Maria
Lepri, Francesca
Wenzeck, Larissa
Blumenthal, Ian
Radicioni, Antonio
Schwarzenberg, Tito Livio
Mandriani, Barbara
Fischetto, Rita
Morris-Rosendahl, Deborah J.
Altmuller, Janine
Reymond, Alexandre
Nurnberg, Peter
Merla, Giuseppe
Dallapiccola, Bruno
Katsanis, Nicholas
Cramer, Patrick
Kubisch, Christian
TI BRF1 mutations alter RNA polymerase III-dependent transcription and
cause neurodevelopmental anomalies
SO GENOME RESEARCH
LA English
DT Article
ID TATA-BINDING PROTEIN; COPY-NUMBER VARIANT; INTELLECTUAL DISABILITY; POL
III; HYPOMYELINATING LEUKODYSTROPHY; PONTOCEREBELLAR HYPOPLASIA;
PREINITIATION COMPLEX; INITIATION COMPLEX; TFIIB; PROMOTERS
AB RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of bif1 in zebraflsh embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III-related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development.
C1 [Borck, Guntram; Sowada, Nadine; Kubisch, Christian] Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany.
[Hog, Friederike; Wenzeck, Larissa] Univ Munich, Gene Ctr Munich, D-81377 Munich, Germany.
[Hog, Friederike; Wenzeck, Larissa] Univ Munich, Dept Biochem, Ctr Integrated Prot Sci CIPSM, D-81377 Munich, Germany.
[Dentici, Maria Lisa; Lepri, Francesca; Dallapiccola, Bruno] Bambino Gesu Pediat Hosp, IRCCS, I-00165 Rome, Italy.
[Tan, Perciliz L.; Kousi, Maria; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27710 USA.
[Medeira, Ana] CHLN, Hosp S Maria, Dept Pediat, Serv Genet, P-1649035 Lisbon, Portugal.
[Gueneau, Lucie; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
[Thiele, Holger; Altmuller, Janine; Nurnberg, Peter] Univ Cologne, CCG, D-50931 Cologne, Germany.
[Blumenthal, Ian] Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA.
[Blumenthal, Ian] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Radicioni, Antonio] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy.
[Schwarzenberg, Tito Livio] Univ Roma La Sapienza, Dept Neonatol, I-00161 Rome, Italy.
[Mandriani, Barbara; Merla, Giuseppe] IRCCS Casa Sollievo Sofferenza, Med Genet Unit, I-71013 San Giovanni Rotondo, Italy.
[Mandriani, Barbara] Univ Brescia, PhD Program, I-25121 Brescia, Italy.
[Fischetto, Rita] AOU Policlin Consorziale, UO Malattie Metabol PO Giovanni 23, I-70120 Bari, Italy.
[Morris-Rosendahl, Deborah J.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England.
[Altmuller, Janine] Univ Cologne, Inst Human Genet, D-50931 Cologne, Germany.
[Nurnberg, Peter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50674 Cologne, Germany.
[Nurnberg, Peter] Univ Cologne, CMMC, D-50931 Cologne, Germany.
[Cramer, Patrick] Max Planck Inst Biophys Chem, Dept Mol Biol, D-37077 Gottingen, Germany.
[Kubisch, Christian] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, D-20246 Hamburg, Germany.
RP Borck, G (reprint author), Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany.
EM guntram.borck@uni-ulm.de
RI Kubisch, Christian/F-1893-2011; Borck, Guntram/F-1868-2015;
Dallapiccola, Bruno/K-8692-2016
OI Kubisch, Christian/0000-0003-4220-0978; Lepri, Francesca
Romana/0000-0001-5331-0473; Katsanis, Nicholas/0000-0002-2480-0171;
Dallapiccola, Bruno/0000-0002-5031-1013
FU Elite Network Bavaria program "Protein Dynamics in Health and Disease";
Deutsche Forschungsgemeinschaft [SFB646, GraKo1721, SFB960, SFB1064];
European Research Council; Jung-Stiftung; Vallee Foundation; Deutsche
Forschungsgemeinschaft; Italian Ministry of Health; Lithuanian-Swiss
Cooperation Program
FX We thank the families for their collaboration. The clinical information
and the patient pictures were uploaded to the web-based Dysmorphology
Diagnostic System (DDS) developed by DYSCERNE-a European Network of
Centres of Expertise for Dysmorphology (EU DG Sanco) and discussed among
the DDS expert panel. We thank Sarah Sainsbury for mapping the BRF1
mutations on the hTFIIB structure; Karl Bertram and All A. Alfaiz for
help with cloning and bioinformatic analyses; Bernd Lapatki and Leopoldo
Zelante for discussions on clinical (including dental) aspects of the
disorder; Birgit Budde, Dagmar Wieczorek, and Hilde van Esch for
providing DNA; and Christelle Golzio and Michael Talkowski for zebrafish
RNA-seq data. F.H. was supported by the Elite Network Bavaria program
"Protein Dynamics in Health and Disease"; P.C. by the Deutsche
Forschungsgemeinschaft (SFB646, GraKo1721, SFB960, SFB1064, CIPSM, NIM),
an Advanced Grant of the European Research Council, the Jung-Stiftung,
and the Vallee Foundation; G.B. by the Deutsche Forschungsgemeinschaft;
G.M. by a grant from the Italian Ministry of Health (Ricerca Corrente
2012-14); and A.R. by the Lithuanian-Swiss Cooperation Program.
NR 56
TC 15
Z9 16
U1 1
U2 14
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD FEB
PY 2015
VL 25
IS 2
BP 155
EP 166
DI 10.1101/gr.176925.114
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA CA5UY
UT WOS:000348974500001
PM 25561519
ER
PT J
AU Malik, WQ
Hochberg, LR
Donoghue, JP
Brown, EN
AF Malik, Wasim Q.
Hochberg, Leigh R.
Donoghue, John P.
Brown, Emery N.
TI Modulation Depth Estimation and Variable Selection in State-Space Models
for Neural Interfaces
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Brain-computer interface (BCI); brain-machine interface (BMI); feature
selection; modulation depth (MD); neural decoding; neural interface;
state-spacemodel; tetraplegia; variable selection
ID PRIMARY MOTOR CORTEX; CORTICAL-NEURONS; INFORMATION; TETRAPLEGIA; GRASP;
REACH; POPULATIONS; KINEMATICS; PREDICTION; ENSEMBLES
AB Rapid developments in neural interface technology are making it possible to record increasingly large signal sets of neural activity. Various factors such as asymmetrical information distribution and across-channel redundancy may, however, limit the benefit of high-dimensional signal sets, and the increased computational complexity may not yield corresponding improvement in system performance. High-dimensional system models may also lead to overfitting and lack of generalizability. To address these issues, we present a generalized modulation depth measure using the state-space framework that quantifies the tuning of a neural signal channel to relevant behavioral covariates. For a dynamical system, we develop computationally efficient procedures for estimating modulation depth from multivariate data. We show that this measure can be used to rank neural signals and select an optimal channel subset for inclusion in the neural decoding algorithm. We present a scheme for choosing the optimal subset based on model order selection criteria. We apply this method to neuronal ensemble spike-rate decoding in neural interfaces, using our framework to relate motor cortical activity with intended movement kinematics. With offline analysis of intracortical motor imagery data obtained from individuals with tetraplegia using the BrainGate neural interface, we demonstrate that our variable selection scheme is useful for identifying and ranking the most information-rich neural signals. We demonstrate that our approach offers several orders of magnitude lower complexity but virtually identical decoding performance compared to greedy search and other selection schemes. Our statistical analysis shows that the modulation depth of human motor cortical single-unit signals is well characterized by the generalized Pareto distribution. Our variable selection scheme has wide applicability in problems involving multisensor signal modeling and estimation in biomedical engineering systems.
C1 [Malik, Wasim Q.; Brown, Emery N.] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Malik, Wasim Q.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Malik, Wasim Q.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA.
[Malik, Wasim Q.; Hochberg, Leigh R.; Donoghue, John P.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA.
[Malik, Wasim Q.; Hochberg, Leigh R.; Donoghue, John P.] Dept Vet Affairs Med Ctr, Ctr Neurorestorat & Neurotechnol, Rehabil R&D Serv, Providence, RI 02908 USA.
[Hochberg, Leigh R.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
RP Malik, WQ (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM wmalik@mgh.harvard.edu; leigh_hochberg@brown.edu;
john_donoghue@brown.edu; enb@neurostat.mit.edu
OI Hochberg, Leigh/0000-0003-0261-2273
FU Department of Defense [W81XWH-09-2-0001]; Department of Veterans Affairs
[B6453R, A6779I, B6310N, B6459L]; National Institutes of Health [R01
DC009899, RC1 HD063931, N01 HD053403, DP1 OD003646, TR01 GM104948];
National Science Foundation [CBET 1159652]; Wings for Life Spinal Cord
Research Foundation; Doris Duke Foundation; MGH Neurological Clinical
Research Institute; MGH Deane Institute for Integrated Research on
Atrial Fibrillation and Stroke; Cyberkinetics Neurotechnology Systems
FX This work was supported in part by the Department of Defense (USAMRAA
Cooperative Agreement W81XWH-09-2-0001), Department of Veterans Affairs
(B6453R, A6779I, B6310N, and B6459L), National Institutes of Health (R01
DC009899, RC1 HD063931, N01 HD053403, DP1 OD003646, TR01 GM104948),
National Science Foundation (CBET 1159652), Wings for Life Spinal Cord
Research Foundation, Doris Duke Foundation, MGH Neurological Clinical
Research Institute, and MGH Deane Institute for Integrated Research on
Atrial Fibrillation and Stroke. The pilot clinical trial, in which
participant S3 was recruited, was sponsored in part by Cyberkinetics
Neurotechnology Systems. The BrainGate clinical trial is directed by
Massachusetts General Hospital. The contents do not necessarily
represent the views of the Department of Defense, Department of Veterans
Affairs, or the United States Government.
NR 40
TC 1
Z9 1
U1 2
U2 12
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD FEB
PY 2015
VL 62
IS 2
BP 570
EP 581
DI 10.1109/TBME.2014.2360393
PG 12
WC Engineering, Biomedical
SC Engineering
GA AZ5ZK
UT WOS:000348297000019
PM 25265627
ER
PT J
AU Cai, WL
Lee, JG
Zhang, D
Kim, SH
Zalis, M
Yoshida, H
AF Cai, Wenli
Lee, June-Goo
Zhang, Da
Kim, Se Hyung
Zalis, Michael
Yoshida, Hiroyuki
TI Electronic Cleansing in Fecal-Tagging Dual-Energy CT Colonography Based
on Material Decomposition and Virtual Colon Tagging
SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
LA English
DT Article
DE Dual-energy CT (DE-CT); electronic cleansing (EC); partial volume effect
(PVE); virtual colonoscopy
ID COMPUTED-TOMOGRAPHY COLONOGRAPHY; AIDED POLYP DETECTION; CATHARTIC
PREPARATION; SEGMENTATION; COLONOSCOPY; RECONSTRUCTION; FEASIBILITY;
EXPERIENCE; LUMEN; AIR
AB Dual-energy CT provides a promising solution to identify tagged fecal materials in electronic cleansing (EC) for fecal-tagging CT colonography (CTC). In this study, we developed a new EC method based on virtual colon tagging (VCT) for minimizing EC artifacts by use of the material decomposition ability in dual-energy CTC images. In our approach, a localized three-material decomposition model decomposes each voxel into a material mixture vector and the first partial derivatives of three base materials: luminal air, soft tissue, and iodine-tagged fecal material. A Poisson-based derivative smoothing algorithm smoothes the derivatives and implicitly smoothes the associated material mixture fields. VCT is a means for marking the entire colonic lumen by virtually elevating the CT value of luminal air as high as that of the tagged fecal materials to differentiate effectively soft-tissue structures from air tagging mixtures. Adual-energy EC scheme based on VCT method, denoted as VCT-EC, was developed, in which the colonic lumen was first virtually tagged and then segmented by its high values in VCT images. The performance of the VCT-EC scheme was evaluated in a phantom study and a clinical study. Our results demonstrated that our VCT-EC scheme may provide a significant reduction of EC artifacts.
C1 [Cai, Wenli; Zhang, Da; Zalis, Michael; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Cai, Wenli; Zhang, Da; Zalis, Michael; Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lee, June-Goo] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA.
[Kim, Se Hyung] Seoul Natl Univ, Dept Radiol, Hosp Coll Med, Seoul 110744, South Korea.
RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
EM cai.wenli@mgh.harvard.edu; junegoo.lee@gmail.com; zhangda82@gmail.com;
shkim@radcom.snu.ac.kr; mzalis@mgh.harvard.edu;
yoshida.hiro@mgh.harvard.edu
FU American Cancer Society [RSG-11-076-01-CCE]
FX This work was supported by Research Scholar Grant RSG-11-076-01-CCE from
the American Cancer Society. Asterisk indicates corresponding author.
NR 43
TC 2
Z9 2
U1 0
U2 4
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9294
EI 1558-2531
J9 IEEE T BIO-MED ENG
JI IEEE Trans. Biomed. Eng.
PD FEB
PY 2015
VL 62
IS 2
BP 754
EP 765
DI 10.1109/TBME.2014.2364837
PG 12
WC Engineering, Biomedical
SC Engineering
GA AZ5ZK
UT WOS:000348297000038
PM 25350911
ER
PT J
AU Woo, J
Stone, M
Prince, JL
AF Woo, Jonghye
Stone, Maureen
Prince, Jerry L.
TI Multimodal Registration via Mutual Information Incorporating Geometric
and Spatial Context
SO IEEE TRANSACTIONS ON IMAGE PROCESSING
LA English
DT Article
DE Multimodal image registration; mutual information; Harris operator
ID FREE-FORM DEFORMATIONS; IMAGE REGISTRATION; NONRIGID REGISTRATION;
TEMPORAL REGISTRATION; MAXIMIZATION; MR; VISUALIZATION; OPTIMIZATION;
REGIONS; MOTION
AB Multimodal image registration is a class of algorithms to find correspondence from different modalities. Since different modalities do not exhibit the same characteristics, finding accurate correspondence still remains a challenge. To deal with this, mutual information (MI)-based registration has been a preferred choice as MI is based on the statistical relationship between both volumes to be registered. However, MI has some limitations. First, MI-based registration often fails when there are local intensity variations in the volumes. Second, MI only considers the statistical intensity relationships between both volumes and ignores the spatial and geometric information about the voxel. In this work, we propose to address these limitations by incorporating spatial and geometric information via a 3D Harris operator. In particular, we focus on the registration between a high-resolution image and a low-resolution image. The MI cost function is computed in the regions where there are large spatial variations such as corner or edge. In addition, the MI cost function is augmented with geometric information derived from the 3D Harris operator applied to the high-resolution image. The robustness and accuracy of the proposed method were demonstrated using experiments on synthetic and clinical data including the brain and the tongue. The proposed method provided accurate registration and yielded better performance over standard registration methods.
C1 [Woo, Jonghye] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Woo, Jonghye] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Stone, Maureen] Univ Maryland Baltimore Cty, Dept Neural & Pain Sci, Baltimore, MD 21250 USA.
[Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA.
RP Woo, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
EM jwoo@mgh.harvard.edu; stone@umaryland.edu; prince@jhu.edu
FU National Institutes of Health [R01CA133015, R00DC012575]
FX This work was supported by the National Institutes of Health under Grant
R01CA133015 and Grant R00DC012575. The associate editor coordinating the
review of this manuscript and approving it for publication was Dr.
Quanzheng Li.
NR 44
TC 7
Z9 7
U1 2
U2 26
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1057-7149
EI 1941-0042
J9 IEEE T IMAGE PROCESS
JI IEEE Trans. Image Process.
PD FEB
PY 2015
VL 24
IS 2
BP 757
EP +
DI 10.1109/TIP.2014.2387019
PG 13
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA AZ7CH
UT WOS:000348375400003
PM 25561595
ER
PT J
AU Li, Y
Lu, Z
Zhang, X
Yu, H
Kirkwood, KL
Lopes-Virella, MF
Huang, Y
AF Li, Y.
Lu, Z.
Zhang, X.
Yu, H.
Kirkwood, K. L.
Lopes-Virella, M. F.
Huang, Y.
TI Metabolic Syndrome Exacerbates Inflammation and Bone Loss in
Periodontitis
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE lipopolysaccharide; palmitic acid; high-fat diet; osteoclast; cytokines;
gene expression
ID FREE FATTY-ACIDS; INSULIN-RESISTANCE; AGGRESSIVE PERIODONTITIS; DISEASE;
ASSOCIATION; OBESITY; MACROPHAGES; EXPRESSION; MICROBIOTA; PALMITATE
AB Clinical studies have shown that metabolic syndrome (MetS) is associated with increased risk of developing periodontitis. However, the underlying mechanisms remain largely unknown. Since it is known that lipopolysaccharide (LPS)-activated toll-like receptor 4 signaling pathways play a crucial role in periodontitis, we hypothesized that MetS enhances LPS-induced periodontal inflammation and alveolar bone loss. In this study, we induced MetS in C57BL/6 mice by feeding them high-fat diet (HFD), and we induced periodontitis by periodontal injection of Aggregatibacter actinomycetemcomitans LPS. We found that mice fed a HFD had significantly increased body weight, plasma lipids, insulin, and insulin resistance when compared with mice fed regular chow, indicating that the mice developed MetS. We also found that a HFD markedly increased LPS-induced alveolar bone loss, osteoclastogenesis, and inflammatory infiltration. Analysis of gene expression in periodontal tissue revealed that HFD and LPS injection cooperatively stimulated expression of cytokines that are known to be involved in periodontal tissue inflammation and osteoclastogenesissuch as interleukin 6, monocyte-chemotactic protein 1, receptor activator of nuclear factor kappa-B ligand, and macrophage colony-stimulating factor. To further understand the potential mechanisms involved in MetS-boosted tissue inflammation, our in vitro studies showed that palmitic acidthe most abundant saturated fatty acid (SFA) and the major SFA in the HFD used in our animal studypotently enhanced LPS-induced proinflammatory gene expression in macrophages. In sum, this study demonstrated that MetS was associated with increased periodontal inflammation and alveolar bone loss in an LPS-induced periodontitis animal model. This study also suggests that SFA palmitic acid may play an important role in MetS-associated periodontitis by enhancing LPS-induced expression of inflammatory cytokines in macrophages.
C1 [Li, Y.; Lu, Z.; Zhang, X.; Lopes-Virella, M. F.; Huang, Y.] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Coll Med, Charleston, SC 29403 USA.
[Yu, H.; Kirkwood, K. L.; Huang, Y.] Med Univ S Carolina, Dept Oral Hlth Sci, Coll Dent Med, Charleston, SC 29403 USA.
[Lopes-Virella, M. F.; Huang, Y.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Med, 114 Doughty St, Charleston, SC 29403 USA.
EM huangyan@musc.edu
FU National Institutes of Health [DE016353]; Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and Development
[5I01BX000854]; National Institute of General Medical Sciences
[P30GM103331]
FX This work was supported by grant DE016353 from the National Institutes
of Health and grant 5I01BX000854 from the Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and Development (to Y.H.).
This study utilized the facilities and resources of the Medical
University of South Carolina Center for Oral Health Research, which is
partially supported by grant P30GM103331 from the National Institute of
General Medical Sciences. The authors declare no potential conflicts of
interest with respect to the authorship and/or publication of this
article.
NR 35
TC 6
Z9 7
U1 2
U2 14
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
EI 1544-0591
J9 J DENT RES
JI J. Dent. Res.
PD FEB
PY 2015
VL 94
IS 2
BP 362
EP 370
DI 10.1177/0022034514561658
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CA1BO
UT WOS:000348647900016
PM 25503900
ER
PT J
AU Xiong, GX
Redding, K
Chen, B
Cohen, AS
Cohen, NA
AF Xiong, Guoxiang
Redding, Kevin
Chen, Bei
Cohen, Akiva S.
Cohen, Noam A.
TI Non-specific Immunostaining by a Rabbit Antibody against Gustducin alpha
Subunit in Mouse Brain
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE taste bud; immunohistochemistry; peptide neutralization; axonal
terminal; polyclonal antibody
ID BITTER TASTE RECEPTORS; SOLITARY CHEMOSENSORY CELLS;
GASTROINTESTINAL-TRACT; BURKHOLDERIA-CEPACIA; SWEET TASTE; RAT-BRAIN;
IMMUNOHISTOCHEMISTRY; EXPRESSION; BUDS; SPECIFICITY
AB Gustducin is a guanosine nucleotide-binding protein functionally coupled with taste receptors and thus originally identified in taste cells of the tongue. Recently, bitter taste receptors and gustducin have been detected in the airways, digestive tracts and brain. The existing studies showing taste receptors and gustducin in the brain were carried out exclusively on frozen sections. In order to avoid the technical shortcomings associated with frozen sectioning, we performed immunofluorescence staining using vibratome-cut sections from mouse brains. Using a rabbit gustducin antibody, we could not detect neurons or astrocytes as reported previously. Rather, we found dense fibers in the nucleus accumbens and periventricular areas. We assumed these staining patterns to be specific after confirmation with conventional negative control staining. For the verification of this finding, we stained gustducin knockout mouse brain and tongue sections with the same rabbit gustducin antibody. Whereas negative staining was confirmed in the tongue, intensive fibers were constantly stained in the brain. Moreover, immunostaining with a goat gustducin antibody could not demonstrate the fibers in the brain tissue. The present study implies a cross immunoreaction that occurs with the rabbit gustducin antibody in mouse brain samples, suggesting that the conventional negative controls may not be sufficient when an immunostaining pattern is to be verified.
C1 [Xiong, Guoxiang; Cohen, Akiva S.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA.
[Redding, Kevin] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
[Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Chen, Bei; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA.
[Cohen, Akiva S.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Xiong, GX (reprint author), Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA.
EM xiong@email.chop.edu
FU Flight Attendants Medical Research Institute
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by a grant from The Flight Attendants Medical Research
Institute and a philanthropic contribution from the RLG Foundation, Inc.
(to NAC).
NR 39
TC 2
Z9 2
U1 0
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
EI 1551-5044
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD FEB
PY 2015
VL 63
IS 2
BP 79
EP 87
DI 10.1369/0022155414562838
PG 9
WC Cell Biology
SC Cell Biology
GA AZ9JP
UT WOS:000348529900001
PM 25411190
ER
PT J
AU Hagiwara, Y
Villarreal, D
Sanchez-Reilly, S
AF Hagiwara, Yuya
Villarreal, Deborah
Sanchez-Reilly, Sandra
TI Present Planning versus Future Planning: We Need a Shift Toward Goals of
Care Education for Physicians
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Letter
C1 [Hagiwara, Yuya; Villarreal, Deborah; Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, San Antonio, TX 78229 USA.
[Villarreal, Deborah; Sanchez-Reilly, Sandra] South Texas Vet Hlth Care Syst, Geriatr Res Educ Clin Ctr, San Antonio, TX USA.
RP Hagiwara, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, 7703 Floyd Curl Dr,MSC 7875, San Antonio, TX 78229 USA.
EM hagiwara@uthscsa.edu
NR 4
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD FEB 1
PY 2015
VL 18
IS 2
BP 99
EP 99
DI 10.1089/jpm.2014.0394
PG 1
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AZ9IE
UT WOS:000348526300004
PM 25546816
ER
PT J
AU Friedrichsdorf, SJ
Postier, A
Dreyfus, J
Osenga, K
Sencer, S
Wolfe, J
AF Friedrichsdorf, Stefan J.
Postier, Andrea
Dreyfus, Jill
Osenga, Kaci
Sencer, Susan
Wolfe, Joanne
TI Improved Quality of Life at End of Life Related to Home-Based Palliative
Care in Children with Cancer
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID TERMINAL CARE; DEATH; HOSPICE; PARENTS; SYMPTOMS; SUPPORT; IMPACT
AB Background: Nearly 2000 children die due to a malignancy in the United States annually. Emerging data suggest that home is the desired location of care for children with cancer at end of life. However, one obstacle to enrollment in a pediatric palliative care (PPC) home care program may be fear that distressing symptoms at end of life cannot be adequately managed outside the hospital.
Objective: To compare the symptom distress and quality-of-life experience for children who received concurrent end-of-life care from a PPC home care program (PPC/Oncology) with that of those who died without exposure to the PPC program (Oncology).
Methods: We conducted a retrospective survey study of a cohort of bereaved parents of children who died of cancer between 2002 and 2008 at a U.S. tertiary pediatric institution.
Results: Sixty bereaved parents were surveyed (50% PPC/Oncology). Prevalence of constipation and high distress from fatigue were more common in the PPC/Oncology group; other distressing symptoms were similar between groups, showing room for improvement. Children who received PPC/Oncology were significantly more likely to have fun (70% versus 45%), to experience events that added meaning to life (89% versus 63%), and to die at home (93% versus 20%).
Conclusions: This is the first North American study to assess outcomes among children with cancer who received concurrent oncology and palliative home care compared with those who received oncology care alone. Symptom distress experiences were similar in groups. However, children enrolled in a PPC home care program appear to have improved quality of life and are more likely to die at home.
C1 [Friedrichsdorf, Stefan J.; Postier, Andrea; Osenga, Kaci] Childrens Hosp & Clin Minnesota, Dept Pain Med Palliat Care & Integrat Med, Minneapolis, MN 55404 USA.
[Sencer, Susan] Childrens Hosp & Clin Minnesota, Dept Hematol Oncol, Minneapolis, MN 55404 USA.
[Dreyfus, Jill] Childrens Hosp & Clin Minnesota, Res Program, Minneapolis, MN 55404 USA.
[Dreyfus, Jill] Childrens Hosp & Clin Minnesota, Sponsored Program, Minneapolis, MN 55404 USA.
[Friedrichsdorf, Stefan J.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA.
[Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA.
[Wolfe, Joanne] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
RP Friedrichsdorf, SJ (reprint author), Childrens Hosp & Clin Minnesota, Dept Pain Med Palliat Care & Integrat Med, 2525 Chicago Ave S, Minneapolis, MN 55404 USA.
EM stefan.friedrichsdorf@childrensMN.org
FU CHC's Internal Research Grant Program (IRGP)
FX This study was funded by CHC's Internal Research Grant Program (IRGP).
The CHC IRGP was not involved in the conduction of the study or the
development of this submission. We are grateful to Peter Lund, MDiv, for
his research assistance and dedication to this project, and we are
appreciative of the parents and families who took the time and energy to
open up and share their very personal perspectives with us.
NR 36
TC 8
Z9 8
U1 0
U2 11
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD FEB 1
PY 2015
VL 18
IS 2
BP 143
EP 150
DI 10.1089/jpm.2014.0285
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AZ9IE
UT WOS:000348526300011
PM 25401507
ER
PT J
AU Shin, JA
Back, AL
AF Shin, Jennifer A.
Back, Anthony L.
TI A Snapshot of the Person Within: Using Smartphone Photos To Understand
Values
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Editorial Material
C1 [Shin, Jennifer A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
[Back, Anthony L.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
RP Shin, JA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM jashin@partners.org
FU NCI NIH HHS [R25CA092203, R25 CA092203]
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD FEB 1
PY 2015
VL 18
IS 2
BP 191
EP 192
DI 10.1089/jpm.2014.0201
PG 2
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AZ9IE
UT WOS:000348526300020
PM 25621599
ER
PT J
AU Goldstein, SA
Evangelista, A
Abbara, S
Arai, A
Asch, FM
Badano, LP
Bolen, MA
Connolly, HM
Cuellar-Calabria, H
Czerny, M
Devereux, RB
Erbel, RA
Fattori, R
Isselbacher, EM
Lindsay, JM
McCulloch, M
Michelena, HI
Nienaber, CA
Oh, JK
Pepi, M
Taylor, AJ
Weinsaft, JW
Zamorano, JL
Dietz, H
Eagle, K
Elefteriades, J
Jondeau, G
Rousseau, H
Schepens, M
AF Goldstein, Steven A.
Evangelista, Arturo
Abbara, Suhny
Arai, Andrew
Asch, Federico M.
Badano, Luigi P.
Bolen, Michael A.
Connolly, Heidi M.
Cuellar-Calabria, Hug
Czerny, Martin
Devereux, Richard B.
Erbel, Raimund A.
Fattori, Rossella
Isselbacher, Eric M.
Lindsay, Joseph M.
McCulloch, Marti
Michelena, Hector I.
Nienaber, Christoph A.
Oh, Jae K.
Pepi, Mauro
Taylor, Allen J.
Weinsaft, Jonathan W.
Zamorano, Jose Luis
Dietz, Harry
Eagle, Kim
Elefteriades, John
Jondeau, Guillaume
Rousseau, Herve
Schepens, Marc
TI Multimodality Imaging of Diseases of the Thoracic Aorta in Adults: From
the American Society of Echocardiography and the European Association of
Cardiovascular Imaging Endorsed by the Society of Cardiovascular
Computed Tomography and Society for Cardiovascular Magnetic Resonance
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
ID PENETRATING ATHEROSCLEROTIC ULCERS; INTRAOPERATIVE TRANSESOPHAGEAL
ECHOCARDIOGRAPHY; STENT-GRAFT IMPLANTATION; CORONARY-ARTERY-DISEASE;
MULTIDETECTOR ROW CT; GIANT-CELL ARTERITIS; ENDOVASCULAR ANEURYSM
REPAIR; 3-DIMENSIONAL MR-ANGIOGRAPHY; CONTRAST-INDUCED NEPHROPATHY;
EXPERT CONSENSUS DOCUMENT
C1 [Goldstein, Steven A.; Asch, Federico M.; Lindsay, Joseph M.; Taylor, Allen J.] Washington Hosp Ctr, Medstar Heart Inst, Washington, DC 20010 USA.
[Evangelista, Arturo; Cuellar-Calabria, Hug] Vall dHebron Univ Hosp, Barcelona, Spain.
[Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Arai, Andrew] Natl Inst Hlth, Bethesda, MD USA.
[Badano, Luigi P.] Univ Padua, Padua, Italy.
[Bolen, Michael A.] Cleveland Clin, Cleveland, OH 44106 USA.
[Connolly, Heidi M.; Michelena, Hector I.; Oh, Jae K.] Mayo Clin, Rochester, MN USA.
[Czerny, Martin] Univ Zurich Hosp, CH-8091 Zurich, Switzerland.
[Devereux, Richard B.; Weinsaft, Jonathan W.] Weill Cornell Med Coll, New York, NY USA.
[Erbel, Raimund A.] Univ Duisburg Essen, West German Heart Ctr, Essen, Germany.
[Fattori, Rossella] San Salvatore Hosp, Pesaro, Italy.
[Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nienaber, Christoph A.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA.
[Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany.
[Pepi, Mauro] IRCCS, Ctr Cardiol Monzino, Milan, Italy.
[Zamorano, Jose Luis] Univ Hosp Ramon y Cajal, Madrid, Spain.
[Dietz, Harry] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Eagle, Kim] Univ Michigan, Ann Arbor, MI 48109 USA.
[Elefteriades, John] Yale Univ, Sch Med, New Haven, CT USA.
[Jondeau, Guillaume] Hop Bichat Claude Bernard, F-75877 Paris, France.
[Rousseau, Herve] Hop Rangueil, Toulouse, France.
[Schepens, Marc] AZ St Jan Brugge, Brugge, Belgium.
RP Goldstein, SA (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA.
EM ase@asecho.org
FU Siemens; GORE; Medtronic; Toshiba; Lantheus Medical Imaging
FX The following authors reported relationships with one or more commercial
interests: Suhny Abbara, MD, serves as a consultant for Perceptive
Informatics. Andrew Arai, MD, receives research support from Siemens.
Luigi P. Badano, MD, PhD, FESC, has received software and equipment from
GE Healthcare, Siemens, and TomTec for research and testing purposes and
is on the speakers' bureau of GE Healthcare. Kim Eagle, MD, received a
research grant from GORE. John Elefteriades, MD, has a book published by
CardioText and is a principal investigator on a grant and clinical trial
from Medtronic. Jae K. Oh, MD, received a research grant from Toshiba
and core laboratory support from Medtronic. Herve Rousseau, MD, serves
as a consultant for GORE, Medtronic, and Bolton. Jonathan W. Weinsaft,
MD, received a research grant from Lantheus Medical Imaging.
NR 440
TC 45
Z9 46
U1 1
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD FEB
PY 2015
VL 28
IS 2
BP 119
EP 182
DI 10.1016/j.echo.2014.11.015
PG 64
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AZ8HU
UT WOS:000348457200002
PM 25623219
ER
PT J
AU Matsushita, K
Sang, YY
Ballew, SH
Shlipak, M
Katz, R
Rosas, SE
Peralta, CA
Woodward, M
Kramer, HJ
Jacobs, DR
Sarnak, MJ
Coresh, J
AF Matsushita, Kunihiro
Sang, Yingying
Ballew, Shoshana H.
Shlipak, Michael
Katz, Ronit
Rosas, Sylvia E.
Peralta, Carmen A.
Woodward, Mark
Kramer, Holly J.
Jacobs, David R.
Sarnak, Mark J.
Coresh, Josef
TI Subclinical Atherosclerosis Measures for Cardiovascular Prediction in
CKD
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CORONARY-ARTERY
CALCIUM; AMERICAN-HEART-ASSOCIATION; INTIMA-MEDIA THICKNESS;
ANKLE-BRACHIAL INDEX; RISK-FACTORS; PRACTICE GUIDELINES; CYSTATIN C;
TASK-FORCE
AB Whether inclusion of the coronary artery calcium score improves cardiovascular risk prediction in individuals with CKD, a population with unique calcium-phosphate homeostasis, is unknown. Among 6553 participants ages 45-84 years without prior cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis, coronary artery calcium score was assessed for cardiovascular risk prediction beyond the Framingham predictors in those with (n=1284) and without CKD and contrasted with carotid intimamedia thickness and ankle-brachial index (two other measures of subclinical atherosclerosis). During a median follow-up of 8.4 years, 650 cardiovascular events (coronary heart disease, stroke, heart failure, and peripheral artery disease) occurred (236 events in subjects with CKD). In Cox proportional hazards models adjusted for Framingham predictors, each subclinical measure was independently associated with cardiovascular outcomes, with larger adjusted hazard ratios (HRs; per 1 SD) for coronary artery calcium score than carotid intima-media thickness or ankle-brachial index in subjects without and with CKD (HR, 1.69; 95% confidence interval [95% CI], 1.45 to 1.97 versus HR, 1.12; 95% Cl, 1.00 to 1.25 and HR, 1.20; 95% Cl, 1.08 to 1.32, respectively). Compared with inclusion of carotid intima-media thickness or ankle-brachial index, inclusion of the coronary artery calcium score led to greater increases in C statistic for predicting cardiovascular disease and net reclassification improvement. Coronary artery calcium score performed best for the prediction of coronary heart disease and heart failure, regardless of CKD status. In conclusion, each measure improved cardiovascular risk prediction in subjects with CKD, with the greatest improvement observed with coronary artery calcium score.
C1 [Matsushita, Kunihiro; Sang, Yingying; Ballew, Shoshana H.; Woodward, Mark; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Shlipak, Michael] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA.
[Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shlipak, Michael] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Shlipak, Michael] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
[Katz, Ronit] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
[Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Peralta, Carmen A.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Kramer, Holly J.] Loyola Univ, Med Ctr, Div Nephrol, Maywood, IL 60153 USA.
[Jacobs, David R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
RP Matsushita, K (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM kmatsush@jhsph.edu
RI Woodward, Mark/D-8492-2015
FU National Heart, Lung, and Blood Institute [N01-HC-95159-N01-HC-95169];
National Center for Research Resource [UL1-RR-024156, UL1-RR-025005]
FX This research was supported by National Heart, Lung, and Blood Institute
Contracts N01-HC-95159-N01-HC-95169 and National Center for Research
Resource Grants UL1-RR-024156 and UL1-RR-025005.
NR 40
TC 23
Z9 25
U1 1
U2 4
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD FEB
PY 2015
VL 26
IS 2
BP 439
EP 447
DI 10.1681/ASN.2014020173
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CA0RG
UT WOS:000348623700021
PM 25145930
ER
PT J
AU Drain, PK
AF Drain, Paul K.
TI Ebola: lessons learned from HIV and tuberculosis epidemics
SO LANCET INFECTIOUS DISEASES
LA English
DT Letter
ID TESTS
C1 [Drain, Paul K.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Drain, Paul K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Drain, PK (reprint author), Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
EM pdrain@partners.org
FU FIC NIH HHS [R24 TW007988]; NIAID NIH HHS [K23 AI108293, T32 AI007433,
P30 AI060354]
NR 4
TC 4
Z9 4
U1 0
U2 11
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD FEB
PY 2015
VL 15
IS 2
BP 146
EP 147
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA AZ7PJ
UT WOS:000348410200012
PM 25749061
ER
PT J
AU Mitra, M
Iezzoni, LI
Zhang, JY
Long-Bellil, LM
Smeltzer, SC
Barton, BA
AF Mitra, Monika
Iezzoni, Lisa I.
Zhang, Jianying
Long-Bellil, Linda M.
Smeltzer, Suzanne C.
Barton, Bruce A.
TI Prevalence and Risk Factors for Postpartum Depression Symptoms Among
Women with Disabilities
SO MATERNAL AND CHILD HEALTH JOURNAL
LA English
DT Article
DE Disability; Postpartum depression; Women with disabilities; Pregnancy
ID PHYSICAL-DISABILITIES; PREGNANT-WOMEN; MATERNAL DEPRESSION; BIRTH
CERTIFICATE; SUBSTANCE USE; IMPACT; EXPERIENCES; MOTHERS; HEALTH;
METAANALYSIS
AB The adverse consequences of postpartum depression on the health of the mother and her child are well documented. However, there is little information on postpartum depression among mothers with disabilities. This study examines the patterns of depression and depressive symptoms before, during and after pregnancy and the association between depression before and during pregnancy and postpartum depression symptomatology (PPD) among women with and without disabilities. Data from the 2009-2011 Rhode Island Pregnancy Risk Assessment Monitoring System (PRAMS) were analyzed in 2013. Almost 30 % (28.9 %; 95 % CI 22.8-35.8) of mothers with disabilities reported often or always feeling down, depressed or sad after childbirth compared to 10 % of those without disabilities (95 % CI 8.9-11.3). Compared to other women in the study, women with disabilities had a greater likelihood for PPD symptoms (RR 1.6, 95 % CI 1.1-2.2) after accounting for sociodemographics, maternal characteristics related to PPD, and depression before and during pregnancy. Adjusting for other covariates, self-reported prenatal diagnosis of depression was not associated with symptoms of PPD and depression during pregnancy was marginally associated with PPD symptomatology for women with disabilities. Women with disabilities are at a greater risk of experiencing symptoms of postpartum depression than other women. Screening for PPD among new mothers with disabilities and timely referral of those with PPD diagnosis are vital to the health of mothers with disabilities and their children.
C1 [Mitra, Monika; Zhang, Jianying; Long-Bellil, Linda M.] Univ Massachusetts, Ctr Hlth Policy & Res, Sch Med, Shrewsbury, MA 01545 USA.
[Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Smeltzer, Suzanne C.] Villanova Univ, Ctr Nursing Res, Villanova, PA 19085 USA.
[Barton, Bruce A.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
RP Mitra, M (reprint author), Univ Massachusetts, Ctr Hlth Policy & Res, Sch Med, 333 South St, Shrewsbury, MA 01545 USA.
EM monika.mitra@umassmed.edu; liezzoni@partners.org;
Jianying.zhang@umassmed.edu; linda.long@umassmed.edu;
Suzanne.smeltzer@villanova.edu; Bruce.barton@umassmed.edu
OI Barton, Bruce/0000-0001-7878-8895
FU NICHD NIH HHS [1R01HD074581, R01 HD074581]
NR 51
TC 5
Z9 5
U1 3
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1092-7875
EI 1573-6628
J9 MATERN CHILD HLTH J
JI Matern. Child Health J.
PD FEB
PY 2015
VL 19
IS 2
SI SI
BP 362
EP 372
DI 10.1007/s10995-014-1518-8
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AZ6TP
UT WOS:000348353600020
PM 24889114
ER
PT J
AU Lee, JJ
Granter, SR
Laga, AC
Saavedra, AP
Zhan, Q
Guo, WM
Xu, SY
Murphy, GF
Lian, CG
AF Lee, Jonathan J.
Granter, Scott R.
Laga, Alvaro C.
Saavedra, Arturo P.
Zhan, Qian
Guo, Weimin
Xu, Shuyun
Murphy, George F.
Lian, Christine G.
TI 5-Hydroxymethylcytosine expression in metastatic melanoma versus nodal
nevus in sentinel lymph node biopsies
SO MODERN PATHOLOGY
LA English
DT Article
ID MELANOCYTIC NEVI; CUTANEOUS NEVI; USEFUL MARKER; SOX2; DIFFERENTIATE;
NESTIN; CELLS; P16
AB Sentinel lymph node biopsies are conducted to stage patients with newly diagnosed melanomas that have histopathological attributes conferring defined levels of metastatic potential. Because benign nevic cells may also form 'deposits' in lymph nodes (nodal nevus), the pathological evaluation for metastatic melanoma within sentinel lymph nodes can be challenging. Twenty-eight sentinel lymph node biopsy cases containing either metastatic melanoma (N= 18) or nodal nevi (N= 10) were retrieved from the archives of the Brigham and Women's Hospital, Department of Pathology (2011-2014). In addition, two sentinel lymph node cases that were favored to represent metastatic disease but whose histopathological features were viewed as equivocal, with melanoma favored, were also included. Dual labeling for the melanocyte lineage marker, MART-1, and the epigenetic marker, 5-hydroxymethylcytosine, a functionally significant indicator that has been shown to distinguish benign nevi from melanoma, was performed on all cases using immunohistochemistry and/or direct immunofluorescence. All (18 of 18) metastatic melanoma cases showed complete loss of 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells, and all (10 of 10) nodal nevus cases demonstrated 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells. In addition, 5-hydroxymethylcytosine staining confirmed the favored diagnoses of metastatic melanoma in the two 'equivocal' cases. Thus, 5-hydroxymethylcytosine may be a useful adjunctive marker to distinguish between benign nodal nevi and metastatic melanoma during the evaluation of sentinel lymph node biopsies for metastatic melanoma.
C1 [Lee, Jonathan J.; Granter, Scott R.; Laga, Alvaro C.; Saavedra, Arturo P.; Zhan, Qian; Guo, Weimin; Xu, Shuyun; Murphy, George F.; Lian, Christine G.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Program Dermatopathol,Med Sch, Boston, MA 02115 USA.
[Saavedra, Arturo P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
RP Murphy, GF (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Program Dermatopathol,Med Sch, 221 Longwood Ave,EBRC Suite 401, Boston, MA 02115 USA.
EM gmurphy@rics.bwh.harvard.edu; cglian@partners.org
RI Guo, Weimin/B-3155-2009;
OI Guo, Weimin/0000-0003-4318-7154; Lian, Christine/0000-0003-4626-1612
FU NIH [5P40CA093683-09]; Women's Hospital; Bristol-Meyers-Squibb
FX These results were shared, in part, at the Brigham and Women's Hospital,
Massachusetts General Hospital, and Harvard Medical School Department of
Pathology Annual Research Celebration (2014) in Boston, MA, USA. This
study is supported by NIH grant 5P40CA093683-09 to the SPORE Core at
Brigham and Women's Hospital. GFM receives funding from
Bristol-Meyers-Squibb for work on melanoma biomarkers (not a funding
source for this study).
NR 23
TC 9
Z9 9
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
IS 2
BP 218
EP 229
DI 10.1038/modpathol.2014.99
PG 12
WC Pathology
SC Pathology
GA CA5NY
UT WOS:000348956300006
PM 25081754
ER
PT J
AU Kamat, SS
Camara, K
Parsons, WH
Chen, DH
Dix, MM
Bird, TD
Howell, AR
Cravatt, BF
AF Kamat, Siddhesh S.
Camara, Kaddy
Parsons, William H.
Chen, Dong-Hui
Dix, Melissa M.
Bird, Thomas D.
Howell, Amy R.
Cravatt, Benjamin F.
TI Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and
ABHD12 interplay
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; SERINE HYDROLASES; ENDOCANNABINOID
2-ARACHIDONOYLGLYCEROL; PHOSPHOLIPASE A(1); HISTAMINE-RELEASE;
GRAVES-DISEASE; X-CHROMOSOME; MAST-CELLS; BRAIN; PHOSPHATIDYLSERINE
AB Lysophosphatidylserines (lyso-PSs) are a class of signaling lipids that regulate immunological and neurological processes. The metabolism of lyso-PSs remains poorly understood in vivo. Recently, we determined that ABHD12 is a major brain lyso-PS lipase, implicating lyso-PSs in the neurological disease polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and cataract (PHARC), which is caused by null mutations in the ABHD12 gene. Here, we couple activity-based profiling with pharmacological and genetic methods to annotate the poorly characterized enzyme ABHD16A as a phosphatidylserine (PS) lipase that generates lyso-PS in mammalian systems. We describe a small-molecule inhibitor of ABHD16A that depletes lyso-PSs from cells, including lymphoblasts derived from subjects with PHARC. In mouse macrophages, disruption of ABHD12 and ABHD16A respectively increases and decreases both lyso-PSs and lipopolysaccharide-induced cytokine production. Finally, Abhd16a(-/-) mice have decreased brain lyso-PSs, which runs counter to the elevation in lyso-PS in Abhd12(-/-) mice. Our findings illuminate an ABHD16A-ABHD12 axis that dynamically regulates lyso-PS metabolism in vivo, designating these enzymes as potential targets for treating neuroimmunological disorders.
C1 [Kamat, Siddhesh S.; Parsons, William H.; Dix, Melissa M.; Cravatt, Benjamin F.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
[Kamat, Siddhesh S.; Parsons, William H.; Dix, Melissa M.; Cravatt, Benjamin F.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Camara, Kaddy; Howell, Amy R.] Univ Connecticut, Dept Chem, Storrs, CT USA.
[Chen, Dong-Hui; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA USA.
[Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Cravatt, BF (reprint author), Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
EM cravatt@scripps.edu
OI Parsons, William/0000-0001-6065-2340
FU US National Institutes of Health [DA033760]; American Chemical Society;
Hewitt Foundation for Medical Research fellowship; Department of
Veterans Affairs Research Funds; US National Science Foundation
[CHE-0809753, CHE-1048717]
FX We are grateful to K. Masuda, A. Viader and K.-L. Hsu for their helpful
discussions, guidance and technical expertise in harvesting tissues; G.
Simon and J. Blankman for helpful discussions; M. Niphakis for advice on
the SAR studies on the beta-lactone scaffolds; O. Ulanovskaya for advice
on generating the shRNA knockdown cell lines; B. Correia for the
guidance on using CIMAGE; C. Joslyn and T. Takei for technical
assistance; and M. Lau for contributions to initial synthetic studies.
This work was supported by the US National Institutes of Health
(DA033760) and the ninth Irving S. Sigal postdoctoral fellowship from
the American Chemical Society (to S.S.K.), a Hewitt Foundation for
Medical Research fellowship (to W.H.P.), the Department of Veterans
Affairs Research Funds (to T.D.B.) and the US National Science
Foundation (CHE-0809753 and CHE-1048717 to A.R.H.).
NR 49
TC 21
Z9 21
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD FEB
PY 2015
VL 11
IS 2
BP 164
EP U116
DI 10.1038/NCHEMBIO.1721
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AZ6WN
UT WOS:000348358800015
PM 25580854
ER
PT J
AU O'Dushlaine, C
Rossin, L
Lee, PH
Duncan, L
Parikshak, NN
Newhouse, S
Ripke, S
Neale, BM
Purcell, SM
Posthuma, D
Nurnberger, JI
Lee, SH
Faraone, SV
Perlis, RH
Mowry, BJ
Thapar, A
Goddard, ME
Witte, JS
Absher, D
Agartz, I
Akil, H
Amin, F
Andreassen, OA
Anjorin, A
Anney, R
Anttila, V
Arking, DE
Asherson, P
Azevedo, MH
Backlund, L
Badner, JA
Bailey, AJ
Banaschewski, T
Barchas, JD
Barnes, MR
Barrett, TB
Bass, N
Battaglia, A
Bauer, M
Bayes, M
Bellivier, F
Bergen, SE
Berrettini, W
Betancur, C
Bettecken, T
Biederman, J
Binder, EB
Black, DW
Blackwood, DHR
Bloss, CS
Boehnke, M
Boomsma, DI
Breuer, R
Bruggeman, R
Cormican, P
Buccola, NG
Buitelaar, JK
Bunney, WE
Buxbaum, JD
Byerley, WF
Byrne, EM
Caesar, S
Cahn, W
Cantor, RM
Casas, M
Chakravarti, A
Chambert, K
Choudhury, K
Cichon, S
Mattheisen, M
Cloninger, CR
Collier, DA
Cook, EH
Coon, H
Cormand, B
Corvin, A
Coryell, WH
Craig, DW
Craig, IW
Crosbie, J
Cuccaro, ML
Curtis, D
Czamara, D
Datta, S
Dawson, G
Day, R
De Geus, EJ
Degenhardt, F
Djurovic, S
Donohoe, GJ
Doyle, AE
Duan, J
Dudbridge, F
Duketis, E
Ebstein, RP
Edenberg, HJ
Elia, J
Ennis, S
Etain, B
Fanous, A
Farmer, AE
Ferrier, IN
Flicldnger, M
Fombonne, E
Foroud, T
Frank, J
Franke, B
Fraser, C
Freedman, R
Freimer, NB
Freitag, CM
Friedl, M
Frisen, L
Gailagher, L
Gejman, PV
Georgieva, L
Gershon, ES
Giegling, I
Gill, M
Gordon, SD
Gordon-Smith, K
Green, EK
Greenwood, TA
Grice, DE
Gross, M
Grozeva, D
Guan, W
Gurling, H
De Haan, L
Haines, JL
Hakonarson, H
Hallmayer, J
Hamilton, SP
Hamshere, ML
Hansen, TF
Hartmann, AM
Hautzinger, M
Heath, AC
Henders, AK
Herms, S
Hickie, IB
Hipolito, M
Hoefels, S
Holsboer, F
Hoogendijk, WJ
Hottenga, JJ
Hultman, CM
Hus, V
Ingason, A
Ising, M
Jamain, S
Jones, EG
Jones, I
Jones, L
Tzeng, JY
Kahler, AK
Kahn, RS
Kandaswamy, R
Keller, MC
Kennedy, JL
Kenny, E
Kent, L
Kim, YJ
Kirov, GK
Klauck, SM
Klei, L
Knowles, JA
Kohli, MA
Koller, DL
Konte, B
Korszun, A
Krabbendam, L
Krasucki, R
Kuntsi, J
Kwan, P
Landen, M
Langstrom, N
Lathrop, M
Lawrence, J
Lawson, WB
Leboyer, M
Ledbetter, DH
Lencz, T
Lesch, KP
Levinson, DF
Lewis, CM
Li, J
Lichtenstein, P
Lieberman, JA
Lin, DY
Linszen, DH
Liu, CY
Lohoff, FW
Loo, SK
Lord, C
Lowe, JK
Lucae, S
MacIntyre, DJ
Madden, PAF
Maestrini, E
Magnusson, PKE
Mahon, PB
Maier, W
Malhotra, AK
Mane, SM
Martin, CL
Martin, NG
Matthews, K
Mattingsdal, M
McCarroll, SA
McGhee, KA
McGough, JJ
McGrath, PJ
McGuffin, P
McInnis, MG
McIntosh, A
McKinney, R
McLean, AW
McMahon, FJ
McMahon, WM
McQuillin, A
Medeiros, H
Medland, SE
Meier, S
Melle, I
Meng, F
Meyer, J
Middeldorp, CM
Middleton, L
Milanova, V
Miranda, A
Monaco, AP
Montgomery, GW
Moran, JL
Moreno-De-Luca, D
Morken, G
Morris, DW
Morrow, EM
Moskvina, V
Muglia, P
Muhleisen, TW
Muir, WJ
Muller-Myhsok, B
Murtha, M
Myers, RM
Myin-Germeys, I
Neale, MC
Nelson, SF
Nievergelt, CM
Nikolov, I
Nimgaonkar, V
Nolen, WA
Nothen, MM
Nwulia, EA
Nyholt, DR
Oades, RD
Olincy, A
Oliveira, G
Olsen, L
Ophoff, RA
Osby, U
Owen, MJ
Palotie, A
Parr, JR
Paterson, AD
Pato, CN
Pato, MT
Penninx, BW
Pergadia, ML
Pericak-Vance, MA
Pickard, BS
Pimm, J
Piven, J
Potash, JB
Poustka, F
Propping, P
Puri, V
Quested, DJ
Quinn, EM
Ramos-Quiroga, JA
Rasmussen, HB
Raychaudhuri, S
Rehnstrom, K
Reif, A
Ribases, M
Rice, JP
Rietschel, M
Roeder, K
Roeyers, H
Rothenberger, A
Rouleau, G
Ruderfer, D
Rujescu, D
Sanders, AR
Sanders, SJ
Santangelo, SL
Sergeant, JA
Schachar, R
Schalling, M
Schatzberg, AF
Scheftner, WA
Schellenberg, GD
Scherer, SW
Schork, NJ
Schulze, TG
Schumacher, J
Schwarz, M
Scolnick, E
Scott, LJ
Shi, JX
Shilling, PD
Shyn, SI
Silverman, JM
Slager, SL
Smalley, SL
Smit, JH
Smith, EN
Sonuga-Barke, EJS
Cair, DS
State, M
Steffens, M
Steinhausen, HC
Strauss, JS
Strohmaier, J
Stroup, TS
Sutdiffe, JS
Szatmari, P
Szelinger, S
Thirumalai, S
Thompson, RC
Todorov, AA
Tozzi, F
Treutlein, J
Uhr, M
Van den Oord, EJCG
Van Grootheest, G
Van Os, J
Vicente, AM
Vieland, VJ
Vincent, JB
Visscher, PM
Walsh, CA
Wassink, TH
Watson, SJ
Weissman, MM
Werge, T
Wienker, TF
Wijsman, EM
Willemsen, G
Williams, N
Willsey, AJ
Witt, SH
Xu, W
Young, AH
Yu, TW
Zammit, S
Zandi, PP
Zhang, P
Zitman, FG
Zollner, S
Devlin, B
Kelsoe, JR
Sklar, P
Daly, MJ
O'Donovan, MC
Craddock, N
Kendler, KS
Weiss, LA
Wray, NR
Zhao, ZM
Geschwind, DH
Sullivan, PF
Smoller, JW
Holmans, PA
Breen, G
AF O'Dushlaine, Colm
Rossin, Lizzy
Lee, Phil H.
Duncan, Laramie
Parikshak, Neelroop N.
Newhouse, Stephen
Ripke, Stephan
Neale, Benjamin M.
Purcell, Shaun M.
Posthuma, Danielle
Nurnberger, John I.
Lee, S. Hong
Faraone, Stephen V.
Perlis, Roy H.
Mowry, Bryan J.
Thapar, Anita
Goddard, Michael E.
Witte, John S.
Absher, Devin
Agartz, Ingrid
Akil, Huda
Amin, Farooq
Andreassen, Ole A.
Anjorin, Adebayo
Anney, Richard
Anttila, Verneri
Arking, Dan E.
Asherson, Philip
Azevedo, Maria H.
Backlund, Lena
Badner, Judith A.
Bailey, Anthony J.
Banaschewski, Tobias
Barchas, Jack D.
Barnes, Michael R.
Barrett, Thomas B.
Bass, Nicholas
Battaglia, Agatino
Bauer, Michael
Bayes, Monica
Bellivier, Frank
Bergen, Sarah E.
Berrettini, Wade
Betancur, Catalina
Bettecken, Thomas
Biederman, Joseph
Binder, Elisabeth B.
Black, Donald W.
Blackwood, Douglas H. R.
Bloss, Cinnamon S.
Boehnke, Michael
Boomsma, Dorret I.
Breuer, Rene
Bruggeman, Richard
Cormican, Paul
Buccola, Nancy G.
Buitelaar, Jan K.
Bunney, William E.
Buxbaum, Joseph D.
Byerley, William F.
Byrne, Enda M.
Caesar, Sian
Cahn, Wiepke
Cantor, Rita M.
Casas, Miguel
Chakravarti, Aravinda
Chambert, Kimberly
Choudhury, Khalid
Cichon, Sven
Mattheisen, Manuel
Cloninger, C. Robert
Collier, David A.
Cook, Edwin H.
Coon, Hilary
Cormand, Bru
Corvin, Aiden
Coryell, William H.
Craig, David W.
Craig, Ian W.
Crosbie, Jennifer
Cuccaro, Michael L.
Curtis, David
Czamara, Darina
Datta, Susmita
Dawson, Geraldine
Day, Richard
De Geus, Eco J.
Degenhardt, Franziska
Djurovic, Srdjan
Donohoe, Gary J.
Doyle, Alysa E.
Duan, Jubao
Dudbridge, Frank
Duketis, Eftichia
Ebstein, Richard P.
Edenberg, Howard J.
Elia, Josephine
Ennis, Sean
Etain, Bruno
Fanous, Ayman
Farmer, Anne E.
Ferrier, I. Nicol
Flicldnger, Matthew
Fombonne, Eric
Foroud, Tatiana
Frank, Josef
Franke, Barbara
Fraser, Christine
Freedman, Robert
Freimer, Nelson B.
Freitag, Christine M.
Friedl, Marion
Frisen, Louise
Gailagher, Louise
Gejman, Pablo V.
Georgieva, Lyudmila
Gershon, Elliot S.
Giegling, Ina
Gill, Michael
Gordon, Scott D.
Gordon-Smith, Katherine
Green, Elaine K.
Greenwood, Tiffany A.
Grice, Dorothy E.
Gross, Magdalena
Grozeva, Detelina
Guan, Weihua
Gurling, Hugh
De Haan, Lieuwe
Haines, Jonathan L.
Hakonarson, Hakon
Hallmayer, Joachim
Hamilton, Steven P.
Hamshere, Marian L.
Hansen, Thomas F.
Hartmann, Annette M.
Hautzinger, Martin
Heath, Andrew C.
Henders, Anjali K.
Herms, Stefan
Hickie, Ian B.
Hipolito, Maria
Hoefels, Susanne
Holsboer, Florian
Hoogendijk, Witte J.
Hottenga, Jouke-Jan
Hultman, Christina M.
Hus, Vanessa
Ingason, Andres
Ising, Marcus
Jamain, Stephane
Jones, Edward G.
Jones, Ian
Jones, Lisa
Tzeng, Jung-Ying
Kaehler, Anna K.
Kahn, Rene S.
Kandaswamy, Radhika
Keller, Matthew C.
Kennedy, James L.
Kenny, Elaine
Kent, Lindsey
Kim, Yunjung
Kirov, George K.
Klauck, Sabine M.
Klei, Lambertus
Knowles, James A.
Kohli, Martin A.
Koller, Daniel L.
Konte, Bettina
Korszun, Ania
Krabbendam, Lydia
Krasucki, Robert
Kuntsi, Jonna
Kwan, Phoenix
Landen, Mikael
Laengstroem, Niklas
Lathrop, Mark
Lawrence, Jacob
Lawson, William B.
Leboyer, Marion
Ledbetter, David H.
Lencz, Todd
Lesch, Klaus-Peter
Levinson, Douglas F.
Lewis, Cathryn M.
Li, Jun
Lichtenstein, Paul
Lieberman, Jeffrey A.
Lin, Dan-Yu
Linszen, Don H.
Liu, Chunyu
Lohoff, Falk W.
Loo, Sandra K.
Lord, Catherine
Lowe, Jennifer K.
Lucae, Susanne
MacIntyre, Donald J.
Madden, Pamela A. F.
Maestrini, Elena
Magnusson, Patrik K. E.
Mahon, Pamela B.
Maier, Wolfgang
Malhotra, Anil K.
Mane, Shrikant M.
Martin, Christa L.
Martin, Nicholas G.
Matthews, Keith
Mattingsdal, Morten
McCarroll, Steven A.
McGhee, Kevin A.
McGough, James J.
McGrath, Patrick J.
McGuffin, Peter
McInnis, Melvin G.
McIntosh, Andrew
McKinney, Rebecca
McLean, Alan W.
McMahon, Francis J.
McMahon, William M.
McQuillin, Andrew
Medeiros, Helena
Medland, Sarah E.
Meier, Sandra
Melle, Ingrid
Meng, Fan
Meyer, Jobst
Middeldorp, Christel M.
Middleton, Lefkos
Milanova, Vihra
Miranda, Ana
Monaco, Anthony P.
Montgomery, Grant W.
Moran, Jennifer L.
Moreno-De-Luca, Daniel
Morken, Gunnar
Morris, Derek W.
Morrow, Eric M.
Moskvina, Valentina
Muglia, Pierandrea
Muehleisen, Thomas W.
Muir, Walter J.
Mueller-Myhsok, Bertram
Murtha, Michael
Myers, Richard M.
Myin-Germeys, Inez
Neale, Michael C.
Nelson, Stan F.
Nievergelt, Caroline M.
Nikolov, Ivan
Nimgaonkar, Vishwajit
Nolen, Willem A.
Noethen, Markus M.
Nwulia, Evaristus A.
Nyholt, Dale R.
Oades, Robert D.
Olincy, Ann
Oliveira, Guiomar
Olsen, Line
Ophoff, Roel A.
Osby, Urban
Owen, Michael J.
Palotie, Aarno
Parr, Jeremy R.
Paterson, Andrew D.
Pato, Carlos N.
Pato, Michele T.
Penninx, Brenda W.
Pergadia, Michele L.
Pericak-Vance, Margaret A.
Pickard, Benjamin S.
Pimm, Jonathan
Piven, Joseph
Potash, James B.
Poustka, Fritz
Propping, Peter
Puri, Vinay
Quested, Digby J.
Quinn, Emma M.
Ramos-Quiroga, Josep Antoni
Rasmussen, Henrik B.
Raychaudhuri, Soumya
Rehnstroem, Karola
Reif, Andreas
Ribases, Marta
Rice, John P.
Rietschel, Marcella
Roeder, Kathryn
Roeyers, Herbert
Rothenberger, Aribert
Rouleau, Guy
Ruderfer, Douglas
Rujescu, Dan
Sanders, Alan R.
Sanders, Stephan J.
Santangelo, Susan L.
Sergeant, Joseph A.
Schachar, Russell
Schalling, Martin
Schatzberg, Alan F.
Scheftner, William A.
Schellenberg, Gerard D.
Scherer, Stephen W.
Schork, Nicholas J.
Schulze, Thomas G.
Schumacher, Johannes
Schwarz, Markus
Scolnick, Edward
Scott, Laura J.
Shi, Jianxin
Shilling, Paul D.
Shyn, Stanley I.
Silverman, Jeremy M.
Slager, Susan L.
Smalley, Susan L.
Smit, Johannes H.
Smith, Erin N.
Sonuga-Barke, Edmund J. S.
Cair, David St.
State, Matthew
Steffens, Michael
Steinhausen, Hans-Christoph
Strauss, John S.
Strohmaier, Jana
Stroup, T. Scott
Sutdiffe, James S.
Szatmari, Peter
Szelinger, Szabocls
Thirumalai, Srinivasa
Thompson, Robert C.
Todorov, Alexandre A.
Tozzi, Federica
Treutlein, Jens
Uhr, Manfred
Van den Oord, Edwin J. C. G.
Van Grootheest, Gerard
Van Os, Jim
Vicente, Astrid M.
Vieland, Veronica J.
Vincent, John B.
Visscher, Peter M.
Walsh, Christopher A.
Wassink, Thomas H.
Watson, Stanley J.
Weissman, Myrna M.
Werge, Thomas
Wienker, Thomas F.
Wijsman, Ellen M.
Willemsen, Gonneke
Williams, Nigel
Willsey, A. Jeremy
Witt, Stephanie H.
Xu, Wei
Young, Allan H.
Yu, Timothy W.
Zammit, Stanley
Zandi, Peter P.
Zhang, Peng
Zitman, Frans G.
Zoellner, Sebastian
Devlin, Bernie
Kelsoe, John R.
Sklar, Pamela
Daly, Mark J.
O'Donovan, Michael C.
Craddock, Nicholas
Kendler, Kenneth S.
Weiss, Lauren A.
Wray, Naomi R.
Zhao, Zhaoming
Geschwind, Daniel H.
Sullivan, Patrick F.
Smoller, Jordan W.
Holmans, Peter A.
Breen, Gerome
CA IIBDGC
Network & Pathway Anal Subgrp Psyc
TI Psychiatric genome-wide association study analyses implicate neuronal,
immune and histone pathways
SO NATURE NEUROSCIENCE
LA English
DT Article
ID DE-NOVO MUTATIONS; SCHIZOPHRENIA; METHYLATION; DISORDERS; AUTISM; BRAIN;
PROMOTERS; BURDEN; LOCI
AB Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
C1 [O'Dushlaine, Colm] Regeneron Pharmaceut Inc, Regeneron Genet Ctr, Tarrytown, NY 10591 USA.
[O'Dushlaine, Colm; Rossin, Lizzy; Duncan, Laramie; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Perlis, Roy H.; Anttila, Verneri; Raychaudhuri, Soumya; Daly, Mark J.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Lee, Phil H.; Perlis, Roy H.; Bergen, Sarah E.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodevelopmental Genet Unit, Boston, MA 02114 USA.
[Duncan, Laramie; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Bergen, Sarah E.; Chambert, Kimberly; McCarroll, Steven A.; Moran, Jennifer L.; Raychaudhuri, Soumya; Scolnick, Edward; Daly, Mark J.; Smoller, Jordan W.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Duncan, Laramie; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Bergen, Sarah E.; Chambert, Kimberly; McCarroll, Steven A.; Moran, Jennifer L.; Raychaudhuri, Soumya; Scolnick, Edward; Daly, Mark J.; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Parikshak, Neelroop N.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Program Neurobehav Genet, Los Angeles, CA 90095 USA.
[Newhouse, Stephen; Asherson, Philip; Collier, David A.; Craig, Ian W.; Farmer, Anne E.; Kuntsi, Jonna; Lewis, Cathryn M.; McGuffin, Peter; Breen, Gerome] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, MRC, London, England.
[Newhouse, Stephen; Breen, Gerome] NIHR, Biomed Res Ctr Mental Hlth, South London & Maudsley NHS Trust & Inst Psychiat, London, England.
[Purcell, Shaun M.; Ruderfer, Douglas] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Gen, New York, NY USA.
[Posthuma, Danielle] Vrije Univ Amsterdam, Dept Funct Gen, Amsterdam, Netherlands.
Vrije Univ Amsterdam, Dept Clin Genet, Amsterdam, Netherlands.
[Posthuma, Danielle] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands.
[Nurnberger, John I.] Indiana Univ, Sch Med, Inst Psychiat Res, Indianapolis, IN 46202 USA.
[Nurnberger, John I.] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Lee, S. Hong; Mowry, Bryan J.; Byrne, Enda M.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA.
[Mowry, Bryan J.] Queensland Ctr Mental Hlth Res, Wacol, Qld, Australia.
[Thapar, Anita; Fraser, Christine; Georgieva, Lyudmila; Gordon-Smith, Katherine; Grozeva, Detelina; Jones, Ian; Kirov, George K.; Moskvina, Valentina; Nikolov, Ivan; Owen, Michael J.; Williams, Nigel; Zammit, Stanley; O'Donovan, Michael C.; Craddock, Nicholas; Holmans, Peter A.] Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Gen, Cardiff CF10 3AX, S Glam, Wales.
[Thapar, Anita; Fraser, Christine; Georgieva, Lyudmila; Jones, Ian; Kirov, George K.; Nikolov, Ivan; Owen, Michael J.; Williams, Nigel; Zammit, Stanley; Sklar, Pamela; O'Donovan, Michael C.; Craddock, Nicholas] Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Cardiff CF10 3AX, S Glam, Wales.
[Goddard, Michael E.] Dept Environm & Primary Ind Victoria, Biosci Res Div, Melbourne, Vic, Australia.
[Goddard, Michael E.] Univ Melbourne, Fac Land & Environm, Melbourne, Vic, Australia.
[Witte, John S.; Foroud, Tatiana; Koller, Daniel L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Absher, Devin; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Agartz, Ingrid; Andreassen, Ole A.; Djurovic, Srdjan; Mattingsdal, Morten; Melle, Ingrid] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, Oslo, Norway.
[Agartz, Ingrid] Diakonhjemmet Hosp Oslo, Dept Res, Oslo, Norway.
[Akil, Huda; Meng, Fan; Thompson, Robert C.; Watson, Stanley J.] Univ Michigan, Mol & Behav Neurosci Inst, Mol Psychiat Lab, Ann Arbor, MI 48109 USA.
[Amin, Farooq] Emory Univ, Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Andreassen, Ole A.; Melle, Ingrid] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0450 Oslo, Norway.
[Anjorin, Adebayo; Bass, Nicholas; Choudhury, Khalid; Gurling, Hugh; Kandaswamy, Radhika; Krasucki, Robert; Lawrence, Jacob; McQuillin, Andrew; Pimm, Jonathan; Puri, Vinay] UCL, Mental Hlth Sci Unit, London, England.
[Anney, Richard; Cormican, Paul; Corvin, Aiden; Donohoe, Gary J.; Gailagher, Louise; Gill, Michael; Kenny, Elaine; Morris, Derek W.; Quinn, Emma M.; Visscher, Peter M.] Trin Coll Dublin, Dept Psychiat, Dublin, Ireland.
[Arking, Dan E.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Azevedo, Maria H.; Oliveira, Guiomar] Univ Coimbra, Fac Med, Coimbra, Portugal.
[Backlund, Lena; Frisen, Louise; Osby, Urban; Schalling, Martin] Karolinska Inst, Ctr Mol Med, Dept Mol Med & Surg, Stockholm, Sweden.
[Badner, Judith A.; Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Bailey, Anthony J.] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada.
[Banaschewski, Tobias] Heidelberg Univ, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherary, Mannheim, Germany.
[Barchas, Jack D.] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA.
[Barnes, Michael R.] GlaxoSmithKline, London, England.
[Barrett, Thomas B.] Portland VA Med Ctr, Portland, OR USA.
[Battaglia, Agatino] Stella Maris Inst Child & Adolescent Neuropsychia, Pisa, Italy.
[Bauer, Michael] Carl Gustav Carus Univ Hosp, Dept Psychiat & Psychotherapy, Dresden, Germany.
[Bayes, Monica] CNAG, PCB, Barcelona, Spain.
[Bellivier, Frank; Etain, Bruno; Jamain, Stephane; Leboyer, Marion] INSERM, U955, Creteil, France.
Univ Paris 07, Paris, France.
Grp Hosp St Louis Lariboisiere, AP HP, Dept Psychiat, Paris, France.
[Bellivier, Frank; Etain, Bruno; Jamain, Stephane; Leboyer, Marion] ENBREC Grp, Fdn FondaMental, Creteil, France.
[Bergen, Sarah E.; Hultman, Christina M.; Kaehler, Anna K.; Landen, Mikael; Laengstroem, Niklas; Lichtenstein, Paul; Magnusson, Patrik K. E.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Berrettini, Wade; Elia, Josephine; Lohoff, Falk W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Betancur, Catalina] INSERM, U952, Paris, France.
CNRS, UMR 7224, Paris, France.
[Betancur, Catalina] Univ Paris 06, Paris, France.
[Bettecken, Thomas; Binder, Elisabeth B.; Czamara, Darina; Holsboer, Florian; Ising, Marcus; Kohli, Martin A.; Lucae, Susanne; Mueller-Myhsok, Bertram; Uhr, Manfred] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Programs Pediat Psychopharmacol & ADHD, Boston, MA 02114 USA.
[Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Black, Donald W.; Coryell, William H.; Potash, James B.; Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Blackwood, Douglas H. R.; MacIntyre, Donald J.; McGhee, Kevin A.; McIntosh, Andrew; McLean, Alan W.; Muir, Walter J.; Pickard, Benjamin S.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.
[Bloss, Cinnamon S.; Schork, Nicholas J.; Smith, Erin N.] Scripps Translat Sci Inst, La Jolla, CA USA.
[Bloss, Cinnamon S.] Scripps Hlth, La Jolla, CA USA.
[Boehnke, Michael; Flicldnger, Matthew; Guan, Weihua; Kwan, Phoenix; Scott, Laura J.; Zhang, Peng; Zoellner, Sebastian] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Boehnke, Michael; Flicldnger, Matthew; Guan, Weihua; Kwan, Phoenix; Scott, Laura J.; Zhang, Peng; Zoellner, Sebastian] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke-Jan; Middeldorp, Christel M.; Willemsen, Gonneke] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Penninx, Brenda W.; Smit, Johannes H.; Van Grootheest, Gerard; Willemsen, Gonneke] Inst Hlth & Care Res, EMGO, Amsterdam, Netherlands.
[Boomsma, Dorret I.; De Geus, Eco J.; Hottenga, Jouke-Jan; Middeldorp, Christel M.; Penninx, Brenda W.] Neurosci Campus Amsterdam, Amsterdam, Netherlands.
[Breuer, Rene; Frank, Josef; Meier, Sandra; Strohmaier, Jana; Treutlein, Jens; Witt, Stephanie H.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Mannheim, Germany.
[Bruggeman, Richard; Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Buccola, Nancy G.] Louisiana State Univ, Hlth Sci Ctr, Sch Nursing, New Orleans, LA USA.
[Buitelaar, Jan K.; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands.
[Bunney, William E.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA.
[Buxbaum, Joseph D.] Seaver Autism Ctr Res & Treatment, Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA.
[Byerley, William F.; Hamilton, Steven P.; Weiss, Lauren A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Byerley, William F.] NCIRE, San Francisco, CA USA.
[Caesar, Sian; Gordon-Smith, Katherine; Jones, Lisa] Univ Birmingham, Dept Psychiat, Birmingham, W Midlands, England.
[Cahn, Wiepke; Kahn, Rene S.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Utrecht Psychiat, Dept Psychiat, Birmingham, W Midlands, England.
[Cantor, Rita M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Casas, Miguel; Ramos-Quiroga, Josep Antoni] Hosp Univ Vail Hebron, CIBERSAM, Ctr Invest Biomed Area Salud Mental, Barcelona, Spain.
[Casas, Miguel; Ramos-Quiroga, Josep Antoni] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, E-08193 Barcelona, Spain.
[Cichon, Sven; Degenhardt, Franziska; Herms, Stefan; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Gen, Bonn, Germany.
INM 1, Res Ctr, Julich, Germany.
[Mattheisen, Manuel; Degenhardt, Franziska; Muehleisen, Thomas W.; Noethen, Markus M.; Propping, Peter; Ribases, Marta; Schumacher, Johannes] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Cichon, Sven; Herms, Stefan] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland.
[Mattheisen, Manuel; Hansen, Thomas F.; Ingason, Andres; Jones, Edward G.; Olsen, Line; Rasmussen, Henrik B.; Werge, Thomas] iPSYCH, Lundbeck Initiat Integrat Psychiat Res, Roskilde, Denmark.
Aarhus Univ, Dept Biomed, Aarhus, Denmark.
[Mattheisen, Manuel] Univ Bonn, Dept Genom Math, Bonn, Germany.
[Cloninger, C. Robert; Heath, Andrew C.; Madden, Pamela A. F.; Pergadia, Michele L.; Todorov, Alexandre A.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Cook, Edwin H.] Univ Illinois, Inst Juvenile Res, Dept Psychiat, Chicago, IL USA.
[Coon, Hilary; McMahon, William M.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA.
[Cormand, Bru] Univ Barcelona, Fac Biol, Dept Genet, Barcelona, Spain.
CIBERER, Biomed Network Res Ctr Rare Dis, Barcelona, Spain.
[Cormand, Bru] IBUB, Barcelona, Spain.
[Craig, David W.; Szelinger, Szabocls] Translat Genom Res Inst, Phoenix, AZ USA.
[Crosbie, Jennifer; Schachar, Russell] Univ Toronto, Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON M5G 1X8, Canada.
[Cuccaro, Michael L.; Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Gen, Miami, FL USA.
[Curtis, David] Univ London, East London NHS Fdn Trust, London, England.
[Czamara, Darina; Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Datta, Susmita] UCL, Genet Inst, London, England.
[Dawson, Geraldine] Autism Speaks, New York, NY USA.
Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Dawson, Geraldine; Piven, Joseph] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC USA.
[Day, Richard; Matthews, Keith] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Div Neurosci, Dundee DD1 9SY, Scotland.
[Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, N-0450 Oslo, Norway.
[Doyle, Alysa E.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Doyle, Alysa E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] NorthShore Univ Hlth Syst, Dept Psychiat & Behav Sci, Evanston, IL USA.
[Duan, Jubao; Gejman, Pablo V.; Sanders, Alan R.] Univ Chicago, Evanston, IL USA.
[Dudbridge, Frank] London Sch Hyg & Trop Med, Dept Noncommun Dis Epidemiol, London WC1, England.
[Duketis, Eftichia; Freitag, Christine M.; Poustka, Fritz] JW Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat Psychosomat & Ps, Frankfurt, Germany.
[Ebstein, Richard P.] Natl Univ Singapore, Dept Psychol, Singapore 117548, Singapore.
[Edenberg, Howard J.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA.
[Elia, Josephine] Univ Penn, AI Dupont Hosp Children, Philadelphia, PA 19104 USA.
[Ennis, Sean] Univ Coll Med Sci, Sch Med, Dublin, Ireland.
[Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Hop H Mondor A Chenevier, AP HP, Dept Psychiat, Creteil, France.
[Fanous, Ayman] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Fanous, Ayman; Neale, Michael C.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Ferrier, I. Nicol; Parr, Jeremy R.; Young, Allan H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Fombonne, Eric] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Fombonne, Eric] Oregon Hlth & Sci Univ, Inst Dev & Disabil, Portland, OR 97201 USA.
[Freedman, Robert; Olincy, Ann] Univ Colorado Denver, Dept Psychiat, Aurora, CO USA.
[Freimer, Nelson B.; Loo, Sandra K.; Nelson, Stan F.; Ophoff, Roel A.; Smalley, Susan L.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA.
[Friedl, Marion; Giegling, Ina; Hartmann, Annette M.; Konte, Bettina; Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany.
[Gordon, Scott D.; Henders, Anjali K.; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Nyholt, Dale R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Green, Elaine K.] Univ Plymouth, Dept Biomed & Biol Sci, Plymouth PL4 8AA, Devon, England.
[Greenwood, Tiffany A.; McKinney, Rebecca; Nievergelt, Caroline M.; Shilling, Paul D.; Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Grice, Dorothy E.] Icahn Sch Med Mt Sinai, OCD & Related Disorders, Div Tics, New York, NY 10029 USA.
[Grice, Dorothy E.; Silverman, Jeremy M.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Gross, Magdalena; Hoefels, Susanne; Maier, Wolfgang] Univ Bonn, Dept Psychiat, Bonn, Germany.
[Guan, Weihua] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
[De Haan, Lieuwe] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands.
[Haines, Jonathan L.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Gen, Div Human, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Hallmayer, Joachim] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA.
[Hamshere, Marian L.; Hautzinger, Martin] Univ Tubingen, Dept Clin & Dev Psychol, Tubingen, Germany.
[Hansen, Thomas F.; Ingason, Andres; Jones, Edward G.; Olsen, Line; Rasmussen, Henrik B.; Werge, Thomas] Copenhagen Univ Hosp, Inst Biol Psychiat, Roskilde, Denmark.
[Hickie, Ian B.] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia.
[Hipolito, Maria; Lawson, William B.; Nwulia, Evaristus A.] Howard Univ, Coll Med, Dept Psychiat & Behav Sci, Washington, DC 20059 USA.
[Hoogendijk, Witte J.] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands.
[Hus, Vanessa] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA.
[Tzeng, Jung-Ying] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA.
[Keller, Matthew C.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA.
[Kennedy, James L.] Ctr Addict & Mental Hlth, Psychiat Neurogenet Sect, Toronto, ON, Canada.
[Kent, Lindsey] Univ St Andrews, Sch Med, St Andrews, Fife, Scotland.
[Kim, Yunjung; Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Klauck, Sabine M.] German Canc Res Ctr, DKFZ, Div Mol Genome Anal, Heidelberg, Germany.
[Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Knowles, James A.; Medeiros, Helena; Pato, Carlos N.; Pato, Michele T.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat, Los Angeles, CA 90033 USA.
[Korszun, Ania] Queen Mary Univ London, Wolfson Inst Preventat Med, London, England.
[Krabbendam, Lydia; Myin-Germeys, Inez; Van Os, Jim] Maastricht Univ Med Ctr, South Limburg Mental Hlth Res & Teaching Network, Dept Psychiat Neuropsychol, Maastricht, Netherlands.
[Landen, Mikael] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden.
[Lathrop, Mark] Ctr Natl Genotypage, Evry, France.
[Ledbetter, David H.; Martin, Christa L.] Autism & Dev Med Inst, Geisinger Hlth Syst, Danville, PA USA.
[Lencz, Todd; Malhotra, Anil K.] Zucker Hillside Hosp Div North Shore, Dept Psychiat, Div Res, Glen Oaks, NY USA.
Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA.
[Lencz, Todd; Malhotra, Anil K.] Yeshiva Univ, Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY USA.
[Lesch, Klaus-Peter] Univ Wurzburg, ADHD Clin Res Unit, Dept Psychiat Psychosomat & Psychotherapy, Div Mol Psychiat, D-97070 Wurzburg, Germany.
[Lesch, Klaus-Peter] Maastricht Univ, Sch Mental Hlth & Neurosci MHENS, Dept Psychiat & Psychol, NL-6200 MD Maastricht, Netherlands.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Li, Jun] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Lieberman, Jeffrey A.; McGrath, Patrick J.] Columbia Univ, New York State Psychiat Inst, New York, NY USA.
[Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Linszen, Don H.] Univ Amsterdam, Acad Med Ctr, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands.
[Liu, Chunyu] Univ Illinois, Inst Human Genet, Dept Psychiat, Chicago, IL USA.
[Loo, Sandra K.; Smalley, Susan L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Lord, Catherine] Weill Cornell Med Coll, Ctr Autism & Developing Brain, White Plains, NY USA.
[Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Lowe, Jennifer K.; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Autism Res & Treatment, Semel Inst, Los Angeles, CA 90095 USA.
[Maestrini, Elena] Univ Bologna, Dept Pharm & Biotechnol, Bologna, Italy.
[Mahon, Pamela B.; Schulze, Thomas G.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Mane, Shrikant M.] Yale Ctr Genome Anal, Orange, CA USA.
[Mattingsdal, Morten] Sorlandet Hosp, Kristiansand, Norway.
[McGough, James J.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Los Angeles, CA 90095 USA.
[McInnis, Melvin G.; Zhang, Peng; Zoellner, Sebastian] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[McIntosh, Andrew; McLean, Alan W.; Muir, Walter J.; Pickard, Benjamin S.] Univ Edinburgh, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
[McMahon, Francis J.] US Natl Inst Hlth Bethesda, Nat Inst Mental Hlth, Bethesda, MD USA.
[Meyer, Jobst] Univ Trier, Dept Neurobehav Genet, Trier, Germany.
[Middleton, Lefkos] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Milanova, Vihra] Alexander Univ Hosp, Psychiat Clin 1, Dept Psychiat, Sofia, Bulgaria.
[Miranda, Ana] Univ Valencia, Dept Dev & Educ Psychol, Valencia, Spain.
[Monaco, Anthony P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Monaco, Anthony P.] Tufts Univ, Off President, Medford, MA 02155 USA.
[Moreno-De-Luca, Daniel; Sanders, Stephan J.; State, Matthew] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Morken, Gunnar] St Olavs Hosp, Dept Psychiat, Trondheim, Norway.
[Morken, Gunnar] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway.
[Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Morrow, Eric M.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Moskvina, Valentina; Holmans, Peter A.] Cardiff Univ, Biostat & Bioinformat Unit, Cardiff, Wales.
[Muglia, Pierandrea; Tozzi, Federica] GlaxoSmithKline Res & Dev Ltd, Neurosci Ctr Excellence Drug Discovery, Verona, Italy.
[Muehleisen, Thomas W.] Univ Bonn, Life & Brain Ctr, Bonn, Germany.
[Murtha, Michael; State, Matthew; Willsey, A. Jeremy] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Nimgaonkar, Vishwajit; Sanders, Stephan J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Nimgaonkar, Vishwajit] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA.
[Oades, Robert D.] Univ Duisburg Essen, Clin Child & Adolescent Psychiat & Psychotherapy, Essen, Germany.
[Oliveira, Guiomar] Pediat Hosp, Ctr Hosp, Res & Clin Training Dept, Coimbra, Portugal.
[Oliveira, Guiomar] Univ Coimbra, Coimbra, Portugal.
[Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Psychiat, Utrecht, Netherlands.
[Palotie, Aarno; Rehnstroem, Karola] Sanger Inst, Cambridge, England.
[Paterson, Andrew D.] Hosp Sick Children, Genet Program, Toronto, ON M5G 1X8, Canada.
[Paterson, Andrew D.] Hosp Sick Children, Genom Biol, Toronto, ON M5G 1X8, Canada.
[Paterson, Andrew D.; Xu, Wei] Univ Toronto, Dalia Lana Sch Publ Hlth, Toronto, ON, Canada.
[Penninx, Brenda W.; Smit, Johannes H.; Van Grootheest, Gerard] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Quested, Digby J.] Univ Oxford, Acad Dept Psychiat, Oxford, England.
[Reif, Andreas] Univ Wurzburg, Dept Psychiat, Wurzburg, Germany.
[Ribases, Marta] Vall Hebron Res Inst, Psychiat Genet Unit, Barcelona, Spain.
[Rice, John P.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA.
[Roeyers, Herbert; Sonuga-Barke, Edmund J. S.] Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium.
[Rothenberger, Aribert] Univ Med Gottingen, Gottingen, Germany.
[Rouleau, Guy] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada.
[Sanders, Stephan J.; State, Matthew; Willsey, A. Jeremy] Yale Univ, Dept Genet, New Haven, CT USA.
[Sanders, Stephan J.] Yale Univ, Program Neurogenet, New Haven, CT USA.
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[Santangelo, Susan L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
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[Schatzberg, Alan F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
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[Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
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[Schork, Nicholas J.; Smith, Erin N.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany.
[Schwarz, Markus] Psychiat Ctr Nordbaden, Wiesloch, Germany.
[Shi, Jianxin] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Shyn, Stanley I.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Slager, Susan L.] Mayo Clin, Rochester, MN USA.
[Sonuga-Barke, Edmund J. S.] Univ Southampton, Acad Unit Psychol, Developmental Brain & Behav Lab, Southampton, Hants, England.
[Cair, David St.] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland.
[Steffens, Michael] Fed Inst Drugs & Med Devices BfArM, Res Dept, Bonn, Germany.
[Steinhausen, Hans-Christoph] Aalborg Univ Hosp, Res Unit Child & Adolescent Psychiat, Aalborg, Denmark.
Univ Basel, Clin Psychol & Epidemiol, Basel, Switzerland.
[Steinhausen, Hans-Christoph] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland.
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Hosp Sick Children, Neurosci & Mental Hlth Program, Toronto, ON M5G 1X8, Canada.
[Szatmari, Peter] Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Thirumalai, Srinivasa] Oxford Hlth NHS Fdn Trust, Marlborough House Secure Unit, Milton Keynes, Bucks, England.
[Van den Oord, Edwin J. C. G.] Virginia Commonwealth Univ, Ctr Biomarker Res & Personalized Med, Richmond, VA USA.
Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal.
[Vicente, Astrid M.] BioFIG, Ctr Biodivers, Funct & Integrat Gen, Lisbon, Portugal.
Inst Gulbenkian Ciencias, Lisbon, Portugal.
[Vicente, Astrid M.] Nationwide Childrens Hosp, Battelle Ctr Math Med, Columbus, OH USA.
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Childrens Hosp, Div Genet, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Ctr Life Sci, Dept Neurol, Boston, MA 02115 USA.
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[Werge, Thomas] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Wienker, Thomas F.] Univ Bonn, Inst Med Biometry, Bonn, Germany.
[Wijsman, Ellen M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Wijsman, Ellen M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Young, Allan H.] Kings Coll London, Inst Psychiat, Ctr Affect Disorders, London, England.
[Yu, Timothy W.] Harvard Univ, Sch Med, Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Zandi, Peter P.] Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA.
[Zitman, Frans G.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, STEP, Dept Psychiat, San Diego, CA USA.
Virginia Commonwealth Univ, Dept Human Mol Genet, Richmond, VA USA.
[Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
[Kendler, Kenneth S.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA.
[Zhao, Zhaoming] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA.
RP Breen, G (reprint author), Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, MRC, London, England.
EM holmanspa@cardiff.ac.uk; gerome.breen@kcl.ac.uk
RI Holmans, Peter/F-4518-2015; Kuntsi, Jonna/G-9750-2011; Zhang,
Peng/N-2920-2014; Mattheisen, Manuel/B-4949-2012; Breen,
Gerome/A-5540-2010; Monaco, Anthony/A-4495-2010; Scherer, Stephen
/B-3785-2013; Franke, Barbara/D-4836-2009; Hansen, Thomas/O-5965-2014;
Paterson, Andrew/A-4088-2011; Melle, Ingrid /B-4858-2011; Schumacher,
Johannes/F-4970-2015; Ruderfer, Douglas/M-5795-2016; Lee, Sang
Hong/A-2569-2011; Lohoff, Falk/M-7951-2016; Lencz, Todd/J-3418-2014;
BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Magnusson,
Patrik/C-4458-2017; Lesch, Klaus-Peter/J-4906-2013;
OI Holmans, Peter/0000-0003-0870-9412; Zhang, Peng/0000-0003-1182-1392;
Mattheisen, Manuel/0000-0002-8442-493X; Breen,
Gerome/0000-0003-2053-1792; Monaco, Anthony/0000-0001-7480-3197;
Scherer, Stephen /0000-0002-8326-1999; Franke,
Barbara/0000-0003-4375-6572; Hansen, Thomas/0000-0001-6703-7762;
Paterson, Andrew/0000-0002-9169-118X; Melle, Ingrid
/0000-0002-9783-548X; Schumacher, Johannes/0000-0001-9217-6457;
Ruderfer, Douglas/0000-0002-2365-386X; Bruggeman,
Richard/0000-0002-3238-8471; Nothen, Markus/0000-0002-8770-2464;
Donohoe, Gary/0000-0003-3037-7426; Oliveira,
Guiomar/0000-0002-7049-1277; Yu, Timothy/0000-0003-2988-7701; Thapar,
Anita/0000-0002-3689-737X; Etain, Bruno/0000-0002-5377-1488; de Geus,
Eco/0000-0001-6022-2666; Cormand, Bru/0000-0001-5318-4382; Betancur,
Catalina/0000-0002-3327-4804; Backlund, Lena/0000-0001-9399-5024;
Gallagher, Louise/0000-0001-9462-2836; Zammit,
Stanley/0000-0002-2647-9211; Myin-Germeys, Inez/0000-0002-3731-4930;
Jamain, Stephane/0000-0002-4321-4100; Greenwood,
Tiffany/0000-0002-6080-6503; Kent, Lindsey/0000-0002-5315-3399; Anney,
Richard/0000-0002-6083-407X; Lee, Sang Hong/0000-0001-9701-2718; Lencz,
Todd/0000-0001-8586-338X; McQuillin, Andrew/0000-0003-1567-2240; Lesch,
Klaus-Peter/0000-0001-8348-153X; Hamilton, Steven/0000-0001-8106-6260;
Bergen, Sarah/0000-0002-5888-0034; Anttila, Verneri/0000-0002-0073-4675;
McMahon, Francis/0000-0002-9469-305X
FU National Institute for Health Research (NIHR) Mental Health Biomedical
Research Centre at South London; Maudsley NHS Foundation Trust; King's
College London; US National Institute of Mental Health (NIMH)
[K99MH101367]; NIMH [U01 MH085520]; Netherlands Scientific Organization
(NOW) [480-05-003]; Dutch Brain Foundation; VU University
FX G.B. and S.N. acknowledge funding support for this work from the
National Institute for Health Research (NIHR) Mental Health Biomedical
Research Centre at South London and Maudsley NHS Foundation Trust and
King's College London. P.H.L. is supported by US National Institute of
Mental Health (NIMH) grant K99MH101367. The PGC Cross-Disorder Group is
supported by NIMH grant U01 MH085520. Statistical analyses were carried
out on the Genetic Cluster Computer, which is fmancially supported by
the Netherlands Scientific Organization (NOW; 480-05-003; principal
investigator D.P.) along with a supplement from the Dutch Brain
Foundation and VU University. Numerous (> 100) grants from government
agencies along with substantial private and foundation support worldwide
enabled the collection of phenotype and genotype data, without which
this research would not be possible.
NR 39
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U1 20
U2 126
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD FEB
PY 2015
VL 18
IS 2
BP 199
EP 209
DI 10.1038/nn.3922
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CA0UM
UT WOS:000348631800010
ER
PT J
AU Reardon, DA
Wen, PY
AF Reardon, David A.
Wen, Patrick Y.
TI GLIOMA IN 2014 Unravelling tumour heterogeneity -implications for
therapy
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID NEWLY-DIAGNOSED GLIOBLASTOMA; BEVACIZUMAB; TEMOZOLOMIDE; TRIAL; IDH1
AB Heterogeneity within and across tumours is increasingly recognized as a critical factor that limits therapeutic progress for many cancers. Key studies reported in 2014 describe previously unappreciated patterns of geographical and temporal heterogeneity for glioblastoma (the mostcommon primary CNS tumour in adults), with important implications for ongoing therapeutic studies evaluating molecular targeted therapies.
C1 [Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA.
RP Reardon, DA (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM david_reardon@dfci.harvard.edu
NR 10
TC 22
Z9 25
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD FEB
PY 2015
VL 12
IS 2
BP 69
EP 70
DI 10.1038/nrclinonc.2014.223
PG 2
WC Oncology
SC Oncology
GA CA4GB
UT WOS:000348861300002
PM 25560529
ER
PT J
AU Smith, TR
Habib, A
Rosenow, JM
Nahed, BV
Babu, MA
Cybulski, G
Fessler, R
Batjer, HH
Heary, RF
AF Smith, Timothy R.
Habib, Ali
Rosenow, Joshua M.
Nahed, Brian V.
Babu, Maya A.
Cybulski, George
Fessler, Richard
Batjer, H. Hunt
Heary, Robert F.
TI Defensive Medicine in Neurosurgery: Does State-Level Liability Risk
Matter?
SO NEUROSURGERY
LA English
DT Article
DE Defensive medicine; Health reform; Liability; Malpractice; Neurosurgery;
Tort
ID MALPRACTICE LITIGATION; PHYSICIANS; CLAIMS; REFORM; DOCTORS; LAW; SUE
AB BACKGROUND: Defensive medicine is prevalent among US neurosurgeons due to the high risk of malpractice claims. This study provides national estimates of US neurosurgeons' defensive behaviors and perceptions.
OBJECTIVE: To examine the relationship of defensive medicine-both "assurance" behaviors and "avoidance" behaviors-to the liability environment.
METHODS: A 51-question online survey was sent to 3344 US neurosurgeon members of the American Board of Neurological Surgeons (ABNS). The survey was anonymous and conducted over 6 weeks in the spring of 2011. The previously validated questionnaire contained questions on neurosurgeon, patient, and practice characteristics; perceptions of the liability environment; and defensive-medicine behaviors. Bivariate and multivariate analyses examined the state liability risk environment as a predictor of a neurosurgeon's likelihood of practicing defensive medicine.
RESULTS: A total of 1026 neurosurgeons completed the survey (31% response rate). Neurosurgeons' perceptions of their state's liability environment generally corresponded well to more objective measures of state-level liability risk because 83% of respondents correctly identified that they were practicing in a high-risk environment. When controlling for surgeon experience, income, high-risk patient load, liability history, and type of patient insurance, neurosurgeons were 50% more likely to practice defensive medicine in high-risk states compared with low-risk-risk states (odds ratio: 1.5, P < .05).
CONCLUSION: Both avoidance and assurance behaviors are prevalent among US neurosurgeons and are correlated with subjective and objective measures of state-level liability risk. Defensive medicine practices do not align with patient-centered care and may contribute to increased inefficiency in an already taxed health care system.
C1 [Smith, Timothy R.; Habib, Ali; Rosenow, Joshua M.; Cybulski, George; Fessler, Richard; Batjer, H. Hunt] Northwestern Univ, Dept Neurol Surg, Chicago, IL 60611 USA.
[Nahed, Brian V.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Babu, Maya A.] Mayo Clin & Mayo Grad Sch Med, Dept Neurol Surg, Rochester, MN USA.
[Heary, Robert F.] UMDNJ New Jersey Med Sch, Dept Neurol Surg, Newark, NJ USA.
RP Smith, TR (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol Surg, 676 N St Clair St,Suite 2210, Chicago, IL 60611 USA.
EM timothy-smith-0@fsm.northwestern.edu
FU Congress of Neurological Surgeons; Council of State Neurosurgical
Societies
FX The authors have no personal, financial, or institutional interest in
any of the drugs, materials, or devices described in this article.
Sources of funding were the Congress of Neurological Surgeons and the
Council of State Neurosurgical Societies.
NR 28
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD FEB
PY 2015
VL 76
IS 2
BP 105
EP 113
DI 10.1227/NEU.0000000000000576
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA AZ3SR
UT WOS:000348147500017
PM 25255258
ER
PT J
AU Torriani, M
Oliveira, AL
Azevedo, DC
Bredella, MA
Yu, EW
AF Torriani, Martin
Oliveira, Adriana L.
Azevedo, Debora C.
Bredella, Miriam A.
Yu, Elaine W.
TI Effects of Roux-en-Y Gastric Bypass Surgery on Visceral and Subcutaneous
Fat Density by Computed Tomography
SO OBESITY SURGERY
LA English
DT Article
DE Obesity; Adipose tissue; Metabolic syndrome; Visceral fat; Surgery;
Computed tomography
ID ADIPOSE-TISSUE; SYSTEMIC INFLAMMATION; SLEEVE GASTRECTOMY; EVOLUTION;
RISK
AB We aimed to test the hypothesis that noninvasive fat density by computed tomography (CT) increases after Roux-en-Y gastric bypass (RYGB) and correlates with improved cardiometabolic risk. We examined 21 obese adults before and 12 months after RYGB and 16 obese nonsurgical controls followed for 12 months. Visceral (VAT) and subcutaneous adipose tissue (SAT) density increased after RYGB (P < 0.0001) while remaining stable in controls (P a parts per thousand yenaEuro parts per thousand 0.1). In RYGB subjects, 12-month increase in VAT density correlated with decreased C-reactive protein (CRP) independent of change in VAT area or BMI (both P < 0.05). Twelve-month increase in SAT density correlated with increased HDL cholesterol independent of change in SAT area (P = 0.048), BMI (P = 0.03), or statin use (P = 0.002), and 1 unit increase in SAT density had increased odds of higher total abdominal fat loss (P = 0.002).
C1 [Torriani, Martin; Oliveira, Adriana L.; Azevedo, Debora C.; Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA.
[Torriani, Martin; Oliveira, Adriana L.; Azevedo, Debora C.; Bredella, Miriam A.; Yu, Elaine W.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Yu, Elaine W.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA.
RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW 6048, Boston, MA 02114 USA.
EM mtorriani@mgh.harvard.edu
FU National Institutes of Health [HD51959, RR025758, DK093713]
FX This study was funded by the National Institutes of Health (Grant
Numbers: HD51959, RR025758 and DK093713).
NR 10
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Z9 7
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0960-8923
EI 1708-0428
J9 OBES SURG
JI Obes. Surg.
PD FEB
PY 2015
VL 25
IS 2
BP 381
EP 385
DI 10.1007/s11695-014-1485-6
PG 5
WC Surgery
SC Surgery
GA AZ3ER
UT WOS:000348111000029
PM 25381117
ER
PT J
AU Papakostas, TD
Le, HG
Chodosh, J
Jacobs, DS
AF Papakostas, Thanos D.
Le, Hong-Gam
Chodosh, James
Jacobs, Deborah S.
TI Prosthetic Replacement of the Ocular Surface Ecosystem as Treatment for
Ocular Surface Disease in Patients with a History of Stevens-Johnson
Syndrome/Toxic Epidermal Necrolysis
SO OPHTHALMOLOGY
LA English
DT Article
ID COST-EFFECTIVENESS THRESHOLD; SCLERAL CONTACT-LENS; VERSUS-HOST-DISEASE;
BOSTON KERATOPROSTHESIS; ERYTHEMA MULTIFORME; MANIFESTATIONS;
MANAGEMENT; THERAPY; COMPLICATIONS; NICE
AB Purpose: To report the visual outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in patients with ocular surface disease related to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).
Design: Retrospective cohort study.
Subjects: We included 86 patients (167 eyes) with history of SJS/TEN who underwent PROSE treatment from January 1, 2006, to January 1, 2011.
Methods: Etiology, previous interventions, change in visual acuity, change in visual function, and duration of follow-up are reported. Paired t test and Friedman test with Dunn's post hoc test for multiple comparisons were used for statistical analysis.
Main Outcome Measures: Visual acuity at last follow-up and visual function based on the National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) at 6 months.
Results: We treated 35 males and 51 females with a history of SJS/TENS; median age was 36 years. The most common reported etiologies for SJS/TENS were antibiotics (n = 25), ibuprofen (n = 15), and lamotrigine (n = 11). The median visual acuity at the initial visit was 20/60 (range, 20/400-20/25; 0.48 logarithm of the minimum angle of resolution [logMAR]), and the visual acuity at completion of customization was 20/25 (range, 20/200-20/20; 0.096 logMAR; P < 0.001), with no decline in median acuity at the end of follow-up. Median duration of follow-up was 16 months. There was a significant improvement in the visual function of the patients based on the NEI VFQ-25 questionnaire (mean of 48 points at baseline vs. mean of 72 points at 6 months; P < 0.001). In addition, there was also an improvement in the self-reported general health of the patients (mean of 57 points at baseline vs. mean of 65 points at 6 months; P < 0.01).
Conclusions: In a large cohort of patients with chronic ocular surface disease related to SJS/TEN, PROSE treatment offers sustained and significant large improvement in visual function and acuity. (C) 2015 by the American Academy of Ophthalmology.
C1 [Papakostas, Thanos D.; Chodosh, James; Jacobs, Deborah S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Le, Hong-Gam; Jacobs, Deborah S.] Boston Fdn Sight, Needham, MA 02494 USA.
RP Jacobs, DS (reprint author), Boston Fdn Sight, 464 Hillside Ave,Suite 205, Needham, MA 02494 USA.
EM djacobs@bostonsight.org
NR 28
TC 8
Z9 8
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2015
VL 122
IS 2
BP 248
EP 253
DI 10.1016/j.ophtha.2014.08.015
PG 6
WC Ophthalmology
SC Ophthalmology
GA AZ5WT
UT WOS:000348290000015
PM 25282251
ER
PT J
AU Qian, CX
Hassanaly, S
Harissi-Dagher, M
AF Qian, Cynthia X.
Hassanaly, Salima
Harissi-Dagher, Mona
TI Anterior Segment Optical Coherence Tomography in the Long-Term Follow-up
and Detection of Glaucoma in Boston Type I Keratoprosthesis
SO OPHTHALMOLOGY
LA English
DT Article
ID UNIVERSITY-OF-CALIFORNIA; CHAMBER ANGLE ASSESSMENT; ULTRASOUND
BIOMICROSCOPY; OUTCOMES; ENDOPHTHALMITIS; COMPLICATIONS; MULTICENTER;
PREVENTION; RESOLUTION; INFECTION
AB Purpose: To evaluate the role of anterior segment (AS) optical coherence tomography (OCT) as a standardized method of imaging Boston type I keratoprosthesis (KPro) after surgery, particularly in the visualization of iris and angle structures.
Design: Prospective case series.
Participants: Twenty patients who underwent KPro implantation in 1 eye.
Methods: Patients underwent AS OCT imaging before surgery. After KPro implantation, patients were imaged using the AS single, dual, and quad scans to obtain transverse images of the eye every 15 degrees over 360 degrees. High-resolution, corneal quad, and anterior chamber scans were also obtained. This imaging protocol allowed juxtaposition and comparison of the same imaging coordinates obtained before surgery and 3, 6, and 12 months after surgery.
Main Outcome Measures: Postoperative visual acuity (VA), glaucoma progression on clinical examination and formal visual field testing, and anatomic angle changes on AS OCT defined by angle closure, peripheral anterior synechiae (PAS), iriseKPro backplate touch, and graftehost interface changes over time.
Results: Mean follow-up was 18.8 +/- 3.2 months. The average preoperative VA was 1.9 +/- 0.5 logarithm of the minimum angle of resolution. After surgery, VA improved to 1.0 +/- 0.9 at last follow-up (P = 0.002). Fourteen of 20 patients had glaucoma before surgery. After surgery, 5 of these patients deteriorated clinically and 1 de novo diagnosis of glaucoma was made. On OCT, the average total degrees of angle closure for all patients increased from 158.5 +/- 158.9 degrees before surgery to 205.4 +/- 154.0 degrees after surgery (P = 0.04). The number of eyes with 360 degrees of PAS increased from 6 of 20 before surgery to 9 of 20 after surgery. Irisebackplate touch was demonstrated in 5 of 20 patients, with an average area of involvement of 24.2 +/- 36.2 degrees. Overall, of the 12 of 20 patients with clear signs of anatomic angle narrowing and synechiae progression on imaging, 3 had glaucoma deterioration detected by clinical examination. In the other 9 patients, angle changes on OCT were not accompanied by any detectable clinical signs of glaucomatous deterioration.
Conclusions: Anterior segment OCT can be used to observe anatomic changes after KPro implantation that cannot be detected otherwise. We were unable to demonstrate a correlation between anatomic features and clinical progression. (C) 2015 by the American Academy of Ophthalmology.
C1 [Qian, Cynthia X.; Hassanaly, Salima; Harissi-Dagher, Mona] Univ Montreal, Dept Ophthalmol, Quebec City, PQ, Canada.
[Qian, Cynthia X.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
RP Harissi-Dagher, M (reprint author), CHUM, Hop Notre Dame, 1560 Sherbrooke E, Montreal, PQ H2L 4M1, Canada.
EM monadagher@hotmail.com
FU Pfizer Investigator-Initiated Research program; American Society of
Cataract and Refractive Surgery research grant; Fonds de Recherche en
Ophtalmologie de l'Universite de Montreal, Montreal, Canada
FX Supported by the Pfizer Investigator-Initiated Research program; an
American Society of Cataract and Refractive Surgery research grant; and
a research grant from the Fonds de Recherche en Ophtalmologie de
l'Universite de Montreal, Montreal, Canada. The sponsor or funding
organization had no role in the design or conduct of this research.
NR 35
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U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2015
VL 122
IS 2
BP 317
EP 325
DI 10.1016/j.ophtha.2014.08.007
PG 9
WC Ophthalmology
SC Ophthalmology
GA AZ5WT
UT WOS:000348290000024
PM 25264027
ER
PT J
AU Ip, MS
Domalpally, A
Sun, JK
Ehrlich, JS
AF Ip, Michael S.
Domalpally, Amitha
Sun, Jennifer K.
Ehrlich, Jason S.
TI Long-term Effects of Therapy with Ranibizumab on Diabetic Retinopathy
Severity and Baseline Risk Factors for Worsening Retinopathy
SO OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MACULAR EDEMA; FOCAL/GRID PHOTOCOAGULATION;
INTRAVITREAL TRIAMCINOLONE; PROLIFERATIVE RETINOPATHY; CLINICAL-TRIAL;
PROGRESSION; COMPLICATIONS; CANDESARTAN; ACETONIDE
AB Purpose: To assess the effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity when administered for up to 3 years, evaluate the effect of delayed initiation of ranibizumab therapy on DR severity, and identify baseline patient characteristics associated with the development of proliferative DR (PDR).
Design: Exploratory analyses of phase III, randomized, double-masked, sham-controlled multicenter clinical trials.
Participants: Adults with diabetic macular edema (DME) (N = 759), baseline best-corrected visual acuity 20/40 to 20/320 Snellen equivalent, and central foveal thickness >= 275 mu m.
Methods: Patients were randomized to monthly 0.3 or 0.5 mg ranibizumab or sham injections. Sham participants could switch to 0.5 mg ranibizumab during the third year (sham/0.5 mg crossover). Baseline risk factors were evaluated to explore potential associations with development of PDR. Time to first development of PDR was analyzed by Kaplan-Meier methods to calculate cumulative probabilities by group.
Main Outcome Measures: Study eye change on the Early Treatment Diabetic Retinopathy Study severity scale and a composite clinical outcome evaluating progression to PDR based on photographic changes plus clinically important events defining PDR.
Results: At month 36, a greater proportion of ranibizumab-treated eyes had >= 2- or >= 3-step DR improvement compared with sham/0.5 mg crossover. A >= 3-step improvement was achieved at 36 months by 3.3%, 15.0%, and 13.2% of sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab-treated eyes, respectively (P < 0.0001). Through 36 months, 39.1% of eyes in the sham/0.5 mg group developed PDR, as measured by composite outcome, compared with 18.3% and 17.1% of eyes treated with 0.3 or 0.5 mg ranibizumab, respectively. The presence of macular capillary nonperfusion at baseline seems to be associated with progression to PDR in ranibizumab-treated eyes but did not meaningfully influence visual acuity improvement in eyes with DME after ranibizumab therapy.
Conclusions: Ranibizumab, as administered to patients with DME for 12 to 36 months in these studies, can both improve DR severity and prevent worsening. Prolonged delays in initiation of ranibizumab therapy may limit this therapeutic effect. Although uncommon, the development of PDR still occurs in a small percentage of eyes undergoing antievascular endothelial growth factor therapy and may be related to the presence of macular nonperfusion. (C) 2015 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
C1 [Ip, Michael S.; Domalpally, Amitha] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med, Madison, WI 53717 USA.
[Sun, Jennifer K.] Joslin Diabet Ctr, Harvard Dept Ophthalmol, Boston, MA 02215 USA.
[Ehrlich, Jason S.] Genentech Inc, San Francisco, CA 94080 USA.
RP Ip, MS (reprint author), Univ Wisconsin, Fundus Photograph Reading Ctr, 8010 Excelsior Dr,Suite 100, Madison, WI 53717 USA.
EM msip@wisc.edu
RI Dagdelen, Selcuk /A-9432-2017
FU Allergan Inc.; Optovue; Genentech, Inc.; Boston Micromachines
FX The author(s) have made the following disclosure(s): M.S.I.:
Consultant/advisor - Eye Technology Ltd, Genentech, Inc., NicOx, Notal
Vision, QLT Phototherapeutics Inc., Regeneron, Sirion; Grant support -
Allergan Inc. J.S.: Consultant - Novartis; Scientific Advisory Board -
Abbott Laboratories; Research support - Optovue, Genentech, Inc., Boston
Micromachines. J.S.E.:Employee - Genentech, Inc. (a member of the Roche
Group); Equity and/or options - Roche. Supported by Genentech, Inc.;
Support for third-party writing assistance was provided by Genentech,
Inc. The sponsor participated in the design and conduct of the study;
collection, management, analysis, and interpretation of the data; and
preparation and review of the manuscript.
NR 25
TC 20
Z9 21
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD FEB
PY 2015
VL 122
IS 2
BP 367
EP 374
DI 10.1016/j.ophtha.2014.08.048
PG 8
WC Ophthalmology
SC Ophthalmology
GA AZ5WT
UT WOS:000348290000029
PM 25439595
ER
PT J
AU Manze, MG
Orner, MB
Glickman, M
Pbert, L
Berlowitz, D
Kressin, NR
AF Manze, Meredith G.
Orner, Michelle B.
Glickman, Mark
Pbert, Lori
Berlowitz, Dan
Kressin, Nancy R.
TI Brief provider communication skills training fails to impact patient
hypertension outcomes
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Hypertension; Blood pressure; Patient-provider communication; Medication
adherence; Patient-centered care
ID BLOOD-PRESSURE CONTROL; WORCESTER-AREA TRIAL; PRIMARY-CARE;
HYPERLIPIDEMIA WATCH; GENDER CONCORDANCE; PHYSICIAN; ADHERENCE;
INTERVENTION; MANAGEMENT; SUPPORT
AB Objectives: Hypertension remains a prevalent risk factor for cardiovascular disease, and improved medication adherence leads to better blood pressure (BP) control. We sought to improve medication adherence and hypertension outcomes among patients with uncontrolled BP through communication skills training targeting providers.
Methods: We conducted a randomized controlled trial to assess the effects of a communication skills intervention for primary care doctors compared to usual care controls, on the outcomes of BP (systolic, diastolic), patient self-reported medication adherence, and provider counseling, assessed at baseline and post-intervention. We enrolled 379 patients with uncontrolled BP; 203 (54%) with follow-up data comprised our final sample. We performed random effects least squares regression analyses to examine whether the provider training improved outcomes, using clinics as the unit of randomization.
Results: In neither unadjusted nor multivariate analyses were significant differences in change detected from baseline to follow-up in provider counseling, medication adherence or BP, for the intervention versus control groups.
Conclusion: The intervention did not improve the outcomes; it may have been too brief and lacked sufficient practice level changes to impact counseling, adherence or BP.
Practice Implications: Future intervention efforts may require more extensive provider training, along with broader systematic changes, to improve patient outcomes. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Manze, Meredith G.] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10035 USA.
[Orner, Michelle B.; Glickman, Mark; Berlowitz, Dan] Bedford VAMC, Ctr Healthcare Org & Implementat Res, Bedford, MA USA.
[Glickman, Mark; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Hlth Policy & Management Dept, Boston, MA USA.
[Pbert, Lori] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA.
[Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
RP Manze, MG (reprint author), CUNY Hunter Coll, Sch Publ Hlth, 2180 3rd Ave,Room 523, New York, NY 10035 USA.
EM meredith.manze@hunter.cuny.edu
FU NIH/National Heart, Lung, and Blood Institute [R01 HL072814]; Health
Services Research and Development Service, Department of Veterans
Affairs [RCS 02-066-1]
FX This study was supported by NIH/National Heart, Lung, and Blood
Institute grant R01 HL072814 (PI: Kressin); Dr Kressin is also supported
by a Senior Research Career Scientist award (RCS 02-066-1) from the
Health Services Research and Development Service, Department of Veterans
Affairs. We thank Peter Davidson, MD, and the clinic and research staff
for their assistance.
NR 34
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U1 1
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD FEB
PY 2015
VL 98
IS 2
BP 191
EP 198
DI 10.1016/j.pec.2014.10.014
PG 8
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA AZ9SL
UT WOS:000348555400010
PM 25468397
ER
PT J
AU Linsky, A
Simon, SR
Bokhour, B
AF Linsky, Amy
Simon, Steven R.
Bokhour, Barbara
TI Patient perceptions of proactive medication discontinuation
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Patient beliefs; Communication; Shared decision making; Medication
safety
ID DECISION-MAKING; RANDOMIZED-TRIAL; HEALTH BELIEFS; OLDER-ADULTS;
PREFERENCES; ADHERENCE; POLYPHARMACY; CARE
AB Objective: While many patients prefer fewer medications, decisions about medication discontinuation involve collaboration between patients and providers. We sought to identify patient perspectives on intentional medication discontinuation in order to optimize medication use.
Methods: We conducted 20 interviews and two focus groups with a convenience sample of patients (22 men, 5 women; mean age 66 years) at two US Veterans Affairs Medical Centers. We queried patients' experiences with and attitudes toward taking multiple medications, preferences about taking fewer medications, and communication with their providers about stopping a medicine. Transcripts were analyzed qualitatively.
Results: Three main themes emerged to create a conceptual model of medication discontinuation from the patient perspective: (1) conflicting views of medication, encompassing the sub-themes of desire for fewer medications, adherence, and specific versus general; (2) importance of patient-provider relationships, encompassing the sub-themes of trust, relying on expertise, shared decision making, and balancing multiple providers; and (3) limited experience with medication discontinuation.
Conclusion: Many patients who have a preference to take fewer medicines do not share their beliefs with providers and recall few instances of provider-initiated medication discontinuation.
Practice implications: Strengthening patient-provider relationships and eliciting patient attitudes about taking fewer medications may enable appropriate discontinuation of unnecessary medications. Published by Elsevier Ireland Ltd.
C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA.
[Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA.
[Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] ENRM Vet Affairs Med Ctr, Boston, MA USA.
[Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Bedford, MA USA.
[Linsky, Amy; Simon, Steven R.; Bokhour, Barbara] ENRM Vet Affairs Med Ctr, Bedford, MA USA.
[Linsky, Amy; Simon, Steven R.] Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA.
[Linsky, Amy; Simon, Steven R.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA.
[Bokhour, Barbara] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
RP Linsky, A (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,Bldg 9,Room 425 152G, Boston, MA 02130 USA.
EM AmylinsIcy@va.gov; Steven.Simon2@va.gov; Barbara.Bokhour@va.gov
FU Department of Veterans Affairs, Veterans Health Administration, Career
Development Award
FX We thank Thomas Marcello, BA and Justice Clark, BA for their assistance
in the coordination and assistance with research activities. We confirm
all patient/personal identifiers have been removed or disguised so the
patient/person(s) described are not identifiable and cannot be
identified through the details of the story. The study was conducted
using resources of the VA Boston Healthcare System. The PI was supported
by a Department of Veterans Affairs, Veterans Health Administration,
Career Development Award. The views expressed in this article are those
of the authors and do not necessarily represent the views of the
Department of Veterans Affairs. The funding organization had no role in
the design and conduct of the study; collection, management, analysis,
and interpretation of the data; preparation, review, or approval of the
manuscript; nor decision to submit the manuscript for publication.
NR 31
TC 9
Z9 9
U1 2
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD FEB
PY 2015
VL 98
IS 2
BP 220
EP 225
DI 10.1016/j.pec.2014.11.010
PG 6
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA AZ9SL
UT WOS:000348555400014
PM 25435516
ER
PT J
AU Chang, CY
Huang, AJ
Palmer, WE
AF Chang, Connie Y.
Huang, Ambrose J.
Palmer, William E.
TI Radiographic Evaluation of Hip Implants
SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY
LA English
DT Article
DE hip arthroplasty; radiograph; evaluation
ID METAL-ON-METAL; PERIPROSTHETIC FEMORAL FRACTURES; RESURFACING
ARTHROPLASTY; VANCOUVER CLASSIFICATION; ILIOPSOAS IMPINGEMENT;
ACETABULAR COMPONENT; SURFACE ARTHROPLASTY; REPLACEMENT; REVISION;
DISLOCATION
AB Serial radiographs are the mainstay in the longitudinal assessment of hip implants. The prosthesis, periprosthetic bone, and juxta-articular soft tissues are inspected for fracture, periosteal reaction, stress shielding, calcar resorption, osteolysis, bony remodeling, metallic debris, and heterotopic ossification. Comparison radiographs best confirm implant migration, subsidence, and aseptic loosening. Infection, particle disease, reaction to metal, and mechanical impingement are important causes of postsurgical pain, but in their earliest stages they may be difficult to diagnose using radiographs. This article addresses the role of radiography following hip arthroplasty.
C1 [Chang, Connie Y.; Huang, Ambrose J.; Palmer, William E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA.
RP Chang, CY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.
EM cychang@mgh.harvard.edu
NR 70
TC 3
Z9 3
U1 0
U2 2
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1089-7860
EI 1098-898X
J9 SEMIN MUSCULOSKEL R
JI Semin. Musculoskelet. Radiol.
PD FEB
PY 2015
VL 19
IS 1
BP 12
EP 20
DI 10.1055/s-0034-1396763
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CA3IE
UT WOS:000348799000003
PM 25633021
ER
PT J
AU Tucker, JD
Gelpi, A
Bangsberg, DR
Grewe, ME
Necochea, R
AF Tucker, Joseph D.
Gelpi, Adriane
Bangsberg, David R.
Grewe, Mary E.
Necochea, Raul
TI The disruptive influence of syphilis cures within specialist venereal
systems: implications for HIV cure preparedness
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Editorial Material
C1 [Tucker, Joseph D.] Int Diagnost Ctr, London WC1E 7HT, England.
[Tucker, Joseph D.; Gelpi, Adriane; Grewe, Mary E.] Univ N Carolina, Inst Global Hlth & Infect Dis, Chapel Hill, NC USA.
[Gelpi, Adriane; Grewe, Mary E.; Necochea, Raul] Univ N Carolina, Dept Social Med, Chapel Hill, NC USA.
[Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA.
[Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Tucker, JD (reprint author), Int Diagnost Ctr, Keppel St, London WC1E 7HT, England.
EM joseph.tucker@post.harvard.edu
FU NIAID NIH HHS [R01 AI108366, P30 AI050410]; PHS HHS [NIAID
R01A108366-01, NIAID P30-AI50410]
NR 10
TC 1
Z9 1
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD FEB
PY 2015
VL 91
IS 1
BP 2
EP 3
DI 10.1136/sextrans-2014-051777
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA AZ5SH
UT WOS:000348279500001
PM 25609463
ER
PT J
AU Koffel, EA
Koffel, JB
Gehrman, PR
AF Koffel, Erin A.
Koffel, Jonathan B.
Gehrman, Philip R.
TI A meta-analysis of group cognitive behavioral therapy for insomnia
SO SLEEP MEDICINE REVIEWS
LA English
DT Review
DE Group therapy; CBT-I; Insomnia
ID RANDOMIZED CONTROLLED-TRIAL; PSYCHIATRIC-DISORDERS; PERSISTENT INSOMNIA;
SLEEP DISTURBANCE; STEPPED CARE; OLDER-ADULTS; EFFICACY; INTERVENTION;
SEVERITY; DISEASE
AB Insomnia is the most common sleep disorder among the general population. Although cognitive behavioral therapy for insomnia (CBT-I) is the psychological treatment of choice, the availability of individual therapy is often not sufficient to meet the demand for treatment. Group treatment can increase the efficiency of delivery, but its efficacy has not been well-established. Randomized controlled trials (RCfs) comparing group CBT-I to a control group in patients with insomnia were identified. A review of 670 unique citations resulted in eight studies that met criteria for analysis. Outcome variables included both qualitative (e.g., sleep quality) and quantitative (e.g., sleep diary) outcomes, as well as depression and pain severity, at both pre- to post-treatment and follow-up (3-12 mo post-treatment). Overall, we found medium to large effect sizes for sleep onset latency, sleep efficiency, and wake after sleep onset and small effect sizes for pain outcomes. Effect sizes remained significant at follow-up, suggesting that treatment gains persist over time. Other variables, including total sleep time, sleep quality, and depression, showed significant improvements, but these findings were limited to the within treatment group analyses. It is clear that group CBT-I is an efficacious treatment. Implications for stepped care models for insomnia are discussed. Published by Elsevier Ltd.
C1 [Koffel, Erin A.] Univ Minnesota, Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA.
[Koffel, Erin A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
[Koffel, Jonathan B.] Univ Minnesota, Biomed Lib, Minneapolis, MN USA.
[Gehrman, Philip R.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Gehrman, Philip R.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Koffel, EA (reprint author), Dept Vet Affairs Med Ctr, 1 Vet Dr, Minneapolis, MN 55417 USA.
EM Erin.Koffel@va.gov
OI Koffel, Jonathan/0000-0003-1723-5087
FU VA [VA999999]
NR 46
TC 23
Z9 24
U1 8
U2 33
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1087-0792
EI 1532-2955
J9 SLEEP MED REV
JI Sleep Med. Rev.
PD FEB
PY 2015
VL 19
BP 6
EP 16
DI 10.1016/j.smrv.2014.05.001
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AZ6NP
UT WOS:000348336600003
PM 24931811
ER
PT J
AU Sonis, S
Elting, L
Keefe, D
Nguyen, H
Grunberg, S
Randolph-Jackson, P
Brennan, M
AF Sonis, Stephen
Elting, Linda
Keefe, Dorothy
Nguyen, Hoang
Grunberg, Steven
Randolph-Jackson, Pamela
Brennan, Michael
CA TRIAD Burden Illness Investigators
TI Unanticipated frequency and consequences of regimen-related diarrhea in
patients being treated with radiation or chemoradiation regimens for
cancers of the head and neck or lung
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Head and neck cancerd; Non-small cell lung cancer; Radiotherapy;
Diarrhea
ID LOCALLY ADVANCED HEAD; CONCOMITANT CISPLATIN; RADIOTHERAPY;
CHEMOTHERAPY; MUCOSITIS; CONCURRENT
AB To better understand the indirect effects of standard courses of radiation therapy (RT) on distant tissue toxicity, we evaluated the frequency, course, and health and economic burden of regimen-related diarrhea in a large, multinational group of patients who were being treated for cancers of the head and neck (HNC) or lung (NSCLC).
In this exploratory, prospective study, 284 patients being treated for HNC and 60 being treated for NSCLC were stratified into four cohorts to evaluate the effect of radiation alone and radiation plus concomitant chemotherapy (CRT) on radiation-induced diarrhea (RID). RID was assessed daily throughout RT using a patient-reported five-point categorical scale. Health and resource use outcomes were evaluated at least weekly during radiation.
Moderate to severe RID was reported in all groups and was worse among patient being treated with concomitant chemoradiation (CRT). Whereas 29 % of patients treated with radiation only developed RID, the incidence was 42 % among CRT-treated patients. Tumor site did not impact the rate of RID, but did impact the rate of development and was more acute in patients being treated for NSCLC than for HNC. Patients with significant RID had worse health and resource use outcomes than did patients without RID regardless of the form of treatment. G-tube placement, weight loss, unplanned office visits, and in-patient days were adversely affected by RID. Not surprisingly, patients treated with CRT had poorer health and resource outcomes than RT only patients, even in the absence of RID.
In addition to local tissue toxicities, our results suggest that focal radiation may also be associated with significant distant tissue-centric injury here represented by RID. While these changes were seen with radiation alone, the addition of chemotherapy increased the incidence and burden of illness. RID adversely impacted resource use. This unanticipated finding supports the hypothesis that focal radiation therapy results in pathobiological changes that extend beyond the radiation field and which can produce distant changes.
C1 [Sonis, Stephen] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sonis, Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Elting, Linda; Nguyen, Hoang] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Keefe, Dorothy] Univ Adelaide, Adelaide, SA, Australia.
[Grunberg, Steven] Univ Vermont, Med Ctr, Burlington, VT USA.
[Randolph-Jackson, Pamela] MedStar Washington Hosp Ctr, Washington, DC USA.
[Brennan, Michael] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Sonis, Stephen] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA.
RP Sonis, S (reprint author), Brigham & Womens Hosp, Div Oral Med, 75 Francis St, Boston, MA 02115 USA.
EM ssonis@partners.org
FU Helsinn, Inc.
FX This study was supported by an unrestricted grant from Helsinn, Inc.
NR 18
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD FEB
PY 2015
VL 23
IS 2
BP 433
EP 439
DI 10.1007/s00520-014-2395-9
PG 7
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA AZ6AB
UT WOS:000348298700019
PM 25123194
ER
PT J
AU Antebi, B
Zhang, ZL
Wang, Y
Lu, ZD
Chen, XD
Ling, J
AF Antebi, Ben
Zhang, ZhiLiang
Wang, Yu
Lu, ZhongDing
Chen, Xiao-Dong
Ling, Jian
TI Stromal-Cell-Derived Extracellular Matrix Promotes the Proliferation and
Retains the Osteogenic Differentiation Capacity of Mesenchymal Stem
Cells on Three-Dimensional Scaffolds
SO Tissue Engineering Part C-Methods
LA English
DT Article
ID PERFUSION BIOREACTOR SYSTEM; BONE-MARROW-CELLS; IN-VITRO; EX-VIVO;
CONSTRUCT DEVELOPMENT; SEEDING DENSITY; SELF-RENEWAL; CULTURE; NICHE;
MICROENVIRONMENT
AB To date, expansion of bone-marrow-derived mesenchymal stem cells (MSCs) is typically carried out on two-dimensional (2D) tissue culture plastic. Since this 2D substratum is very different from the physiological situation, MSCs gradually lose their unique multipotent properties during expansion. Recently, the role of the extracellular matrix (ECM) microenvironment ("niche") in facilitating and regulating stem cell behavior in vivo has been elucidated. As a result, investigators have shifted their efforts toward developing three-dimensional (3D) scaffolds capable of functioning like the native tissue ECM. In this study, we demonstrated that stromal-cell-derived ECM, formed within a collagen/hydroxyapatite (Col/HA) scaffold to mimic the bone marrow "niche," promoted MSC proliferation and preserved their differentiation capacity. The ECM was synthesized by MSCs to reconstitute the tissue-specific 3D microenvironment in vitro. Following deposition of the ECM inside Col/HA scaffold, the construct was decellularized and reseeded with MSCs to study their behavior. The data showed that MSCs cultured on the ECM-Col/HA scaffolds grew significantly faster than the cells from the same batch cultured on the regular Col/HA scaffolds. In addition, MSCs cultured on the ECM-Col/HA scaffolds retained their "stemness" and osteogenic differentiation capacity better than MSCs cultured on regular Col/HA scaffolds. When ECM-Col/HA scaffolds were implanted into immunocompromised mice, with or without loading MSCs, it was found that those scaffolds formed less bone as compared with regular Col/HA scaffolds (i.e., without ECM), in both cases of with or without loading MSCs. The in vivo study further confirmed that the ECM-Col/HA scaffold was a suitable mimic of the bone marrow "niche." This novel 3D stromal-cell-derived ECM system has the potential to be developed into a biomedical platform for regenerative medicine applications.
C1 [Antebi, Ben; Ling, Jian] SW Res Inst, Microencapsulat & Nanomat Dept, San Antonio, TX 78238 USA.
[Antebi, Ben; Ling, Jian] Univ Texas Hlth Sci Ctr San Antonio, Univ Texas San Antonio, Biomed Engn Program, San Antonio, TX 78229 USA.
[Zhang, ZhiLiang; Wang, Yu; Lu, ZhongDing; Chen, Xiao-Dong] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA.
[Chen, Xiao-Dong] South Texas Vet Hlth Care Syst, Audie L Murphy Div Hosp, San Antonio, TX USA.
RP Ling, J (reprint author), SW Res Inst, Microencapsulat & Nanomat Dept, 6220 Culebra Rd, San Antonio, TX 78238 USA.
EM chenx4@uthscsa.edu; jling@swri.org
FU National Heart, Lung, and Blood Institute [R21 HL102775]
FX This work was supported by the National Heart, Lung, and Blood
Institute: R21 HL102775.
NR 46
TC 6
Z9 6
U1 4
U2 15
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3384
EI 1937-3392
J9 TISSUE ENG PART C-ME
JI Tissue Eng. Part C-Methods
PD FEB 1
PY 2015
VL 21
IS 2
BP 171
EP 181
DI 10.1089/ten.tec.2014.0092
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA CA6HR
UT WOS:000349012400007
PM 24965227
ER
PT J
AU Peev, MP
Chang, YC
King, DR
Yeh, DD
Kaafarani, H
Fagenholz, PJ
De Moya, MA
Velmahos, GC
AF Peev, Miroslav P.
Chang, Yuchiao
King, David R.
Yeh, Daniel D.
Kaafarani, Haytham
Fagenholz, Peter J.
De Moya, Marc A.
Velmahos, George C.
TI Delayed Laparotomy After Selective Non-operative Management of
Penetrating Abdominal Injuries
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID GUNSHOT WOUNDS; ROUTINE LAPAROTOMY; TRAUMA CENTER; ABDOMEN;
CONSERVATISM; STANDARD; STILL
AB Main concern during the practice of selective non-operative management (SNOM) for abdominal stab wounds (SW) and gunshot wounds (GSW) is the potential for harm in patients who fail SNOM and receive a delayed laparotomy (DL). The aim of this study is to determine whether such patients suffer adverse sequelae because of delays in diagnosis and treatment when managed under a structured SNOM protocol.
190 patients underwent laparotomy after an abdominal GSW or SW (5/04-10/12). Patients taken to operation within 120 min of admission were included in the early laparotomy (EL) group (n =153, 80.5 %) and the remaining in the DL group (n =37, 19.5 %). Outcomes included mortality, hospital stay, and postoperative complications.
The median time from hospital arrival to operation was 43 min (range: 17-119) for EL patients and 249 min (range: 122-1,545) for DL patients. The average number and type of injuries were similar among the groups. Mortality and negative laparotomy were observed only in the EL group. There was no significant difference in the hospital stay between the groups. The overall complications were higher in the EL group (44.4 vs. 24.3 %, p =0.026). DL was independently associated with a lower likelihood for complications (OR 0.39, 95 % CI 0.16-0.98, p =0.045). Individual review of all DL patients did not reveal an incident in which complications could be directly attributed to the delay.
In a structured protocol, patients who fail SNOM and require an operation are recognized and treated promptly. The delay in operation does not cause unnecessary morbidity or mortality.
C1 [Peev, Miroslav P.; Chang, Yuchiao; King, David R.; Yeh, Daniel D.; Kaafarani, Haytham; Fagenholz, Peter J.; De Moya, Marc A.; Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[Peev, Miroslav P.; Chang, Yuchiao; King, David R.; Yeh, Daniel D.; Kaafarani, Haytham; Fagenholz, Peter J.; De Moya, Marc A.; Velmahos, George C.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Peev, MP (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM miroslav.peev@tufts.edu; gvelmahos@mgh.harvard.edu
OI King, David/0000-0003-1028-1478
NR 20
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
EI 1432-2323
J9 WORLD J SURG
JI World J.Surg.
PD FEB
PY 2015
VL 39
IS 2
BP 380
EP 386
DI 10.1007/s00268-014-2813-7
PG 7
WC Surgery
SC Surgery
GA AZ4XK
UT WOS:000348224100014
PM 25277981
ER
PT J
AU Chambers, KJ
Pearse, A
Coveney, J
Rogers, S
Kamani, D
Sritharan, N
Randolph, GW
AF Chambers, Kyle J.
Pearse, Allison
Coveney, Jonathan
Rogers, Sarah
Kamani, Dipti
Sritharan, Niranjan
Randolph, Gregory W.
TI Respiratory Variation Predicts Optimal Endotracheal Tube Placement for
Intra-operative Nerve Monitoring in Thyroid and Parathyroid Surgery
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID RECURRENT LARYNGEAL NERVE; PATTERNS; PLAUDITS; PITFALLS; INJURY
AB Intra-operative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) during thyroid and parathyroid surgery is thought to aid in identification and dissection of the RLN. While utilization of IONM is increasing, one area of variability in its application is the assessment of adequate endotracheal tube electrode placement for IONM during the case. The main objective of this study is to assess the overall success of utilizing respiratory variation to confirm proper endotracheal tube placement for RLN monitoring.
A prospective study of RLN monitoring during thyroid and parathyroid surgery at an academic referral center.
Fifty-five cases were included. Fifty (91 %) achieved optimal respiratory variation during endotracheal tube position. Five (9 %) required repeat laryngoscopy to confirm correct endotracheal tube placement following patient positioning. For the respiratory variation group, average amplitude achieved during initial vagus, maximum vagus, initial RLN, and maximal RLN was 700 (+/- 474) mA, 921 (+/- 616) mA, 887 (+/- 584) mA, and 1330 (+/- 843) mA during evoked stimulation, respectively. For the repeat laryngoscopy group, average amplitude achieved during initial vagus, maximum vagus, initial RLN, and maximal RLN evoked stimulation was 591 (+/- 364) mA, 959 (+/- 306) mA, 771 (+/- 424) mA, and 1462 (+/- 855) mA during evoked stimulation, respectively. There was no statistical difference between the two groups for average initial vagus amplitude (p = 0.62), average maximum vagus amplitude (p = 0.89), average initial RLN amplitude (p = 0.67), or average maximum RLN amplitude (p = 0.74).
The findings of this study support the International Neural Monitoring Study Group recommendation that confirmation of endotracheal tube electrode placement be performed either by confirmation of adequate respiratory variation or by repeat direct laryngoscopy.
C1 [Chambers, Kyle J.; Pearse, Allison; Coveney, Jonathan; Rogers, Sarah; Kamani, Dipti; Sritharan, Niranjan] Harvard Univ, Div Thyroid & Parathyroid Endocrine Surg, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02138 USA.
[Randolph, Gregory W.] Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Kamani, D (reprint author), Harvard Univ, Div Thyroid & Parathyroid Endocrine Surg, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm,Sch Med, Boston, MA 02138 USA.
EM dipti_kamani@meei.harvard.edu; Gregory_Randolph@meei.harvard.edu
FU John and Claire Bertucci Thyroid Research fund
FX This work was funded by the John and Claire Bertucci Thyroid Research
fund.
NR 23
TC 3
Z9 3
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
EI 1432-2323
J9 WORLD J SURG
JI World J.Surg.
PD FEB
PY 2015
VL 39
IS 2
BP 393
EP 399
DI 10.1007/s00268-014-2820-8
PG 7
WC Surgery
SC Surgery
GA AZ4XK
UT WOS:000348224100016
PM 25297816
ER
PT J
AU Shamji, MH
Bellido, V
Scadding, GW
Layhadi, JA
Cheung, DKM
Calderon, MA
Asare, A
Gao, Z
Turka, LA
Tchao, N
Togias, A
Phippard, D
Durham, SR
AF Shamji, M. H.
Bellido, V.
Scadding, G. W.
Layhadi, J. A.
Cheung, D. K. M.
Calderon, M. A.
Asare, A.
Gao, Z.
Turka, L. A.
Tchao, N.
Togias, A.
Phippard, D.
Durham, S. R.
TI Effector cell signature in peripheral blood following nasal allergen
challenge in grass pollen allergic individuals
SO ALLERGY
LA English
DT Article
DE basophils; IL-4; nasal allergen challenge; seasonal allergic rhinitis; T
cells
ID DENDRITIC CELLS; INDUCED RHINITIS; MESSENGER-RNA; MUCOSA; PROVOCATION;
MEDIATORS; RESPONSES; RELEASE; IMMUNOTHERAPY; EOSINOPHILS
AB BackgroundSeveral studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge.
MethodsTwelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay).
ResultsRobust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1h) response and modest significant changes during the late (1-24h) response. Sequential peaks in peripheral blood basophil activation markers were observed (CD107a at 3h, CD63 at 6h, and CD203c(bright) at 24h). T effector/memory cells (CD4(+)CD25(lo)) were increased at 6h and accompanied by increases in CD80(+) and CD86(+) plasmacytoid dendritic cells (pDCs). Ex vivo grass antigen-driven T-cell proliferative responses and the frequency of IL-4(+)CD4(+) T cells were significantly increased at 6h after NAC when compared to the control day.
ConclusionBasophil, T-cell, and dendritic cell activation increased the frequency of allergen-driven IL-4(+)CD4(+) T cells, and T-cell proliferative responses are detectable in the periphery after NAC. These data confirm systemic cellular activation following a local nasal provocation.
C1 [Shamji, M. H.; Layhadi, J. A.; Cheung, D. K. M.; Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Immunomodulat & Tolerance Grp, London SW7 2AZ, England.
[Bellido, V.; Scadding, G. W.; Layhadi, J. A.; Cheung, D. K. M.; Calderon, M. A.; Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2AZ, England.
[Asare, A.; Gao, Z.; Turka, L. A.; Tchao, N.; Phippard, D.] Immune Tolerance Network, Bethesda, MD USA.
[Turka, L. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Togias, A.] NIAID, Bethesda, MD 20892 USA.
RP Durham, SR (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Natl Heart & Lung Inst, Sir Alexander Fleming Bldg, London SW7 2AZ, England.
EM s.durham@imperial.ac.uk
FU Immune Tolerance Network (NIH), an international clinical research
consortium headquartered at the University of California San Francisco
[N01 AI15416]; National Institute of Allergy and Infectious Diseases;
Juvenile Diabetes Research Foundation; Wellcome Trust; Royal Brompton
Hospital Charitable Trust Fund
FX This research was performed with the support of the Immune Tolerance
Network (NIH Contract #N01 AI15416; www.immunetolerance.org), an
international clinical research consortium headquartered at the
University of California San Francisco and supported by the National
Institute of Allergy and Infectious Diseases and the Juvenile Diabetes
Research Foundation. Dr Guy Scadding is supported by a Wellcome Trust
Clinical Fellowship. This research was also supported by a grant from
the Royal Brompton Hospital Charitable Trust Fund.
NR 31
TC 7
Z9 8
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
EI 1398-9995
J9 ALLERGY
JI Allergy
PD FEB
PY 2015
VL 70
IS 2
BP 171
EP 179
DI 10.1111/all.12543
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA AZ0UM
UT WOS:000347960300005
PM 25377909
ER
PT J
AU Liu, KD
Yang, W
Go, AS
Anderson, AH
Feldman, HI
Fischer, MJ
He, J
Kallem, RR
Kusek, JW
Master, SR
Miller, ER
Rosas, SE
Steigerwalt, S
Tao, KX
Weir, MR
Hsu, CY
AF Liu, Kathleen D.
Yang, Wei
Go, Alan S.
Anderson, Amanda H.
Feldman, Harold I.
Fischer, Michael J.
He, Jiang
Kallem, Radhakrishna R.
Kusek, John W.
Master, Stephen R.
Miller, Edgar R., III
Rosas, Sylvia E.
Steigerwalt, Susan
Tao, Kaixiang
Weir, Matthew R.
Hsu, Chi-yuan
CA CRIC Study Investigators
TI Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of
Cardiovascular Disease and Death in CKD: Results From the Chronic Renal
Insufficiency Cohort (CRIC) Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Neutrophil gelatinase-associated lipocalin (NGAL); renal tubular injury;
renal tubular dysfunction; biomarker; chronic kidney disease (CKD);
Chronic Renal Insufficiency Cohort (CRIC) Study; cardiovascular disease;
ischemic atherosclerotic event
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; INJURY MOLECULE-1
KIM-1; HEART-FAILURE; ATHEROSCLEROSIS RISK; ALL-CAUSE; NGAL; MORTALITY;
DAMAGE; BIOMARKERS
AB Background: Chronic kidney disease is common and is associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about the risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration-based markers (such as serum creatinine or albuminuria).
Study Design: Cohort study, CRIC (Chronic Renal Insufficiency Cohort) Study.
Setting & Participants: 3,386 participants with estimated glomerular filtration rate of 20 to 70 mL/min/1.73 m(2) enrolled from June 2003 through August 2008.
Predictor: Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration.
Outcomes: Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke, or peripheral artery disease), and death through March 2011.
Measurements: Urine NGAL measured at baseline with a 2-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories).
Results: There were 428 heart failure events (during 16,383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16,584 person-years of follow-up), and 522 deaths (during 18,214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors, and cardiac medications, higher urine NGAL levels remained associated independently with ischemic atherosclerotic events (adjusted HR for the highest [>49.5 ng/mL] vs lowest [<= 6.9 ng/mL] quintile, 1.83 [95% CI, 1.20-2.81]; HR per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths.
Limitations: Urine NGAL was measured only once.
Conclusions: Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were associated independently with future ischemic atherosclerotic events, but not with heart failure events or deaths. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Liu, Kathleen D.; Hsu, Chi-yuan] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Yang, Wei; Anderson, Amanda H.; Feldman, Harold I.; Kallem, Radhakrishna R.; Tao, Kaixiang] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Go, Alan S.; Hsu, Chi-yuan] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Fischer, Michael J.] Jesse Brown VAMC, Dept Med, Chicago, IL USA.
[Fischer, Michael J.] Univ Illinois Hosp & Hlth Sci Syst, Chicago, IL USA.
[He, Jiang] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD USA.
[Master, Stephen R.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA.
[Miller, Edgar R., III] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Rosas, Sylvia E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA.
[Rosas, Sylvia E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Steigerwalt, Susan] St John Hosp & Med Ctr, St Claire Specialty Phys, Detroit, MI USA.
[Weir, Matthew R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
RP Hsu, CY (reprint author), Univ Calif San Francisco, Div Nephrol, 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA.
EM hsuchi@medicine.ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028,
U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at
the University of Pennsylvania Clinical and Translational Science Award
NIH/National Center for Advancing Translational Sciences (NCATS)
[UL1TR000003]; Johns Hopkins University grant [UL1 TR-000424];
University of Maryland General Clinical Research Center grant [M01
RR-16500]; Clinical and Translational Science Collaborative of Cleveland
from the NCATS component of the NIH [UL1TR000439]; NIH Roadmap for
Medical Research, Michigan Institute for Clinical and Health Research
grant [UL1TR000433]; University of Illinois at Chicago Clinical and
Translational Science Award [UL1RR029879]; Tulane University
Translational Research in Hypertension and Renal Biology grant
[P30GM103337]; Kaiser Permanente NIH/National Center for Research
Resources UCSF-CTSI grant [UL1 RR-024131]; CKD Biomarker Consortium
[U01DK85649]
FX Funding for the CRIC Study was obtained under a cooperative agreement
from the National Institute of Diabetes and Digestive and Kidney
Diseases (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021,
U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition,
this work was supported in part by the following: the Perelman School of
Medicine at the University of Pennsylvania Clinical and Translational
Science Award NIH/National Center for Advancing Translational Sciences
(NCATS) UL1TR000003, Johns Hopkins University grant UL1 TR-000424,
University of Maryland General Clinical Research Center grant M01
RR-16500, Clinical and Translational Science Collaborative of Cleveland,
grant UL1TR000439 from the NCATS component of the NIH and NIH Roadmap
for Medical Research, Michigan Institute for Clinical and Health
Research grant UL1TR000433, University of Illinois at Chicago Clinical
and Translational Science Award UL1RR029879, Tulane University
Translational Research in Hypertension and Renal Biology grant
P30GM103337, and Kaiser Permanente NIH/National Center for Research
Resources UCSF-CTSI grant UL1 RR-024131. Drs Liu, Go, Feldman, and Hsu
also are supported by grant U01DK85649 as members of the CKD Biomarker
Consortium.
NR 41
TC 12
Z9 14
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD FEB
PY 2015
VL 65
IS 2
BP 267
EP 274
DI 10.1053/j.ajkd.2014.07.025
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA AZ4MT
UT WOS:000348196400013
PM 25311702
ER
PT J
AU Wang, H
Xu, ZP
Wu, AS
Dong, YL
Zhang, YY
Yue, Y
Xie, ZC
AF Wang, Hui
Xu, Zhipeng
Wu, Anshi
Dong, Yuanlin
Zhang, Yiying
Yue, Yun
Xie, Zhongcong
TI 2-Deoxy-D-Glucose Enhances Anesthetic Effects in Mice
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID PROTECTS HIPPOCAMPAL-NEURONS; ISOFLURANE-INDUCED APOPTOSIS; COMPLEX-I
FUNCTION; CAENORHABDITIS-ELEGANS; MITOCHONDRIAL-FUNCTION;
GENERAL-ANESTHESIA; INDUCED NEUROTOXICITY; VOLATILE-ANESTHETICS;
RESPIRATORY-CHAIN; L-CARNITINE
AB BACKGROUND: The mechanisms of general anesthesia by volatile drugs remain largely unknown. Mitochondrial dysfunction and reduction in energy levels have been suggested to be associated with general anesthesia status. 2-Deoxy-D-glucose (2-DG), an analog of glucose, inhibits hexokinase and reduces cellular levels of adenosine triphosphate (ATP). 3-Nitropropionic acid is another compound which can deplete ATP levels. In contrast, idebenone and l-carnitine could rescue deficits of energy. We therefore sought to determine whether 2-DG and/or 3-nitropropionic acid can enhance the anesthetic effects of isoflurane, and whether idebenone and l-carnitine can reverse the actions of 2-DG.
METHODS: C57BL/6J mice (8 months old) received different concentrations of isoflurane with and without the treatments of 2-DG, 3-nitropropionic acid, idebenone, and l-carnitine. Isoflurane-induced loss of righting reflex (LORR) was determined in the mice. ATP levels in H4 human neuroglioma cells were assessed after these treatments. Finally, 31P-magnetic resonance spectroscopy was used to determine the effects of isoflurane on brain ATP levels in the mice.
RESULTS: 2-DG enhanced isoflurane-induced LORR (P = 0.002, N = 15). 3-Nitropropionic acid also enhanced the anesthetic effects of isoflurane (P = 0.005, N = 15). Idebenone (idebenone + saline versus idebenone + 2-DG: P = 0.165, N = 15), but not l-carnitine (l-carnitine + saline versus l-carnitine + 2-DG: P < 0.0001, N = 15), inhibited the effects of 2-DG on enhancing isoflurane-induced LORR in the mice, as evidenced by 2-DG not enhancing isoflurane-induced LORR in the mice pretreated with idebenone. Idebenone (idebenone + saline versus idebenone + 2-DG: P = 0.177, N = 6), but not l-carnitine (l-carnitine + saline versus l-carnitine + 2-DG: P = 0.029, N = 6), also mitigated the effects of 2-DG on reducing ATP levels in cells, as evidenced by 2-DG not decreasing ATP levels in the cells pretreated with idebenone. Finally, isoflurane decreased ATP levels in both cultured cells and mouse brains (beta-ATP: P = 0.003, N = 10; beta-ATP/phosphocreatine: P = 0.006, N = 10; beta-ATP/inorganic phosphate: P = 0.001, N = 10).
CONCLUSIONS: These results from our pilot studies have established a system and generated a hypothesis that 2-DG enhances anesthetic effects via reducing energy levels. These findings should promote further studies to investigate anesthesia mechanisms.
C1 [Wang, Hui; Wu, Anshi; Yue, Yun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Anesthesia, Beijing, Peoples R China.
[Wang, Hui; Xu, Zhipeng; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02129 USA.
[Wang, Hui; Xu, Zhipeng; Dong, Yuanlin; Zhang, Yiying; Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA USA.
[Xu, Zhipeng] Chinese Peoples Liberat Army Gen Hosp, Anesthesia & Operat Ctr, Beijing, Peoples R China.
RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Geriatr Anesthesia Res Unit, Dept Anesthesia Crit Care & Pain Med, 149 13th St,Room 4310, Boston, MA 02129 USA.
EM zxie@mgh.harvard.edu
FU National Institutes of Health, Bethesda, MD [R21AG038994, R01 GM088801,
R01 AG041274]; Investigator-Initiated Research Grant from Alzheimer's
Association, Chicago, IL; Cure Alzheimer's Fund, Wellesley, MA; China
National Science Foundation Overseas Young Scholars Collaboration
Research Award [NSF30928026]
FX This research was supported by R21AG038994, R01 GM088801, and R01
AG041274 from National Institutes of Health, Bethesda, MD,
Investigator-Initiated Research Grant from Alzheimer's Association,
Chicago, IL, and Cure Alzheimer's Fund, Wellesley, MA (to ZX), and China
National Science Foundation Overseas Young Scholars Collaboration
Research Award NSF30928026 (to YY and ZX).
NR 51
TC 7
Z9 7
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD FEB
PY 2015
VL 120
IS 2
BP 312
EP 319
DI 10.1213/ANE.0000000000000520
PG 8
WC Anesthesiology
SC Anesthesiology
GA AZ3PG
UT WOS:000348138700008
PM 25390277
ER
PT J
AU Hilgendorf, I
Swirski, FK
Robbins, CS
AF Hilgendorf, Ingo
Swirski, Filip K.
Robbins, Clinton S.
TI Monocyte Fate in Atherosclerosis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE atherosclerosis; cardiovascular disease; inflammation; macrophage;
monocyte
ID ACUTE MYOCARDIAL-INFARCTION; LOW-DENSITY-LIPOPROTEIN; STEM-CELL
PROLIFERATION; HEMATOPOIETIC PROGENITOR CELLS; ACUTE CORONARY SYNDROMES;
RECEPTOR KNOCKOUT MICE; ISCHEMIC-HEART FAILURE; CLASS-A OVEREXPRESSION;
MARROW-DERIVED CELLS; BONE-MARROW
AB Monocytes and their descendant macrophages are essential to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease. Lipid-laden macrophages, known as foam cells, reside in early lesions and advanced atheromata. Our understanding of how monocytes accumulate in the growing lesion, differentiate, ingest lipids, and contribute to disease has advanced substantially over the last several years. These cells' remarkable phenotypic and functional complexity is a therapeutic opportunity: in the future, treatment and prevention of cardiovascular disease and its complications may involve specific targeting of atherogenic monocytes/macrophages and their products.
C1 [Hilgendorf, Ingo] Univ Freiburg, Ctr Heart, Dept Cardiol & Angiol, D-79106 Freiburg, Germany.
[Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Robbins, Clinton S.] Univ Toronto, Toronto Gen Res Inst, Peter Munk Cardiac Ctr, Dept Lab Med, Toronto, ON M5G 1L7, Canada.
[Robbins, Clinton S.] Univ Toronto, Toronto Gen Res Inst, Peter Munk Cardiac Ctr, Dept Pathobiol & Immunol, Toronto, ON M5G 1L7, Canada.
RP Hilgendorf, I (reprint author), Univ Freiburg, Ctr Heart, Dept Cardiol & Angiol 1, Hugstetter St 55, D-79106 Freiburg, Germany.
EM ingo.hilgendorf@universitaets-herzzentrum.de; clint.robbins@utoronto.ca
FU DFG (German Research Foundation) [HI 1573/2-1]; Canadian Institutes of
Health Research [311523]; Peter Munk Chair in Aortic Disease Research
FX This work was supported in part by DFG (German Research Foundation)
grant HI 1573/2-1 (to I. Hilgendorf), the Canadian Institutes of Health
Research grant 311523 (to C.S. Robbins), and the Peter Munk Chair in
Aortic Disease Research (to C.S. Robbins).
NR 110
TC 27
Z9 28
U1 3
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD FEB
PY 2015
VL 35
IS 2
BP 272
EP 279
DI 10.1161/ATVBAHA.114.303565
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA AZ4TE
UT WOS:000348215100006
PM 25538208
ER
PT J
AU Abdelbaky, A
Corsini, E
Figueroa, AL
Subramanian, S
Fontanez, S
Emami, H
Hoffmann, U
Narula, J
Tawakol, A
AF Abdelbaky, Amr
Corsini, Erin
Figueroa, Amparo L.
Subramanian, Sharath
Fontanez, Sara
Emami, Hamed
Hoffmann, Udo
Narula, Jagat
Tawakol, Ahmed
TI Early aortic valve inflammation precedes calcification: A longitudinal
FDG-PET/CT study
SO ATHEROSCLEROSIS
LA English
DT Article
DE Aortic valve calcification; FED-PET; Aortic valve inflammation
ID POSITRON-EMISSION-TOMOGRAPHY; CORONARY-ARTERY CALCIUM; DISEASE
PROGRESSION; RISK-FACTORS; STENOSIS; ATHEROSCLEROSIS;
FLUORODEOXYGLUCOSE; DETERMINANTS; POPULATION; SCLEROSIS
AB Objectives: Recent data shows a relationship between aortic valve (AV) inflammation and calcification. However, direct evidence linking early valve inflammation (prior to hemodynamic compromise) to subsequent calcium (Ca) deposition is lacking in humans. We sought to test the hypothesis whether local AV inflammation predisposes to subsequent AV Ca deposition. Methods: We identified 111 individuals (age 60[ 49, 68], 50.5% male) without active cancer or aortic stenosis who underwent 2 PET/CT studies 1-5 years apart for cancer surveillance. AV inflammation was determined by measuring FDG uptake (maximum standardized uptake value, SUVmax) within the AV on baseline PET/CT. Subsequent deposition of AV Ca was determined by comparing baseline and follow-up CT scans, determined as an increase in AV Ca volume score (CaVS). Patients were classified as "non-progressors" or "progressors" based on Square Root difference in CaVS (using a pre-determined cut-off value of 2.5). CT and PET measurements were conducted by 2 mutually blinded laboratories. Results: During follow-up, AV Ca increased in 23 patients (20.2%) classified as "progressors", of whom 9 (9.2%) demonstrated subsequent 'incident' AV Ca. The AV SUVmax (mean +/- SD) was higher in progressors vs. non-progressors (2.03 +/- 0.52 vs. 1.74 +/- 0.36, p = 0.02) and especially in patients with-vs. without-incident AV Ca (2.28 +/- 0.42 vs. 1.73 +/- 0.36, p < 0.001). Moreover, AV inflammation (AV SUVmax) independently predicted subsequent calcification after adjusting for cardiovascular risk factors [OR (95%CI): 4.99 (1.30-19.15), p = 0.02]. Conclusion: The findings suggest that early AV inflammation may predispose to AV sclerosis. The evaluation of valvular metabolic activity may prove useful for developing a better understanding of calcific valve disease. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Abdelbaky, Amr; Corsini, Erin; Figueroa, Amparo L.; Subramanian, Sharath; Fontanez, Sara; Emami, Hamed; Hoffmann, Udo; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Narula, Jagat] Mt Sinai Sch Med, Div Cardiol, New York, NY USA.
[Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM atawakol@mgh.harvard.edu
OI Corsini, Erin/0000-0003-4715-0244
NR 36
TC 10
Z9 10
U1 1
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD FEB
PY 2015
VL 238
IS 2
BP 165
EP 172
DI 10.1016/j.atherosclerosis.2014.11.026
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AZ1UL
UT WOS:000348023000003
PM 25525744
ER
PT J
AU Shahian, DM
Normand, SLT
AF Shahian, David M.
Normand, Sharon-Lise T.
TI What is a performance outlier?
SO BMJ QUALITY & SAFETY
LA English
DT Editorial Material
ID PROFILING HOSPITAL PERFORMANCE; 30-DAY MORTALITY-RATES; QUALITY-OF-CARE;
RISK-ADJUSTMENT; SURGICAL QUALITY; CARDIAC-SURGERY; INSTITUTIONAL
PERFORMANCE; BYPASS-SURGERY; FUNNEL PLOTS; OUTCOMES
C1 [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Dept Surg, Boston, MA 02114 USA.
[Shahian, David M.] Harvard Univ, Sch Med, Boston, MA USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, Dept Surg, 55 Fruit St, Boston, MA 02114 USA.
EM dshahian@partners.org
NR 47
TC 9
Z9 9
U1 1
U2 8
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-5415
EI 2044-5423
J9 BMJ QUAL SAF
JI BMJ Qual. Saf.
PD FEB
PY 2015
VL 24
IS 2
BP 95
EP 99
DI 10.1136/bmjqs-2015-003934
PG 5
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA AZ4PC
UT WOS:000348203800003
PM 25605952
ER
PT J
AU Singh, H
Sittig, DF
AF Singh, Hardeep
Sittig, Dean F.
TI Advancing the science of measurement of diagnostic errors in healthcare:
the Safer Dx framework
SO BMJ QUALITY & SAFETY
LA English
DT Article
ID ADVERSE EVENTS; MALPRACTICE CLAIMS; PATIENT SAFETY;
HOSPITALIZED-PATIENTS; AMBULATORY-CARE; MEDICAL-RECORD; ORGANIZATIONS;
SURVEILLANCE; SETTINGS; IMPROVE
AB Diagnostic errors are major contributors to harmful patient outcomes, yet they remain a relatively understudied and unmeasured area of patient safety. Although they are estimated to affect about 12 million Americans each year in ambulatory care settings alone, both the conceptual and pragmatic scientific foundation for their measurement is under-developed. Health care organizations do not have the tools and strategies to measure diagnostic safety and most have not integrated diagnostic error into their existing patient safety programs. Further progress toward reducing diagnostic errors will hinge on our ability to overcome measurement-related challenges. In order to lay a robust groundwork for measurement and monitoring techniques to ensure diagnostic safety, we recently developed a multifaceted framework to advance the science of measuring diagnostic errors (The Safer Dx framework). In this paper, we describe how the framework serves as a conceptual foundation for system-wide safety measurement, monitoring and improvement of diagnostic error. The framework accounts for the complex adaptive sociotechnical system in which diagnosis takes place (the structure), the distributed process dimensions in which diagnoses evolve beyond the doctor's visit (the process) and the outcomes of a correct and timely "safe diagnosis" as well as patient and health care outcomes (the outcomes). We posit that the Safer Dx framework can be used by a variety of stakeholders including researchers, clinicians, health care organizations and policymakers, to stimulate both retrospective and more proactive measurement of diagnostic errors. The feedback and learning that would result will help develop subsequent interventions that lead to safer diagnosis, improved value of health care delivery and improved patient outcomes.
C1 [Singh, Hardeep] Michael E DeBakey VA Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX USA.
[Singh, Hardeep] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Sittig, Dean F.] Univ Texas Sch Biomed Informat, Houston, TX USA.
[Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA.
RP Singh, H (reprint author), VA Med Ctr 152,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hardeeps@bcm.edu
FU VA Health Services Research and Development Service [CRE 12-033]; VA
National Center for Patient Safety; Agency for Health Care Research and
Quality [R01HS022087]; Houston VA HSR&D Center for Innovations in
Quality, Effectiveness and Safety [CIN 13-413]
FX HS is supported by the VA Health Services Research and Development
Service (CRE 12-033; Presidential Early Career Award for Scientists and
Engineers USA 14-274), the VA National Center for Patient Safety and the
Agency for Health Care Research and Quality (R01HS022087). This work is
supported in part by the Houston VA HSR&D Center for Innovations in
Quality, Effectiveness and Safety (CIN 13-413). HS presented the Safer
Dx framework to the Institute of Medicine Diagnostic Error in Health
Care Consensus Study Committee on 6 August 2014.
NR 59
TC 17
Z9 17
U1 2
U2 12
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-5415
EI 2044-5423
J9 BMJ QUAL SAF
JI BMJ Qual. Saf.
PD FEB
PY 2015
VL 24
IS 2
BP 103
EP 110
DI 10.1136/bmjqs-2014-003675
PG 8
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA AZ4PC
UT WOS:000348203800005
PM 25589094
ER
PT J
AU Turan, S
Thiele, S
Tafaj, O
Brix, B
Atay, Z
Abali, S
Haliloglu, B
Bereket, A
Bastepe, M
AF Turan, Serap
Thiele, Susanne
Tafaj, Olta
Brix, Bettina
Atay, Zeynep
Abali, Saygin
Haliloglu, Belma
Bereket, Abdullah
Bastepe, Murat
TI Evidence of hormone resistance in a pseudo-pseudohypoparathyroidism
patient with a novel paternal mutation in GNAS
SO BONE
LA English
DT Article
DE Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism; GNAS; Hormone
resistance
ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; XL-ALPHA-S; MATERNAL TRANSMISSION;
GROWTH-HORMONE; GS-ALPHA; GENE; PSEUDOPSEUDOHYPOPARATHYROIDISM;
DEFICIENCY; G(S)ALPHA; LOCUS
AB Context: Loss-of-function GNAS mutations lead to hormone resistance and Albright's hereditary osteodystrophy (AHO) when maternally inherited, i.e. pseudohypoparathyroidism-Ia (PHPIa), but cause AHO alone when located on the paternal allele, i.e. pseudoPHP (PPHP).
Objective: We aimed to establish the molecular diagnosis in a patient with AHO and evidence of hormone resistance.
Case: The patient is a female who presented at the age of 13.5 years with short stature and multiple AHO features. No evidence for TSH or gonadotropin-resistance was present. Serum calcium and vitamin D levels were normal. However, serum PTH was elevated on multiple occasions (64-178 pg/mL, normal: 9-52) and growth hormone response to clonidine or L-DOPA was blunted, suggesting hormone resistance and PHP-Ia. The patient had diminished erythrocyte Gm activity and a novel heterozygous GNAS mutation (c.328 G>C; p.A109P). The mother lacked the mutation, and the father's DNA was not available. Hence, a diagnosis of PPHP also appeared possible, supported by low birth weight and a lack of AHO features associated predominantly with PHP-Ia, i.e. obesity and cognitive impairment. To determine the parental origin of the mutation, we amplified the paternally expressed A/B and biallelically expressed Gs alpha transcripts from the patient's peripheral blood RNA. While both wild-type and mutant nucleotides were detected in the Gs alpha amplicon, only the mutant nucleotide was present in the A/B amplicon, indicating that the mutation was paternal.
Conclusion: These findings suggest that PTH and other hormone resistance may not be an exclusive feature of PHP-Ia and could also be observed in patients with PPHP. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Turan, Serap; Atay, Zeynep; Abali, Saygin; Haliloglu, Belma; Bereket, Abdullah] Marmara Univ, Dept Pediat Endocrinol, Istanbul, Turkey.
[Thiele, Susanne; Brix, Bettina] Med Univ Lubeck, Div Expt Paediat Endocrinol & Diabet, Lubeck, Germany.
[Tafaj, Olta; Bastepe, Murat] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St Thier 10, Boston, MA 02114 USA.
EM serap.turan@marmara.edu.tr; bastepe@helix.mgh.harvard.edu
FU NIH/NIDDK [RO1DK073911]; University of Luebeck [E48-2013]
FX Molecular genetic studies were funded in part by the NIH/NIDDK grant to
M.B. (RO1DK073911) and a grant of the University of Luebeck to
S.T.2 (E48-2013).
NR 29
TC 6
Z9 7
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD FEB
PY 2015
VL 71
BP 53
EP 57
DI 10.1016/j.bone.2014.10.006
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AY7XU
UT WOS:000347770000007
PM 25464124
ER
PT J
AU Wasfy, MM
DeLuca, J
Wang, F
Berkstresser, B
Ackerman, KE
Eisman, A
Lewis, GD
Hutter, AM
Weiner, RB
Baggish, AL
AF Wasfy, Meagan M.
DeLuca, James
Wang, Francis
Berkstresser, Brant
Ackerman, Kathryn E.
Eisman, Aaron
Lewis, Gregory D.
Hutter, Adolph M.
Weiner, Rory B.
Baggish, Aaron L.
TI ECG findings in competitive rowers: normative data and the prevalence of
abnormalities using contemporary screening recommendations
SO BRITISH JOURNAL OF SPORTS MEDICINE
LA English
DT Article
ID EARLY REPOLARIZATION PATTERN; SUDDEN CARDIAC DEATH; T-WAVE;
CLINICAL-SIGNIFICANCE; CONSENSUS STATEMENT; EUROPEAN-SOCIETY; SEATTLE
CRITERIA; OF-CARDIOLOGY; UNITED-STATES; ENDURANCE
AB Background/aim The international governing body for competitive rowing recently mandated the inclusion of 12-lead ECG during preparticipation screening. We therefore sought to describe normative ECG characteristics and to examine the prevalence of abnormal ECG findings as defined by contemporary athlete ECG interpretation criteria among competitive rowers.
Methods Competitive rowers (n=330, 56% male) underwent standard 12-lead ECG at the time of collegiate preparticipation screening. ECGs were analysed quantitatively to develop a sport-specific normative database and then for the presence of abnormalities in accordance with the 2010 European Society of Cardiology (ESC) recommendations and 2013 'Seattle Criteria.'
Results 94% of rowers had one or more training-related ECG patterns including sinus bradycardia (51%), sinus arrhythmia (55%), and incomplete right bundle branch block (42%). Males were more likely than females to have isolated voltage criteria for left ventricular hypertrophy (LVH) (51% vs 8%, p<0.001) and early repolarisation pattern (76% vs 23%, p<0.001). Application of the 2010 ESC criteria, compared to the Seattle criteria, resulted in the classification of a significantly greater number of abnormal ECGs (47% vs 4%; p<0.001). The detection of true pathology, accomplished by both interpretation criteria, was confined to a single case of ventricular pre-excitation.
Conclusions Training-related ECG patterns with several gender-based differences are common among competitive rowers. The diagnostic accuracy and downstream clinical implications of ECG-inclusive preparticipation screening among rowers will be dictated by the choice and future refinement of ECG interpretation criteria.
C1 [Wasfy, Meagan M.; DeLuca, James; Eisman, Aaron; Lewis, Gregory D.; Hutter, Adolph M.; Weiner, Rory B.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA.
[Wang, Francis; Berkstresser, Brant; Baggish, Aaron L.] Harvard Univ Hlth Serv, Cambridge, MA USA.
[Ackerman, Kathryn E.] Boston Childrens Hosp, Div Sports Med, Boston, MA USA.
[Ackerman, Kathryn E.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey Suite 5B, Boston, MA 02114 USA.
EM abaggish@partners.org
FU American Heart Association [FTF2220328]
FX The authors wish to thank Harvard crew coaches Charlie Butt, Linda Muri,
William Manning, and Billy Boyce and for their on-going partnership. The
authors acknowledge the late Harry Parker for his steadfast support of
the Harvard Athlete Initiative and his firm belief in the value of sport
science. The authors wish to thank Ms. Deborah McDonald for clerical
oversight. This study was funded, in part by a research grant from the
American Heart Association FTF2220328 (ALB).
NR 34
TC 11
Z9 11
U1 1
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-3674
EI 1473-0480
J9 BRIT J SPORT MED
JI Br. J. Sports Med.
PD FEB
PY 2015
VL 49
IS 3
BP 200
EP 206
DI 10.1136/bjsports-2014-093919
PG 7
WC Sport Sciences
SC Sport Sciences
GA AZ2OY
UT WOS:000348073800014
PM 25202138
ER
PT J
AU Coutinho, JF
Goncalves, OF
Maia, L
Vasconcelos, CF
Perrone-McGovern, K
Simon-Dack, S
Hernandez, K
Oliveira-Silva, P
Mesquita, AR
Sampaio, A
AF Coutinho, Joana Fernandes
Goncalves, Oscar Filipe
Maia, Liliana
Vasconcelos, Cristiana Fernandes
Perrone-McGovern, Kristin
Simon-Dack, Stephanie
Hernandez, Kristina
Oliveira-Silva, Patricia
Mesquita, Ana Raquel
Sampaio, Adriana
TI Differential activation of the default mode network in jet lagged
individuals
SO CHRONOBIOLOGY INTERNATIONAL
LA English
DT Article
DE Brain; default mode network; jet lag
ID ANTERIOR CINGULATE CORTEX; FUNCTIONAL CONNECTIVITY; COGNITIVE DEFICITS;
COPING STRATEGIES; CORTISOL-LEVELS; SOCIAL PHOBIA; BRAIN; PERFORMANCE;
MEMORY; SHIFT
AB Long-term exposure to transmeridian flights has been shown to impact cognitive functioning. Nevertheless, the immediate effects of jet lag in the activation of specific brain networks have not been investigated. We analyzed the impact of short-term jet lag on the activation of the default mode network (DMN). A group of individuals who were on a transmeridian flight and a control group went through a functional magnetic resonance imaging acquisition. Statistical analysis was performed to test for differences in the DMN activation between groups. Participants from the jet lag group presented decreased activation in the anterior nodes of the DMN, specifically in bilateral medial prefrontal and anterior cingulate cortex. No areas of increased activation were observed for the jet lag group. These results may be suggestive of a negative impact of jet lag on important cognitive functions such as introspection, emotional regulation and decision making in a few days after individuals arrive at their destination.
C1 [Coutinho, Joana Fernandes; Goncalves, Oscar Filipe; Maia, Liliana; Oliveira-Silva, Patricia; Mesquita, Ana Raquel; Sampaio, Adriana] Univ Minho, Sch Psychol, CIPsi, Neuropsychophysiol Lab, P-4710057 Braga, Portugal.
[Goncalves, Oscar Filipe] Northeastern Univ, Bouve Coll Hlth Sci, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA.
[Goncalves, Oscar Filipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Spaulding Ctr Neuromodulat, Boston, MA USA.
[Goncalves, Oscar Filipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA.
[Vasconcelos, Cristiana Fernandes] Hosp Sto Antonio, CHP, Dept Neuroradiol, Oporto, Portugal.
[Perrone-McGovern, Kristin] Ball State Univ, Dept Counseling Psychol & Guidance Serv, Muncie, DE USA.
[Simon-Dack, Stephanie; Hernandez, Kristina] Ball State Univ, Dept Psychol Sci, Muncie, DE USA.
RP Coutinho, JF (reprint author), Univ Minho, Sch Psychol, Campus Gualtar, P-4710057 Braga, Portugal.
EM joanafpc@gmail.com
RI Goncalves, Oscar/G-5278-2010; Perrone-McGovern, Kristin/J-9558-2012;
Sampaio, Adriana/C-8361-2011;
OI Goncalves, Oscar/0000-0003-2735-9155; Perrone-McGovern,
Kristin/0000-0003-0506-1892; Sampaio, Adriana/0000-0001-7347-1282;
Coutinho, Joana/0000-0002-1562-0099; Mesquita, Ana/0000-0002-9635-2355
FU Portuguese Foundation for Science and Technology (FCT) - FEDER (POFC -
COMPETE) [PIC/IC/83290/2007]; FCT [SFRH/BPD/75014/2010]; Bial Foundation
[87/12]; Competitive Factors Operational Programme COMPETE - Portuguese
Foundation for Science and Technology [PTDC/PSI-PCL/115316/2009]
FX This study was funded by the Portuguese Foundation for Science and
Technology (FCT): PIC/IC/83290/2007, which is supported by FEDER (POFC -
COMPETE). Joana Coutinho was funded by a FCT postdoctoral grant (number:
SFRH/BPD/75014/2010) and Bial Foundation (grant number 87/12). Liliana
Maia is supported by the Competitive Factors Operational Programme
COMPETE - by national funds from the Portuguese Foundation for Science
and Technology (grant PTDC/PSI-PCL/115316/2009).
NR 43
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0742-0528
EI 1525-6073
J9 CHRONOBIOL INT
JI Chronobiol. Int.
PD FEB
PY 2015
VL 32
IS 1
BP 143
EP 149
DI 10.3109/07420528.2014.955187
PG 7
WC Biology; Physiology
SC Life Sciences & Biomedicine - Other Topics; Physiology
GA AZ6AI
UT WOS:000348299800015
PM 25180985
ER
PT J
AU Bernson-Leung, M
Ananth, P
Shusterman, S
AF Bernson-Leung, Miya
Ananth, Prasanna
Shusterman, Suzanne
TI Neuroblastoma Presenting as Facial Nerve Palsy and Bulging Tympanic
Membrane
SO CLINICAL PEDIATRICS
LA English
DT Article
ID METASTATIC NEUROBLASTOMA; PARALYSIS; CHILDREN
C1 [Bernson-Leung, Miya; Ananth, Prasanna; Shusterman, Suzanne] Boston Childrens Hosp, Boston, MA 02215 USA.
[Ananth, Prasanna; Shusterman, Suzanne] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Bernson-Leung, M (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave,Fegan 11, Boston, MA 02215 USA.
EM miya.bernson-leung@childrens.harvard.edu
OI Bernson-Leung, Miya/0000-0002-7766-2323
NR 10
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
EI 1938-2707
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD FEB
PY 2015
VL 54
IS 2
BP 183
EP 185
DI 10.1177/0009922814534314
PG 3
WC Pediatrics
SC Pediatrics
GA AZ4NA
UT WOS:000348197200012
PM 24817076
ER
PT J
AU Singh, A
Lester, C
Drapp, R
Hu, DZ
Glimcher, LH
Jones, D
AF Singh, Anju
Lester, Chantel
Drapp, Rebecca
Hu, Dorothy Z.
Glimcher, Laurie H.
Jones, Dallas
TI Tetraspanin CD9 and ectonucleotidase CD73 identify an
osteochondroprogenitor population with elevated osteogenic properties
SO DEVELOPMENT
LA English
DT Article
DE Osteochondroprogenitor; Osteoblast; Skeletal stem cell
ID MESENCHYMAL STEM-CELLS; PROGENITOR CELLS; REGENERATION; BONES
AB Cell-based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life that can differentiate to remodel or repair the fractured bone. However, cell-based skeletal repair in the clinic is still in its infancy, mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here, we took acombined approachof high-throughput screening, flow-based cell sorting and in vivo transplantation to isolate markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105(+) mesenchymal cells and that these cells readily form bone upon transplantation. In addition, we have used Thy1.2 and the ectonucleotidase CD73 to identify subsets within the CD9(+) population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties.
C1 [Singh, Anju] NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Lester, Chantel] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
[Drapp, Rebecca] N Carolina State Univ, Coll Vet Med, Raleigh, NC 27607 USA.
[Hu, Dorothy Z.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Glimcher, Laurie H.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Jones, Dallas] Abide Therapeut, San Diego, CA 92121 USA.
RP Singh, A (reprint author), NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
EM anju.singh@nih.gov; lglimche@med.cornell.edu
FU National Institutes of Health [HD055601, K99AR055668]; Arthritis
Foundation
FX This work was supported by National Institutes of Health grants
[HD055601 to L.H.G. and K99AR055668 to D.J.]. A.S. was supported by a
fellowship from the Arthritis Foundation. Deposited in PMC for release
after 12 months.
NR 20
TC 1
Z9 1
U1 0
U2 3
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD FEB 1
PY 2015
VL 142
IS 3
BP 438
EP 443
DI 10.1242/dev.113571
PG 6
WC Developmental Biology
SC Developmental Biology
GA AZ5HT
UT WOS:000348251800005
PM 25564652
ER
PT J
AU Gillern, SM
Mahmoud, NN
Paulson, EC
AF Gillern, Suzanne M.
Mahmoud, Najjia N.
Paulson, E. Carter
TI Local Excision for Early Stage Rectal Cancer in Patients Over Age 65
Years: 2000-2009
SO DISEASES OF THE COLON & RECTUM
LA English
DT Article
DE Local excision; Patterns of care; Rectal cancer; Survey of Epidemiology
and End Results-Medicare
ID LYMPH-NODE METASTASIS; TRANSANAL ENDOSCOPIC MICROSURGERY; LONG-TERM
SURVIVAL; COLORECTAL-CANCER; RADICAL SURGERY; T1; CARCINOMA; THERAPY;
RISK; ADENOCARCINOMA
AB BACKGROUND: Local excision of rectal cancer is an attractive option because it avoids the morbidity of radical resection. Concerns have arisen during the past decade, however, regarding substandard oncologic results.
OBJECTIVE: Using the most recent Survey of Epidemiology and End Results-Medicare data, we examined the change in the use of local excision for rectal cancer from 2000 to 2009 and examined patient, surgeon, and hospital factors related to its use.
DESIGN: This study is a retrospective cohort study.
SETTINGS: This study was conducted at a tertiary care medical center using Survey of Epidemiology and End Results-Medicare data.
PATIENTS: Patients with pathologic Tis, T1, or T2 rectal cancer who were >65 years of age and underwent primary radical resection or local excision between 2000 and 2009 were included in this study.
MAIN OUTCOME MEASURES: The change in the use of local excision for rectal cancer from 2000 to 2009 was the main outcome measured.
RESULTS: A total of 8966 patients were identified. The use of local excision decreased significantly between 2000 and 2009. Women and patients who were older and had more comorbidities were significantly more likely to undergo local excision. Having a colorectal surgeon perform the surgery increased the odds of local excision by 1.5 times (p < 0.001). Similar trends were seen in patients operated on at the National Cancer Institute (OR, 1.7; p < 0.001) and teaching hospitals (OR, 1.2; p = 0.003). Younger surgeons were more likely to perform local excisions. For surgeons graduating in 1980-1989 or 1990 and after, the odds of local excision were 1.40 (p = 0.001) and 2.1 (p < 0.001) compared with surgeons graduating before 1970.
LIMITATIONS: The study was limited by the retrospective design, and the data were collected by multiple healthcare officials in their representative institutions.
CONCLUSIONS: In patient >65 years of age, the odds of undergoing local excision for early stage rectal cancer decreased significantly between 2000 and 2009, coincident with evidence of oncologic inferiority. However, there was still significant variation in its use. More studies are needed to better understand these variations in an attempt to bring more uniformity to the use of local excision in early stage rectal cancer.
C1 [Gillern, Suzanne M.; Mahmoud, Najjia N.; Paulson, E. Carter] Hosp Univ Penn, Dept Gen Surg, Div Colon & Rectal Surg, Philadelphia, PA 19104 USA.
[Paulson, E. Carter] Philadelphia VA Med Ctr, Dept Gen Surg, Philadelphia, PA USA.
RP Paulson, EC (reprint author), Surg Business Off, 3900 Woodland Ave,PVAMC 5th Floor, Philadelphia, PA 19104 USA.
EM paulsone@uphs.upenn.edu
FU Thomas B. and Jeannette E. Laws McCabe Fund
FX Funding for this research was provided by the Thomas B. and Jeannette E.
Laws McCabe Fund.
NR 33
TC 3
Z9 4
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0012-3706
EI 1530-0358
J9 DIS COLON RECTUM
JI Dis. Colon Rectum
PD FEB
PY 2015
VL 58
IS 2
BP 172
EP 178
DI 10.1097/DCR.0000000000000279
PG 7
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA AZ4IZ
UT WOS:000348186000008
PM 25585074
ER
PT J
AU Leonard, MM
Serena, G
Sturgeon, C
Fasano, A
AF Leonard, Maureen M.
Serena, Gloria
Sturgeon, Craig
Fasano, Alessio
TI Genetics and celiac disease: the importance of screening
SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Review
DE celiac disease; genetic risk; HLA; screening
ID INTESTINAL BARRIER FUNCTION; PEDIATRIC-GASTROENTEROLOGY; TISSUE
TRANSGLUTAMINASE; INCREASED PREVALENCE; MULTIPLE COMMON; RISK VARIANTS;
AT-RISK; HLA; ASSOCIATION; DIAGNOSIS
AB The prevalence of celiac disease (CD) is increasing. Despite an increased awareness and an improvement in diagnostic testing, the majority of individuals with CD remain undiagnosed. Currently, genetic testing in screening for CD is used only to exclude a diagnosis or reinforce a strong clinical suspicion. In this paper, we review the most current literature regarding genetic testing in CD. In response to important data revealing that an individual's HLA haplotype is one of the strongest known predictors of CD, we propose genetic screening for at-risk infants to stratify individuals based on genetic risk to ultimately create genetic specific screening algorithms.
C1 [Leonard, Maureen M.; Serena, Gloria; Sturgeon, Craig; Fasano, Alessio] Massachusetts Gen Hosp, Ctr Celiac Res, Mucosal Immunol & Biol Res Ctr, Boston, MA 02111 USA.
[Leonard, Maureen M.; Serena, Gloria; Sturgeon, Craig; Fasano, Alessio] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA 02111 USA.
[Serena, Gloria; Sturgeon, Craig] Univ Maryland, Sch Med, Grad Program Life Sci, Baltimore, MD 21201 USA.
RP Leonard, MM (reprint author), Massachusetts Gen Hosp, Ctr Celiac Res, Mucosal Immunol & Biol Res Ctr, 165 Cambridge St, Boston, MA 02111 USA.
EM Mleonard7@mgh.harvard.edu
NR 68
TC 3
Z9 3
U1 3
U2 26
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1747-4124
EI 1747-4132
J9 EXPERT REV GASTROENT
JI Expert Rev. Gastroenterol. Hepatol.
PD FEB
PY 2015
VL 9
IS 2
BP 209
EP 215
DI 10.1586/17474124.2014.945915
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AZ1ZZ
UT WOS:000348035400010
PM 25294637
ER
PT J
AU Pins, A
Mihm, MC
Hoang, MP
AF Pins, Adrian
Mihm, Martin C., Jr.
Hoang, Mai P.
TI BAP1 and BRAFV600E expression in benign and malignant melanocytic
proliferations
SO HUMAN PATHOLOGY
LA English
DT Article
DE BAP1; BRAFV600E; Immunohistochemistry; Nevi; Melanoma
ID SPITZ TUMORS; GERMLINE MUTATIONS; BRAF MUTATION; MELANOMA; UVEAL; NEVI;
PREDISPOSE; DIAGNOSIS; BRCA1
AB BAPI (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAPI mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP] germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Pins, Adrian; Mihm, Martin C., Jr.; Hoang, Mai P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pins, Adrian; Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02114 USA.
[Pins, Adrian; Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA.
EM mhoang@mgh.harvard.edu
NR 24
TC 0
Z9 0
U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD FEB
PY 2015
VL 46
IS 2
BP 239
EP 245
DI 10.1016/j.humpath.2014.10.015
PG 7
WC Pathology
SC Pathology
GA AZ5QI
UT WOS:000348274600010
ER
PT J
AU Geyer, JT
Subramaniyam, S
Jiang, YW
Elemento, O
Ferry, JA
de Leval, L
Nakashima, MO
Liu, YC
Martin, P
Mathew, S
Orazi, A
Tam, W
AF Geyer, Julia Turbiner
Subramaniyam, Shivakumar
Jiang, Yanwen
Elemento, Olivier
Ferry, Judith A.
de Leval, Laurence
Nakashima, Megan O.
Liu, Yen-Chun
Martin, Peter
Mathew, Susan
Orazi, Attilio
Tam, Wayne
TI Lymphoblastic transformation of follicular lymphoma: a clinicopathologic
and molecular analysis of 7 patients
SO HUMAN PATHOLOGY
LA English
DT Article
DE Follicular lymphoma; Lymphoblastic transformation; MYC rearrangement;
Double hit lymphoma; TdT staining
ID B-CELL LYMPHOMA; MYC GENE REARRANGEMENT; PLASMABLASTIC LYMPHOMA;
POOR-PROGNOSIS; TRANSLOCATION; LEUKEMIA; NEOPLASMS; FEATURES;
TRANSDIFFERENTIATION; GENERATION
AB Approximately 30% of patients with follicular lymphoma (FL) transform to a more aggressive malignancy, most commonly diffuse large B cell lymphoma. Rarely, FL transformation results in clinical findings, histology, and immunophenotype reminiscent of B-Iymphoblastic leukemia/lymphoma. We report the largest series to date with detailed analysis of 7 such patients. Lymphoblastic transformation occurred on average 2 years after initial diagnosis of FL. Five patients had prior intensive chemotherapy. Two patients developed mature high-grade lymphoma, followed by the lymphoblastic transformation. FL had BCL2 gene rearrangement in 4 of 5 cases. High-grade transformation was accompanied by MYC gene rearrangement (5 of 5). Transformation was characterized by expression of TdT, loss of Bcl6, variable loss of immunoglobulin light chain, and persistence of Pax-5, Bcl2, and CD10. Whole-exome sequencing in 1 case revealed presence of several actionable mutations (CD79B, CCND3, CDK12). FL, aggressive mature B cell lymphoma, and lymphoblastic transformation were clonally related in 6 evaluable cases. After transformation, survival ranged from 1 to 14 months. Four patients died of disease, 2 were in remission after stem cell transplant, and 1 was alive with disease. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Geyer, Julia Turbiner; Subramaniyam, Shivakumar; Liu, Yen-Chun; Mathew, Susan; Orazi, Attilio; Tam, Wayne] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA.
[Jiang, Yanwen; Elemento, Olivier] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA.
[Jiang, Yanwen; Martin, Peter] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[de Leval, Laurence] Inst Univ Pathol, CH-1011 Lausanne, Switzerland.
[Nakashima, Megan O.] Cleveland Clin, Dept Pathol & Lab Med, Cleveland, OH 44195 USA.
RP Geyer, JT (reprint author), New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Pathol & Lab Med, 525 East 68th St, New York, NY 10065 USA.
EM jut9021@med.cornll.edu
NR 37
TC 7
Z9 7
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD FEB
PY 2015
VL 46
IS 2
BP 260
EP 271
DI 10.1016/j.humpath.2014.10.021
PG 12
WC Pathology
SC Pathology
GA AZ5QI
UT WOS:000348274600013
PM 25529125
ER
PT J
AU Arku, RE
Adamkiewicz, G
Vallarino, J
Spengler, JD
Levy, DE
AF Arku, R. E.
Adamkiewicz, G.
Vallarino, J.
Spengler, J. D.
Levy, D. E.
TI Seasonal variability in environmental tobacco smoke exposure in public
housing developments
SO INDOOR AIR
LA English
DT Article
DE Indoor air pollution; Second-hand smoke; Particulate matter; Airborne
nicotine; Seasonal patterns; Multiunit housing
ID SECONDHAND SMOKE; UNITED-STATES; INDOOR; PENETRATION; NONSMOKERS;
CHILDREN; MONITOR; OUTDOOR; FINE; RISK
AB The risk of tobacco smoking and second-hand smoke (SHS) exposure combined are the leading contributors to disease burden in high-income countries. Recent studies and policies are focusing on reducing exposure to SHS in multiunit housing (MUH), especially public housing. We examined seasonal patterns of SHS levels within indoor common areas located on Boston Housing Authority (BHA) properties. We measured weekly integrated and continuous fine particulate matter (PM2.5) and passive airborne nicotine in six buildings of varying building and occupant characteristics in summer 2012 and winter 2013. The average weekly indoor PM2.5 concentration across all six developments was 9.2g/m(3), higher during winter monitoring period (10.3g/m(3)) compared with summer (8.0g/m(3)). Airborne nicotine concentrations ranged from no detection to about 5000ng/m(3) (mean 311ng/m(3)). Nicotine levels were significantly higher in the winter compared with summer (620 vs. 85ng/m(3); 95% CI: 72-998). Smoking-related exposures within Boston public housing vary by season, building types, and resident smoking policy. Our results represent exposure disparities that may contribute to health disparities in low-income communities and highlight the potential importance of efforts to mitigate SHS exposures during winter when outdoor-indoor exchange rates are low and smokers may tend to stay indoors. Our findings support the use of smoke-free policy as an effective tool to eliminate SHS exposure and protect non-smokers, especially residents of MUH.
C1 [Arku, R. E.; Adamkiewicz, G.; Vallarino, J.; Spengler, J. D.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA.
[Levy, D. E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Levy, D. E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Adamkiewicz, G (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr, Room 404K WEST,401 Pk Dr, Boston, MA 02215 USA.
EM gadamkie@hsph.harvard.edu
FU Flight Attendants Medical Research Institute; Harvard School of Public
Health; National Cancer Institute's Lung Cancer Disparities Center grant
[P50CA148596]
FX This work was conducted with support from the Flight Attendants Medical
Research Institute, the Harvard School of Public Health, and the
National Cancer Institute's Lung Cancer Disparities Center grant
#P50CA148596. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the funders. We
thank Charles Perrino at the University of California, Berkeley, for
preparing and analyzing all passive nicotine monitors.
NR 34
TC 10
Z9 10
U1 0
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0905-6947
EI 1600-0668
J9 INDOOR AIR
JI Indoor Air
PD FEB
PY 2015
VL 25
IS 1
BP 13
EP 20
DI 10.1111/ina.12121
PG 8
WC Construction & Building Technology; Engineering, Environmental; Public,
Environmental & Occupational Health
SC Construction & Building Technology; Engineering; Public, Environmental &
Occupational Health
GA AZ3GM
UT WOS:000348115500003
PM 24750252
ER
PT J
AU Herrera, BS
Hasturk, H
Kantarci, A
Freire, MO
Nguyen, O
Kansal, S
Van Dyke, TE
AF Herrera, Bruno S.
Hasturk, Hatice
Kantarci, Alpdogan
Freire, Marcelo O.
Nguyen, Olivia
Kansal, Shevali
Van Dyke, Thomas E.
TI Impact of Resolvin E1 on Murine Neutrophil Phagocytosis in Type 2
Diabetes
SO INFECTION AND IMMUNITY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; HEMOGLOBIN A(1C) LEVELS;
PORPHYROMONAS-GINGIVALIS; LIPID MEDIATORS; ANTIINFLAMMATORY ACTIONS;
MACROPHAGE INFILTRATION; VASCULAR INFLAMMATION; PERIODONTAL-DISEASE;
INSULIN-RESISTANCE; INDUCED COLITIS
AB Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (db/db), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (ERV1), and a newly bred strain of db/ERV1 mice, were used to determine the impact of RvE1 on the phagocytosis of Porphyromonas gingivalis in T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeled P. gingivalis, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate the in vivo impact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis of P. gingivalis in WT animals but had no impact in db/db animals. In ERV1-transgenic and ERV1-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals. In vivo dorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis of P. gingivalis in the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressing ERV1.
C1 [Herrera, Bruno S.; Hasturk, Hatice; Kantarci, Alpdogan; Freire, Marcelo O.; Nguyen, Olivia; Kansal, Shevali; Van Dyke, Thomas E.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA.
RP Van Dyke, TE (reprint author), Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA.
EM tvandyke@forsyth.org
FU USPHS from the National Institutes of Dental and Craniofacial Research
[DE015566, DE018917, DE023584]; Sunstar Americas
FX This study was supported by USPHS grants DE015566, DE018917, and
DE023584 from the National Institutes of Dental and Craniofacial
Research. S.K. was supported by an unrestricted educational grant from
Sunstar Americas.
NR 60
TC 9
Z9 9
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD FEB
PY 2015
VL 83
IS 2
BP 792
EP 801
DI 10.1128/IAI.02444-14
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AZ0ST
UT WOS:000347955700033
PM 25486994
ER
PT J
AU Jin, JO
Zhang, W
Du, JY
Yu, Q
AF Jin, Jun-O
Zhang, Wei
Du, Jiang-yuan
Yu, Qing
TI BDCA1-Positive Dendritic Cells (DCs) Represent a Unique Human Myeloid DC
Subset That Induces Innate and Adaptive Immune Responses to
Staphylococcus aureus Infection (vol 82, pg 4466, 2014)
SO INFECTION AND IMMUNITY
LA English
DT Correction
C1 [Jin, Jun-O; Zhang, Wei; Du, Jiang-yuan] Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China.
[Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA.
RP Jin, JO (reprint author), Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China.
NR 1
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD FEB
PY 2015
VL 83
IS 2
BP 849
EP 849
DI 10.1128/IAI.02857-14
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AZ0ST
UT WOS:000347955700040
ER
PT J
AU Cotter, EW
Kelly, NR
Mitchell, KS
Mazzeo, SE
AF Cotter, Elizabeth W.
Kelly, Nichole R.
Mitchell, Karen S.
Mazzeo, Suzanne E.
TI An Investigation of Body Appreciation, Ethnic Identity, and Eating
Disorder Symptoms in Black Women
SO JOURNAL OF BLACK PSYCHOLOGY
LA English
DT Article
DE body appreciation; validity; reliability; ethnic identity; eating
disorder symptoms
ID AFRICAN-AMERICAN COLLEGE; QUESTIONNAIRE EDE-Q; SELF-REPORT
QUESTIONNAIRE; THIN-IDEAL; BULIMIC SYMPTOMATOLOGY; CONSTRUCT-VALIDITY;
PREVENTION PROGRAM; IMAGE ASSESSMENT; CAUCASIAN WOMEN; NEGATIVE AFFECT
AB Positive body image, such as body appreciation or acceptance, has gone largely unexamined in women of color in comparison with more pathological body attitudes. In an effort to promote and extend positive body image research, this study examined the reliability and validity of the Body Appreciation Scale (BAS) in Black college women, as well as the relation between ethnic identity and body appreciation. Participants were 228 Black college women (M age = 19.89, SD = 4.57). The relation between BAS scores and measures of appearance evaluation, self-esteem, Western beauty ideal internalization, eating disordered behavior, and teasing was examined to investigate convergent and divergent validity. Results supported the construct validity of this measure. Similar to previous research, a confirmatory factor analysis supported a unidimensional factor structure. Ethnic identity was moderately, positively associated with body appreciation. Western beauty ideal internalization mediated the relation between ethnic identity and eating, weight, and shape concerns. Overall, findings support the use of the BAS with Black college women.
C1 [Cotter, Elizabeth W.; Kelly, Nichole R.; Mazzeo, Suzanne E.] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Mitchell, Karen S.] VA Boston Healthcare Syst, Boston, MA USA.
[Mitchell, Karen S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Cotter, EW (reprint author), Virginia Commonwealth Univ, Dept Psychol, 806 W Franklin St,POB 842018, Richmond, VA 23284 USA.
EM ecotter@vcu.edu
NR 94
TC 2
Z9 2
U1 9
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0095-7984
EI 1552-4558
J9 J BLACK PSYCHOL
JI J. Black Psychol.
PD FEB
PY 2015
VL 41
IS 1
BP 3
EP 25
DI 10.1177/0095798413502671
PG 23
WC Psychology, Multidisciplinary
SC Psychology
GA AZ1CA
UT WOS:000347976700001
ER
PT J
AU Han, SH
Mallampalli, RK
AF Han, SeungHye
Mallampalli, Rama K.
TI The Acute Respiratory Distress Syndrome: From Mechanism to Translation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Review
ID ACUTE LUNG INJURY; NEUTROPHIL EXTRACELLULAR TRAPS; MESENCHYMAL
STEM-CELLS; PATTERN-RECOGNITION RECEPTORS; DIAGNOSED MULTIPLE-MYELOMA;
TOLL-LIKE RECEPTORS; MOLECULAR-PATTERNS; MITOCHONDRIAL-DNA; NLRP3
INFLAMMASOME; UBIQUITIN LIGASE
AB The acute respiratory distress syndrome (ARDS) is a form of severe hypoxemic respiratory failure that is characterized by inflammatory injury to the alveolar capillary barrier, with extravasation of protein-rich edema fluid into the airspace. Although many modalities to treat ARDS have been investigated over the past several decades, supportive therapies remain the mainstay of treatment. In this article, we briefly review the definition, epidemiology, and pathophysiology of ARDS and present emerging aspects of ARDS pathophysiology that encompass modulators of the innate immune response, damage signals, and aberrant proteolysis that may serve as a foundation for future therapeutic targets.
C1 [Han, SeungHye; Mallampalli, Rama K.] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
[Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA.
[Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA.
RP Mallampalli, RK (reprint author), Univ Pittsburgh, UPMC Montefiore, Dept Med, Div Pulm Allergy & Crit Care Med, NW 628, Pittsburgh, PA 15213 USA.
EM mallampallirk@upmc.edu
FU National Institutes of Health [R01 HL096376, R01 HL097376, R01 HL098174,
R01 HL081784, 1UH2HL123502, P01 HL114453]; U.S. Department of Veterans
Affairs
FX This work was supported by a Merit Review Award from the U.S. Department
of Veterans Affairs and National Institutes of Health Grants R01
HL096376, R01 HL097376, R01 HL098174, R01 HL081784, 1UH2HL123502, and
P01 HL114453 (to R.K.M.). This material is based upon work that was
supported in part by the Biomedical Laboratory Research and Development,
Office of Research and Development, Veterans Health Administration, U.S.
Department of Veterans Affairs.
NR 89
TC 24
Z9 30
U1 5
U2 24
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD FEB 1
PY 2015
VL 194
IS 3
BP 855
EP 860
DI 10.4049/jimmunol.1402513
PG 6
WC Immunology
SC Immunology
GA AZ3NK
UT WOS:000348134000003
PM 25596299
ER
PT J
AU Kant, CD
Akiyama, Y
Tanaka, K
Shea, S
Yamada, Y
Connolly, SE
Marino, J
Tocco, G
Benichou, G
AF Kant, Cavit D.
Akiyama, Yoshinobu
Tanaka, Katsunori
Shea, Susan
Yamada, Yohei
Connolly, Sarah E.
Marino, Jose
Tocco, Georges
Benichou, Gilles
TI Both Rejection and Tolerance of Allografts Can Occur in the Absence of
Secondary Lymphoid Tissues
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID REGULATORY T-CELLS; B-INDUCING KINASE; DENDRITIC LEUKOCYTES; INDIRECT
RECOGNITION; GRAFT-REJECTION; IN-VIVO; INTRAVENOUS-INJECTION; CARDIAC
ALLOGRAFTS; SKIN ALLOGRAFTS; SOLUBLE-ANTIGEN
AB In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs.
C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Res Ctr, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Thier 807,55 Fruit St, Boston, MA 02114 USA.
EM gbenichou@partners.org
FU National Institutes of Health [R21AI100278, R03AI094235]
FX This work was supported by National Institutes of Health Grants
R21AI100278 and R03AI094235 (to G.B.).
NR 60
TC 1
Z9 1
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD FEB 1
PY 2015
VL 194
IS 3
BP 1364
EP 1371
DI 10.4049/jimmunol.1401157
PG 8
WC Immunology
SC Immunology
GA AZ3NK
UT WOS:000348134000056
PM 25535285
ER
PT J
AU Enamandram, M
Duncan, LM
Kimball, AB
AF Enamandram, Monica
Duncan, Lyn M.
Kimball, Alexandra B.
TI Delivering value in dermatology: Insights from skin cancer detection in
routine clinical visits
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE basal cell carcinoma; nonmelanoma skin cancer; quality improvement;
screening; skin cancer incidence; squamous cell carcinoma; value in
health care delivery
ID MELANOMA
AB Background: There are increasing demands to demonstrate and report on outcomes in dermatology. Skin cancer diagnosis through skin examination has been well studied, and is promising as a value-delivering intervention.
Objective: This study seeks to identify the rate of skin cancer diagnosis during routine visits to a large tertiary dermatology clinic.
Methods: Medical records of patients presenting for routine dermatologic care at Massachusetts General Hospital between March 28 and September 28, 2012, were retrospectively reviewed. All patients given a diagnosis of nonmelanoma skin cancer (NMSC) confirmed on biopsy specimen were identified. Billing data were used to identify the total number of patients evaluated during the study period.
Results: NMSC was diagnosed in 1266 skin biopsy specimens from 1047 (7.0%) of the 14,829 patients who presented for routine care. In all, 55% of patients with NMSC were men (mean age 70 years). Chief symptoms of patients with NMSC included general dermatologic concerns (37%), routine cancer screening (43%), and specific lesion(s) of concern (19%).
Limitations: Retrospective design and restriction to a single institution may limit the generalizability of our findings.
Conclusion: The incidence of NMSC in routine dermatology is high; these findings validate the value of care provided by dermatologists and highlight the likely increasing need for their diagnostic skills as the population ages in the United States.
C1 [Enamandram, Monica; Kimball, Alexandra B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Duncan, Lyn M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Suite 240, Boston, MA 02114 USA.
EM Harvardskinstudies@partners.org
NR 13
TC 1
Z9 1
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD FEB
PY 2015
VL 72
IS 2
BP 310
EP 313
DI 10.1016/j.jaad.2014.10.030
PG 4
WC Dermatology
SC Dermatology
GA AY9YH
UT WOS:000347903200019
PM 25484266
ER
PT J
AU Sheu, J
Hawryluk, EB
Guo, DJ
London, WB
Huang, JT
AF Sheu, Johanna
Hawryluk, Elena B.
Guo, Dongjing
London, Wendy B.
Huang, Jennifer T.
TI Voriconazole phototoxicity in children: A retrospective review
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Review
DE nonmelanoma skin cancer; pediatrics; photosensitivity; phototoxicity;
squamous cell cancer; voriconazole
ID SQUAMOUS-CELL CARCINOMA; RECIPIENTS RECEIVING VORICONAZOLE; ORGAN
TRANSPLANT RECIPIENTS; TRIAZOLE ANTIFUNGAL AGENT; SKIN-CANCER;
PEDIATRIC-PATIENTS; FUNGAL-INFECTIONS; ZYGOMYCOSIS; SURVEILLANCE;
PROPHYLAXIS
AB Background: Voriconazole, an antifungal agent, is associated with various cutaneous reactions, including phototoxicity, accelerated photoaging, and skin cancer. Incidence and risk factors for these reactions in children have not been well described.
Objective: We sought to determine the incidence of and factors associated with phototoxic reactions and nonmelanoma skin cancer in pediatric patients treated with voriconazole.
Methods: This was a retrospective analysis of 430 pediatric patients treated with voriconazole between 2003 and 2013 at Boston Children's Hospital.
Results: Incidence of phototoxicity was 20% in all children treated with voriconazole and 47% in children treated for 6 months or longer. Factors associated with phototoxicity included white race, cystic fibrosis, cumulative treatment time, and cumulative dose. Four patients (1%) had nonmelanoma skin cancer; all experienced a phototoxic reaction during voriconazole treatment. Of those with phototoxicity, 5% were discontinued on voriconazole, 6% were referred to dermatology, and 26% received counseling about sun protection from their primary physician.
Limitations: Our study is limited by its retrospective design and potential referral bias associated with a tertiary-care center.
Conclusions: Voriconazole-associated phototoxicity is relatively common in children and may lead to nonmelanoma skin cancer. However, those with phototoxic reactions are often continued on therapy, rarely referred to dermatology, and infrequently counseled on sun protection.
C1 [Sheu, Johanna; Hawryluk, Elena B.; London, Wendy B.; Huang, Jennifer T.] Harvard Univ, Sch Med, Boston, MA USA.
[Sheu, Johanna; Hawryluk, Elena B.; Huang, Jennifer T.] Boston Childrens Hosp, Dermatol Program, Div Allergy & Immunol, Dept Med, Boston, MA 02115 USA.
[Guo, Dongjing; London, Wendy B.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Guo, Dongjing; London, Wendy B.; Huang, Jennifer T.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Huang, JT (reprint author), Boston Childrens Hosp, Dermatol Program, Fegan Sixth Floor,300 Longwood Ave, Boston, MA 02115 USA.
EM jennifer.huang@childrens.harvard.edu
NR 29
TC 6
Z9 8
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD FEB
PY 2015
VL 72
IS 2
BP 314
EP 320
DI 10.1016/j.jaad.2014.10.023
PG 7
WC Dermatology
SC Dermatology
GA AY9YH
UT WOS:000347903200020
PM 25481710
ER
PT J
AU Mossanen, M
Calvert, JK
Holt, SK
James, AC
Wright, JL
Harper, JD
Krieger, JN
Gore, JL
AF Mossanen, Matthew
Calvert, Joshua K.
Holt, Sarah K.
James, Andrew C.
Wright, Jonathan L.
Harper, Jonathan D.
Krieger, John N.
Gore, John L.
TI Overuse of Antimicrobial Prophylaxis in Community Practice Urology
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urologic surgical procedures; antibiotic prophylaxis; physician's
practice patterns; drug resistance; bacterial; quality of health care
ID CLOSTRIDIUM-DIFFICILE COLITIS; INFECTION-PREVENTION-PROJECT;
LENGTH-OF-STAY; SURGERY; MORTALITY; RISK
AB Purpose: We examined index urological surgeries to assess utilization patterns of antimicrobial prophylaxis in a large, community based population.
Materials and Methods: From the Premier Perspectives Database we identified patients who underwent inpatient urological surgeries that are considered index procedures by the ABU (American Board of Urology), including radical prostatectomy, partial or radical nephrectomy, radical cystectomy, ureteroscopy, shock wave lithotripsy, transurethral resection of the prostate, percutaneous nephrostolithotomy, transvaginal surgery, inflatable penile prosthesis, brachytherapy, transurethral resection of bladder tumor and cystoscopy. Procedures were identified based on ICD-9 procedure codes for 2007 to 2012. Antimicrobial administration, class and duration were abstracted from patient billing data. The class and duration of antimicrobials concordant with the 2008 AUA Best Practice Policy Statement was used to determine compliance.
Results: The overall compliance rate was 53%, ranging from 0.6% for radical cystectomy to 97% for shock wave lithotripsy. Antimicrobial use consistent with AUA Best Practices included the appropriate class in 67% of cases (range 34% to 80%) and the recommended duration in 78% (range 1.2% to 98%). Average prophylaxis duration for procedures for which it is recommended ranged from 1.1 days after brachytherapy to 10.3 days after radical cystectomy. The compliance rate increased from 46% overall in 2007 to 59% overall in 2012.
Conclusions: We documented considerable variation in antimicrobial prophylaxis for urological surgery. Compliance with AUA Best Practices increased with time but overall rates remain less than 60%. Efforts are needed to better understand the reasons for variation from recommended antimicrobial prophylaxis for common inpatient urological procedures to help decrease resultant complications and improve outcomes.
C1 [Mossanen, Matthew] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
Vet Affairs Puget Sound Hlth Care Syst, Div Urol, Seattle, WA USA.
RP Mossanen, M (reprint author), Univ Washington, Dept Urol, 1959 Northeast Pacific St,BB-1115,Box 356510, Seattle, WA 98195 USA.
EM mnmoss@uw.edu
FU NIDDK NIH HHS [P01 DK043881]
NR 21
TC 10
Z9 10
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD FEB
PY 2015
VL 193
IS 2
BP 543
EP 547
DI 10.1016/j.juro.2014.08.107
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA AY6YZ
UT WOS:000347709800042
PM 25196654
ER
PT J
AU Cooley, CZ
Stockmann, JP
Armstrong, BD
Sarracanie, M
Lev, MH
Rosen, MS
Wald, LL
AF Cooley, Clarissa Zimmerman
Stockmann, Jason P.
Armstrong, Brandon D.
Sarracanie, Mathieu
Lev, Michael H.
Rosen, Matthew S.
Wald, Lawrence L.
TI Two-Dimensional Imaging in a Lightweight Portable MRI Scanner without
Gradient Coils
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE portable MRI; low-field MRI; nonlinear SEMs; Halbach magnet; parallel
imaging
ID MAGNETIC-RESONANCE; PHASE GRADIENTS; NMR; FIELD; RECONSTRUCTION; ARRAY;
DESIGN
AB PurposeAs the premiere modality for brain imaging, MRI could find wider applicability if lightweight, portable systems were available for siting in unconventional locations such as intensive care units, physician offices, surgical suites, ambulances, emergency rooms, sports facilities, or rural healthcare sites.
MethodsWe construct and validate a truly portable (<100 kg) and silent proof-of-concept MRI scanner which replaces conventional gradient encoding with a rotating lightweight cryogen-free, low-field magnet. When rotated about the object, the inhomogeneous field pattern is used as a rotating spatial encoding magnetic field (rSEM) to create generalized projections which encode the iteratively reconstructed two-dimensional (2D) image. Multiple receive channels are used to disambiguate the nonbijective encoding field.
ResultsThe system is validated with experimental images of 2D test phantoms. Similar to other nonlinear field encoding schemes, the spatial resolution is position dependent with blurring in the center, but is shown to be likely sufficient for many medical applications.
ConclusionThe presented MRI scanner demonstrates the potential for portability by simultaneously relaxing the magnet homogeneity criteria and eliminating the gradient coil. This new architecture and encoding scheme shows convincing proof of concept images that are expected to be further improved with refinement of the calibration and methodology. Magn Reson Med 73:872-883, 2015. (c) 2014 Wiley Periodicals, Inc.
C1 [Cooley, Clarissa Zimmerman; Stockmann, Jason P.; Armstrong, Brandon D.; Sarracanie, Mathieu; Rosen, Matthew S.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Cooley, Clarissa Zimmerman] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Stockmann, Jason P.; Armstrong, Brandon D.; Sarracanie, Mathieu; Rosen, Matthew S.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
[Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Lev, Michael H.; Rosen, Matthew S.; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA.
[Wald, Lawrence L.] Harvard MIT Div Hlth Sci Technol, Cambridge, MA USA.
RP Cooley, CZ (reprint author), 149 13th St,Room 2301, Charlestown, MA 02129 USA.
EM clzimmer@mit.edu
RI Wald, Lawrence/D-4151-2009
FU Department of Defense, Defense Medical Research and Development Program,
Applied Research and Advanced Technology Development Award
[W81XWH-11-2-0076 (DM09094)]; NIH [P41EB015896, T32DC00038]; NIH
Blueprint for Neuroscience Research [T90DA022759/R90DA023427]
FX Grant sponsor: The Department of Defense, Defense Medical Research and
Development Program, Applied Research and Advanced Technology
Development Award; Grant number: W81XWH-11-2-0076 (DM09094); Grant
sponsor: NIH; Grant numbers: P41EB015896, T32DC00038; Grant sponsor: NIH
Blueprint for Neuroscience Research; Grant number:
T90DA022759/R90DA023427.
NR 36
TC 12
Z9 12
U1 3
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD FEB
PY 2015
VL 73
IS 2
BP 872
EP 883
DI 10.1002/mrm.25147
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AZ3PO
UT WOS:000348139500048
PM 24668520
ER
PT J
AU Swanson, RA
AF Swanson, Raymond A.
TI Brain glycogen - vestigial no more
SO METABOLIC BRAIN DISEASE
LA English
DT Editorial Material
ID IN-VIVO; GLUCOSE DEPRIVATION; ENERGY-METABOLISM; CEREBRAL GLYCOGEN;
NEURONAL-ACTIVITY; WHITE-MATTER; ASTROCYTES; NEUROTRANSMITTERS;
HYPOGLYCEMIA; STIMULATION
C1 [Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Swanson, Raymond A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
EM Raymond.Swanson@ucsf.edu
NR 24
TC 0
Z9 0
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7490
EI 1573-7365
J9 METAB BRAIN DIS
JI Metab. Brain Dis.
PD FEB
PY 2015
VL 30
IS 1
BP 251
EP 253
DI 10.1007/s11011-014-9596-2
PG 3
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA AZ2GS
UT WOS:000348053100032
PM 25060966
ER
PT J
AU Delpech, JC
Madore, C
Joffre, C
Aubert, A
Kang, JX
Nadjar, A
Laye, S
AF Delpech, Jean-Christophe
Madore, Charlotte
Joffre, Corinne
Aubert, Agnes
Kang, Jing Xuan
Nadjar, Agnes
Laye, Sophie
TI Transgenic Increase in n-3/n-6 Fatty Acid Ratio Protects Against
Cognitive Deficits Induced by an Immune Challenge through Decrease of
Neuroinflammation
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID AGED MICE; MICROGLIAL ACTIVATION; SIGNALING PATHWAY; SICKNESS BEHAVIOR;
WATER MAZE; FAT-1 MICE; LIPOPOLYSACCHARIDE; BRAIN; EXPRESSION; MEMORY
AB Polyunsaturated fatty acids (PUFAs) display immunomodulatory properties in the brain, n-3 PUFAs being able to reduce inflammation whereas n-6 PUFAs are more pro-inflammatory. It has been extensively demonstrated that exposure to a peripheral immune challenge leads to the production and release of inflammatory mediators in the brain in association with cognitive deficits. The question arises whether n-3 PUFA supplementation could downregulate the brain inflammatory response and subsequent cognitive alterations. In this study, we used a genetically modified mouse line carrying the fat-1 gene from the roundworm Caenorhabditis elegans, encoding an n-3 PUFA desaturase that catalyzes conversion of n-6 into n-3 PUFA. Consequently, these mice display endogenously elevated n-3 PUFA tissue contents. Fat-1 mice or wild-type (WT) littermates were injected peripherally with lipopolysaccharide (LPS), a bacterial endotoxin, to induce an inflammatory episode. Our results showed that LPS altered differently the phenotype of microglia and the expression of cytokines and chemokines in Fat-1 and WT mice. In Fat-1 mice, pro-inflammatory factors synthesis was lowered compared with WT mice, whereas anti-inflammatory mechanisms were favored 24 h after LPS treatment. Moreover, LPS injection impaired spatial memory in WT mice, whereas interestingly, the Fat-1 mice showed normal cognitive performances. All together, these data suggest that the central n-3 PUFA increase observed in Fat-1 mice modulated the brain innate immune system activity, leading to the protection of animals against LPS-induced pro-inflammatory cytokine production and subsequent spatial memory alteration.
C1 [Delpech, Jean-Christophe; Madore, Charlotte; Joffre, Corinne; Aubert, Agnes; Nadjar, Agnes; Laye, Sophie] INRA, UMR 1286, F-33076 Bordeaux, France.
[Delpech, Jean-Christophe; Madore, Charlotte; Joffre, Corinne; Aubert, Agnes; Nadjar, Agnes; Laye, Sophie] Univ Bordeaux, UMR 1286, Bordeaux, France.
[Kang, Jing Xuan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kang, Jing Xuan] Harvard Univ, Sch Med, Boston, MA USA.
RP Laye, S (reprint author), INRA, UMR 1286, F-33076 Bordeaux, France.
EM sophie.laye@bordeaux.inra.fr
NR 60
TC 18
Z9 19
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD FEB
PY 2015
VL 40
IS 3
BP 525
EP 536
DI 10.1038/npp.2014.196
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AY6ET
UT WOS:000347660900001
PM 25228141
ER
PT J
AU Jacobs, EG
Holsen, LM
Lancaster, K
Makris, N
Whitfield-Gabrieli, S
Remington, A
Weiss, B
Buka, S
Klibanski, A
Goldstein, JM
AF Jacobs, Emily G.
Holsen, Laura M.
Lancaster, Katie
Makris, Nikos
Whitfield-Gabrieli, Sue
Remington, Anne
Weiss, Blair
Buka, Stephen
Klibanski, Anne
Goldstein, Jill M.
TI 17 beta-Estradiol Differentially Regulates Stress Circuitry Activity in
Healthy and Depressed Women
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID ESTROGEN-RECEPTOR-BETA; PITUITARY-ADRENAL AXIS;
CORTICOTROPIN-RELEASING-FACTOR; FEMALE RHESUS-MONKEYS; ALPHA
MESSENGER-RNA; SEX-DIFFERENCES; PREFRONTAL CORTEX; MOOD DISORDERS;
PREMENSTRUAL-SYNDROME; MAJOR DEPRESSION
AB Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17 beta-estradiol (E-2) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E-2 during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E-2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E-2 modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E-2 conditions were attenuated under high E-2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex difference in MDD risk.
C1 [Jacobs, Emily G.; Holsen, Laura M.; Remington, Anne; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, Boston, MA 02115 USA.
[Jacobs, Emily G.; Holsen, Laura M.; Remington, Anne; Weiss, Blair; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Jacobs, Emily G.; Holsen, Laura M.; Makris, Nikos; Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA 02120 USA.
[Lancaster, Katie] Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA.
[Makris, Nikos; Whitfield-Gabrieli, Sue; Goldstein, Jill M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA.
[Makris, Nikos; Whitfield-Gabrieli, Sue; Goldstein, Jill M.] MIT, Charlestown, MA USA.
[Whitfield-Gabrieli, Sue] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Buka, Stephen] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA.
[Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Jacobs, EG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, One Brigham Circle, Boston, MA 02120 USA.
EM egjacobs@nmr.mgh.harvard.edu
FU Office for Research on Women's Health (ORWH); National Institute of
Mental Health [ORWH-NIMH SCOR P50 MH082679]; NIMH [T32 MH016259]; NICHD
(BIRCWH) [K12 HD051959]
FX This study was supported by the Office for Research on Women's Health
(ORWH) and National Institute of Mental Health (ORWH-NIMH SCOR P50
MH082679; Goldstein, Tobet, Handa, PIs). Dr Jacobs was supported by the
NIMH T32 MH016259 and the NICHD (BIRCWH) K12 HD051959. The authors
declare no conflict of interest.
NR 90
TC 9
Z9 9
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD FEB
PY 2015
VL 40
IS 3
BP 566
EP 576
DI 10.1038/npp.2014.203
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AY6ET
UT WOS:000347660900005
PM 25113601
ER
PT J
AU Wang, ZH
Butner, JD
Kerketta, R
Cristini, V
Deisboeck, TS
AF Wang, Zhihui
Butner, Joseph D.
Kerketta, Romica
Cristini, Vittorio
Deisboeck, Thomas S.
TI Simulating cancer growth with multiscale agent-based modeling
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Mathematical modeling; Signaling pathway; Tumor growth and invasion;
Drug discovery; Translational research
ID CELLULAR-AUTOMATON MODEL; TUMOR-GROWTH; BREAST-CANCER; LUNG-CANCER;
SOLID TUMOR; MATHEMATICAL-MODEL; CROSS-SCALE; EVOLUTION; HYBRID;
MIGRATION
AB There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Wang, Zhihui; Kerketta, Romica; Cristini, Vittorio] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA.
[Butner, Joseph D.; Cristini, Vittorio] Univ New Mexico, Dept Chem Engn, Albuquerque, NM 87131 USA.
[Butner, Joseph D.; Cristini, Vittorio] Univ New Mexico, Ctr Biomed Engn, Albuquerque, NM 87131 USA.
[Cristini, Vittorio] King Abdulaziz Univ, Fac Sci, Dept Math, Jeddah 21589, Saudi Arabia.
[Deisboeck, Thomas S.] ThinkMotu LLC, Wellesley, MA 02481 USA.
RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
EM zwang@salud.unm.edu; ts.deisboeck@thinkmotu.com
RI Cristini, Vittorio/N-3540-2013; Faculty of, Sciences, KAU/E-7305-2017
FU National Science Foundation [DMS-1263742]; National Institutes of Health
Grant (NIH) [1U54CA149196, 1U54CA143837, 1U54CA151668, 1U54CA143907];
University of New Mexico Cancer Center Victor and Ruby Hansen Surface
Professorship in Molecular Modeling of Cancer; New Mexico Cancer
Nanoscience and Microsystems Training Center (CNTC) fellowship;
Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging;
Department of Radiology at Massachusetts General Hospital
FX This work has been supported in part by the National Science Foundation
Grant DMS-1263742 (Z.W., V.C.), the National Institutes of Health Grant
(NIH) 1U54CA149196, 1U54CA143837, 1U54CA151668, and 1U54CA143907 (V.C.),
the University of New Mexico Cancer Center Victor and Ruby Hansen
Surface Professorship in Molecular Modeling of Cancer (V.C.), the New
Mexico Cancer Nanoscience and Microsystems Training Center (CNTC)
fellowship (R.K.), and the Harvard-MIT (HST) Athinoula A. Martinos
Center for Biomedical Imaging and the Department of Radiology at
Massachusetts General Hospital (T.S.D.). Finally, we apologize to our
colleagues whose works could not be cited due to space limitations.
NR 92
TC 23
Z9 23
U1 3
U2 52
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD FEB
PY 2015
VL 30
BP 70
EP 78
DI 10.1016/j.semcancer.2014.04.001
PG 9
WC Oncology
SC Oncology
GA AZ2UE
UT WOS:000348086900009
PM 24793698
ER
PT J
AU Hafner, S
Wagner, K
Wepler, M
Matallo, J
Groger, M
McCook, O
Scheuerle, A
Huber-Lang, M
Frick, M
Weber, S
Stahl, B
Jung, B
Calzia, E
Georgieff, M
Moller, P
Dietl, P
Radermacher, P
Wagner, F
AF Hafner, Sebastian
Wagner, Katja
Wepler, Martin
Matallo, Jose
Groeger, Michael
McCook, Oscar
Scheuerle, Angelika
Huber-Lang, Markus
Frick, Manfred
Weber, Sandra
Stahl, Bettina
Jung, Birgit
Calzia, Enrico
Georgieff, Michael
Moeller, Peter
Dietl, Paul
Radermacher, Peter
Wagner, Florian
TI PHYSIOLOGICAL AND IMMUNE-BIOLOGICAL CHARACTERIZATION OF A LONG-TERM
MURINE MODEL OF BLUNT CHEST TRAUMA
SO SHOCK
LA English
DT Article
DE Cytokines; heme oxygenase 1; nuclear factor-kappa B; nitrotyrosine;
purinergic receptors; mitochondrial respiration
ID INDUCED LUNG INJURY; P2X(7) RECEPTOR; MECHANICAL VENTILATION;
EXTRACELLULAR ATP; CONTUSION; MICE; INFLAMMATION; DIAPHRAGM; RESPONSES;
CARDIOPULMONARY
AB Blunt chest trauma causes pulmonary and systemic inflammation. It is still a matter of debate whether the long-term course of this inflammatory response is associated with persistent impairment of lung function. We hypothesized that an increase of inflammatory biomarkers may still be present at later time points after blunt chest trauma, eventually, despite normalized lung mechanics and gas exchange. Anesthetized spontaneously breathing male C57BL/6J mice underwent a blast waveYinduced blunt chest trauma or sham procedure. Twelve and 24 h later, blood gases and lung mechanics were measured, together with blood, bronchoalveolar lavage (BAL), and tissue cytokine concentrations (multiplex cytokine kit); heme oxygenase 1 (HO-1), activated caspase-3, Bcl-x(L), and Bax expression (Western blotting); nuclear factor-kappa B activation (electrophoretic mobility shift assay); nitrotyrosine formation; and purinergic (P2XR4 and P2XR7) receptor expression (immunohistochemistry). Histological damage was assessed by hematoxylin and eosin and periodic acid-Schiff staining. High-resolution respirometry allowed assessing mitochondrial respiration in diaphragm biopsies. Chest trauma significantly increased tissue and BAL cytokine levels, associated with a significant increase in HO-1, purinergic receptor expression, and tissue nitrotyrosine formation. In contrast, lung mechanics, gas exchange, and histological damage did not show any significant difference between sham and trauma groups. Activation of the immune response remains present at later time points after murine blunt chest trauma. Discordance of the increased local inflammatory response and preserved pulmonary function may be explained by a dissociation of the immune response and lung function, such as previously suggested after experimental sepsis.
C1 [Hafner, Sebastian; Wagner, Katja; Matallo, Jose; Groeger, Michael; McCook, Oscar; Weber, Sandra; Stahl, Bettina; Calzia, Enrico; Radermacher, Peter; Wagner, Florian] Univ Ulm Klinikum, Inst Anasthesiol Pathophysiol & Verfahrensentwick, D-89081 Ulm, Germany.
[Hafner, Sebastian; Wagner, Katja; Wepler, Martin; Georgieff, Michael; Wagner, Florian] Univ Ulm Klinikum, Anasthesiol Klin, D-89081 Ulm, Germany.
[Wepler, Martin] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Scheuerle, Angelika; Moeller, Peter] Univ Ulm Klinikum, Inst Pathol, D-89081 Ulm, Germany.
[Huber-Lang, Markus] Univ Ulm Klinikum, Klin Unfallchirurg Hand Plast & Wiederherstellung, D-89081 Ulm, Germany.
[Frick, Manfred; Dietl, Paul] Univ Ulm, Inst Allgemeine Physiol, D-89069 Ulm, Germany.
[Jung, Birgit] Boehringer Ingelheim Pharma GmbH & Co KG, Dept Pulm Res, Biberach, Germany.
RP Radermacher, P (reprint author), Univ Ulm Klinikum, Inst Anasthesiol Pathophysiol & Verfahrensentwick, Helmholtzstr 8-1, D-89081 Ulm, Germany.
EM peter.radermacher@uni-ulm.de
RI Frick, Manfred/E-1374-2012
FU Ministry of Science, Research, Arts of Baden-Wurttemberg [Az:
32-7533.-6-10/15/5]; Ulm University
FX This work was supported by a grant from the Ministry of Science,
Research, Arts of Baden-Wurttemberg (Az: 32-7533.-6-10/15/5 to P.R.) and
by a grant from Ulm University (3.4S Senior Clinician Scientist to
F.W.).
NR 37
TC 6
Z9 6
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD FEB
PY 2015
VL 43
IS 2
BP 140
EP 147
DI 10.1097/SHK.0000000000000277
PG 8
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AZ3PS
UT WOS:000348139900007
PM 25526372
ER
PT J
AU Nassour, I
Kautza, B
Rubin, M
Escobar, D
Luciano, J
Loughran, P
Gomez, H
Scott, J
Gallo, D
Brumfield, J
Otterbein, LE
Zuckerbraun, BS
AF Nassour, Ibrahim
Kautza, Benjamin
Rubin, Mark
Escobar, Daniel
Luciano, Jason
Loughran, Patricia
Gomez, Hernando
Scott, Jeffrey
Gallo, David
Brumfield, John
Otterbein, Leo E.
Zuckerbraun, Brian S.
TI CARBON MONOXIDE PROTECTS AGAINST HEMORRHAGIC SHOCK AND
RESUSCITATION-INDUCED MICROCIRCULATORY INJURY AND TISSUE INJURY
SO SHOCK
LA English
DT Article
DE Endothelium; carbon monoxide-releasing molecule; sinusoid; adhesion
molecule
ID HEME OXYGENASE-1; ORGAN FAILURE; P-SELECTIN; EXPRESSION; ACTIVATION;
STRESS; APOPTOSIS; ADHESION; LIVER; DYSFUNCTION
AB Traumatic injury is a significant cause of morbidity and mortality worldwide. Microcirculatory activation and injury from hemorrhage contribute to organ injury. Many adaptive responses occur within the microcirculatory beds to limit injury including upregulation of heme oxygenase (HO) enzymes, the rate-limiting enzymes in the breakdown of heme to carbon monoxide (CO), iron, and biliverdin. Here we tested the hypothesis that CO abrogates trauma-induced injury and inflammation protecting the microcirculatory beds. Methods: C57Bl/6 mice underwent sham operation or hemorrhagic shock to a mean arterial pressure of 25 mmHg for 120 minutes. Mice were resuscitated with lactated Ringer's at 2x the volume of maximal shed blood. Mice were randomized to receive CO-releasing molecule or inactive CO-releasing molecule at resuscitation. A cohort of mice was pretreated with tin protoporphyrin-IX to inhibit endogenous CO generation by HOs. Primary mouse liver sinusoidal endothelial cells were cultured for in vitro experiments. Results: Carbon monoxide-releasing molecule protected against hemorrhagic shock/resuscitation organ injury and systemic inflammation and reduced hepatic sinusoidal endothelial injury. Inhibition of HO activity with tin protoporphyrin-IX exacerbated liver hepatic sinusoidal injury. Hemorrhagic shock/resuscitation in vivo or cytokine stimulation in vitro resulted in increased endothelial expression of adhesion molecules that was associated with decreased leukocyte adhesion in vivo and in vitro. Conclusions: Hemorrhagic shock/resuscitation is associated with endothelial injury. Heme oxygenase enzymes and CO are involved in part in diminishing this injury and may prove useful as a therapeutic adjunct that can be harnessed to protect against endothelial activation and damage.
C1 [Nassour, Ibrahim; Kautza, Benjamin; Rubin, Mark; Escobar, Daniel; Luciano, Jason; Loughran, Patricia; Gomez, Hernando; Brumfield, John; Zuckerbraun, Brian S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Scott, Jeffrey; Gallo, David; Otterbein, Leo E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Brumfield, John; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Zuckerbraun, BS (reprint author), F1200PUH,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM zuckerbraunbs@upmc.edu
OI Nassour, Ibrahim/0000-0002-9845-1074
FU National Institutes of Health [R01 GM082830]; Veterans Affairs Merit
Award [1I01BX000566]; Department of Defense [DM102439, 5R01GM088666];
CIMIT Center for Integration of Medicine and Innovative Technology
FX This work is supported by National Institutes of Health grants R01
GM082830 (B.S.Z.), Veterans Affairs Merit Award 1I01BX000566 (B.S.Z.),
and Department of Defense DM102439 (B.S.Z.), 5R01GM088666 (L.E.O.) and
CIMIT Center for Integration of Medicine and Innovative Technology
(L.E.O.).
NR 34
TC 6
Z9 6
U1 2
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1073-2322
EI 1540-0514
J9 SHOCK
JI Shock
PD FEB
PY 2015
VL 43
IS 2
BP 166
EP 171
DI 10.1097/SHK.0000000000000264
PG 6
WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease
SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System
& Cardiology
GA AZ3PS
UT WOS:000348139900010
PM 25243427
ER
PT J
AU Tian, HJ
Li, CS
Scott, TP
Montgomery, SR
Phan, K
Lao, LF
Zhang, W
Li, YW
Hayashi, T
Takahashi, S
Alobaidaan, R
Ruangchainikom, M
Zhao, KW
Brochmann, EJ
Murray, SS
Wang, JC
Daubs, MD
AF Tian, Haijun
Li, Chen-Shuang
Scott, Trevor P.
Montgomery, Scott R.
Phan, Kevin
Lao, Lifeng
Zhang, Wei
Li, Yawei
Hayashi, Tetsuo
Takahashi, Shinji
Alobaidaan, Raed
Ruangchainikom, Monchai
Zhao, Ke-Wei
Brochmann, Elsa J.
Murray, Samuel S.
Wang, Jeffrey C.
Daubs, Michael D.
TI Secreted phosphoprotein 24 kD inhibits nerve root inflammation induced
by bone morphogenetic protein-2
SO SPINE JOURNAL
LA English
DT Article
DE Secreted phosphoprotein 24 kD; Bone morphogenetic protein-2; Nerve root
inflammation; Spine surgery; Posterior lumbar fusion; Complications
ID GENE-RELATED PEPTIDE; BINDING PEPTIDE; SENSORY NEURONS; RODENT MODEL;
SURGERY; FUSION; ARTHRODESIS; EXPRESSION; RECOVERY; INJURY
AB BACKGROUND CONTEXT: Bone morphogenetic protein-2 (BMP-2) has been used to successfully promote spine fusion, but side-effects including nerve inflammation have been observed.
PURPOSE: To investigate the direct neurotoxic effects of BMP-2 and test the hypotheses that the use of BMP binding proteins, such as secreted phosphoprotein 24 kD (Spp24), can reduce or eliminate these effects.
STUDY DESIGN: In vitro experiments and in vivo analysis in a rodent model.
METHODS: In vitro, dorsal root ganglion cells were cultured in the presence of BMP-2 with and without Spp24 and calcitonin gene-related peptide and Substance P, markers of neuroinflammation, were measured by immunohistochemistry. In vivo, rats underwent a left-sided laminotomy at L5 to expose the S1 nerve root and were randomized into four different groups according to the intervention at the laminotomy site: collagen sponge only (no BMP-2 or Spp24), BMP-2 in a collagen sponge only, BMP-2 in a collagen sponge+an empty collagen sponge to act as a barrier, and BMP-2 in a collagen sponge+Spp24 in a collagen sponge to act as a barrier. Functional evaluation was done using the Basso, Beattie, and Bresnahan scale and immunohistochemical analyses were performed using calcitonin gene-related peptide and Substance P staining.
RESULTS: The neuroinflammatory effects of BMP-2 in vitro were ameliorated by the addition of Spp24. Similarly, in vivo, Spp24 reduced the expression of markers on neuroinflammation in animals treated with BMP-2 and also improved the function after BMP-2 administration.
CONCLUSIONS: These results confirm that BMP binding proteins have great potential as adjuvant therapies to limit BMP-2 related side-effects in spine surgery. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Tian, Haijun] Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed Surg, Shanghai 200003, Peoples R China.
[Tian, Haijun; Scott, Trevor P.; Montgomery, Scott R.; Phan, Kevin; Lao, Lifeng; Zhang, Wei; Li, Yawei; Hayashi, Tetsuo; Takahashi, Shinji; Alobaidaan, Raed; Ruangchainikom, Monchai] Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA 90024 USA.
[Li, Chen-Shuang] Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China.
[Zhao, Ke-Wei; Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA.
[Brochmann, Elsa J.; Murray, Samuel S.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, North Hills, CA 91343 USA.
[Brochmann, Elsa J.; Murray, Samuel S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Wang, Jeffrey C.] Univ So Calif, Keck Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90033 USA.
[Daubs, Michael D.] Univ Nevada, Sch Med, Dept Surg, Div Orthopaed Surg, Las Vegas, NV 89102 USA.
RP Tian, HJ (reprint author), Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed Surg, 415 Fengyang Rd, Shanghai 200003, Peoples R China.
EM haijuntianmd@gmail.com
FU AO Spine; Dept. VA; AO Foundation; Cervical Spine Research Society; AO
Spine of North America
FX HT: Nothing to disclose. C-SL: Nothing to disclose. TPS: Nothing to
disclose. SRM: Nothing to disclose. KP: Nothing to disclose. LL: Nothing
to disclose. WZ: Nothing to disclose. YL: Nothing to disclose. TH:
Nothing to disclose. ST: Fellowship Support: AO Spine (B). RA: Nothing
to disclose. MR: Nothing to disclose. K-WZ: Nothing to disclose. EJB:
Grants: Dept. VA (G, Paid directly to institution). SSM: Grants: Dept.
VA (F, Paid directly to institution). JCW: Royalties: Stryker (B),
Osprey (C), Aesculap (B), Biomet (F), Amedica (D), Seaspine (D), Synthes
(C), Alphatech (E); Stock Ownership: Fziomed (2,500 shares, less than
1%), Alphatech (14,619 shares, less than 1%); Private Investments:
Promethean Spine (B investment, less than 1% of entity, unknown amount
of shares), Paradigm Spine (B investment, less than 1% of entity,
unknown amount of shares), Benevenue (C investment, less than 1% of
entity, unknown amount of shares), Nexgen (B investment, less than 1% of
entity, unknown amount of shares), Pioneer (B investment, less than 1%
of entity, unknown amount of shares), Amedica (D investment, less than
1% of entity, unknown amount of shares), Vertiflex (B investment, less
than 1% of entity, unknown amount of shares), Electrocore (C investment,
less than 1% of entity, unknown amount of shares), Surgitech (C
investment, less than 1% of entity, unknown amount of shares), Axiomed
(25,000 shares, less than 1% of entity), VG Innovations (5,000 options,
less than 1% of entity), Corespine (2,000 options valued at less than 1%
of company), Expanding Ortho (33,000 options valued at less than 1% of
company), Syndicom (66,125 shares valued at less than 1% of company),
Osprey (10 options, less than 1% of company), Amedica (35,416 options,
less than 1% of company), Bone Biologics (51,255 shares, less than 1% of
company), Curative Biosciences (1,875 options, less than 1% of company),
Pearldriver (25,000 options, less than 1% of company); Board of
Directors: NASS (nonfinancial, reimbursement for travel for board
meetings), CSRS (nonfinancial, reimbursement for travel for board
meetings), AO Foundation (E, combined for honorariums for educational
activities and reimbursements for international travel for this
nonprofit foundation, which requires me to travel internationally on
multiple trips and allows for business class travel on international
trips), Collaborative Spine Research Foundation (nonfinancial,
reimbursement for travel for board meetings); Fellowship Support: AO
Foundation (E, Paid directly to institution). MDD: Grant: Cervical Spine
Research Society (C, Paid directly to institution); Royalties:
Depuy-Synthes Spine (F); Consulting: Depuy-Synthes Spine (B); Fellowship
Support: AO Spine of North America (E, Paid directly to institution).
NR 25
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-9430
EI 1878-1632
J9 SPINE J
JI Spine Journal
PD FEB 1
PY 2015
VL 15
IS 2
BP 314
EP 321
DI 10.1016/j.spinee.2014.09.021
PG 8
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA AZ2DX
UT WOS:000348045900019
PM 25264179
ER
PT J
AU Bicket, MC
Horowitz, JM
Benzon, HT
Cohen, SP
AF Bicket, Mark C.
Horowitz, Joshua M.
Benzon, Honorio T.
Cohen, Steven P.
TI Epidural injections in prevention of surgery for spinal pain: systematic
review and meta-analysis of randomized controlled trials
SO SPINE JOURNAL
LA English
DT Review
DE Epidural steroid injection; Surgery; Back pain; Radicular pain; Low back
pain; Systematic review; Meta-analysis
ID LOW-BACK-PAIN; LUMBAR DISC HERNIATION; OUTCOMES-RESEARCH-TRIAL; NERVE
ROOT COMPRESSION; STEROID INJECTIONS; DOUBLE-BLIND; RADICULAR PAIN;
CORTICOSTEROID INJECTIONS; SUBGROUP-ANALYSIS; TRANSFORAMINAL INJECTION
AB BACKGROUND CONTEXT: Low back pain is debilitating and costly, especially for patients not responding to conservative therapy and requiring surgery.
PURPOSE: Our objective was to determine whether epidural steroid injections (ESI) have a surgery-sparing effect in patients with spinal pain.
STUDY DESIGN/SETTING: The study design was based on a systematic review and meta-analysis.
METHODS: Databases searched included Cochrane, PubMed, and EMBASE. The primary analysis evaluated randomized controlled trials (RCTs) in which treatment groups received ESI and control groups underwent control injections. Secondary analyses involved RCTs comparing surgery with ESI, and subgroup analyses of trials comparing surgery with conservative treatment in which the operative disposition of subjects who received ESI were evaluated.
RESULTS: Of the 26 total studies included, only those evaluating the effect of ESI on the need for surgery as a primary outcome examined the same patient cohort, providing moderate evidence that patients who received ESI were less likely to undergo surgery than those who received control treatment. For studies examining surgery as a secondary outcome, ESI demonstrated a trend to reduce the need for surgery for short-term (<1 year) outcomes (risk ratio, 0.68; 95% confidence interval, 0.41-1.13; p=.14) but not long-term (>= 1 year) outcomes (0.95, 0.77-1.19, p=.68). Secondary analyses provided low-level evidence suggesting that between one-third and half of patients considering surgery who undergo ESI can avoid surgery.
CONCLUSIONS: Epidural steroid injections may provide a small surgery-sparing effect in the short term compared with control injections and reduce the need for surgery in some patients who would otherwise proceed to surgery. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Bicket, Mark C.; Horowitz, Joshua M.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA.
[Horowitz, Joshua M.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA.
[Benzon, Honorio T.] Northwestern Sch Med, Dept Anesthesiol, Chicago, IL 60611 USA.
[Cohen, Steven P.] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21029 USA.
[Cohen, Steven P.] Walter Reed Natl Mil Med Ctr, Dept Anesthesiol, Bethesda, MD 20889 USA.
RP Bicket, MC (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM mbicket@partners.org
FU Centers for Rehabilitation Sciences Research, Uniformed Services
University of the Health Sciences, Bethesda, MD, USA [111726]
FX The authors would like to acknowledge Lieutenant Colonel Scott R.
Griffith, MD, US Army Pain Management Consultant and Walter Reed Pain
Medicine Program Director, and Commander Steven Hanling, MD, US Navy
Pain Management Consultant and Naval Medical Center-San Diego Pain
Medicine Program Director, for their assistance validating the technical
quality scale. Neither received compensation for their contribution to
this work. This study was funded in part by Grant 111726 of the Centers
for Rehabilitation Sciences Research, Uniformed Services University of
the Health Sciences, Bethesda, MD, USA. The funding organization played
no role in any of the following aspects of this study: design and
conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the
manuscript; and decision to submit the manuscript for publication.
NR 71
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-9430
EI 1878-1632
J9 SPINE J
JI Spine Journal
PD FEB 1
PY 2015
VL 15
IS 2
BP 348
EP 362
DI 10.1016/j.spinee.2014.10.011
PG 15
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA AZ2DX
UT WOS:000348045900023
PM 25463400
ER
PT J
AU Stuckey, DW
Hingtgen, SD
Karakas, N
Rich, BE
Shah, K
AF Stuckey, Daniel W.
Hingtgen, Shawn D.
Karakas, Nihal
Rich, Benjamin E.
Shah, Khalid
TI Engineering Toxin-Resistant Therapeutic Stem Cells to Treat Brain Tumors
SO STEM CELLS
LA English
DT Article
DE Cytotoxin; Stem cell; Molecular imaging; Glioblastoma; Targeted therapy
ID GROWTH-FACTOR RECEPTOR; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; PHASE-II
TRIAL; PSEUDOMONAS EXOTOXIN; RECOMBINANT IMMUNOTOXIN; DIPHTHERIA-TOXIN;
GENE-THERAPY; GLIOBLASTOMA-MULTIFORME; CANCER-TREATMENT; HEMATOLOGIC
MALIGNANCIES
AB Pseudomonas exotoxin (PE) potently blocks protein synthesis by catalyzing the inactivation of elongation factor-2 (EF-2). Targeted PE-cytotoxins have been used as antitumor agents, although their effective clinical translation in solid tumors has been confounded by off-target delivery, systemic toxicity, and short chemotherapeutic half-life. To overcome these limitations, we have created toxin-resistant stem cells by modifying endogenous EF-2, and engineered them to secrete PE-cytotoxins that target specifically expressed (interleukin-13 receptor subunit alpha-2) or overexpressed (epidermal growth factor receptor) in glioblastomas (GBM). Molecular analysis correlated efficacy of PE-targeted cytotoxins with levels of cognate receptor expression, and optical imaging was applied to simultaneously track the kinetics of protein synthesis inhibition and GBM cell viability in vivo. The release of IL13-PE from biodegradable synthetic extracellular matrix (sECM) encapsulated stem cells in a clinically relevant GBM resection model led to increased long-term survival of mice compared to IL13-PE protein infusion. Moreover, multiple patient-derived GBM lines responded to treatment, underscoring its clinical relevance. In sum, integrating stem cell-based engineering, multimodal imaging, and delivery of PE-cytotoxins in a clinically relevant GBM model represents a novel strategy and a potential advancement in GBM therapy.
C1 [Stuckey, Daniel W.; Hingtgen, Shawn D.; Karakas, Nihal; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA USA.
[Stuckey, Daniel W.; Hingtgen, Shawn D.; Karakas, Nihal; Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Shah, Khalid] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Rich, Benjamin E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Rich, Benjamin E.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Shah, K (reprint author), Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA 02114 USA.
EM kshah@mgh.harvard.edu
FU U.S. National Institutes of Health [R01CA138922, R01CA173077]
FX We thank G. Prestwich (University of Utah) and T. Zarembinski (Biotime,
Inc.) for providing us with synthetic extracellular matrix gels, G.
Mohapatra (Massachusetts General Hospital) for genome sequencing
analysis, and Sara Pignatta (Biosciences Laboratory, Istituto
Scientifico Romagnolo per lo Studio e la Cura dei Tumori) for
experimental assistance during the review process. This work was
supported by U.S. National Institutes of Health Grants R01CA138922
(K.S.) and R01CA173077 (K.S.).
NR 55
TC 6
Z9 7
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD FEB
PY 2015
VL 33
IS 2
BP 589
EP 600
DI 10.1002/stem.1874
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA AZ4RW
UT WOS:000348211300024
PM 25346520
ER
PT J
AU Zhu, WB
Casper, A
Libal, NL
Murphy, SJ
Bodhankar, S
Offner, H
Alkayed, NJ
AF Zhu, Wenbin
Casper, Amanda
Libal, Nicole L.
Murphy, Stephanie J.
Bodhankar, Sheetal
Offner, Halina
Alkayed, Nabil J.
TI Preclinical Evaluation of Recombinant T Cell Receptor Ligand RTL1000 as
a Therapeutic Agent in Ischemic Stroke
SO TRANSLATIONAL STROKE RESEARCH
LA English
DT Article
DE Ischemic stroke; Neurobehavioral evaluation; Immunotherapy; Recombinant
T cell receptor ligand; HLA-DR2 transgenic mice
ID CLASS-II CONSTRUCTS; FUNCTIONAL RECOVERY; MICE; ACTIVATION; MYELIN;
RECOMMENDATIONS; INFLAMMATION; LYMPHOCYTES; TOLERANCE; SEVERITY
AB Recombinant T cell Receptor Ligand 1000 (RTL1000), a partial human major histocompatibility complex (MHC) molecule coupled to a human myelin peptide, reduces infarct size after experimental stroke in HLA-DRB1*1502 transgenic (DR2-Tg) mice. In this study, we characterized the therapeutic time window of opportunity for RTL1000; we explored the efficacy of a single dose of RTL1000 administration and determined if RTL1000 affords long-term neurobehavioral functional improvement after ischemic stroke. Male DR2-Tg mice underwent 60 min of intraluminal reversible middle cerebral artery occlusion (MCAO). RTL1000 or vehicle was injected 4, 6, or 8 h after MCAO, followed by three daily injections. In the single-dose study, one-time injection of RTL1000 was applied 4 h after MCAO. Cortical, striatal, and hemispheric infarct sizes were measured 24 or 96 h after stroke. Behavioral testing, including neuroscore evaluation, open field, paw preference, and novel object recognition, was performed up to 28 days after stroke. Our data showed that RTL1000 significantly reduced the infarct size 96 h after MCAO when the first injection was given at 4 and 6 h, but not 8 h, after the onset of stroke. A single dose of 400 or 100 mu g RTL1000 also significantly reduced the infarct size 24 h after MCAO. Behavioral testing showed that RTL1000 treatment used 4 h after MCAO improved long-term cognitive outcome 28 days after stroke. Taken together, RTL1000 protects against acute injury if applied within a 6-h time window and improves long-term functional recovery after experimental stroke in DR2-Tg mice.
C1 [Zhu, Wenbin; Casper, Amanda; Libal, Nicole L.; Murphy, Stephanie J.; Offner, Halina; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA.
[Bodhankar, Sheetal; Offner, Halina; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Murphy, Stephanie J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA.
[Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA.
[Bodhankar, Sheetal; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA.
RP Alkayed, NJ (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA.
EM alkayedn@ohsu.edu
FU NIH [NS076013]; Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development, Biomedical
Laboratory Research and Development
FX This work was supported by NIH Grants #NS076013 (STTR) and by the
Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Biomedical Laboratory Research and
Development.
NR 32
TC 9
Z9 9
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-4483
EI 1868-601X
J9 TRANSL STROKE RES
JI Transl. Stroke Res.
PD FEB
PY 2015
VL 6
IS 1
BP 60
EP 68
DI 10.1007/s12975-014-0373-7
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AZ3IT
UT WOS:000348121500008
PM 25270354
ER
PT J
AU Malte, CA
Dennis, PA
Saxon, AJ
McFall, M
Carmody, TP
Unger, W
Beckham, JC
AF Malte, Carol A.
Dennis, Paul A.
Saxon, Andrew J.
McFall, Miles
Carmody, Timothy P.
Unger, William
Beckham, Jean C.
TI Tobacco use trajectories among a large cohort of treated smokers with
posttraumatic stress disorder
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Smoking cessation; Posttraumatic stress disorder; Veterans; Major
depressive disorder; Relapse
ID MENTAL-HEALTH-CARE; SMOKING-CESSATION; NICOTINE DEPENDENCE;
GENERAL-POPULATION; CIGARETTE-SMOKING; MAJOR DEPRESSION; ELECTRONIC
DIARY; FOLLOW-UP; RELAPSE; ABSTINENCE
AB Introduction: This study identified distinct tobacco use trajectories across 18 months in 943 veteran smokers with posttraumatic stress disorder (PTSD) in order to describe quit and relapse patterns, examine associations between trajectory groups on baseline characteristics and cessation service utilization, and explore group differences in mental health outcomes.
Methods: Veterans who participated in a muldsite, randomized trial of integrated smoking cessation care were grouped using k-means clustering based on reported daily tobacco use between baseline and 18 months. Four trajectory clusters were identified: no reduction (62%), temporary reduction (11%), late sustained reduction (9%) and early sustained reduction (18%).
Results: Median quit times in the early, late, temporary, and no reduction groups were 451, 141.5, 97, and 2 days, respectively. Compared to the early reduction group, the temporary reduction group exhibited higher baseline depression (p < 0.01) and anxiety (p < 0.01), but did not differ in treatment received, with both groups attending significantly more cessation visits (p < 0.001) and more likely to receive recommended pharmacotherapy (p < 0.001) than the no reduction group-between baseline and 6 months. The early reduction group exhibited lower depression relative to the no reduction (p < 0.01) and temporary reduction (p < 0.01) groups across all assessments between baseline and 18 months. Differences were not observed between groups in depressive or PTSD symptom change over time between baseline and 18 months.
Conclusions: Tobacco use trajectories among treated smokers with PTSD vary distinctly. Characteristics of identified subgroups may lead to targeted interventions among smokers with PTSD and potentially other psychiatric disorders. Published by Elsevier Ltd.
C1 [Malte, Carol A.; Saxon, Andrew J.; McFall, Miles] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Dennis, Paul A.] Durham Vet Affairs Med Ctr, Res & Dev Serv, Durham, NC USA.
[Saxon, Andrew J.; McFall, Miles] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Carmody, Timothy P.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
[Carmody, Timothy P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Unger, William] Providence Vet Affairs Med Ctr, Providence, RI USA.
[Beckham, Jean C.] Vet Affairs Mid Atlantic Reg Mental Illness Res E, Durham, NC USA.
[Beckham, Jean C.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
RP Malte, CA (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, 1660 S Columbian Way,S-116 ATC, Seattle, WA 98108 USA.
EM Carol.Malte@va.gov
FU U.S. Department of Veterans Affairs, Office of Research and Development
Cooperative Studies Program (CSP) [519]; Veterans Affairs Puget Sound
Center of Excellence in Substance Abuse Treatment and Education; U.S.
Department of Veterans Affairs, Office of Clinical Research and
Development; Veterans Affairs Mid-Atlantic Mental Illness Research,
Education, and Clinical Center
FX This material is based upon work supported by the U.S. Department of
Veterans Affairs, Office of Research and Development Cooperative Studies
Program (CSP #519). The Veterans Affairs Puget Sound Center of
Excellence in Substance Abuse Treatment and Education, the U.S.
Department of Veterans Affairs, Office of Clinical Research and
Development, and the Veterans Affairs Mid-Atlantic Mental Illness
Research, Education, and Clinical Center provided additional support.
The views expressed in this article are those of the authors and do not
necessarily reflect the position or policy of the U.S. Department of
Veterans Affairs.
NR 37
TC 1
Z9 1
U1 5
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD FEB
PY 2015
VL 41
BP 238
EP 246
DI 10.1016/j.addbeh.2014.10.034
PG 9
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA AY3PZ
UT WOS:000347496500037
PM 25452071
ER
PT J
AU Corey, KE
Vuppalanchi, R
Wilson, LA
Cummings, OW
Chalasani, N
AF Corey, K. E.
Vuppalanchi, R.
Wilson, L. A.
Cummings, O. W.
Chalasani, N.
CA NASH CRN
TI NASH resolution is associated with improvements in HDL and triglyceride
levels but not improvement in LDL or non-HDL-C levels
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; FATTY LIVER-DISEASE;
CORONARY-HEART-DISEASE; NONALCOHOLIC STEATOHEPATITIS; FOLLOW-UP; RISK;
ATHEROSCLEROSIS; DYSLIPIDEMIA; PIOGLITAZONE; PREDICTION
AB BackgroundNonalcoholic steatohepatitis (NASH) is associated with dyslipidemia and cardiovascular disease (CVD).
AimTo determine the relationship between resolution of NASH and dyslipidemia.
MethodsIndividuals in the Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial with paired liver biopsies and fasting lipid levels were included (N=222). In the PIVENS trial individuals were randomised to pioglitazone 30mg, vitamin E 800IU or placebo for 96weeks. Change in lipid levels at 96weeks was compared between those with and without NASH resolution.
ResultsDyslipidemia at baseline was frequent, with low high-density lipoprotein (HDL) (<40mg/dL in men or <50mg/dL in women) in 63%, hypertriglyceridaemia (150mg/dL) in 46%, hypercholesterolaemia (200mg/dL) in 47% and triglycerides (TG)/HDL >5.0 in 25%. Low-density lipoprotein (LD) 160mg/dL was found in 16% and elevated non-HDL cholesterol (non-HDL-C) (130mg/dL) in 73%. HDL increased with NASH resolution but decreased in those without resolution (2.9mg/dL vs. -2.5mg/dL, P<0.001). NASH resolution was associated with significant decreases in TG and TG/HDL ratio compared to those without resolution (TG: -21.1 vs. -2.3mg/dL, P=0.03 and TG/HDL: -0.7 vs. 0.1, P=0.003). Non-HDL-C, LDL and cholesterol decreased over 96weeks in both groups, but there was no significant difference between groups. Treatment group did not impact lipids.
ConclusionsNASH resolution is associated with improvements in TG and HDL but not in other cardiovascular disease risk factors including LDL and non-HDL-C levels. Individuals with resolution of NASH may still be at increased risk of cardiovascular disease. identifier: NCT00063622.
C1 [Corey, K. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vuppalanchi, R.; Cummings, O. W.; Chalasani, N.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Wilson, L. A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Corey, KE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM kcorey@partners.org
RI Vaughn, Ivana/B-6138-2016;
OI Vaughn, Ivana/0000-0002-7201-0289; Vuppalanchi, Raj/0000-0003-0637-1577
FU NIH [K23DK099422-0]; National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) [U01DK061718, U01DK061728, U01DK061731,
U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730,
U01DK061713]; National Center for Advancing Translational Sciences
(NCATS) [UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150,
UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100,
UL1TR000004, UL1TR000423, UL1TR000058, UL1TR000067, UL1TR000454]
FX Declaration of funding interests: KEC receives support from the NIH
K23DK099422-0. The Nonalcoholic Steatohepatitis Clinical Research
Network (NASH CRN) is supported by the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718,
U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737,
U01DK061738, U01DK061730, U01DK061713) and by the National Center for
Advancing Translational Sciences (NCATS) in conduct of NASH CRN Studies
(grants UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424,
UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004,
UL1TR000423, UL1TR000058, UL1TR000067, UL1TR000454).
NR 31
TC 6
Z9 6
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-2813
EI 1365-2036
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD FEB
PY 2015
VL 41
IS 3
BP 301
EP 309
DI 10.1111/apt.13035
PG 9
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA AY8XZ
UT WOS:000347835300006
PM 25429853
ER
PT J
AU Gottlieb, LM
Tirozzi, KJ
Manchanda, R
Burns, AR
Sandel, MT
AF Gottlieb, Laura M.
Tirozzi, Karen J.
Manchanda, Rishi
Burns, Abby R.
Sandel, Megan T.
TI Moving Electronic Medical Records Upstream Incorporating Social
Determinants of Health
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; HOUSEHOLD FOOD INSECURITY;
NATIONAL-HEALTH; CHILDREN; BEHAVIOR; ADOLESCENTS; ADULTHOOD; SECURITY;
RISKS
AB Background: Knowledge of the biological pathways and mechanisms connecting social factors with health has increased exponentially over the past 25 years, yet in most clinical settings, screening and intervention around social determinants of health are not part of standard clinical care. Electronic medical records provide new opportunities for assessing and managing social needs in clinical settings, particularly those serving vulnerable populations.
Purpose: To illustrate the feasibility of capturing information and promoting interventions related to social determinants of health in electronic medical records.
Methods: Three case studies were examined in which electronic medical records have been used to collect data and address social determinants of health in clinical settings.
Results: From these case studies, we identified multiple functions that electronic medical records can perform to facilitate the integration of social determinants of health into clinical systems, including screening, triaging, referring, tracking, and data sharing.
Conclusions: If barriers related to incentives, training, and privacy can be overcome, electronic medical record systems can improve the integration of social determinants of health into health care delivery systems. More evidence is needed to evaluate the impact of such integration on health care outcomes before widespread adoption can be recommended. (C) 2015 American Journal of Preventive Medicine
C1 [Gottlieb, Laura M.] Univ Calif San Francisco, Sch Med, Dept Family & Community Med, San Francisco, CA 94118 USA.
[Burns, Abby R.] Univ Calif Berkeley, Sch Social Welf, Berkeley, CA 94720 USA.
[Manchanda, Rishi] HealthBegins, Los Angeles, CA USA.
[Manchanda, Rishi] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Tirozzi, Karen J.] Hlth Leads, Res & Dev, Boston, MA USA.
[Sandel, Megan T.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Hlth Policy, Natl Ctr Med Legal Partnership, Washington, DC USA.
RP Gottlieb, LM (reprint author), Univ Calif San Francisco, Sch Med, 3333 Calif St,Suite 465, San Francisco, CA 94118 USA.
EM gottliebl@chc.ucsf.edu
FU Lisa and John Pritzker Family Fund; Kresge Foundation; Robert Wood
Johnson Foundation
FX Laura Gottlieb's work on this project was supported by the Lisa and John
Pritzker Family Fund. The funding agency played no role in the design
and conduct of the study; collection, management, analysis, and
interpretation of the data; or preparation, review, or approval of the
manuscript. Gottlieb is employed by the University of California, San
Francisco and is Co-Founder of HealthBegins.; Megan Sandel's work on
this project was supported by the Kresge and Robert Wood Johnson
Foundations. Neither funding agency played a role in the design and
conduct of the study; collection, management, analysis, and
interpretation of the data; or preparation, review, or approval of the
manuscript. Sandel is also Medical Director of the National Center for
Medical-Legal Partnership.
NR 26
TC 15
Z9 15
U1 3
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD FEB
PY 2015
VL 48
IS 2
BP 215
EP 218
DI 10.1016/j.amepre.2014.07.009
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA AZ2YY
UT WOS:000348096300015
PM 25217095
ER
PT J
AU Evans, AT
Loeb, KR
Shulman, HM
Hassan, S
Qiu, WC
Hockenbery, DM
Ioannou, GN
Chauncey, TR
Gretch, DR
McDonald, GB
AF Evans, Ashley T.
Loeb, Keith R.
Shulman, Howard M.
Hassan, Sajida
Qiu, Wan Chong
Hockenbery, David M.
Ioannou, George N.
Chauncey, Thomas R.
Gretch, David R.
McDonald, George B.
TI Fibrosing Cholestatic Hepatitis C After Hematopoietic Cell
Transplantation Report of 3 Fatal Cases
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE hepatitis C virus; fibrosing cholestatic hepatitis; hematopoietic cell
transplantation; liver disease; mycophenolate mofetil; in situ
hybridization
ID BONE-MARROW-TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; VIRUS-INFECTION;
LIVER-TRANSPLANTATION; BILIARY OBSTRUCTION; PREVENTION; RECIPIENTS;
DISEASE; COMPLICATIONS; TRANSMISSION
AB Development of liver disease after hematopoietic cell transplantation is common and the causes diverse. Infection by hepatitis C virus (HCV) can be seen in patients who are chronically infected before transplant or from passage of virus from an infected donor; the normal 10-year course of hepatitis C after transplant is one of waxing and waning of serum aminotransferase enzymes, with little morbidity. In the series of 3 patients reported here, the course of hepatitis C was rapidly fatal, with the onset of jaundice at day 60 to 80 after transplant and liver histology typical of fibrosing cholestatic hepatitis (marked bile ductular proliferation, ballooned hepatocytes, and associated collagenous fibrosis centered around ductules). The bile ductular reaction pattern varied from elongated structures without a recognizable lumen to a pattern of cuboidal cells with a clear lumen. There was significant cholestasis with bile within hepatocytes and canalicular bile plugs. In situ HCV RNA hybridization studies from 1 patient showed a robust infection with high levels of HCV-infected hepatocytes and active viral replication. All 3 patients were on immunosuppressive drugs after transplant, including mycophenolate mofetil (MMF), which irreversibly inhibits inosine monophosphate dehydrogenase, on which T and B lymphocytes are dependent. We speculate that fatal fibrosing cholestatic hepatitis C in these cases was related to the immunosuppressive effects of MMF, as we had not recognized this presentation of HCV infection before the introduction of MMF.
C1 [Evans, Ashley T.; Hockenbery, David M.; Ioannou, George N.; Chauncey, Thomas R.; McDonald, George B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Loeb, Keith R.; Shulman, Howard M.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA.
[Qiu, Wan Chong; Gretch, David R.] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA.
[Loeb, Keith R.; Shulman, Howard M.; Hassan, Sajida; Hockenbery, David M.; McDonald, George B.] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98104 USA.
[Ioannou, George N.; Chauncey, Thomas R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP McDonald, GB (reprint author), Fred Hutchinson Canc Res Ctr, Gastroenterol Hepatol Sect D5 114, 1100 Fairview Ave North, Seattle, WA 98109 USA.
EM gmcdonal@fhcrc.org
NR 38
TC 6
Z9 6
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD FEB
PY 2015
VL 39
IS 2
BP 212
EP 220
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA AZ0SP
UT WOS:000347955200008
PM 25517948
ER
PT J
AU Tompkins, RG
AF Tompkins, Ronald G.
TI Survival From Burns in the New Millennium 70 Years' Experience From a
Single Institution
SO ANNALS OF SURGERY
LA English
DT Review
DE burn centers; burns; mortality; survival; verification
ID STANDARD OPERATING PROCEDURES; PROMPT ESCHAR EXCISION; BENCHMARKING
OUTCOMES; PULMONARY-LESIONS; MORTALITY; INJURIES; CHILDREN; THERAPY;
PATIENT
AB Objective: This review explores the series of published analyses from Massachusetts General Hospital to better understand how changes in medical specialization of burn medicine likely enabled the most important increase in survival from burns in the past 70 years.
Background: Seventy years ago, survival from the most serious burn injuries was not possible even in the most advanced countries until critical advances were introduced. Insights into those few medical advances that actually impacted survival might be better understood from the consideration of a continuous series of survival analyses over 7 decades at Massachusetts General Hospital.
Methods: Mortality data from previously reported probit and logit analyses from thousands of patients treated at Massachusetts General Hospital were reviewed. A comparison of mortality from these prior mortality analyses from a more recent multicenter study and a national data set was performed.
Results: The only giant leap forward in survival occurred during the 1970s, with no improvement during either the preceding or subsequent 30-year intervals. Despite the many modern advances that have been added to the care of these patients since 1984, although these may have represented medical progress, these advances did not impact survival.
Conclusions: Survival rates from burn injury may have been maximized by current treatment approaches within medical centers of excellence in burn medicine. Further efforts to improve the quality of life of survivors of burn injury should ultimately have very favorable impact upon the long-term outcomes in these patients who now survive such devastating injuries.
C1 [Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA.
RP Tompkins, RG (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 1302, Boston, MA 02114 USA.
EM rtomp-kins@mgh.harvard.edu
FU National Institute of General Medical Sciences [P50GM021700,
T32GM007035, U54GM062119, R24GM102656, R01GM101401]
FX Supported by the following grants from the National Institute of General
Medical Sciences: P50GM021700, T32GM007035, U54GM062119, R24GM102656,
and R01GM101401. The authors declare no conflicts of interest.
NR 29
TC 8
Z9 8
U1 3
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-4932
EI 1528-1140
J9 ANN SURG
JI Ann. Surg.
PD FEB
PY 2015
VL 261
IS 2
BP 263
EP 268
DI 10.1097/SLA.0000000000000623
PG 6
WC Surgery
SC Surgery
GA AY8AP
UT WOS:000347777100034
PM 24670865
ER
PT J
AU Lawson, EH
Zingmond, DS
Hall, BL
Louie, R
Brook, RH
Ko, CY
AF Lawson, Elise H.
Zingmond, David S.
Hall, Bruce Lee
Louie, Rachel
Brook, Robert H.
Ko, Clifford Y.
TI Comparison Between Clinical Registry and Medicare Claims Data on the
Classification of Hospital Quality of Surgical Care
SO ANNALS OF SURGERY
LA English
DT Article
DE surgery; quality measurement; clinical registry; administrative claims
ID POSTOPERATIVE ADVERSE EVENTS; IMPROVEMENT PROGRAM; ADMINISTRATIVE DATA;
RISK ADJUSTMENT; HEALTH-CARE; NSQIP; ASSOCIATION; MORTALITY; OUTCOMES;
VOLUME
AB Objective: To compare the classification of hospital statistical outlier status as better or worse performance than expected for postoperative complications using Medicare claims versus clinical registry data.
Background: Controversy remains as to the most favorable data source for measuring postoperative complications for pay-for-performance and public reporting polices.
Methods: Patient-level records (2005-2008) were linked between the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) and Medicare inpatient claims. Hospital statistical outlier status for better or worse performance than expected was assessed using each data source for superficial surgical site infection (SSI), deep/organ-space SSI, any SSI, urinary tract infection, pneumonia, sepsis, deep venous thrombosis, pulmonary embolism, venous thromboembolism, and myocardial infarction by developing hierarchical multivariable logistic regression models. Kappa statistics and correlation coefficients assessed agreement between the data sources.
Results: A total of 192 hospitals with 110,987 surgical patients were included. Agreement on hospital rank for complication rates between Medicare claims and ACS-NSQIP was poor-to-moderate (weighted kappa: 0.18-0.48). Of hospitals identified as statistical outliers for better or worse performance by Medicare claims, 26% were also identified as outliers by ACS-NSQIP. Of outliers identified by ACS-NSQIP, 16% were also identified as outliers by Medicare claims. Agreement between the data sources on hospital outlier status classification was uniformly poor (weighted kappa: -0.02-0.34).
Conclusions: Despite using the same statistical methodology with each data source, classification of hospital outlier status as better or worse performance than expected for postoperative complications differed substantially between ACS-NSQIP and Medicare claims.
C1 [Lawson, Elise H.; Ko, Clifford Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.
[Lawson, Elise H.; Hall, Bruce Lee; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA.
[Lawson, Elise H.; Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Zingmond, David S.; Louie, Rachel; Brook, Robert H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Hall, Bruce Lee] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Hall, Bruce Lee] Barnes Jewish Hosp, St Louis, MO 63110 USA.
[Hall, Bruce Lee] Washington Univ, Ctr Hlth Policy, St Louis, MO USA.
[Hall, Bruce Lee] Washington Univ, Olin Business Sch, St Louis, MO USA.
[Hall, Bruce Lee] John Cochran Vet Affairs Med Ctr, Dept Surg, St Louis, MO USA.
[Brook, Robert H.] RAND Corp, Santa Monica, CA USA.
[Brook, Robert H.] UCLA Jonathan & Karin Fielding Sch Publ Hlth, Los Angeles, CA USA.
RP Lawson, EH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA.
EM elawson@mednet.ucla.edu
FU VA Health Services Research and Development program [RWJ 65-020];
American College of Surgeons through the Robert Wood Johnson Foundation
Clinical Scholars Program; Centers for Medicare and Medicaid Services
(CMS)
FX E.H.L.'s time was supported by the VA Health Services Research and
Development program (RWJ 65-020) and the American College of Surgeons
through the Robert Wood Johnson Foundation Clinical Scholars Program.
This study was funded by a contract from the Centers for Medicare and
Medicaid Services (CMS). The remaining authors have nothing to declare.
NR 26
TC 7
Z9 7
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-4932
EI 1528-1140
J9 ANN SURG
JI Ann. Surg.
PD FEB
PY 2015
VL 261
IS 2
BP 290
EP 296
DI 10.1097/SLA.0000000000000707
PG 7
WC Surgery
SC Surgery
GA AY8AP
UT WOS:000347777100038
PM 25569029
ER
PT J
AU Yao, K
Liederbach, E
Tang, R
Lei, L
Czechura, T
Sisco, M
Howard, M
Hulick, PJ
Winchester, DJ
Coopey, SB
Smith, BL
AF Yao, Katharine
Liederbach, Erik
Tang, Rong
Lei, Lan
Czechura, Tomasz
Sisco, Mark
Howard, Michael
Hulick, Peter J.
Winchester, David J.
Coopey, Suzanne B.
Smith, Barbara L.
TI Nipple-Sparing Mastectomy in BRCA1/2 Mutation Carriers: An Interim
Analysis and Review of the Literature
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID BILATERAL PROPHYLACTIC MASTECTOMY; RISK-REDUCING SURGERY; BREAST-CANCER;
AREOLA COMPLEX; FAMILY-HISTORY; FOLLOW-UP; RECONSTRUCTION; REDUCTION;
PREDICTORS; SURVIVAL
AB There are few large-scale studies that have examined outcomes for BRCA1/2 carriers who have undergone nipple-sparing mastectomy (NSM). The objective of our study was to examine incidental cancers, operative complications, and locoregional recurrences in BRCA1/2 mutation carriers who underwent NSM for both risk reduction and cancer treatment.
This was a retrospective review of pathology results and outcomes of 201 BRCA1/2 carriers from two different institutions who underwent NSM from 2007 to 2014.
NSM was performed in 397 breasts of 201 BRCA1/2 carriers. One hundred and twenty-five (62.2 %) patients had a BRCA1 mutation and 76 (37.8 %) had a BRCA2 mutation; 150 (74.6 %) patients underwent NSM for risk reduction and 51 (25.4 %) for cancer. Incidental cancers were found in four (2.7 %) of the 150 risk-reduction patients and two (3.9 %) of the 51 cancer patients. The nipple-areolar complex (NAC) was involved with cancer in three (5.8 %) patients. No prophylactic mastectomy had a positive NAC margin. There was loss of the NAC in seven breasts (1.8 %) and flap necrosis in ten (2.5 %) breasts. With a mean follow-up of 32.6 months (1-76 months), there have been four cancer events-three in cancer patients and one in a risk-reduction patient but none at the NAC.
NSM in BRCA1/2 carriers is associated with a low rate of complications and locoregional recurrence but these patients require long-term follow-up in both the cancer and risk-reduction setting.
C1 [Yao, Katharine; Liederbach, Erik; Czechura, Tomasz; Sisco, Mark; Howard, Michael; Winchester, David J.] NorthShore Univ HealthSyst, Evanston Hosp, Dept Surg, Evanston, IL 60201 USA.
[Hulick, Peter J.] NorthShore Univ HealthSyst, Ctr Med Genet, Dept Med, Evanston, IL USA.
[Tang, Rong; Lei, Lan; Coopey, Suzanne B.; Smith, Barbara L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Yao, Katharine; Sisco, Mark; Howard, Michael; Winchester, David J.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
RP Yao, K (reprint author), NorthShore Univ HealthSyst, Evanston Hosp, Dept Surg, Evanston, IL 60201 USA.
EM kyao@northshore.org
FU Auxiliary of Evanston Hospital ACE Breast Research Fund; Glenbrook
Hospital ACE Breast Research Fund
FX The authors acknowledge the Auxiliary of Evanston and Glenbrook
Hospitals ACE Breast Research Fund for their generous support of this
project through the breast research fellowship program.
NR 31
TC 17
Z9 17
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2015
VL 22
IS 2
BP 370
EP 376
DI 10.1245/s10434-014-3883-3
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA AY8QH
UT WOS:000347817900006
PM 25023546
ER
PT J
AU Sheth, RA
Feldman, AS
Walker, TG
AF Sheth, Rahul A.
Feldman, Adam S.
Walker, T. Gregory
TI Renoduodenal Fistula After Transcatheter Embolization of Renal
Angiomyolipoma
SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
DE Angiomyolipoma; Complication; Embolization
ID ARTERIAL EMBOLIZATION; COMPLICATION
AB Transcatheter embolization of renal angiomyolipomas is a routinely performed, nephron-sparing procedure with a favorable safety profile. Complications from this procedure are typically minor in severity, with postembolization syndrome the most common minor complication. Abscess formation is a recognized but uncommon major complication of this procedure and is presumably due to superinfection of the infarcted tissue after arterial embolization. In this case report, we describe the formation of a renoduodenal fistula after embolization of an angiomyolipoma, complicated by intracranial abscess formation and requiring multiple percutaneous drainage procedures and eventual partial nephrectomy.
C1 [Sheth, Rahul A.; Walker, T. Gregory] Massachusetts Gen Hosp, Div Intervent Radiol, Dept Radiol, Boston, MA 02114 USA.
[Feldman, Adam S.] Massachusetts Gen Hosp, Div Urol, Dept Surg, Boston, MA 02114 USA.
RP Walker, TG (reprint author), Massachusetts Gen Hosp, Div Intervent Radiol, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM tgwalker@partners.org
NR 10
TC 2
Z9 2
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0174-1551
EI 1432-086X
J9 CARDIOVASC INTER RAD
JI Cardiovasc. Interv. Radiol.
PD FEB
PY 2015
VL 38
IS 1
BP 232
EP 235
DI 10.1007/s00270-014-0887-0
PG 4
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AY8RH
UT WOS:000347820600030
PM 24722895
ER
PT J
AU Viaud, S
Daillere, R
Boneca, IG
Lepage, P
Langella, P
Chamaillard, M
Pittet, MJ
Ghiringhelli, F
Trinchieri, G
Goldszmid, R
Zitvogel, L
AF Viaud, S.
Daillere, R.
Boneca, I. G.
Lepage, P.
Langella, P.
Chamaillard, M.
Pittet, M. J.
Ghiringhelli, F.
Trinchieri, G.
Goldszmid, R.
Zitvogel, L.
TI Gut microbiome and anticancer immune response: really hot Sh(star)t!
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Review
ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE
RECEPTORS; GERM-FREE MICE; INDUCED COLITIS; COLON TUMORIGENESIS;
BETA-GLUCURONIDASE; COLORECTAL-CANCER; INNATE IMMUNITY; LUNG-CANCER
AB The impact of gut microbiota in eliciting innate and adaptive immune responses beneficial for the host in the context of effective therapies against cancer has been highlighted recently. Chemotherapeutic agents, by compromising, to some extent, the intestinal integrity, increase the gut permeability and selective translocation of Gram-positive bacteria in secondary lymphoid organs. There, anticommensal pathogenic Th17 T-cell responses are primed, facilitating the accumulation of Th1 helper T cells in tumor beds after chemotherapy as well as tumor regression. Importantly, the redox equilibrium of myeloid cells contained in the tumor microenvironment is also influenced by the intestinal microbiota. Hence, the anticancer efficacy of alkylating agents (such as cyclophosphamide) and platinum salts (oxaliplatin, cis-platin) is compromised in germ-free mice or animals treated with antibiotics. These findings represent a paradigm shift in our understanding of the mode of action of many compounds having an impact on the host-microbe mutualism.
C1 [Viaud, S.; Daillere, R.; Zitvogel, L.] INSERM, Gustave Roussy, U1015, F-94805 Villejuif, France.
[Viaud, S.; Daillere, R.; Zitvogel, L.] Univ Paris Sud, Le Kremlin Bicetre, France.
[Boneca, I. G.] INSERM, Unit Biol & Genet Bacterial Cell Wall, Paris, France.
[Boneca, I. G.] INSERM, Grp Avenir, Paris, France.
[Lepage, P.; Langella, P.] Inst Natl Rech Agronom, Micalis UMR1319, Jouy En Josas, France.
[Lepage, P.; Langella, P.] AgroParisTech, Micalis UMR1319, F-78350 Jouy En Josas, France.
[Chamaillard, M.] Univ Lille Nord France, Lille, France.
[Chamaillard, M.] Inst Pasteur, Ctr Infect & Immun Lille, F-59019 Lille, France.
[Chamaillard, M.] CNRS, Unite Mixte Rech, Lille, France.
[Chamaillard, M.] INSERM, F-59045 Lille, France.
[Pittet, M. J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Pittet, M. J.] Harvard Univ, Sch Med, Boston, MA USA.
[Ghiringhelli, F.] INSERM, Ctr Georges Francois, U866, Dijon, France.
[Ghiringhelli, F.] INSERM, Grp Avenir, Dijon, France.
[Ghiringhelli, F.] Univ Bourgogne, Fac Med, Dijon, France.
[Trinchieri, G.; Goldszmid, R.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Zitvogel, L.] Ctr Invest Clin Biotherapie CICBT 507, Villejuif, France.
RP Zitvogel, L (reprint author), INSERM, Gustave Roussy, U1015, 114 Rue Edouard Vaillant, F-94805 Villejuif, France.
EM laurence.zitvogel@gustaveroussy.fr
RI Chamaillard, Mathias/L-6542-2013; Lepage, Patricia/D-4362-2014; Boneca,
Ivo/H-1677-2014
OI Chamaillard, Mathias/0000-0002-0243-9717; Boneca,
Ivo/0000-0001-8122-509X
FU Institut National du Cancer (INCa); Ligue contre le cancer (LIGUE
labellisee); SIRIC Socrate; LABEX; PACRI Onco-Immunology; European
Research Council [202283]; ISREC Foundation
FX We thank our colleagues from the Gustave Roussy animal facility and
Institut Pasteur axenic mice facility. This work was supported by
Institut National du Cancer (INCa), la Ligue contre le cancer (LIGUE
labellisee), SIRIC Socrate, LABEX and PACRI Onco-Immunology, European
Research Council starting grant (PGN from SHAPE to VIR no. 202283 to
IGB) and ISREC Foundation.
NR 134
TC 19
Z9 21
U1 10
U2 50
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD FEB
PY 2015
VL 22
IS 2
SI SI
BP 199
EP 214
DI 10.1038/cdd.2014.56
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AY9AR
UT WOS:000347842500003
PM 24832470
ER
PT J
AU Matro, JM
Li, T
Cristofanilli, M
Hughes, ME
Ottesen, RA
Weeks, JC
Wong, YN
AF Matro, Jennifer M.
Li, Tianyu
Cristofanilli, Massimo
Hughes, Melissa E.
Ottesen, Rebecca A.
Weeks, Jane C.
Wong, Yu-Ning
TI Inflammatory Breast Cancer Management in the National Comprehensive
Cancer Network: The Disease, Recurrence Pattern, and Outcome
SO CLINICAL BREAST CANCER
LA English
DT Article
DE Brain metastases; Inflammatory breast cancer; Metastatic breast cancer;
Multimodality therapy; Triple negative breast cancer
ID NERVOUS-SYSTEM METASTASES; CIRCULATING TUMOR-CELLS; BRAIN METASTASES;
MULTIMODALITY TREATMENT; PROGNOSTIC FACTORS; NATURAL-HISTORY; SURVIVAL;
CARCINOMA; EPIDEMIOLOGY; SITES
AB IBC is a unique entity with aggressive clinical features, predictable recurrence patterns, and poor prognosis. The high rate of recurrence, especially in the CNS, suggests that new strategies for surveillance and follow-up are needed for earlier detection or prevention of brain metastases.
Background: Inflammatory breast cancer (IBC) is an uncommon clinicopathologic entity characterized by rapid progression and aggressive behavior. We used the National Comprehensive Cancer Network (NCCN) Outcomes Database to characterize recurrence patterns and outcomes. Methods: Patients with newly diagnosed IBC treated between 1999 and 2009 at 12 NCCN institutions were identified, and baseline characteristics were obtained. Patients had multimodality therapy if they received 2 of 3 treatments: surgery, perioperative (neoadjuvant or adjuvant) chemotherapy, or perioperative radiation. The first site of recurrence/metastatic diagnosis was identified. Overall survival was calculated on the basis of stage at diagnosis and receipt of multimodality therapy. Results: We identified 673 patients, of whom 195(29%) had metastatic disease at presentation. Median follow-up was 29 months. Of patients in stage III, 82% received > 1 treatment modality. Among 203 patients in stage III with recurrence, the most frequent sites of first recurrence were bone (28%), central nervous system (CNS), lung, and liver (all 21%). Human epidermal growth factor receptor 2 positive and triple negative subtypes had higher rates of CNS recurrence (P = .001). Median survival was 66 months (95% confidence interval [CI], 54-107) for stage III and 26 months (95% CI, 22-33) for stage IV. Among 82% of patients in stage III receiving multimodality therapy, the median survival was 107 months (95% CI, 71 to not reached). Conclusions: This large, retrospective, multi-institutional study confirms the aggressive clinical features, unique recurrence patterns, and adverse prognosis of IBC. The high rate of CNS recurrence among high-risk subtypes, despite the inflammatory nature of the breast cancer, suggests that new strategies are needed for earlier detection or prevention of brain metastases to improve long-term prognosis.
C1 [Matro, Jennifer M.; Li, Tianyu; Wong, Yu-Ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Cristofanilli, Massimo] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Hughes, Melissa E.; Weeks, Jane C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ottesen, Rebecca A.] City Hope Canc Ctr, Duarte, CA USA.
RP Matro, JM (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
EM Jennifer.matro@uphs.upenn.edu
FU [P30 CA006927]; [K07CA136995-01]; [P50 CA 89393]
FX TL, MC, and N-YW were supported by P30 CA006927. N-YW was also supported
by K07CA136995-01. Data collection was supported by P50 CA 89393 to Dana
Farber Cancer Institute.
NR 36
TC 8
Z9 8
U1 0
U2 8
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1526-8209
EI 1938-0666
J9 CLIN BREAST CANCER
JI Clin. Breast Cancer
PD FEB
PY 2015
VL 15
IS 1
BP 1
EP 7
DI 10.1016/j.clbc.2014.05.005
PG 7
WC Oncology
SC Oncology
GA AZ1QF
UT WOS:000348012400001
PM 25034439
ER
PT J
AU Mayer, EL
Gropper, AB
Harris, L
Gold, JM
Parker, L
Kuter, I
Come, S
Najita, JS
Guo, H
Winer, EP
Burstein, HJ
AF Mayer, Erica L.
Gropper, Adrienne B.
Harris, Lyndsay
Gold, Julie M.
Parker, Leroy
Kuter, Irene
Come, Steven
Najita, Julie S.
Guo, Hao
Winer, Eric P.
Burstein, Harold J.
TI Long-Term Follow-Up After Preoperative Trastuzumab and Chemotherapy for
HER2-Overexpressing Breast Cancer
SO CLINICAL BREAST CANCER
LA English
DT Article
DE Anthracycline; Cardiotoxicity; Neoadjuvant therapy; Pathologic complete
response
ID SURGICAL ADJUVANT BREAST; PATHOLOGICAL COMPLETE RESPONSE; TRIAL
COMPARING DOXORUBICIN; NEOADJUVANT THERAPY; RANDOMIZED-TRIAL; BOWEL
PROJECT; SYSTEMIC THERAPY; PLUS TRASTUZUMAB; NSABP B-31; OPEN-LABEL
AB Documentation of long-term outcomes following HER2-directed therapy is an emerging research area. We conducted a retrospective analysis of survival and toxicity outcomes using data from early trials of neoadjuvant trastuzumab with chemotherapy. We find that the association between pathologic complete response (pCR) and recurrence-free survival (RFS) persists at long-term follow-up, and that rare late cardiotoxicity might occur in patients re-treated with cardiotoxic agents.
Background: Neoadjuvant chemotherapy and trastuzumab is an established treatment for locally advanced HER2-positive breast cancer, providing favorable rates of clinical response and pCR. Minimal data describe long-term outcomes after neoadjuvant HER2-directed therapy. This study aimed to explore long-term efficacy and toxicity after neoadjuvant trastuzumab and chemotherapy for HER2-positive breast cancer. Patients and Methods: Eligible patients participated in 1 of 2 single-arm phase II neoadjuvant trials, receiving either paclitaxel/trastuzumab (TH) or vinorelbine/trastuzumab (NH) for stage II-III HER2-positive disease. Postoperative chemotherapy, with or without trastuzumab, was offered. Charts were reviewed to identify recurrence, death, and treatment-related toxicities. Association of long-term outcomes with baseline characteristics and pathological response to primary therapy was explored. Results: Eighty patients were identified; 33 (41.3%) received TH and 47 (58.8%) received NH. Fourteen (17.5%) had pCR at surgery. Most (96.3%) received anthracycline-based adjuvant chemotherapy; 78.7% of NH patients also received adjuvant trastuzumab. At a median follow-up of 8.8 years, 23 (28.8%) patients have experienced recurrence, with 16 breast cancer-related deaths. Four-year RFS in patients with pCR was 92.9% (95% confidence interval [CI], 79.4%-100%) versus 72.4% without pCR (95% CI, 63.9%-82.1%). All initial symptomatic cardiotoxicity resolved during extended follow-up. New symptomatic cardiotoxicity in long-term follow-up was rare, primarily occurring in patients requiring retreatment with a cardiotoxic agent. Conclusion: Neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer resulted in favorable long-term survival with minimal late toxicity. Trends in this data set suggest an association between pCR and improved long-term RFS. Retreatment with cardiotoxic agents might increase risk of late cardiotoxicity.
C1 [Mayer, Erica L.; Parker, Leroy; Najita, Julie S.; Guo, Hao; Winer, Eric P.; Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA.
[Gropper, Adrienne B.] Brigham & Womens Hosp, Boston, MA USA.
[Harris, Lyndsay] Case Comprehens Canc Ctr, Cleveland, OH USA.
[Gold, Julie M.] Mt Kisco Med Grp, Mt Kisco, NY USA.
[Kuter, Irene] Massachusetts Gen Hosp, Boston, MA USA.
[Come, Steven] Beth Israel Deaconess Med Ctr, Boston, MA USA.
RP Mayer, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
EM emayer@partners.org
RI Guo, Hao/E-8921-2015
OI Guo, Hao/0000-0003-1658-0989
NR 32
TC 3
Z9 3
U1 3
U2 13
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1526-8209
EI 1938-0666
J9 CLIN BREAST CANCER
JI Clin. Breast Cancer
PD FEB
PY 2015
VL 15
IS 1
BP 24
EP 30
DI 10.1016/j.clbc.2014.07.010
PG 7
WC Oncology
SC Oncology
GA AZ1QF
UT WOS:000348012400004
PM 25205424
ER
PT J
AU Priyadharshini, B
Turka, LA
AF Priyadharshini, Bhavana
Turka, Laurence A.
TI T-cell energy metabolism as a controller of cell fate in transplantation
SO CURRENT OPINION IN ORGAN TRANSPLANTATION
LA English
DT Review
DE AMP-activated protein kinase; immunometabolism; mammalian target of
rapamycin; regulatory T cells; transplantation
ID DENDRITIC CELLS; ACID-METABOLISM; TRYPTOPHAN CATABOLISM; EFFECTOR
FUNCTION; ACTIVATION; MTOR; MEMORY; DIFFERENTIATION; TOLERANCE; PATHWAYS
AB Purpose of review
To highlight some of the recent developments in the novel field of immunometabolism and the therapeutic potential of the many regulatory components of this immunometabolic network for transplantation.
Recent findings
In response to cytokines, changes in nutrients, and other alterations in the local milieu, immune cells are capable of changing their internal metabolic pathways to meet their energy demands. Recent studies demonstrate that activated T effectors (Th1 and Th17) are supported by aerobic glycolysis, whereas regulatory T cells and CD8 memory T cells favor fatty acid oxidation and lipid biosynthesis through mitochondrial oxidative phosphorylation. These bioenergetic processes are dependent upon the activation of metabolic sensors such as mammalian target of rapamycin and AMP-activated protein kinase, respectively, indicating that the cross-talk between immunity and metabolism can shape the fate and function of immune cells. Finally, exciting new studies suggest that differences in the bioenergetic mechanisms within the various immune subsets may selectively be exploited for regulating the immune responses.
Summary
In this review, we will discuss the metabolic signatures adopted by various immune cells during tolerance versus immunity and the promising avenues that can be modulated by targeting metabolic pathways with either nutrition or pharmacological intervention for establishing long-term transplantation tolerance.
C1 [Priyadharshini, Bhavana; Turka, Laurence A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Ctr Transplantat Sci, Boston, MA USA.
RP Turka, LA (reprint author), 149,13th St,Room 5101, Boston, MA 02129 USA.
EM lturka@partners.org
FU NIH [R21AI105607, P01HL018646]
FX This work was funded by the NIH grants R21AI105607 and P01HL018646 (to
L.A.T.).
NR 53
TC 6
Z9 6
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1087-2418
EI 1531-7013
J9 CURR OPIN ORGAN TRAN
JI Curr. Opin. Organ Transpl.
PD FEB
PY 2015
VL 20
IS 1
BP 21
EP 28
DI 10.1097/MOT.0000000000000149
PG 8
WC Transplantation
SC Transplantation
GA AY7DD
UT WOS:000347720600004
PM 25563988
ER
PT J
AU Granados, JMM
Benichou, G
Kawai, T
AF Granados, Jose M. M.
Benichou, Gilles
Kawai, Tatsuo
TI Hematopoietic stem cell infusion/transplantation for induction of
allograft tolerance
SO CURRENT OPINION IN ORGAN TRANSPLANTATION
LA English
DT Review
DE allograft tolerance; chimerism; donor bone marrow transplantation;
hematopoietic stem cell transplantation; kidney transplantation;
vascularized composite allograft
ID BONE-MARROW-TRANSPLANTATION; NONINHERITED MATERNAL ANTIGENS;
TOTAL-LYMPHOID IRRADIATION; MISMATCHED RENAL-TRANSPLANTATION; MIXED
ALLOGENEIC CHIMERISM; MEMORY T-CELLS; NONHUMAN-PRIMATES; DENDRITIC
CELLS; MAINTENANCE IMMUNOSUPPRESSION; KIDNEY-TRANSPLANTATION
AB Purpose of review
The present review updates the current status of basic, preclinical, and clinical research on donor hematopoietic stem cell infusion for allograft tolerance induction.
Recent findings
Recent basic studies in mice provide evidence of significant involvement of both central deletional and peripheral regulatory mechanisms in induction and maintenance of allograft tolerance effected through a mixed chimerism approach with donor hematopoietic stem cell infusion. The presence of heterologous memory T cells in primates hampers the induction of persistent chimerism. Durable mixed chimerism, however, now has been recently induced in inbred major histocompatibility complex-mismatched swine, resulting in tolerance of vascularized composite tissue allografts. In clinical transplantation, allograft tolerance has been achieved in human leukocyte antigen-mismatched kidney transplantation after the induction of transient mixed chimerism or persistent full donor chimerism.
Summary
Tolerance induction in clinical kidney transplantation has been achieved by donor hematopoietic stem cell infusion. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, and to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications.
C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Ctr Transplantat Sci, Boston, MA USA.
RP Kawai, T (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, MGH White 521,55 Fruit St, Boston, MA 02114 USA.
EM tkawai@mgh.harvard.edu
FU NIH [AI102405-01, PO-1 HL 18646-25]
FX The present article was supported in part by NIH AI102405-01, PO-1 HL
18646-25.
NR 97
TC 5
Z9 5
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1087-2418
EI 1531-7013
J9 CURR OPIN ORGAN TRAN
JI Curr. Opin. Organ Transpl.
PD FEB
PY 2015
VL 20
IS 1
BP 49
EP 56
DI 10.1097/MOT.0000000000000159
PG 8
WC Transplantation
SC Transplantation
GA AY7DD
UT WOS:000347720600008
PM 25563992
ER
PT J
AU Wasfy, MM
Baggish, AL
AF Wasfy, Meagan M.
Baggish, Aaron L.
TI T-wave inversions in athletes: a sheep in wolf's clothing?
SO HEART
LA English
DT Editorial Material
ID EUROPEAN-SOCIETY; CRITERIA; CARDIOLOGY
C1 [Wasfy, Meagan M.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA.
[Baggish, Aaron L.] Harvard Univ, Hlth Serv, Cambridge, MA 02138 USA.
RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, 55 Fruit St,Yawkey Suite 5B, Boston, MA 02114 USA.
EM abaggish@partners.org
NR 8
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD FEB 1
PY 2015
VL 101
IS 3
BP 167
EP 168
DI 10.1136/heartjnl-2014-306988
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AZ1BK
UT WOS:000347975200003
PM 25432978
ER
PT J
AU Berny-Lang, MA
Darling, CE
Frelinger, AL
Barnard, MR
Smith, CS
Michelson, AD
AF Berny-Lang, M. A.
Darling, C. E.
Frelinger, A. L., III
Barnard, M. R.
Smith, C. S.
Michelson, A. D.
TI Do immature platelet levels in chest pain patients presenting to the
emergency department aid in the diagnosis of acute coronary syndrome?
SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
LA English
DT Article
DE Acute coronary syndrome; emergency medicine; immature platelet fraction;
myocardial infarction; platelets
ID DUAL ANTIPLATELET THERAPY; MYOCARDIAL-INFARCTION; RETICULATED PLATELETS;
ARTERY-DISEASE; HEART-DISEASE; VOLUME; SIZE; FRACTION; TURNOVER; ASPIRIN
AB IntroductionEarly and accurate identification of acute coronary syndrome (ACS) vs. noncardiac chest pain in patients presenting to the emergency department (ED) is problematic and new diagnostic markers are needed. Previous studies reported that elevated mean platelet volume (MPV) is associated with ACS and predictive of cardiovascular risk. MPV is closely related to the immature platelet fraction (IPF), and recent studies have suggested that IPF may be a more sensitive marker of ACS than MPV. The objective of the present study was to determine whether the measurement of IPF assists in the diagnosis of ACS in patients presenting to the ED with chest pain.
MethodsIn this single-center, prospective, cross-sectional study, adult patients presenting to the ED with chest pain and/or suspected ACS were considered for enrollment. Blood samples from 236 ACS-negative and 44 ACS-positive patients were analyzed in a Sysmex XE-2100 for platelet count, MPV, IPF, and the absolute count of immature platelets (IPC).
ResultsTotal platelet counts, MPV, IPF, and IPC were not statistically different between ACS-negative and ACS-positive patients. The IPF was 4.62.7% and 5.0 +/- 2.8% (mean +/- SD, P=0.24), and the IPC was 10.0 +/- 4.6 and 11.5 +/- 7.5x10(3)/L (P=0.27) for ACS-negative and ACS-positive patients, respectively.
ConclusionIn 280 patients presenting to the ED with chest pain and/or suspected ACS, no differences in IPF, IPC or MPV were observed in ACS-negative vs. ACS-positive patients, suggesting that these parameters do not assist in the diagnosis of ACS.
C1 [Berny-Lang, M. A.; Frelinger, A. L., III; Barnard, M. R.; Michelson, A. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Boston Childrens Hosp, Ctr Platelet Res Studies,Div Hematol Oncol, Boston, MA 02115 USA.
[Darling, C. E.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA.
[Smith, C. S.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA.
RP Michelson, AD (reprint author), Boston Childrens Hosp, Karp 08213,300 Longwood Ave, Boston, MA 02115 USA.
EM alan.michelson@childrens.harvard.edu
FU NIH [5T32HL007574-31]; Society for Academic Emergency Medicine (SAEM),
Des Plaines, IL; Sysmex Corporation
FX The authors thank Michelle Maynard for excellent technical assistance.
MAB was supported by an NIH T32 Training Grant (5T32HL007574-31). CED
was supported in part by a Research Training Grant from the Society for
Academic Emergency Medicine (SAEM), Des Plaines, IL. This study was
funded in part by a grant from Sysmex Corporation; however, Sysmex
Corporation had no role in the study design; in the collection, analysis
and interpretation of data; in the writing of the manuscript; or in the
decision to submit the manuscript for publication.
NR 34
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1751-5521
EI 1751-553X
J9 INT J LAB HEMATOL
JI Int. J. Lab. Hematol.
PD FEB
PY 2015
VL 37
IS 1
BP 112
EP 119
DI 10.1111/ijlh.12250
PG 8
WC Hematology
SC Hematology
GA AY9NB
UT WOS:000347876600020
PM 24806286
ER
PT J
AU Goyal, L
Wadlow, RC
Blaszkowsky, LS
Wolpin, BM
Abrams, TA
McCleary, NJ
Sheehan, S
Sundaram, E
Karol, MD
Chen, J
Zhu, AX
AF Goyal, Lipika
Wadlow, Raymond C.
Blaszkowsky, Lawrence S.
Wolpin, Brian M.
Abrams, Thomas A.
McCleary, Nadine Jackson
Sheehan, Susan
Sundaram, Eamala
Karol, Michael D.
Chen, John
Zhu, Andrew X.
TI A phase I and pharmacokinetic study of ganetespib (STA-9090) in advanced
hepatocellular carcinoma
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Hepatocellular carcinoma; STA-9090; Ganetespib; Phase I; Heat shock
protein inhibitors; Pharmacokinetics; Hepatic dysfunction
ID CELL LUNG-CANCER; HSP90 INHIBITOR; HUMAN LIVER; SORAFENIB; THERAPY;
SAFETY; GELDANAMYCIN; DEGRADATION; DOXORUBICIN; EXPRESSION
AB Background Ganetespib (STA-9090) is an Hsp90 inhibitor that downregulates VEGFR, c-MET, HER2, IGF-IR, EGFR, and other Hsp90 client proteins involved in hepatocarcinogenesis, thereby making it an attractive therapy for HCC. This Phase I study was performed to establish the safety, tolerability, recommended Phase 2 dose (RP2D), and preliminary clinical activity of ganetespib in previously treated patients with advanced HCC. Methods Patients with advanced HCC, Child-Pugh A cirrhosis, progression on or intolerance to sorafenib, and ECOG PS a parts per thousand currency signaEuro parts per thousand 1 were enrolled in a standard 3x3 dose escalation study at doses of 100 mg/m(2), 150 mg/m(2), and 200 mg/m(2) IV given on days 1, 8, and 15 of each 28-day cycle. Objective response by RECIST version 1.1 criteria was evaluated by CT/MRI every 8 weeks. Results Fourteen patients were enrolled in this trial and received at least one dose of the study drug. Of the 14 patients: median age, 57 years old; male 71 %; Asian 36 %; HCC etiology (HBV 36 %, HCV 43 %, Hemachromatosis 7 %, unknown 21 %); Child Pugh Class (A 93 %, B 7 %); median number of prior treatments 2; median baseline AFP 70.1 ng/mL. The RP2D was determined to be 200 mg/m(2). The most commonly seen AEs were diarrhea (93 %), fatigue (71 %), AST elevation (64 %), and hyperglycemia (64 %). The most common Gr 3/4 AEs were hyperglycemia (21 %) and lipasemia (21 %). One (7 %) patient had a fatal AE, septic shock, within 30 days of receiving the study drug. One dose-limiting toxicity, grade 3 lipasemia, was observed at the 100 mg/m(2) dose. Pharmacokinetics studies showed a t(1/2), CL, T-max, and V-ss of 6.45 h, 48.28 L/h (25.56 L/h/m(2)), 0.76 h, and 191 L (100.4 L/m(2)), respectively. No objective responses were seen; one patient (7 %) had stable disease at 16 weeks. Median time to progression was 1.8 months, and median overall survival was 7.2 months. Conclusion Ganetespib had a manageable safety profile in patients with advanced HCC who had progressed on at least one line of systemic therapy. The pharmacokinetic profile showed that ganetespib exposure in patients with mild hepatic dysfunction is similar to that seen in patients with normal liver function. Ganetespib showed limited clinical benefit in patients with advanced HCC in this phase I trial.
C1 [Goyal, Lipika; Blaszkowsky, Lawrence S.; Sheehan, Susan; Sundaram, Eamala; Zhu, Andrew X.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Wolpin, Brian M.; Abrams, Thomas A.; McCleary, Nadine Jackson] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Goyal, Lipika; Blaszkowsky, Lawrence S.; Wolpin, Brian M.; Abrams, Thomas A.; McCleary, Nadine Jackson; Zhu, Andrew X.] Harvard Univ, Sch Med, Boston, MA USA.
[Wadlow, Raymond C.] Virginia Canc Specialists, Fairfax, VA USA.
[Karol, Michael D.; Chen, John] Synta Pharmaceut Corp, Lexington, MA USA.
RP Goyal, L (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,LH PB 220, Boston, MA 02114 USA.
EM lgoyal@partners.org
FU Synta Pharmaceuticals
FX We received research support for this trial from Synta Pharmaceuticals.
NR 37
TC 7
Z9 7
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD FEB
PY 2015
VL 33
IS 1
BP 128
EP 137
DI 10.1007/s10637-014-0164-8
PG 10
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AZ0QI
UT WOS:000347949400014
PM 25248753
ER
PT J
AU Schiff, D
Kesari, S
de Groot, J
Mikkelsen, T
Drappatz, J
Coyle, T
Fichtel, L
Silver, B
Walters, I
Reardon, D
AF Schiff, David
Kesari, Santosh
de Groot, John
Mikkelsen, Tom
Drappatz, Jan
Coyle, Thomas
Fichtel, Lisa
Silver, Bruce
Walters, Ian
Reardon, David
TI Phase 2 study of CT-322, a targeted biologic inhibitor of VEGFR-2 based
on a domain of human fibronectin, in recurrent glioblastoma
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Glioblastoma; Adnectin; Anti-angiogenic therapy; VEGF receptor;
Irinotecan
ID BEVACIZUMAB PLUS IRINOTECAN; ADNECTIN INHIBITOR; TRIAL
AB VEGF signaling through VEGFR-2 is the major factor in glioblastoma angiogenesis. CT-322, a pegylated protein engineered from the 10th type III human fibronectin domain, binds the VEGFR-2 extracellular domain with high specificity and affinity to block VEGF-induced VEGFR-2 signaling. This study evaluated CT-322 in an open-label run-in/phase 2 setting to assess its efficacy and safety in recurrent glioblastoma. Eligible patients had 1st, 2nd or 3rd recurrence of glioblastoma with measurable tumor on MRI and no prior anti-angiogenic therapy. The initial CT-322 dose was 1 mg/kg IV weekly, with plans to escalate subsequent patients to 2 mg/kg weekly if tolerated; within each CT-322 dose cohort, patients were randomized to +/- irinotecan IV semiweekly. The primary endpoint was 6-month progression-free survival (PFS-6). Sixty-three patients with a median age of 56 were treated, the majority at first recurrence. One-third experienced serious adverse events, of which four were at least possibly related to study treatment (two intracranial hemorrhages and two infusion reactions). Twenty-nine percent of subjects developed treatment-emergent hypertension. The PFS-6 rate in the CT-322 monotherapy groups was 18.6 and 0.0 % in the 1 and 2 mg/kg treatment groups, respectively; results from the 2 mg/kg group indicated that the null hypothesis that PFS-6 a parts per thousand currency sign12 % could not be rejected. The study was terminated prior to reaching the planned enrollment for all treatment groups because data from the completed CT-322 2 mg/kg monotherapy treatment arm revealed insufficient efficacy. Despite biological activity and a tolerable side effect profile, CT-322 failed to meet the prespecified threshold for efficacy in recurrent glioblastoma.
C1 [Schiff, David] Univ Virginia, Neurooncol Ctr, Charlottesville, VA 22908 USA.
[Kesari, Santosh; Drappatz, Jan] Dana Farber Canc Inst, Boston, MA 02115 USA.
[de Groot, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA.
[Coyle, Thomas] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Fichtel, Lisa] South Texas Oncol & Hematol, San Antonio, TX USA.
[Silver, Bruce] Adnexus, Waltham, MA USA.
[Walters, Ian] Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
[Reardon, David] Duke Univ, Durham, NC USA.
RP Schiff, D (reprint author), Univ Virginia, Neurooncol Ctr, Box 800432, Charlottesville, VA 22908 USA.
EM ds4jd@virginia.edu
FU Bristol-Myers-Squibb; Adnexus
FX Ian Walters was employed by and owned stock in Bristol-Myers-Squibb at
the time of the study, and Bruce Silver was a paid consultant to
Bristol-Myers-Squibb and Adnexus. The remaining authors report no
conflict of interest.
NR 19
TC 8
Z9 8
U1 0
U2 10
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD FEB
PY 2015
VL 33
IS 1
BP 247
EP 253
DI 10.1007/s10637-014-0186-2
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AZ0QI
UT WOS:000347949400027
PM 25388940
ER
PT J
AU Courtney, CL
Ethun, KF
Villinger, F
Ruprecht, RM
Byrareddy, SN
AF Courtney, Cynthia L.
Ethun, Kelly F.
Villinger, Francois
Ruprecht, Ruth M.
Byrareddy, Siddappa N.
TI Massive occlusive thrombosis of the pulmonary artery in pigtailed
macaques chronically infected with R5-tropic simian-human
immunodeficiency virus
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article
DE pulmonary arterial hypertension; SHIV; SIV
ID VASCULAR-LESIONS; HYPERTENSION; REPLICATION; SIV; ENV
AB BackgroundPulmonary arterial hypertension (PAH) has been identified as a serious complication of HIV infection.
Methods and ResultsHere, we report sudden death in two pigtailed macaques (Macaca nemestrina) chronically infected (similar to 1-2years post-infection) with an R5 SHIV strain. At necropsy, total occlusion of the pulmonary artery by a large fibrin thrombus was present in both animals.
ConclusionThis report describes pulmonary vascular lesions similar to PAH in R5 SHIV-infected pigtail macaques.
C1 [Courtney, Cynthia L.; Ethun, Kelly F.; Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Courtney, Cynthia L.; Ethun, Kelly F.; Villinger, Francois; Byrareddy, Siddappa N.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Courtney, Cynthia L.; Ethun, Kelly F.; Villinger, Francois; Byrareddy, Siddappa N.] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
[Ruprecht, Ruth M.] Texas Biomed Res Inst, San Antonio, TX USA.
[Ruprecht, Ruth M.; Byrareddy, Siddappa N.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ruprecht, Ruth M.; Byrareddy, Siddappa N.] Harvard Univ, Sch Med, Boston, MA USA.
RP Byrareddy, SN (reprint author), Emory Univ, Dept Pathol & Lab Med, 101 Woodruff Circle,Room 2337A, Atlanta, GA 30322 USA.
EM siddappa.n.byrareddy@emory.edu
FU NIH [R21 NS063877, R37 AI034266, P51OD11132]
FX The authors thank the animal care and pathology staff of the YNPRC for
their excellent care of the animals and technical support for this
study. This work was supported by NIH grants R21 NS063877 and R37
AI034266 to RMR as well as base grant P51OD11132 to the Yerkes National
Primate Research Center.
NR 13
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0047-2565
EI 1600-0684
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD FEB
PY 2015
VL 44
IS 1
BP 35
EP 39
DI 10.1111/jmp.12142
PG 5
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA AY7HU
UT WOS:000347732500005
PM 25174584
ER
PT J
AU Smith, JA
Stallons, LJ
Collier, JB
Chavin, KD
Schnellmann, RG
AF Smith, Joshua A.
Stallons, L. Jay
Collier, Justin B.
Chavin, Kenneth D.
Schnellmann, Rick G.
TI Suppression of Mitochondrial Biogenesis through Toll-Like Receptor
4-Dependent Mitogen-Activated Protein Kinase Kinase/Extracellular
Signal-Regulated Kinase Signaling in Endotoxin-Induced Acute Kidney
Injury
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ACUTE-RENAL-FAILURE; PERITUBULAR CAPILLARY DYSFUNCTION;
ISCHEMIA-REPERFUSION INJURY; CRITICALLY-ILL PATIENTS; MEK1/2 INHIBITOR;
TNF-ALPHA; SEPSIS; CELLS; LPS; INFLAMMATION
AB Although disruption of mitochondrial homeostasis and biogenesis (MB) is a widely accepted pathophysiologic feature of sepsis-induced acute kidney injury (AKI), the molecular mechanisms responsible for this phenomenon are unknown. In this study, we examined the signaling pathways responsible for the suppression of MB in a mouse model of lipopolysaccharide (LPS)-induced AKI. Downregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), a master regulator of MB, was noted at the mRNA level at 3 hours and protein level at 18 hours in the renal cortex, and was associated with loss of renal function after LPS treatment. LPS-mediated suppression of PGC-1 alpha led to reduced expression of downstream regulators of MB and electron transport chain proteins along with a reduction in renal cortical mitochondrial DNA content. Mechanistically, Toll-like receptor 4 (TLR4) knockout mice were protected from renal injury and disruption of MB after LPS exposure. Immunoblot analysis revealed activation of tumor progression locus 2/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (TPL-2/MEK/ERK) signaling in the renal cortex by LPS. Pharmacologic inhibition of MEK/ERK signaling attenuated renal dysfunction and loss of PGC-1 alpha, and was associated with a reduction in proinflammatory cytokine (e.g., tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta) expression at 3 hours after LPS exposure. Neutralization of TNF-alpha also blocked PGC-1 alpha suppression, but not renal dysfunction, after LPS-induced AKI. Finally, systemic administration of recombinant tumor necrosis factor-alpha alone was sufficient to produce AKI and disrupt mitochondrial homeostasis. These findings indicate an important role for the TLR4/MEK/ERK pathway in both LPS-induced renal dysfunction and suppression of MB. TLR4/MEK/ERK/TNF-alpha signaling may represent a novel therapeutic target to prevent mitochondrial dysfunction and AKI produced by sepsis.
C1 [Smith, Joshua A.; Stallons, L. Jay; Collier, Justin B.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA.
[Chavin, Kenneth D.] Med Univ S Carolina, Div Transplant Surg, Dept Surg, Charleston, SC 29425 USA.
[Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA.
RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Drug Discovery & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA.
EM schnell@musc.edu
FU National Institutes of Health National Institute of General Medical
Sciences [GM084147, P20-GM103542-02]; National Institutes of Health
National Center for Research Resources [UL1-RR029882, C06-RR015455];
Biomedical Laboratory Research and Development Program of the Department
of Veterans Affairs [5I01 BX-000851]; South Carolina Clinical and
Translational Research Institute at the Medical University of South
Carolina
FX This work was supported in part by the National Institutes of Health
National Institute of General Medical Sciences [Grants GM084147 (to
R.G.S.) and P20-GM103542-02 (to South Carolina COBRE in Oxidants, Redox
Balance, and Stress Signaling]; the National Institutes of Health
National Center for Research Resources [Grant UL1-RR029882]; the
Biomedical Laboratory Research and Development Program of the Department
of Veterans Affairs [Grant 5I01 BX-000851 (to R.G.S.)]; and the South
Carolina Clinical and Translational Research Institute at the Medical
University of South Carolina. Animal facilities were funded by the
National Institutes of Health National Center for Research Resources
[Grant C06-RR015455].
NR 59
TC 11
Z9 11
U1 0
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD FEB
PY 2015
VL 352
IS 2
BP 346
EP 357
DI 10.1124/jpet.114.221085
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AY8RY
UT WOS:000347822200018
PM 25503387
ER
PT J
AU Chevalier, L
Goldfarb, E
Miller, J
Hoeppner, B
Gorrindo, T
Birnbaum, RJ
AF Chevalier, Lydia
Goldfarb, Elizabeth
Miller, Jessica
Hoeppner, Bettina
Gorrindo, Tristan
Birnbaum, Robert J.
TI Gaps in Preparedness of Clergy and Healthcare Providers to Address
Mental Health Needs of Returning Service Members
SO JOURNAL OF RELIGION & HEALTH
LA English
DT Article
DE Educational needs assessment; Mixed methods; Post-traumatic stress
disorder; Service members; Traumatic brain injury
ID POSTTRAUMATIC-STRESS-DISORDER; CORONARY-HEART-DISEASE; VETERANS;
DECISIONS; AFGHANISTAN; DISPARITIES; DEPRESSION; TRAUMA; FAITH; PTSD
AB To elucidate gaps in the preparedness of clergy and healthcare providers to care for service members (SM) with deployment-related mental health needs. Participants identified clinically relevant symptoms in a standardized video role play of a veteran with deployment-related mental health needs and discussed their preparedness to deal with SM. Clergy members identified suicide and depression most often, while providers identified difficulty sleeping, low energy, nightmares and irritability. Neither clergy nor providers felt prepared to minister to or treat SM with traumatic brain injury. Through a mixed methods approach, we identified gaps in preparedness of clergy and healthcare providers in dealing with the mental health needs of SM.
C1 [Chevalier, Lydia; Goldfarb, Elizabeth; Miller, Jessica; Hoeppner, Bettina; Gorrindo, Tristan; Birnbaum, Robert J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Hoeppner, Bettina; Gorrindo, Tristan; Birnbaum, Robert J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Chevalier, L (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Ste 744, Boston, MA 02114 USA.
EM lydia.chevalier5@gmail.com
NR 26
TC 1
Z9 1
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-4197
EI 1573-6571
J9 J RELIG HEALTH
JI J. Relig. Health
PD FEB
PY 2015
VL 54
IS 1
BP 327
EP 338
DI 10.1007/s10943-014-9917-0
PG 12
WC Public, Environmental & Occupational Health; Religion
SC Public, Environmental & Occupational Health; Religion
GA AY9UL
UT WOS:000347895800027
PM 25112409
ER
PT J
AU Maker, AV
Carrara, S
Jamieson, NB
Pelaez-Luna, M
Lennon, AM
Dal Molin, M
Scarpa, A
Frulloni, L
Brugge, WR
AF Maker, Ajay V.
Carrara, Silvia
Jamieson, Nigel B.
Pelaez-Luna, Mario
Lennon, Anne Marie
Dal Molin, Marco
Scarpa, Aldo
Frulloni, Luca
Brugge, William R.
TI Cyst Fluid Biomarkers for Intraductal Papillary Mucinous Neoplasms of
the Pancreas: A Critical Review from the International Expert Meeting on
Pancreatic Branch-Duct-Intraductal Papillary Mucinous Neoplasms
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Review
ID FINE-NEEDLE-ASPIRATION; HELICOBACTER-PYLORI INFECTION;
NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; BIOLOGICAL BEHAVIOR; PRECURSOR
LESIONS; GNAS MUTATIONS; MESSENGER-RNA; CORE PROTEINS; CELL-LINES
C1 [Maker, Ajay V.] Univ Illinois, Dept Surg, Div Surg Oncol, Chicago, IL 60680 USA.
[Carrara, Silvia] Ist Clin Humanitas, Digest Endoscopy Unit, Rozzano, Italy.
[Jamieson, Nigel B.] Univ Glasgow, Dept Surg, Glasgow G12 8QQ, Lanark, Scotland.
[Pelaez-Luna, Mario] Univ Nacl Autonoma Mexico, Dept Gastroenterol, Inst Nacl Ciencias Med & Nutr, Sch Med, Mexico City 04510, DF, Mexico.
[Lennon, Anne Marie] Johns Hopkins Univ, Dept Med, Div Gastroenterol, Baltimore, MD USA.
[Dal Molin, Marco] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Scarpa, Aldo] Univ Verona, Dept Pathol & Diagnost, I-37100 Verona, Italy.
[Frulloni, Luca] Univ Verona, Dept Med, Gastroenterol Sect, I-37100 Verona, Italy.
[Brugge, William R.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA.
RP Maker, AV (reprint author), 835 S Wolcott Ave MC 790, Chicago, IL 60612 USA.
EM amaker@uic.edu
RI scarpa, aldo/K-6832-2016;
OI scarpa, aldo/0000-0003-1678-739X; Frulloni, Luca/0000-0001-7417-2655
FU NCI NIH HHS [R01CA176828, K08 CA190855, R01 CA176828]
NR 102
TC 14
Z9 15
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
EI 1879-1190
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD FEB
PY 2015
VL 220
IS 2
BP 243
EP 253
DI 10.1016/j.jamcollsurg.2014.11.001
PG 11
WC Surgery
SC Surgery
GA AY9XX
UT WOS:000347902000014
PM 25592469
ER
PT J
AU Lee, KH
Haneuse, S
Schrag, D
Dominici, F
AF Lee, Kyu Ha
Haneuse, Sebastien
Schrag, Deborah
Dominici, Francesca
TI Bayesian semiparametric analysis of semicompeting risks data:
investigating hospital readmission after a pancreatic cancer diagnosis
SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS
LA English
DT Article
DE Bayesian survival analysis; Illness-death models; Reversible jump Markov
chain Monte Carlo methods; Semicompeting risks; Shared frailty
ID COMPETING RISKS; MULTISTATE MODELS; RECURRENT EVENTS; TERMINAL EVENTS;
UNITED-STATES; ASSOCIATION; SURVIVAL; DEATH
AB In the USA, the Centers for Medicare and Medicaid Services use 30-day readmission, following hospitalization, as a proxy outcome to monitor quality of care. These efforts generally focus on treatable health conditions, such as pneumonia and heart failure. Expanding quality-of-care systems to monitor conditions for which treatment options are limited or non-existent, such as pancreatic cancer, is challenging because of the non-trivial force of mortality; 30-day mortality for pancreatic cancer is approximately 30%. In the statistical literature, data that arise when the observation of the time to some non-terminal event is subject to some terminal event are referred to as semicompeting risks data'. Given such data, scientific interest may lie in at least one of three areas: estimation or inference for regression parameters, characterization of dependence between the two events and prediction given a covariate profile. Existing statistical methods focus almost exclusively on the first of these; methods are sparse or non-existent, however, when interest lies with understanding dependence and performing prediction. We propose a Bayesian semiparametric regression framework for analysing semicompeting risks data that permits the simultaneous investigation of all three of the aforementioned scientific goals. Characterization of the induced posterior and posterior predictive distributions is achieved via an efficient Metropolis-Hastings-Green algorithm, which has been implemented in an R package. The framework proposed is applied to data on 16051 individuals who were diagnosed with pancreatic cancer between 2005 and 2008, obtained from Medicare part A. We found that increased risk for readmission is associated with a high comorbidity index, a long hospital stay at initial hospitalization, non-white race, being male and discharge to home care.
C1 [Lee, Kyu Ha; Haneuse, Sebastien; Dominici, Francesca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Lee, KH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
EM klee@hsph.harvard.edu
FU National Cancer Institute [P01 CA134294-02]; National Institutes of
Health [ES012044, K18 HS021991, R01 CA181360-01]
FX We thank Dr Yun Wang at the Harvard School of Public Heath for
assistance and consultation on the Medicare pancreatic cancer data set.
We are also grateful for helpful comments from the Joint Editor, an
Associate Editor and two referees. This work was supported by National
Cancer Institute grant P01 CA134294-02 and National Institutes of Health
grants ES012044, K18 HS021991 and R01 CA181360-01.
NR 42
TC 7
Z9 7
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0035-9254
EI 1467-9876
J9 J R STAT SOC C-APPL
JI J. R. Stat. Soc. Ser. C-Appl. Stat.
PD FEB
PY 2015
VL 64
IS 2
BP 253
EP 273
DI 10.1111/rssc.12078
PG 21
WC Statistics & Probability
SC Mathematics
GA AY9TM
UT WOS:000347893400002
PM 25977592
ER
PT J
AU Elias, PZ
Spector, M
AF Elias, Paul Z.
Spector, Myron
TI Treatment of penetrating brain injury in a rat model using collagen
scaffolds incorporating soluble Nogo receptor
SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
LA English
DT Article
DE penetrating brain injury; collagen scaffold; rat brain; Nogo receptor;
traumatic brain injury; brain tissue engineering
ID SPINAL-CORD-INJURY; AXONAL REGENERATION; MOLECULAR-MECHANISMS;
TAU-PROTEIN; IN-VITRO; MACROPHAGES; INFLAMMATION; OLIGODENDROCYTES;
DEGENERATION; IMPLANTATION
AB Injuries and diseases of the central nervous system (CNS) have the potential to cause permanent loss of brain parenchyma, with severe neurological consequences. Cavitary defects in the brain may afford the possibility of treatment with biomaterials that fill the lesion site while delivering therapeutic agents. This study examined the treatment of penetrating brain injury (PBI) in a rat model with collagen biomaterials and a soluble Nogo receptor (sNgR) molecule. sNgR was aimed at neutralizing myelin proteins that hinder axon regeneration by inducing growth cone collapse. Scaffolds containing sNgR were implanted in the brains of adult rats 1 week after injury and analysed 4 weeks or 8 weeks later. Histological analysis revealed that the scaffolds filled the lesion sites, remained intact with open pores and were infiltrated with cells and extracellular matrix. Immunohistochemical staining demonstrated the composition of the cellular infiltrate to include macrophages, astrocytes and vascular endothelial cells. Isolated regions of the scaffold borders showed integration with surrounding viable brain tissue that included neurons and oligodendrocytes. While axon regeneration was not detected in the scaffolds, the cellular infiltration and vascularization of the lesion site demonstrated a modification of the injury environment with implications for regenerative strategies. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Elias, Paul Z.] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Elias, Paul Z.; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA.
[Spector, Myron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
RP Elias, PZ (reprint author), VA Boston Healthcare Syst, Tissue Engn Labs, Mail Stop 151,Room D1-151,150 S Huntington Ave, Boston, MA 02130 USA.
EM pzelias@alum.mit.edu
FU US Department of Veterans Affairs, Veterans Health Administration,
Rehabilitation Research and Development Service
FX The research reported here was supported by the US Department of
Veterans Affairs, Veterans Health Administration, Rehabilitation
Research and Development Service. We thank Dr. Daniel Lee and Dr. Paul
Weinreb at Biogen Idec for generously providing the soluble Nogo
receptor. We also thank Alix Weaver for assistance with H&E staining. No
competing financial interests exist.
NR 67
TC 2
Z9 2
U1 2
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-6254
EI 1932-7005
J9 J TISSUE ENG REGEN M
JI J. Tissue Eng. Regen. Med.
PD FEB
PY 2015
VL 9
IS 2
BP 137
EP 150
DI 10.1002/term.1621
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Engineering, Biomedical
SC Cell Biology; Biotechnology & Applied Microbiology; Engineering
GA AZ0RU
UT WOS:000347953100005
PM 23038669
ER
PT J
AU Stahl, JE
AF Stahl, James E.
TI Trust and Recognition: Coming to Terms with Models
SO MEDICAL DECISION MAKING
LA English
DT Editorial Material
C1 [Stahl, James E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Stahl, JE (reprint author), Massachusetts Gen Hosp, MGH Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM jstahl@mgh.harvard.edu
NR 6
TC 1
Z9 1
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD FEB
PY 2015
VL 35
IS 2
BP 136
EP 138
DI 10.1177/0272989X14563080
PG 3
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA AZ2HF
UT WOS:000348054300002
PM 25510875
ER
PT J
AU Enns, EA
Cipriano, LE
Simons, CT
Kong, CY
AF Enns, Eva A.
Cipriano, Lauren E.
Simons, Cyrena T.
Kong, Chung Yin
TI Identifying Best-Fitting Inputs in Health-Economic Model Calibration: A
Pareto Frontier Approach
SO MEDICAL DECISION MAKING
LA English
DT Article
DE health-economic model; calibration; Pareto frontier; model uncertainty;
parameter uncertainty; parameter estimation; calibration uncertainty
ID NATURAL-HISTORY MODEL; MULTIOBJECTIVE GENETIC ALGORITHM;
COST-EFFECTIVENESS ANALYSIS; BAYESIAN CALIBRATION; AORTIC-STENOSIS;
CERVICAL-CANCER; DISEASE
AB Background. To identify best-fitting input sets using model calibration, individual calibration target fits are often combined into a single goodness-of-fit (GOF) measure using a set of weights. Decisions in the calibration process, such as which weights to use, influence which sets of model inputs are identified as best-fitting, potentially leading to different health economic conclusions. We present an alternative approach to identifying best-fitting input sets based on the concept of Pareto-optimality. A set of model inputs is on the Pareto frontier if no other input set simultaneously fits all calibration targets as well or better. Methods. We demonstrate the Pareto frontier approach in the calibration of 2 models: a simple, illustrative Markov model and a previously published cost-effectiveness model of transcatheter aortic valve replacement (TAVR). For each model, we compare the input sets on the Pareto frontier to an equal number of best-fitting input sets according to 2 possible weighted-sum GOF scoring systems, and we compare the health economic conclusions arising from these different definitions of best-fitting. Results. For the simple model, outcomes evaluated over the best-fitting input sets according to the 2 weighted-sum GOF schemes were virtually nonoverlapping on the cost-effectiveness plane and resulted in very different incremental cost-effectiveness ratios ($79,300 [95% CI 72,500-87,600] v. $139,700 [ 95% CI 79,900-182,800] per quality-adjusted life-year [ QALY] gained). Input sets on the Pareto frontier spanned both regions ($79,000 [ 95% CI 64,900-156,200] per QALY gained). The TAVR model yielded similar results. Conclusions. Choices in generating a summary GOF score may result in different health economic conclusions. The Pareto frontier approach eliminates the need to make these choices by using an intuitive and transparent notion of optimality as the basis for identifying best-fitting input sets.
C1 [Enns, Eva A.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA.
[Cipriano, Lauren E.] Univ Western Ontario, Ivey Business Sch, London, ON, Canada.
[Simons, Cyrena T.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Kong, Chung Yin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Kong, Chung Yin] Harvard Univ, Sch Med, Boston, MA USA.
RP Kong, CY (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM joey@mgh-ita.org
RI Cipriano, Lauren/C-3521-2017
OI Cipriano, Lauren/0000-0001-5568-4516
FU National Cancer Institute [K25CA133141]
FX Financial support for this study was provided in part by the National
Cancer Institute (K25CA133141). The funding agreement ensured the
authors' independence in designing the study, interpreting the data, and
writing and publishing the report. Revision accepted for publication 22
February 2014.
NR 39
TC 4
Z9 4
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD FEB
PY 2015
VL 35
IS 2
BP 170
EP 182
DI 10.1177/0272989X14528382
PG 13
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA AZ2HF
UT WOS:000348054300008
PM 24799456
ER
PT J
AU Codella, J
Safdar, N
Heffernan, R
Alagoz, O
AF Codella, James
Safdar, Nasia
Heffernan, Rick
Alagoz, Oguzhan
TI An Agent-based Simulation Model for Clostridium difficile Infection
Control
SO MEDICAL DECISION MAKING
LA English
DT Article
DE Clostridium difficile; simulation methods; agent-based simulation;
infectious disease control; hospital-acquired infections
ID PSEUDOMEMBRANOUS COLITIS; ORAL VANCOMYCIN; ENVIRONMENTAL SURFACES;
HOSPITALIZED-PATIENTS; REDUCE TRANSMISSION; RISK-FACTORS; DISEASE;
DIARRHEA; CONTAMINATION; MORTALITY
AB Background. Control of Clostridium difficile infection (CDI) is an increasingly difficult problem for health care institutions. There are commonly recommended strategies to combat CDI transmission, such as oral vancomycin for CDI treatment, increased hand hygiene with soap and water for health care workers, daily environmental disinfection of infected patient rooms, and contact isolation of diseased patients. However, the efficacy of these strategies, particularly for endemic CDI, has not been well studied. The objective of this research is to develop a valid, agent-based simulation model (ABM) to study C. difficile transmission and control in a midsized hospital. Methods. We develop an ABM of a midsized hospital with agents such as patients, health care workers, and visitors. We model the natural progression of CDI in a patient using a Markov chain and the transmission of CDI through agent and environmental interactions. We derive input parameters from aggregate patient data from the 2007-2010 Wisconsin Hospital Association and published medical literature. We define a calibration process, which we use to estimate transition probabilities of the Markov model by comparing simulation results to benchmark values found in published literature. Results. In a comparison of CDI control strategies implemented individually, routine bleach disinfection of CDI-positive patient rooms provides the largest reduction in nosocomial asymptomatic colonization (21.8%) and nosocomial CDIs (42.8%). Additionally, vancomycin treatment provides the largest reduction in relapse CDIs (41.9%), CDI-related mortalities (68.5%), and total patient length of stay (21.6%). Conclusion. We develop a generalized ABM for CDI control that can be customized and further expanded to specific institutions and/or scenarios. Additionally, we estimate transition probabilities for a Markov model of natural CDI progression in a patient through calibration.
C1 [Codella, James; Alagoz, Oguzhan] Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA.
[Heffernan, Rick] Bur Communicable Dis & Emergency Response, Wisconsin Div Publ Hlth, Madison, WI USA.
[Safdar, Nasia] Univ Wisconsin Hosp & Clin, Dept Med, Madison, WI 53792 USA.
[Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Alagoz, O (reprint author), Univ Wisconsin, Dept Ind & Syst Engn, 3242 Mech Engn Bldg,1513 Univ Ave, Madison, WI 53706 USA.
EM alagoz@engr.wisc.edu
FU CTSA program of NCRR NIH [2UL1TR000427]; National Science Foundation,
Division of Civil, Mechanical and Manufacturing Innovation
[CMMI-0844423]; VA MERIT award
FX Supported through grant 2UL1TR000427 from the CTSA program of NCRR NIH
and grant CMMI-0844423 from the National Science Foundation, Division of
Civil, Mechanical and Manufacturing Innovation. Nasia Safdar is
supported by a VA MERIT award. Revision accepted for publication 18 June
2014.
NR 55
TC 3
Z9 3
U1 1
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD FEB
PY 2015
VL 35
IS 2
BP 211
EP 229
DI 10.1177/0272989X14545788
PG 19
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA AZ2HF
UT WOS:000348054300011
PM 25112595
ER
PT J
AU Carlson, SJ
Nandivada, P
Chang, MI
Mitchell, PD
O'Loughlin, A
Cowan, E
Gura, KM
Nose, V
Bistrian, BR
Puder, M
AF Carlson, Sarah J.
Nandivada, Prathima
Chang, Melissa I.
Mitchell, Paul D.
O'Loughlin, Alison
Cowan, Eileen
Gura, Kathleen M.
Nose, Vania
Bistrian, Bruce R.
Puder, Mark
TI The addition of medium-chain triglycerides to a purified fish oil-based
diet alters inflammatory profiles in mice
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Medium-chain triglycerides; Fish oil; Parenteral nutrition; Inflammation
ID TOTAL PARENTERAL-NUTRITION; FATTY-ACID DEFICIENCY;
TUMOR-NECROSIS-FACTOR; INTESTINAL FAILURE; ARACHIDONIC-ACID;
LIVER-DISEASE; DOCOSAHEXAENOIC ACID; TREATED RATS; GUINEA-PIGS;
ENDOTOXIN
AB Objective. Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development.
Materials/methods. Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCI), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment.
Results. All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-alpha response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response.
Conclusion. These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Carlson, Sarah J.; Nandivada, Prathima; Chang, Melissa I.; O'Loughlin, Alison; Cowan, Eileen; Puder, Mark] Boston Childrens Hosp, Dept Surg, Boston, MA USA.
[Carlson, Sarah J.; Nandivada, Prathima; Chang, Melissa I.; O'Loughlin, Alison; Cowan, Eileen; Puder, Mark] Boston Childrens Hosp, Vasc Biol Program, Boston, MA USA.
[Mitchell, Paul D.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA.
[Gura, Kathleen M.] Boston Childrens Hosp, Dept Pharm, Boston, MA USA.
[Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bistrian, Bruce R.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
RP Puder, M (reprint author), 300 Longwood Ave Fegan 3, Boston, MA 02115 USA.
EM mark.puder@childrens.harvard.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health [F532 HD 071715-02];
National Research Service Award Institutional Training Grant of the
National Institutes of Health [2T32DK007754-14, 5 T32 HD007466-16, 5 T32
HD007466-17]; Joshua Ryan Rappaport Research Fellowship; Boston
Children's Hospital Department of Surgery; Vascular Biology Program
FX Research reported in this publication was supported by the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
of the National Institutes of Health under award number F532 HD
071715-02. Further research support was also given by the National
Research Service Award Institutional Training Grant of the National
Institutes of Health under award numbers 2T32DK007754-14, 5 T32
HD007466-16 and 5 T32 HD007466-17, the Joshua Ryan Rappaport Research
Fellowship, and the Boston Children's Hospital Department of Surgery and
the Vascular Biology Program. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institutes of Health.
NR 38
TC 7
Z9 7
U1 2
U2 22
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD FEB
PY 2015
VL 64
IS 2
BP 274
EP 282
DI 10.1016/j.metabol.2014.10.005
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AY5CG
UT WOS:000347590300016
PM 25458829
ER
PT J
AU Cote, CJ
Sui, JH
Anderson, TA
Bhattacharya, ST
Shank, ES
Tuason, PM
August, DA
Zibaitis, A
Firth, PG
Fuzaylov, G
Leeman, MR
Mai, CL
Roberts, JD
AF Cote, Charles J.
Sui, Jinghu
Anderson, Thomas Anthony
Bhattacharya, Somaletha T.
Shank, Erik S.
Tuason, Pacifico M.
August, David A.
Zibaitis, Audrius
Firth, Paul G.
Fuzaylov, Gennadiy
Leeman, Michael R.
Mai, Christine L.
Roberts, Jesse D., Jr.
TI Continuous noninvasive cardiac output in children: is this the next
generation of operating room monitors? Initial experience in 402
pediatric patients
SO PEDIATRIC ANESTHESIA
LA English
DT Article
DE monitoring; physiologic; cardiac; safety; adverse events; intraoperative
ID CONGENITAL HEART-DISEASE; ELECTRICAL VELOCIMETRY; PULSE OXIMETRY;
SINGLE-BLIND; ECHOCARDIOGRAPHY; SURGERY; THERMODILUTION; BIOIMPEDANCE;
CARDIOMETRY
AB BackgroundElectrical Cardiometry (EC) estimates cardiac parameters by measuring changes in thoracic electrical bioimpedance during the cardiac cycle. The ICON (R), using four electrocardiogram electrodes (EKG), estimates the maximum rate of change of impedance to peak aortic blood acceleration (based on the premise that red blood cells change from random orientation during diastole (high impedance) to an aligned state during systole (low impedance)).
ObjectiveTo determine whether continuous cardiac output (CO) data provide additional information to current anesthesia monitors that is useful to practitioners.
MethodsAfter IRB approval and verbal consent, 402 children were enrolled. Data were uploaded to our anesthesia record at one-minute intervals. Ten-second measurements (averaged over the previous 20 heart beats) were downloaded to separate files for later comparison with routine OR monitors.
ResultsData from 374 were in the final cohort (loss of signal or improper lead placement); 292012 measurements during 58049min of anesthesia were made in these children (1day to 19years and 1 to 107kg). Four events had a 25% reduction in cardiac index at least 1min before a clinically important change in other monitored parameters; 18 events in 14 children confirmed manifestations of other hemodynamic measures; eight events may have represented artifacts because the observed measurements did not seem to fit the clinical parameters of the other monitors; three other events documented decreased stroke index with extreme tachycardia.
ConclusionsElectrical cardiometry provides real-time cardiovascular information regarding developing hemodynamic events and successfully tracked the rapid response to interventions in children of all sizes. Intervention decisions must be based on the combined data from all monitors and the clinical situation. Our experience suggests that this type of monitor may be an important addition to real-time hemodynamic monitoring.
C1 [Cote, Charles J.; Anderson, Thomas Anthony; Bhattacharya, Somaletha T.; Shank, Erik S.; Tuason, Pacifico M.; August, David A.; Zibaitis, Audrius; Firth, Paul G.; Fuzaylov, Gennadiy; Leeman, Michael R.; Mai, Christine L.; Roberts, Jesse D., Jr.] Massachusetts Gen Hosp, MassGen Hosp Children, Dept Anesthesia Crit & Pain Management, Div Pediat Anesthesia, Boston, MA 02114 USA.
[Sui, Jinghu] Chinese Acad Med Sci, Plast Surg Hosp, Dept Anesthesiol, Beijing 100730, Peoples R China.
RP Cote, CJ (reprint author), Harvard Univ, Sch Med, Div Pediat Anesthesia, MassGen Hosp Children, 55 Fruit St, Boston, MA 02114 USA.
EM cjcote@partners.org
FU ICON(R) Cardiotronic/ Osypka Medical, Inc., La Jolla, CA
FX This study was approved by IRB of the Massachusetts General Hospital
Boston MA and FDAAA trial registered (NCT01499615). This research was
supported in part through the loan of two devices ICON (R) Cardiotronic/
Osypka Medical, Inc., 7463 Draper Ave, La Jolla, CA 92037, and a
research fellow supported by a study grant from the People's Republic of
China.
NR 31
TC 8
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1155-5645
EI 1460-9592
J9 PEDIATR ANESTH
JI Pediatr. Anesth.
PD FEB
PY 2015
VL 25
IS 2
BP 150
EP 159
DI 10.1111/pan.12441
PG 10
WC Anesthesiology; Pediatrics
SC Anesthesiology; Pediatrics
GA AY8FP
UT WOS:000347790200007
PM 24916144
ER
PT J
AU Schweidenback, CTH
Emerman, AB
Jambhekar, A
Blower, MD
AF Schweidenback, Caterina T. H.
Emerman, Amy B.
Jambhekar, Ashwini
Blower, Michael D.
TI Evidence for multiple, distinct ADAR-containing complexes in Xenopus
laevis
SO RNA
LA English
DT Article
DE A-to-I editing; RNA editing; dsRNA; RNP
ID DOUBLE-STRANDED-RNA; BICOID MESSENGER-RNA; MAJOR DEVELOPMENTAL
TRANSITION; CYTOPLASMIC STRESS GRANULES; FIBROBLAST-GROWTH-FACTOR; LARGE
GENE LISTS; ADENOSINE-DEAMINASE; TRANSLATIONAL CONTROL; HUMAN
TRANSCRIPTOME; FUNCTIONAL-ANALYSIS
AB ADAR (adenosine deaminase acting on RNA) is an RNA-editing enzyme present in most metazoans that converts adenosines in double-stranded RNA targets into inosines. Although the RNA targets of ADAR-mediated editing have been extensively cataloged, our understanding of the cellular function of such editing remains incomplete. We report that long, double-stranded RNA added to Xenopus laevis egg extract is incorporated into an ADAR-containing complex whose protein components resemble those of stress granules. This complex localizes to microtubules, as assayed by accumulation on meiotic spindles. We observe that the length of a double-stranded RNA influences its incorporation into the microtubule-localized complex. ADAR forms a similar complex with endogenous RNA, but the endogenous complex fails to localize to microtubules. In addition, we characterize the endogenous, ADAR-associated RNAs and discover that they are enriched for transcripts encoding transcriptional regulators, zinc-finger proteins, and components of the secretory pathway. Interestingly, association with ADAR correlates with previously reported translational repression in early embryonic development. This work demonstrates that ADAR is a component of two, distinct ribonucleoprotein complexes that contain different types of RNAs and exhibit diverse cellular localization patterns. Our findings offer new insight into the potential cellular functions of ADAR.
C1 [Schweidenback, Caterina T. H.; Emerman, Amy B.; Jambhekar, Ashwini; Blower, Michael D.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Schweidenback, Caterina T. H.; Emerman, Amy B.; Jambhekar, Ashwini; Blower, Michael D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Blower, MD (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM blower@molbio.mgh.harvard.edu
FU National Institutes of Health (NIH) RO1 [RO1GM086434]; Burroughs
Wellcome Fund Career Award in the Biomedical Sciences; NIH [F32
GM090533]; National Science Foundation (NSF) GRFP
FX We are grateful to Brenda Bass for generously sharing plasmids,
antibodies, and knowledge and to Michael Jantsch, John Sommerville, and
Bruce Schnapp for kindly providing antibodies. We thank the MGH
Sequencing Core for sequencing our Illumina libraries, members of the
Blower laboratory for critically reading this manuscript, and Elijah
Carrier for help optimizing Western blot conditions. This research was
funded with the following grants: National Institutes of Health (NIH)
RO1 (RO1GM086434) (M.D.B.), Burroughs Wellcome Fund Career Award in the
Biomedical Sciences (M.D.B.), NIH F32 GM090533 (C.T.H.S.), National
Science Foundation (NSF) GRFP (A.B.E.).
NR 94
TC 1
Z9 1
U1 0
U2 0
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
EI 1469-9001
J9 RNA
JI RNA
PD FEB
PY 2015
VL 21
IS 2
BP 279
EP 295
DI 10.1261/rna.047787.114
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AZ2AG
UT WOS:000348036400012
PM 25519486
ER
PT J
AU Campbell, JD
Liu, G
Luo, LQ
Xiao, J
Gerrein, J
Juan-Guardela, B
Tedrow, J
Alekseyev, YO
Yang, IV
Correll, M
Geraci, M
Quackenbush, J
Sciurba, F
Schwartz, DA
Kaminski, N
Johnson, WE
Monti, S
Spira, A
Beane, J
Lenburg, ME
AF Campbell, Joshua D.
Liu, Gang
Luo, Lingqi
Xiao, Ji
Gerrein, Joseph
Juan-Guardela, Brenda
Tedrow, John
Alekseyev, Yuriy O.
Yang, Ivana V.
Correll, Mick
Geraci, Mark
Quackenbush, John
Sciurba, Frank
Schwartz, David A.
Kaminski, Naftali
Johnson, W. Evan
Monti, Stefano
Spira, Avrum
Beane, Jennifer
Lenburg, Marc E.
TI Assessment of microRNA differential expression and detection in
multiplexed small RNA sequencing data
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE microRNA; differential expression; detection; sequencing; multiplexing;
coverage
ID PATHWAYS
AB Small RNA sequencing can be used to gain an unprecedented amount of detail into the microRNA transcriptome. The relatively high cost and low throughput of sequencing bases technologies can potentially be offset by the use of multiplexing. However, multiplexing involves a trade-off between increased number of sequenced samples and reduced number of reads per sample (i.e., lower depth of coverage). To assess the effect of different sequencing depths owing to multiplexing on microRNA differential expression and detection, we sequenced the small RNA of lung tissue samples collected in a clinical setting by multiplexing one, three, six, nine, or 12 samples per lane using the Illumina HiSeq 2000. As expected, the numbers of reads obtained per sample decreased as the number of samples in a multiplex increased. Furthermore, after normalization, replicate samples included in distinct multiplexes were highly correlated (R > 0.97). When detecting differential microRNA expression between groups of samples, microRNAs with average expression >1 reads per million (RPM) had reproducible fold change estimates (signal to noise) independent of the degree of multiplexing. The number of microRNAs detected was strongly correlated with the log(2) number of reads aligning to microRNA loci (R = 0.96). However, most additional microRNAs detected in samples with greater sequencing depth were in the range of expression which had lower fold change reproducibility. These findings elucidate the trade-off between increasing the number of samples in a multiplex with decreasing sequencing depth and will aid in the design of large-scale clinical studies exploring microRNA expression and its role in disease.
C1 [Campbell, Joshua D.; Gerrein, Joseph; Johnson, W. Evan; Monti, Stefano; Spira, Avrum; Lenburg, Marc E.] Boston Univ, Bioinformat Grad Program, Boston, MA 02215 USA.
[Campbell, Joshua D.; Liu, Gang; Luo, Lingqi; Xiao, Ji; Gerrein, Joseph; Johnson, W. Evan; Monti, Stefano; Spira, Avrum; Beane, Jennifer; Lenburg, Marc E.] Boston Univ, Sect Computat Biomed, Med Ctr, Boston, MA 02118 USA.
[Juan-Guardela, Brenda; Tedrow, John; Sciurba, Frank; Kaminski, Naftali] Univ Pittsburgh, Med Ctr, Simmons Ctr Interstitial Lung Dis, Pittsburgh, PA 15213 USA.
[Juan-Guardela, Brenda; Tedrow, John; Sciurba, Frank; Kaminski, Naftali] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA 15213 USA.
[Alekseyev, Yuriy O.; Lenburg, Marc E.] Boston Univ, Dept Pathol & Lab Med, Sch Med, Boston, MA 02118 USA.
[Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO 80206 USA.
[Yang, Ivana V.; Schwartz, David A.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
[Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Correll, Mick; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Geraci, Mark] Univ Colorado, Dept Med, Sch Med, Aurora, CO 80045 USA.
RP Lenburg, ME (reprint author), Boston Univ, Bioinformat Grad Program, Boston, MA 02215 USA.
EM mlenburg@bu.edu
RI Lenburg, Marc/B-8027-2008; Liu, Geoffrey/N-4421-2016;
OI Lenburg, Marc/0000-0002-5760-4708; Beane-Ebel,
Jennifer/0000-0002-6699-2132; Gerrein, Joseph/0000-0002-5833-1609
FU National Heart, Lung, and Blood Institute [RC2HL101715-01]; National
Cancer Institute's Early Detection Research Network of the National
Institutes of Health [U01CA152751]
FX We thank the reviewers for their constructive feedback. This work was
funded by the National Heart, Lung, and Blood Institute (RC2HL101715-01)
and the National Cancer Institute's Early Detection Research Network
(U01CA152751) of the National Institutes of Health.
NR 14
TC 2
Z9 2
U1 1
U2 13
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1355-8382
EI 1469-9001
J9 RNA
JI RNA-Publ. RNA Soc.
PD FEB
PY 2015
VL 21
IS 2
BP 164
EP 171
DI 10.1261/rna.046060.114
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AZ2AG
UT WOS:000348036400002
PM 25519487
ER
PT J
AU An, G
Qin, XQ
Acharya, C
Xu, Y
Deng, SH
Shi, LH
Zang, MR
Sui, WW
Yi, SH
Li, ZJ
Hao, M
Feng, XY
Jin, FY
Zou, DH
Qi, JY
Zhao, YZ
Tai, YT
Wang, JX
Qiu, LG
AF An, Gang
Qin, Xiaoqi
Acharya, Chirag
Xu, Yan
Deng, Shuhui
Shi, Lihui
Zang, Meirong
Sui, Weiwei
Yi, Shuhua
Li, Zengjun
Hao, Mu
Feng, Xiaoyan
Jin, Fengyan
Zou, Dehui
Qi, Junyuan
Zhao, Yaozhong
Tai, Yu-Tzu
Wang, Jianxing
Qiu, Lugui
TI Multiple myeloma patients with low proportion of circulating plasma
cells had similar survival with primary plasma cell leukemia patients
SO ANNALS OF HEMATOLOGY
LA English
DT Article
DE Multiple myeloma; Circulating plasma cells; Primary plasma cell leukemia
ID IN-SITU HYBRIDIZATION; WORKING GROUP; INTERGROUPE-FRANCOPHONE; GENETIC
ABERRATIONS; TRANSPLANTATION; PREDICTOR; CLASSIFICATION; ABNORMALITIES;
PROGRESSION; INTERPHASE
AB The common features shared by primary plasma cell leukemia (pPCL) and multiple myeloma (MM) with circulating plasma cells (CPCs) are peripheral blood invasion and expansion of plasma cells independent of the protective bone marrow (BM) microenvironment niche. However, few studies have addressed the relationship between pPCL and MM with CPCs. Here, we quantitated the number CPCs by conventional morphology in 767 patients with newly diagnosed MM; their clinic features were compared with those of 33 pPCL cases. When the presence of CPCs was defined as more than 2 % plasma cells per 100 nucleated cells on Wright-Giemsa stained peripheral blood smears, the incidence of MM with CPCs was 14.1 % in newly diagnosed MM. Patients with CPCs shared many clinical features with pPCL, especially clinical parameters related to tumor burden. However, no commonalities were found in immunophenotyping and cytogenetics. The prognosis of pPCL was poor, with a median progression free survival (PFS) of 12 months and an overall survival (OS) of 15 months. MM patients with CPCs had a clearly inferior PFS and OS as compared with the control cohort. Most interestingly, although the CPCs were not high enough to meet the diagnostic criteria for pPCL, the survival of MM patients with CPCs was comparable with that of pPCL, with a median PFS of 17 months and an OS of 25 months.
C1 [An, Gang; Qin, Xiaoqi; Xu, Yan; Deng, Shuhui; Shi, Lihui; Zang, Meirong; Sui, Weiwei; Yi, Shuhua; Li, Zengjun; Hao, Mu; Feng, Xiaoyan; Zou, Dehui; Qi, Junyuan; Zhao, Yaozhong; Wang, Jianxing; Qiu, Lugui] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China.
[An, Gang; Qin, Xiaoqi; Xu, Yan; Deng, Shuhui; Shi, Lihui; Zang, Meirong; Sui, Weiwei; Yi, Shuhua; Li, Zengjun; Hao, Mu; Feng, Xiaoyan; Zou, Dehui; Qi, Junyuan; Zhao, Yaozhong; Wang, Jianxing; Qiu, Lugui] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.
[An, Gang; Qin, Xiaoqi; Xu, Yan; Deng, Shuhui; Shi, Lihui; Zang, Meirong; Sui, Weiwei; Yi, Shuhua; Li, Zengjun; Hao, Mu; Feng, Xiaoyan; Zou, Dehui; Qi, Junyuan; Zhao, Yaozhong; Wang, Jianxing; Qiu, Lugui] Peking Union Med Coll, Tianjin, Peoples R China.
[Jin, Fengyan] Jilin Univ, Ctr Canc, Hosp 1, Changchun 130023, Peoples R China.
[Acharya, Chirag; Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Acharya, Chirag; Tai, Yu-Tzu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Ctr, Boston, MA 02115 USA.
RP Qiu, LG (reprint author), Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin, Peoples R China.
EM drqiu99@medmail.com.cn
FU National Natural Science Fund [81400175, 81172255, 81370632]; Clinical
Research Program from Ministry of Health, China; Special Key Anticancer
Research and Development Program of Tianjin Municipality
[12ZCDZSY17600]; Union Youth Research Fund of Peking Union Medical
College; Doctoral Foundation [20131106120037]
FX The present study was supported by the National Natural Science Fund
(81400175, 81172255, 81370632), the Clinical Research Program from
Ministry of Health, China (Key project 2010 to 2012), the Special Key
Anticancer Research and Development Program of Tianjin Municipality
(12ZCDZSY17600), the Union Youth Research Fund of Peking Union Medical
College (2012-2013), the Doctoral Foundation (20131106120037).
NR 27
TC 5
Z9 5
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-5555
EI 1432-0584
J9 ANN HEMATOL
JI Ann. Hematol.
PD FEB
PY 2015
VL 94
IS 2
BP 257
EP 264
DI 10.1007/s00277-014-2211-0
PG 8
WC Hematology
SC Hematology
GA AY6ML
UT WOS:000347680200010
PM 25231928
ER
PT J
AU Beste, LA
Green, PK
Ioannou, GN
AF Beste, Lauren A.
Green, Pamela K.
Ioannou, George N.
TI Boceprevir and telaprevir-based regimens for the treatment of hepatitis
C virus in HIV/HCV coinfected patients
SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Article
DE hepatitis C virus; hepatitis C virus; HIV; protease inhibitor; veterans
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TREATMENT-NAIVE PATIENTS; ALPHA-2A PLUS
RIBAVIRIN; HEPATOCELLULAR-CARCINOMA; PEGINTERFERON ALPHA-2A; PHASE-2
TRIAL; VIROLOGICAL RESPONSE; INTERFERON ALPHA-2A; HIV COINFECTION;
TRIPLE THERAPY
AB Background and aim Hepatitis C virus (HCV) treatment in patients coinfected with HIV has historically been limited by poor efficacy and medication toxicities. Direct-acting antivirals (e.g. boceprevir and telaprevir) improve treatment results in clinical trials, but little is known about the outcomes in community-based coinfected populations. This project aimed to describe the real-world effectiveness of boceprevir-based or telaprevir-based therapies in HIV/HCV coinfected patients.
Materials and methods We identified HIV/HCV coinfected patients of all genotypes in the Veterans Affairs healthcare system who initiated pegylated interferon and ribavirin with or without boceprevir or telaprevir from June 2011 to November 2012 (n = 134).
Results Sustained virologic response (SVR) was higher in genotype 1 patients receiving boceprevir or telaprevir [ n = 62, SVR = 50.0%, 95% confidence interval (CI) 37-63] versus pegylated interferon/ribavirin alone (n = 48, SVR = 33.3%, 95% CI 20-47). Patients with genotypes 2/3 treated with pegylated interferon/ribavirin (n = 24) achieved an SVR of 41.7% (95% CI 20-63). Only a few patients (15-25%) of each genotype completed more than 44 of 48 projected weeks. Treatment with boceprevir or telaprevir was the only characteristic independently associated with SVR in genotype 1 (adjusted odds ratio 2.2, 95% CI 1.1-4.7).
Conclusion Addition of boceprevir or telaprevir to pegylated interferon/ribavirin improves treatment response in genotype 1 HIV/HCV coinfected patients. Treatment response is similar to reports from HCV monoinfected Veterans Affairs patients but lower than those reported in clinical trials. Early treatment discontinuation was common. (C) 2015 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Beste, Lauren A.] Vet Affairs Puget Sound Hlth Care Syst, Primary Care Serv, Seattle, WA 98108 USA.
[Beste, Lauren A.; Green, Pamela K.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA.
[Beste, Lauren A.] Univ Washington, Dept Internal Med, Div Gen Internal Med, Seattle, WA 98195 USA.
[Ioannou, George N.] Univ Washington, Dept Internal Med, Div Gastroenterol, Seattle, WA 98195 USA.
[Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA 98108 USA.
RP Beste, LA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111-GI, Seattle, WA 98108 USA.
EM lauren.beste@va.gov
FU VA Puget Sound Health Care System (Seattle, Washington); Clinical
Science Research and Development, Office of Research and Development,
Veterans Affairs [I01CX000320]
FX This material is the result of work supported by resources from the VA
Puget Sound Health Care System (Seattle, Washington). The study was
funded by a Merit Review grant (I01CX000320), Clinical Science Research
and Development, Office of Research and Development, Veterans Affairs
(GNI).
NR 23
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0954-691X
EI 1473-5687
J9 EUR J GASTROEN HEPAT
JI Eur. J. Gastroenterol. Hepatol.
PD FEB
PY 2015
VL 27
IS 2
BP 123
EP 129
DI 10.1097/MEG.0000000000000241
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AX9UZ
UT WOS:000347248700002
PM 25503739
ER
PT J
AU Rosendorff, C
AF Rosendorff, Clive
TI Diuretics and potassium
SO JOURNAL OF HYPERTENSION
LA English
DT Letter
C1 [Rosendorff, Clive] Icahn Sch Med Mt Sinai, Mt Sinai Heart, Bronx, NY USA.
[Rosendorff, Clive] Icahn Sch Med Mt Sinai, Dept Med, Bronx, NY USA.
[Rosendorff, Clive] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM clive.rosendorff@va.gov
NR 4
TC 1
Z9 1
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0263-6352
EI 1473-5598
J9 J HYPERTENS
JI J. Hypertens.
PD FEB
PY 2015
VL 33
IS 2
BP 421
EP 422
DI 10.1097/HJH.0000000000000457
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AY2CM
UT WOS:000347396100030
PM 25535881
ER
PT J
AU Wang, P
Duan, D
Zhou, X
Li, X
Yang, J
Deng, M
Xu, Y
AF Wang, P.
Duan, D.
Zhou, X.
Li, X.
Yang, J.
Deng, M.
Xu, Y.
TI Relationship between expression of human gingival beta-defensins and
levels of periodontopathogens in subgingival plaque
SO JOURNAL OF PERIODONTAL RESEARCH
LA English
DT Article
DE antimicrobial cationic peptides; bacteria; beta-defensins; dental
plaque; periodontitis
ID POLYMERASE-CHAIN-REACTION; DENTICOLA SUPPRESSES EXPRESSION; ORAL
EPITHELIAL-CELLS; REAL-TIME PCR; HUMAN BETA-DEFENSIN-1;
PORPHYROMONAS-GINGIVALIS; ANTIMICROBIAL PEPTIDES; GENE-EXPRESSION;
ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; FUSOBACTERIUM-NUCLEATUM
AB Background and ObjectiveHuman beta-defensins (hBDs) are a group of antimicrobial peptides important in epithelial innate immunity, and their differential expression is associated with periodontal diseases. The aim of this study was to explore relationships among hBDs, total subgingival bacteria and periodontopathogens in healthy subjects and in patients with chronic periodontitis.
Material and MethodsThe periodontal clinical parameters of 29 healthy subjects and 25 patients with chronic periodontitis were recorded. The relative expression of hBD1, hBD2 and hBD3 genes in gingival biopsies was measured using real-time PCR. The numbers of total bacteria and of Treponema denticola, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Tannerella forsythia in subgingival plaque were quantified by real-time PCR. Data were analyzed using the Mann-Whitney U-test and Spearman's rank correlation test.
ResultsNo significant differences in expression of the hBD genes were found between the group of healthy subjects and the group of patients with chronic periodontitis. Total bacteria and T.denticola were detected in all participants. F.nucleatum and T.forsythia were detected in all patients with chronic periodontitis and in 86.21% and 51.72%, respectively, of healthy volunteers. P.gingivalis and A.actinomycetemcomitans were detected in 24.14% and 17.24%, respectively, of the healthy group and in 84.00% and 12.00%, respectively, of the chronic periodontitis group. The prevalence of all bacteria, except A.actinomycetemcomitans, was significantly higher in the group of patients with chronic periodontitis than in the group of healthy subjects (p<0.05). A significant, negative correlation was observed between total bacteria and hBD-2 (r=-0.384, p=0.011). Upon analyzing the data in different groups, total bacteria and hBD-2 were significantly correlated (r=-0.492, p=0.026) only in the group of healthy subjects.
ConclusionThe negative correlations between hBD-2 and total bacteria, especially in the group of healthy subjects, indicate that hBDs may play an important role by limiting an increase of bacterial load at the initial stage of periodontitis.
C1 [Wang, P.; Duan, D.; Zhou, X.; Li, X.; Yang, J.; Xu, Y.] State Key Lab Oral Dis, Chengdu, Peoples R China.
[Wang, P.] Forsyth Inst, Ctr Periodontol, Dept Appl Oral Sci, Cambridge, MA USA.
[Deng, M.] Univ N Carolina, Sch Dent, Oral Biol Program, Chapel Hill, NC USA.
[Xu, Y.] Sichuan Univ, Dept Periodontol, West China Sch Stomatol, Chengdu SICHUAN UNI, Peoples R China.
RP Xu, Y (reprint author), Sichuan Univ, Dept Periodontol, West China Sch Stomatol, 14,Sect 3,Renmin Nan Rd, Chengdu SICHUAN UNI, Peoples R China.
EM schuehih@sohu.com
OI deng, meng/0000-0002-9051-7534
FU Science and Technology Department of Sichuan Province [2011FZ0044];
National Science Foundation of China [30872872]
FX The authors thank Dr Bo Han, Dr Ming Xuan, Dr YunLong Wu and Dr Jun Wu
at the Department of Oral Surgery, West China School of Stomatology,
Sichuan University for collecting the gingival tissues. The authors
thank Dr Xiaoshan Wang (Epidemiology and Biostatistics Core, The Forsyth
Institute) for his statistical assistance. This study was financially
supported by the Foundation 2011FZ0044 from Science and Technology
Department of Sichuan Province and National Science Foundation of China
(30872872).
NR 56
TC 2
Z9 3
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3484
EI 1600-0765
J9 J PERIODONTAL RES
JI J. Periodont. Res.
PD FEB
PY 2015
VL 50
IS 1
BP 113
EP 122
DI 10.1111/jre.12187
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA AY3EO
UT WOS:000347467600013
PM 24814979
ER
PT J
AU Garnett, BR
Masyn, KE
Austin, SB
Williams, DR
Viswanath, K
AF Garnett, Bernice R.
Masyn, Katherine E.
Austin, S. Bryn
Williams, David R.
Viswanath, Kasisomayajula
TI Coping Styles of Adolescents Experiencing Multiple Forms of
Discrimination and Bullying: Evidence From a Sample of Ethnically
Diverse Urban Youth
SO JOURNAL OF SCHOOL HEALTH
LA English
DT Article
DE discrimination; bullying; coping style; latent class analysis;
adolescents
ID AFRICAN-AMERICAN ADOLESCENTS; RACIAL-DISCRIMINATION; DEPRESSION;
VICTIMIZATION; MASSACHUSETTS; ATTRIBUTIONS; PREVALENCE; ADJUSTMENT;
BEHAVIORS; SYMPTOMS
AB BACKGROUNDWe used a latent class analysis (LCA) to characterize coping styles of urban youth and examined if coping styles moderated the association between experiencing discrimination and bullying and depressive symptoms.
METHODSThe data come from the 2006 Boston Youth Survey, where students were asked to select 2 behaviors they do most often when they are upset, from a list of 15 options. A total of 927 (75%) students contributed to the LCA analytic sample (44% non-Hispanic Blacks, 29% Hispanics, and 58% girls). Relative and absolute fit indices determined the number of classes. An interaction term between types of discrimination and bullying experienced and coping style tested for moderation.
RESULTSThe LCA revealed that a 3-class solution had the best fit (Lo-Mendell-Rubin likelihood ratio test, 4-class vs 3-class, p-value .12). The largest coping style class was characterized by high endorsement of distractive coping strategies (59%), the second class was characterized by using supportive coping strategies (27%), and the third class was characterized by using avoidance coping strategies (12%). We found a significant interaction between discrimination and coping style for depressive symptoms.
CONCLUSIONSThe relationship between experiencing discrimination and depression varied based on coping style and the type of discrimination and bullying experienced.
C1 [Garnett, Bernice R.] Univ Vermont, Coll Educ & Social Serv, Burlington, VT 05405 USA.
[Masyn, Katherine E.] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA.
[Austin, S. Bryn; Williams, David R.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Austin, S. Bryn] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA.
[Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Hlth Commun Core,Dana Farber Harvard Canc Ctr, Boston, MA 02215 USA.
RP Garnett, BR (reprint author), Univ Vermont, Coll Educ & Social Serv, 533 Waterman Bldg,85 South Prospect St, Burlington, VT 05405 USA.
EM bgarnett@uvm.edu; katherine_masyn@gse.harvard.edu;
bryn.austin@childrens.harvard.edu; dwilliam@hsph.harvard.edu;
Vish_Viswanath@dfci.harvard.edu
NR 40
TC 2
Z9 2
U1 2
U2 34
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4391
EI 1746-1561
J9 J SCHOOL HEALTH
JI J. Sch. Health
PD FEB
PY 2015
VL 85
IS 2
BP 109
EP 117
DI 10.1111/josh.12225
PG 9
WC Education & Educational Research; Education, Scientific Disciplines;
Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Education & Educational Research; Health Care Sciences & Services;
Public, Environmental & Occupational Health
GA AY4II
UT WOS:000347541000005
PM 25564979
ER
PT J
AU Foster, DW
Langdon, KJ
Schmidt, NB
Zvolensky, M
AF Foster, Dawn W.
Langdon, Kirsten J.
Schmidt, Norman B.
Zvolensky, Michael
TI Smoking Processes, Panic, and Depressive Symptoms Among
Treatment-Seeking Smokers
SO SUBSTANCE USE & MISUSE
LA English
DT Article
DE Smoking; anxiety; panic; depression; cigarettes; tobacco; motives
ID ANXIETY SENSITIVITY; CESSATION TREATMENT; CIGARETTE-SMOKING;
PSYCHIATRIC-DISORDERS; OUTCOME EXPECTANCIES; ATTACK HISTORY; MOTIVES;
DEPENDENCE; NICOTINE; PATTERNS
AB Objectives: The present study evaluated the relative contribution of panic and depressive symptoms in relation to past cessation difficulties and smoking motives among treatment-seeking daily smokers. Methods: The sample included 392 treatment-seeking daily smokers (47.07% female; M-age = 35.48; SD = 13.56), who reported smoking an average of 10 or more cigarettes daily for at least one year. Results: Findings indicated that panic and depressive symptoms were significantly associated with quit problems as well as addictive and negative affect motives for smoking. However, depressive symptoms were not associated with habitual smoking motives. Conclusions: Differential patterns of associations with smoking-based processes imply that although panic and depression are related, there are important distinctions. Such data highlight the need for additional research to examine the putative role of panic and depressive symptoms in relation to smoking behaviors to further elucidate the mechanisms through which panic, depression, and smoking impact one another.
C1 [Foster, Dawn W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06519 USA.
[Langdon, Kirsten J.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA.
[Langdon, Kirsten J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Schmidt, Norman B.] Florida State Univ, Dept Psychol, Anxiety & Behav Hlth Clin, Tallahassee, FL 32306 USA.
[Zvolensky, Michael] Univ Houston, Dept Psychol, Houston, TX USA.
RP Foster, DW (reprint author), Yale Univ, Sch Med, Dept Psychiat, 34 Pk St, New Haven, CT 06519 USA.
EM dawn.foster@yale.edu
FU National Institute of Mental Health [R01 MH076629-01]; National
Institute on Drug Abuse [K12-DA-000167]
FX This project was supported by National Institute of Mental Health grant
R01 MH076629-01 (Drs. Zvolensky and Schmidt). Additionally, preparation
of this manuscript was supported in part by National Institute on Drug
Abuse grant K12-DA-000167 (Dr. Foster). NIMH and NIDA had no direct role
in the study design, collection, analysis or interpretation of the data,
writing the manuscript, or the decision to submit the paper for
publication. The contents of this manuscript do not necessarily
represent the policy of the NIMH or NIDA, and as such, endorsement by
the Federal Government should not be assumed.
NR 40
TC 0
Z9 0
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1082-6084
EI 1532-2491
J9 SUBST USE MISUSE
JI Subst. Use Misuse
PD FEB
PY 2015
VL 50
IS 3
BP 394
EP 402
DI 10.3109/10826084.2014.984849
PG 9
WC Substance Abuse; Psychiatry; Psychology
SC Substance Abuse; Psychiatry; Psychology
GA AY0YR
UT WOS:000347321100014
PM 25496170
ER
PT J
AU Pond, GR
Bellmunt, J
Rosenberg, JE
Bajorin, DF
Regazzi, AM
Choueiri, TK
Qu, AQ
Niegisch, G
Albers, P
Necchi, A
Di Lorenzo, G
Fougeray, R
Wong, YN
Sridhar, SS
Ko, YJ
Milowsky, MI
Galsky, MD
Sonpavde, G
AF Pond, G. R.
Bellmunt, J.
Rosenberg, J. E.
Bajorin, D. F.
Regazzi, A. M.
Choueiri, T. K.
Qu, A. Q.
Niegisch, G.
Albers, P.
Necchi, A.
Di Lorenzo, G.
Fougeray, R.
Wong, Y. -N.
Sridhar, S. S.
Ko, Y. -J.
Milowsky, M. I.
Galsky, M. D.
Sonpavde, G.
TI Impact of the Number of Prior Lines of Therapy and Prior Perioperative
Chemotherapy in Patients Receiving Salvage Therapy for Advanced
Urothelial Carcinoma: Implications for Trial Design
SO CLINICAL GENITOURINARY CANCER
LA English
DT Article
DE Advanced; Number of prior regimens; Prior perioperative chemotherapy;
Prognosis; Salvage therapy; Urothelial carcinoma
ID TRANSITIONAL-CELL CARCINOMA; METASTATIC BREAST-CANCER; RANDOMIZED
PHASE-III; OPEN-LABEL; INTERNAL VALIDATION; COLORECTAL-CANCER; 2ND-LINE
THERAPY; SOLID TUMORS; SINGLE GROUP; DOUBLE-BLIND
AB This analysis of patients from prospective trials of salvage therapy for advanced urothelial carcinoma did not identify a prognostic effect for number of prior lines of therapy and prior perioperative chemotherapy. Performance status, hemoglobin, liver metastasis, and time from prior chemotherapy were prognostic for outcomes. These findings allow trials to use uniform eligibility criteria, which will enhance accrual and improve interpretability.
Background: The differential impact of the number of prior lines of therapy and the setting of prior therapy (perioperative or metastatic) is unclear in advanced urothelial carcinoma. Patients and Methods: Ten phase II trials of salvage chemotherapy, biologic agent therapy, or both, enrolling 731 patients, were available. Data on the number of prior lines of therapy and the setting of prior therapy were required in addition to known previously recognized prognostic factors: time from prior chemotherapy, hemoglobin level, performance status, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of the number of prior lines and prior perioperative therapy with overall survival (OS) as the primary clinical endpoint. Trial was a stratification factor. Results: A total of 711 patients were evaluable. The overall median progression-free survival and OS were 2.7 and 6.8 months, respectively. The number of prior lines was 1 in 559 patients (78.6%), 2 in 111 (15.6%), 3 in 29 (4.1%), 4 in 10 (1.4%), and 5 in 2 (0.3%). Prior perioperative chemotherapy was given to 277 (39.1%) and chemotherapy for metastatic disease to 454 (64.1%). The number of prior lines was not independently associated with OS (hazard ratio, 0.99; 95% CI, 0.86-1.14). Prior perioperative chemotherapy was a favorable factor for OS on univariate but not multivariate analysis. Conclusion: The number of prior lines of therapy and prior perioperative chemotherapy were not independently prognostic in patients with urothelial carcinoma receiving salvage therapy. Adoption of these data in salvage therapy trials should enhance accrual, the interpretability of results, and drug development.
C1 [Pond, G. R.] McMaster Univ, Hamilton, NY USA.
[Bellmunt, J.] Univ Hosp del Mar, Inst Hosp del Mar Invest Med, Barcelona, Spain.
[Rosenberg, J. E.; Bajorin, D. F.; Regazzi, A. M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Choueiri, T. K.; Qu, A. Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Choueiri, T. K.; Qu, A. Q.] Harvard Univ, Sch Med, Boston, MA USA.
[Niegisch, G.; Albers, P.] Univ Dusseldorf, Dusseldorf, Germany.
[Necchi, A.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy.
[Di Lorenzo, G.] Univ Naples Federico II, Naples, Italy.
[Fougeray, R.] Inst Rech Pierre Fabre, Boulogne, France.
[Wong, Y. -N.] Fox Chase Canc Ctr, Philadelphia, PA USA.
[Sridhar, S. S.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Ko, Y. -J.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Milowsky, M. I.] Univ N Carolina, Chapel Hill, NC USA.
[Galsky, M. D.] Mt Sinai Sch Med, Tisch Canc Ctr Inst, New York, NY USA.
[Sonpavde, G.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
RP Sonpavde, G (reprint author), Univ Alabama Birmingham, Ctr Comprehens Canc, 1802 6th Ave S,NP2540B, Birmingham, AL 35294 USA.
EM gsonpavde@uabmc.edu
OI Regazzi, Ashley/0000-0002-6019-1852; Niegisch,
Gunter/0000-0001-6929-8691; Rosenberg, Jonathan/0000-0003-2637-4249;
Necchi, Andrea/0000-0002-3007-2756
NR 28
TC 5
Z9 5
U1 1
U2 6
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
EI 1938-0682
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD FEB
PY 2015
VL 13
IS 1
BP 71
EP 79
DI 10.1016/j.clgc.2014.06.004
PG 9
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA AY2HR
UT WOS:000347410100018
PM 24993933
ER
PT J
AU Parekh, A
Chen, MH
Graham, P
Mahal, BA
Hirsch, AE
Nakabayashi, M
Evan, C
Kantoff, PW
Martin, NE
Nguyen, PL
AF Parekh, Arti
Chen, Ming-Hui
Graham, Powell
Mahal, Brandon A.
Hirsch, Ariel E.
Nakabayashi, Mari
Evan, Carolyn
Kantoff, Philip W.
Martin, Neil E.
Nguyen, Paul L.
TI Role of Androgen Deprivation Therapy in Early Salvage Radiation Among
Patients With Prostate-Specific Antigen Level of 0.5 or Less
SO CLINICAL GENITOURINARY CANCER
LA English
DT Article
DE ADT; Prostate cancer; Salvage therapy; Surgical margins; Ultrasensitive
PSA
ID RADICAL PROSTATECTOMY; CANCER; RADIOTHERAPY; RECURRENCE; MEN
AB In this study, we examine the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy in modern patients followed with ultrasensitive prostate-specific antigen (PSA). In these 108 patients who received radical prostatectomy and salvage radiation at a PSA of 0.5 or less, we found that ADT was associated with a decreased risk of recurrence. This benefit appeared limited to men with negative margins, which suggests that men with positive margins and PSA <= 0.5 may be good candidates for salvage radiation alone. Background: The Radiation Therapy Oncology Group 96-01 randomized trial demonstrated the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy for an increasing prostate-specific antigen (PSA) after prostatectomy, but it is unknown whether modern patients followed with ultrasensitive PSA and salvaged at a low PSA (ie, <= 0.5) also benefit from ADT. Patients and Methods: The cohort comprised 108 patients who received radical prostatectomy (RP), were followed by ultrasensitive PSA, and received salvage radiotherapy at a PSA of 0.5 or less. Sixty patients had negative margins, and 48 patients had positive margins at RP. Cox multivariable regression analysis was performed to identify factors associated with time to secondary PSA failure and included PSA at salvage, year of treatment, Gleason score, ADT use, margin status, T stage, and PSA doubling time. Occurrence of distant metastases was documented. Results: Median follow-up after radiation was 63.09 months. A total of 24 patients had a distant metastasis. In all patients, ADT use was associated with a decreased risk of recurrence (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.79; P = .006). On subgroup analysis, ADT was associated with a decreased risk of failure among patients with negative margins (HR, 0.27; 95% CI, 0.12-0.61; P = .002), but not among men with positive margins (HR, 0.78; 95% CI, 0.29-2.10; P = .63). Conclusions: Even patients followed with ultrasensitive PSA and salvaged early with a PSA <= 0.5 seem to benefit from the addition of ADT to salvage radiation. However, this benefit seemed to be limited to men with negative margins; thus, men with positive margins and PSA <= 0.5 may be good candidates for salvage radiation alone.
C1 [Parekh, Arti; Graham, Powell; Mahal, Brandon A.; Martin, Neil E.; Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02215 USA.
[Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT USA.
[Hirsch, Ariel E.] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA.
[Nakabayashi, Mari; Evan, Carolyn; Kantoff, Philip W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA.
RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02215 USA.
EM pnguyen@LROC.harvard.edu
RI Martin, Neil/E-2193-2014
OI Martin, Neil/0000-0002-8164-8516
FU Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard
Medical Schoo; Fitz's Cancer Warriors; Prostate Cancer Foundation
FX This work was supported by the Doris Duke Charitable Foundation Clinical
Research Fellowship at Harvard Medical School, Fitz's Cancer Warriors,
Hugh Simons in Honor of Frank and Anne Simons, David and Cynthia Chapin,
The Prostate Cancer Foundation, and a grant from an anonymous family
foundation.
NR 12
TC 1
Z9 1
U1 0
U2 2
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
EI 1938-0682
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD FEB
PY 2015
VL 13
IS 1
BP E1
EP E6
DI 10.1016/j.clgc.2014.06.0161
PG 6
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA AY2HR
UT WOS:000347410100001
PM 25103271
ER
PT J
AU Lee, RJ
Cohen, NA
AF Lee, Robert J.
Cohen, Noam A.
TI Role of the bitter taste receptor T2R38 in upper respiratory infection
and chronic rhinosinusitis
SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Review
DE acyl-homoserine lactone; bacterial infection; host-pathogen
interactions; interkingdom signaling; nitric oxide
ID SOLITARY CHEMOSENSORY CELLS; QUORUM-SENSING MOLECULES; NITRIC-OXIDE;
PSEUDOMONAS-AERUGINOSA; BRUSH CELLS; ANTIMICROBIAL ACTIVITY;
CYSTIC-FIBROSIS; AIRWAY; PERCEPTION; EXPRESSION
AB Purpose of review
Taste receptor family 2 (T2R) bitter taste receptors were originally identified and named on the basis of their role in type 2 taste cells of the tongue, in which they serve to detect the presence of potentially harmful ingested chemicals. In 2009, researchers demonstrated that airway epithelial cells also express T2R receptors, but their role in airway physiology and human disease has only recently begun to be identified.
Recent findings
Recent research has demonstrated that at least one airway T2R receptor, taste receptor family 2 isoform 38 protein (T2R38) is activated by secreted bacterial products. Activation of T2R38 in sinonasal epithelial cells stimulates nitric oxide production, increasing ciliary beating and directly killing bacteria. Clinical studies have also found correlations of TAS2R38 genotype with susceptibility to gram-negative upper respiratory infection and established T2R38 as an independent risk factor for chronic rhinosinusitis requiring sinus surgery.
Summary
These recent studies identify a role for T2R38 in sinonasal innate immunity and chronic rhinosinusitis. Clinical implications include the potential development of T2R38-directed topical therapies, as well as using taste testing and/or genotyping to predict susceptibility to infection. Further studies are needed to more clearly determine how TAS2R38 genotype affects patient outcomes in chronic rhinosinusitis and other upper airway diseases.
C1 [Lee, Robert J.; Cohen, Noam A.] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA.
[Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA.
RP Cohen, NA (reprint author), Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Div Rhinol, Hosp Univ Penn Ravdin Bldg,5th Floor,3400 Spruce, Philadelphia, PA 19104 USA.
EM noam.cohen@uphs.upenn.edu
OI Cohen, Noam/0000-0002-9462-3932; Lee, Robert/0000-0001-5826-6686
FU Flight Attendants Medical Research Institute [082478]
FX Some of the research described here was supported by a grant from the
Flight Attendants Medical Research Institute (082478) and a
philanthropic contribution from the RLG Foundation, Inc., both to N.A.C.
NR 77
TC 13
Z9 14
U1 7
U2 32
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1528-4050
EI 1473-6322
J9 CURR OPIN ALLERGY CL
JI Curr. Opin. Allergy Clin. Immunol.
PD FEB
PY 2015
VL 15
IS 1
BP 14
EP 20
DI 10.1097/ACI.0000000000000120
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA AX9ZX
UT WOS:000347258500002
PM 25304231
ER
PT J
AU Levitsky, LL
AF Levitsky, Lynne L.
TI Disorders of growth and development: new genetics, new endocrinology,
and new environmental challenges
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Editorial Material
C1 [Levitsky, Lynne L.] Massachusetts Gen Hosp, Dept Pediat, Pediat Endocrine Unit, Boston, MA 02114 USA.
RP Levitsky, LL (reprint author), Harvard Univ, Sch Med, 175 Cambridge St, Boston, MA 02114 USA.
EM LLevitsky@mgh.harvard.edu
NR 0
TC 1
Z9 1
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD FEB
PY 2015
VL 22
IS 1
BP 34
EP 34
DI 10.1097/MED.0000000000000129
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AX6IW
UT WOS:000347027000007
PM 25546636
ER
PT J
AU Levitsky, LL
Luria, AHO
Hayes, FJ
Lin, AE
AF Levitsky, Lynne L.
Luria, Anne H. O'Donnell
Hayes, Frances J.
Lin, Angela E.
TI Turner syndrome: update on biology and management across the life span
SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
LA English
DT Article
DE aortic dissection; estrogen therapy; recombinant growth hormone therapy;
short stature; Turner syndrome
ID IDIOPATHIC SHORT STATURE; MULLERIAN HORMONE-LEVELS; BICUSPID
AORTIC-VALVE; X-CHROMOSOME; PUBERTAL DEVELOPMENT; MAGNETIC-RESONANCE;
MATERNAL PLASMA; CLINICAL-TRIAL; GH DEFICIENCY; SELF-ESTEEM
AB Purpose of reviewWe review recent understanding of the pathophysiology, molecular biology, and management of Turner syndrome.Recent findingsSophisticated genetic techniques are able to detect mosaicism in one-third of individuals previously thought to have monosomy X. Prenatal detection using maternal blood should permit noninvasive detection of most fetuses with an X chromosome abnormality. Disproportionate growth with short limbs has been documented in this condition, and a target gene of short stature homeobox, connective tissue growth factor (Ctgf), has been described. Liver disease is more common in Turner syndrome than previously recognized. Most girls have gonadal failure. Spontaneous puberty and menarche is more commonly seen in girls with XX mosaicism. Low-dose estrogen replacement therapy may be given early to induce a more normal onset and tempo of puberty. Oocyte donation for assisted reproduction carries a substantial risk, particularly if the woman has known cardiac or aortic disease. Neurodevelopmental differences in Turner syndrome are beginning to be correlated with differences in brain anatomy.SummaryAn increased understanding of the molecular basis for aspects of this disorder is now developing. In addition, a renewed focus on health maintenance through the life span should provide better general and targeted healthcare for these girls and women.
C1 [Levitsky, Lynne L.] Massachusetts Gen Hosp, Dept Pediat, Pediatr Endocrine Unit, Boston, MA 02114 USA.
[Luria, Anne H. O'Donnell] Harvard Univ, Sch Med, Genet Residency Program, Boston, MA 02114 USA.
[Luria, Anne H. O'Donnell; Lin, Angela E.] Boston Childrens Hosp, Boston, MA USA.
[Hayes, Frances J.] Massachusetts Gen Hosp, Dept Med, Reproduct Endocrine Unit, Boston, MA 02114 USA.
Mass Gen Hosp Children, Gegenet Unit, Boston, MA 02114 USA.
RP Levitsky, LL (reprint author), Harvard Univ, Sch Med, 175 Cambridge St, Boston, MA 02114 USA.
EM LLevitsky@mgh.harvard.edu
OI O'Donnell-Luria, Anne/0000-0001-6418-9592
NR 90
TC 4
Z9 4
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD FEB
PY 2015
VL 22
IS 1
BP 65
EP 72
DI 10.1097/MED.0000000000000128
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AX6IW
UT WOS:000347027000012
PM 25517026
ER
PT J
AU Lambertini, M
Ginsburg, ES
Partridge, AH
AF Lambertini, Matteo
Ginsburg, Elizabeth S.
Partridge, Ann H.
TI Update on fertility preservation in young women undergoing breast cancer
and ovarian cancer therapy
SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY
LA English
DT Review
DE BRCA1 and BRCA2 mutations; breast cancer; fertility issues; ovarian
cancer; young women
ID PREIMPLANTATION GENETIC DIAGNOSIS; IN-VITRO FERTILIZATION; HORMONE
AGONISTS; CONSERVATIVE MANAGEMENT; SPARING SURGERY; PREMENOPAUSAL WOMEN;
AMERICAN-SOCIETY; RANDOMIZED-TRIAL; MATURED OOCYTES; BRCA2 MUTATION
AB Purpose of review
The purpose of the article is to review the available options for fertility preservation in patients with breast and ovarian cancer, and the special issues faced by BRCA mutation carriers.
Recent findings
Future fertility is an important consideration for many young patients with cancer. There are both experimental and standard available strategies for patients with breast and ovarian cancer to preserve fertility, and each has potential advantages and disadvantages.
Summary
Embryo cryopreservation is widely available with a highly successful track record. Improvements in laboratory techniques have led to oocyte cryopreservation recently being recategorized as nonexperimental. Conservative gynecologic surgery is a standard consideration for patients with stage I ovarian cancer who desire future fertility. Ovarian tissue cryopreservation as well as ovarian suppression with luteinizing hormone-releasing hormone analogs during chemotherapy are considered experimental methods at this time, although recent data suggest both safety and efficacy for the use of luteinizing hormone-releasing hormone analogs in women receiving (neo)adjuvant chemotherapy for breast cancer. Special issues should be considered for women with BRCA mutations because of the need to undergo preventive surgery at young age. Multidisciplinary teams and well functioning relationships between the oncology and reproductive units are crucial to manage the fertility issues of young women with cancer.
C1 [Lambertini, Matteo; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Lambertini, Matteo] IRCCS AOU San Martino IST, Dept Med Oncol, UO Oncol Med 2, Genoa, Italy.
[Ginsburg, Elizabeth S.] Brigham & Womens Hosp, Ctr Infertil & Reprod Surg, Boston, MA 02115 USA.
RP Partridge, AH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM Ann_Partridge@dfci.harvard.edu
OI Lambertini, Matteo/0000-0003-1797-5296
NR 93
TC 14
Z9 14
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-872X
EI 1473-656X
J9 CURR OPIN OBSTET GYN
JI Curr. Opin. Obstet. Gynecol.
PD FEB
PY 2015
VL 27
IS 1
BP 98
EP 107
DI 10.1097/GCO.0000000000000138
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AX9WZ
UT WOS:000347251200016
PM 25490381
ER
PT J
AU Basch, E
Autio, KA
Smith, MR
Bennett, AV
Weitzman, AL
Scheffold, C
Sweeney, C
Rathkopf, DE
Smith, DC
George, DJ
Higano, CS
Harzstark, AL
Sartor, AO
Gordon, MS
Vogelzang, NJ
de Bono, JS
Haas, NB
Corn, PG
Schimmoller, F
Scher, HI
AF Basch, Ethan
Autio, Karen A.
Smith, Matthew R.
Bennett, Antonia V.
Weitzman, Aaron L.
Scheffold, Christian
Sweeney, Christopher
Rathkopf, Dana E.
Smith, David C.
George, Daniel J.
Higano, Celestia S.
Harzstark, Andrea L.
Sartor, A. Oliver
Gordon, Michael S.
Vogelzang, Nicholas J.
de Bono, Johann S.
Haas, Naomi B.
Corn, Paul G.
Schimmoller, Frauke
Scher, Howard I.
TI Effects of Cabozantinib on Pain and Narcotic Use in Patients with
Castration-resistant Prostate Cancer: Results from a Phase 2
Nonrandomized Expansion Cohort
SO EUROPEAN UROLOGY
LA English
DT Article
DE mCRPC; Pain control; Patient-reported outcomes; Phase 2 trial; Quality
of life; Tyrosine kinase inhibitor
ID MITOXANTRONE PLUS PREDNISONE; REPORTED OUTCOMES; CLINICAL-TRIALS;
RANDOMIZED-TRIAL; END-POINTS; RECOMMENDATIONS; CHEMOTHERAPY; MET;
METASTASIS; INHIBITOR
AB Background: Pain negatively affects quality of life for cancer patients. Preliminary data in metastatic castration-resistant prostate cancer (mCRPC) suggested a benefit of the oral tyrosine kinase inhibitor cabozantinib to pain palliation.
Objective: Prospective evaluation of cabozantinib's benefits on pain and narcotic use in mCRPC.
Design, setting, and participants: This was a nonrandomized expansion (NRE) cohort (n = 144) of a phase 2 randomized discontinuation trial in docetaxel-refractory mCRPC patients. Pain and interference of symptoms with sleep and general activity were electronically self-reported daily for 7-d intervals at baseline and regularly scheduled throughout the study. Mean per-patient scores were calculated for each interval. Narcotic use was recorded daily during the same intervals. Intervention: Open-label cabozantinib (100 mg or 40 mg).
Outcome measurements and statistical analysis: The following stringent response definition was used: clinically meaningful pain reduction (>= 30% improvement in mean scores from baseline) confirmed at a later interval without concomitant increases in narcotics. Only patients with moderate or severe baseline pain were analyzed.
Results and limitations: Sixty-five patients with moderate or severe baseline pain were evaluable. Of these, 27 (42%) experienced pain palliation according to the stringent response definition. Thirty-seven patients (57%) had clinically meaningful pain relief at two consecutive intervals, reported >= 6 wk apart in the majority. Forty-four patients (68%) had palliation at one or more intervals; 36 (55%) decreased narcotics use during one or more intervals. Clinically meaningful pain reduction was associated with significant (p <= 0.001) improvements in sleep quality and general activity. A limitation of this study was its open-label design.
Conclusions: Cabozantinib demonstrated clinically meaningful pain palliation, reduced or eliminated patients' narcotic use, and improved patient functioning, thus meriting prospective validation in phase 3 studies.
Patient summary: We evaluated the potential of cabozantinib to improve symptoms in patients with metastatic prostate cancer that no longer responds to standard therapies. We saw a promising reduction in pain and reduced need for narcotic painkillers. Larger, well-controlled trials are necessary to confirm these findings. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Basch, Ethan; Bennett, Antonia V.] Univ N Carolina, Canc Outcomes Res Program, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA.
[Autio, Karen A.; Rathkopf, Dana E.; Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA.
[Autio, Karen A.; Scher, Howard I.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Smith, Matthew R.] Massachusetts Gen Hosp, Genitourinary Oncol Program, Boston, MA 02114 USA.
[Weitzman, Aaron L.; Scheffold, Christian; Schimmoller, Frauke] Exelixis Inc, Clin Dev, San Francisco, CA USA.
[Sweeney, Christopher] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Smith, David C.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[George, Daniel J.] Duke Univ, Med Ctr, Durham, NC USA.
[Higano, Celestia S.] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA 98195 USA.
[Harzstark, Andrea L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sartor, A. Oliver] Tulane Univ, Tulane Canc Ctr, New Orleans, LA 70118 USA.
[Gordon, Michael S.] Pinnacle Oncol Hematol, Scottsdale, AZ USA.
[Vogelzang, Nicholas J.] Comprehens Canc Ctr Nevada, Las Vegas, NV USA.
[de Bono, Johann S.] Royal Marsden Hosp, Drug Dev Unit, Sutton, Surrey, England.
[Haas, Naomi B.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Corn, Paul G.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA.
RP Basch, E (reprint author), Univ N Carolina, Canc Outcomes Res Program, 170 Manning Dr CB 7305,Phys Off Bldg,Suite 3185, Chapel Hill, NC 27599 USA.
EM Ebasch@med.unc.edu
OI Rathkopf, Dana/0000-0002-4503-7582
FU Exelixis, Inc.; US Department of Defense (DOD) Prostate Cancer Clinical
Trials Consortium at Memorial Sloan-Kettering Cancer Center; Prostate
Cancer Foundation; National Cancer Institute; DOD [W81XWH-11-1-0639]
FX This study was sponsored by Exelixis, Inc. Employees of the sponsor were
involved in study design, collection of the data, management of the
data, manuscript review, and manuscript writing. Additional funding was
provided by the US Department of Defense (DOD) Prostate Cancer Clinical
Trials Consortium at Memorial Sloan-Kettering Cancer Center and the
Prostate Cancer Foundation. E. Basch's research is supported by grants
from the National Cancer Institute and the DOD (grant W81XWH-11-1-0639);
this work does not represent the views or opinions of the DOD.
NR 34
TC 12
Z9 13
U1 5
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD FEB
PY 2015
VL 67
IS 2
BP 310
EP 318
DI 10.1016/j.eururo.2014.02.013
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA AX6LJ
UT WOS:000347033500038
PM 24631409
ER
PT J
AU Economopoulos, KP
Stamou, A
Sergentanis, TN
AF Economopoulos, Konstantinos P.
Stamou, Aliki
Sergentanis, Theodoros N.
TI Re: Luis Felipe Brandao, Riccardo Autorino, Humberto Laydner, et al.
Robotic Versus Laparoscopic Adrenalectomy: A Systematic Review and
Meta-analysis. Eur Urol 2014; 65: 1154-61
SO EUROPEAN UROLOGY
LA English
DT Letter
C1 [Economopoulos, Konstantinos P.; Sergentanis, Theodoros N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Economopoulos, Konstantinos P.; Stamou, Aliki; Sergentanis, Theodoros N.] Soc Jr Doctors, Athens, Greece.
[Sergentanis, Theodoros N.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
RP Economopoulos, KP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 101 Merrimack St, Boston, MA 02114 USA.
EM keconomopoulos@mgh.harvard.edu
OI Economopoulos, Konstantinos/0000-0003-4856-0405; Sergentanis, Theodoros
N./0000-0002-9355-5528
NR 5
TC 1
Z9 1
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD FEB
PY 2015
VL 67
IS 2
BP E32
EP E32
DI 10.1016/j.eururo.2014.09.052
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA AX6LJ
UT WOS:000347033500009
PM 25311953
ER
PT J
AU Coleman, CN
Sullivan, JM
Bader, JL
Murrain-Hill, P
Koerner, JF
Garrett, AL
Weinstock, DM
Case, C
Hrdina, C
Adams, SA
Whitcomb, RC
Graeden, E
Shankman, R
Lant, T
Maidment, BW
Hatchett, RC
AF Coleman, C. Norman
Sullivan, Julie M.
Bader, Judith L.
Murrain-Hill, Paula
Koerner, John F.
Garrett, Andrew L.
Weinstock, David M.
Case, Cullen, Jr.
Hrdina, Chad
Adams, Steven A.
Whitcomb, Robert C.
Graeden, Ellie
Shankman, Robert
Lant, Timothy
Maidment, Bert W.
Hatchett, Richard C.
TI PUBLIC HEALTH AND MEDICAL PREPAREDNESS FOR A NUCLEAR DETONATION: THE
NUCLEAR INCIDENT MEDICAL ENTERPRISE
SO HEALTH PHYSICS
LA English
DT Article
DE National Council on Radiation Protection and Measurements; emergency
planning; nuclear war; radiological terrorism
ID SCARCE RESOURCES; RADIATION VICTIMS; GLOBAL CONSENSUS; DECISION-MODEL;
MASS-CASUALTY; MANAGEMENT; EMERGENCIES; ALLOCATION; TRIAGE; TOOLS
AB Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience, and ideas. Public health and medical planning require a complex, multifaceted systematic approach involving federal, state, local, tribal, and territorial governments; private sector organizations; academia; industry; international partners; and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a "bottom-up" systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication, and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided.
C1 [Coleman, C. Norman; Sullivan, Julie M.; Bader, Judith L.; Murrain-Hill, Paula; Koerner, John F.; Garrett, Andrew L.; Shankman, Robert] Dept Hlth & Human Serv, Off Emergency Management, Off Assistant Secretary Preparedness & Response, Washington, DC USA.
[Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Weinstock, David M.; Case, Cullen, Jr.] Natl Marrow Donor Program, Radiat Injury Treatment Network, Minneapolis, MN USA.
[Hrdina, Chad] Dept Hlth & Human Serv, Off Policy & Planning, Off Assistant Secretary Preparedness & Response, Washington, DC USA.
[Adams, Steven A.] Ctr Dis Control & Prevent, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA USA.
[Whitcomb, Robert C.] Ctr Dis Control & Prevent, Radiat Studies Branch, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Graeden, Ellie] Gryphon Sci LLC, Rockville, MD USA.
[Lant, Timothy; Hatchett, Richard C.] Dept Hlth & Human Serv, Biomed Adv Res & Dev Author, Off Assistant Secretary Preparedness & Response, Washington, DC USA.
[Maidment, Bert W.] NIAID, Radiat Nucl Countermeasures Program, NIH, Bethesda, MD 20892 USA.
RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
EM ccoleman@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 53
TC 9
Z9 9
U1 2
U2 23
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD FEB
PY 2015
VL 108
IS 2
BP 149
EP 160
DI 10.1097/HP.0000000000000249
PG 12
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AX6YN
UT WOS:000347064100011
PM 25551496
ER
PT J
AU Lee, J
Jeon, JY
Meyerhardt, JA
AF Lee, Junga
Jeon, Justin Y.
Meyerhardt, Jeffrey A.
TI Diet and Lifestyle in Survivors of Colorectal Cancer
SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Colorectal cancer; Cancer survival; Lifestyle factors; Epigenetics
ID BODY-MASS INDEX; III COLON-CANCER; RECREATIONAL PHYSICAL-ACTIVITY;
TREATMENT-RELATED TOXICITY; ADJUVANT CHEMOTHERAPY; RECTAL-CANCER;
DIAGNOSIS; IMPACT; GROWTH; ASSOCIATION
AB Much research supports the association between diet and lifestyle in the development of colorectal cancer. Recent studies have demonstrated an association between various energy balance host factors (obesity, physical inactivity, and certain dietary factors) and outcomes. This review summarizes the impact of modifiable lifestyle factors, including prediagnosis and postdiagnosis adiposity, physical activity, and diet, on the prognosis of patients with colorectal cancer. The article focuses on associations of these factors in survivors of stage I to III colorectal cancer, and summarizes the possible mechanisms for the association between modifiable lifestyle factors and the prognosis of patients with colorectal cancer.
C1 [Lee, Junga; Jeon, Justin Y.] Yonsei Univ, Exercise Med Ctr Canc & Diabet Patients, Dept Sport & Leisure Studies, Seoul 120749, South Korea.
[Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM jmeyerhardt@partners.org
FU NCI NIH HHS [P50 CA127003, R01 CA149222, R01 CA169141, U54 CA155626]
NR 53
TC 8
Z9 8
U1 6
U2 24
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8588
EI 1558-1977
J9 HEMATOL ONCOL CLIN N
JI Hematol. Oncol. Clin. North Am.
PD FEB
PY 2015
VL 29
IS 1
BP 1
EP +
DI 10.1016/j.hoc.2014.09.005
PG 28
WC Oncology; Hematology
SC Oncology; Hematology
GA AX5FD
UT WOS:000346951300002
PM 25475570
ER
PT J
AU Chan, CHF
Cusack, JC
Ryan, DP
AF Chan, Carlos H. F.
Cusack, James C.
Ryan, David P.
TI A Critical Look at Local-Regional Management of Peritoneal Metastasis
SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Colorectal cancer; Carcinomatosis; Cytoreductive surgery; Hyperthermic
intraperitoneal chemotherapy; Systemic chemotherapy
ID HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; COLORECTAL-CANCER; SYSTEMIC
CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; RANDOMIZED-TRIAL; CARCINOMATOSIS;
ORIGIN; SURVIVAL
AB For patients with stage IV colorectal cancer, the presence of peritoneal metastases is a poor prognostic feature. Despite the improvement in systemic therapy, long-term survival remains poor for patients with peritoneal carcinomatosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be associated with long-term survival in patients who have limited peritoneal disease, particularly those who can have complete cytoreduction. Whether the possible benefit of CRS and HIPEC is from the surgical resection of all disease or the combination of CRS and HIPEC remains unclear.
C1 [Chan, Carlos H. F.; Cusack, James C.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA 02114 USA.
[Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Div Med Oncol, Boston, MA 02114 USA.
RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Med Oncol, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA.
EM DPRYAN@mgh.harvard.edu
NR 20
TC 4
Z9 4
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8588
EI 1558-1977
J9 HEMATOL ONCOL CLIN N
JI Hematol. Oncol. Clin. North Am.
PD FEB
PY 2015
VL 29
IS 1
BP 153
EP +
DI 10.1016/j.hoc.2014.09.006
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA AX5FD
UT WOS:000346951300009
PM 25475577
ER
PT J
AU Denny, BT
Fan, J
Liu, X
Ochsner, KN
Guerreri, S
Mayson, SJ
Rimsky, L
McMaster, A
New, AS
Goodman, M
Siever, LJ
Koenigsberg, HW
AF Denny, Bryan T.
Fan, Jin
Liu, Xun
Ochsner, Kevin N.
Guerreri, Stephanie
Mayson, Sarah Jo
Rimsky, Liza
McMaster, Antonia
New, Antonia S.
Goodman, Marianne
Siever, Larry J.
Koenigsberg, Harold W.
TI Elevated amygdala activity during reappraisal anticipation predicts
anxiety in avoidant personality disorder
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Avoidant personality disorder; Reappraisal; Anticipation; Anxiety; FMRI;
Amygdala
ID GENERALIZED SOCIAL PHOBIA; COGNITIVE REAPPRAISAL; EMOTION REGULATION;
BORDERLINE; PICTURES; BRAIN
AB Background: Avoidant personality disorder is characterized by pervasive anxiety, fear of criticism, disapproval, and rejection, particularly in anticipation of exposure to social situations. An important but underexplorecl question concerns whether anxiety in avoidant patients is associated with an impaired ability to engage emotion regulatory strategies in anticipation of and during appraisal of negative social stimuli.
Methods: We examined the use of an adaptive emotion regulation strategy, cognitive reappraisal, in avoidant patients. In addition to assessing individual differences in state and trait anxiety levels, self-reported affect as well as measures of neural activity were compared between 17 avoidant patients and 21 healthy control participants both in anticipation of and during performance of a reappraisal task.
Results: Avoidant patients showed greater state and trait related anxiety relative to healthy participants. In addition, relative to healthy participants, avoidant patients showed pronounced amygdala hyper-reactivity during reappraisal anticipation, and this hyper reactivity effect was positively associated with increasing self reported anxiety levels. Limitations: Our finding of exaggerated amygdala activity during reappraisal anticipation could reflect anxiety about the impending need to reappraise, anxiety about the certainty of an upcoming negative image, or anxiety relating to anticipated scrutiny of task responses by the experimenters. While we believe that all of these possibilities are consistent with the phenomenology of avoidant personality disorder, future research may clarify this ambiguity.
Conclusions: These results suggest that amygclala reactivity in anticipation of receiving negative social information may represent a key component of the neural mechanisms underlying the heightened anxiety present in avoidant patients. Published by Elsevier B.V.
C1 [Denny, Bryan T.; Fan, Jin; Guerreri, Stephanie; Mayson, Sarah Jo; Rimsky, Liza; McMaster, Antonia; New, Antonia S.; Goodman, Marianne; Siever, Larry J.; Koenigsberg, Harold W.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Fan, Jin] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
[Fan, Jin] CUNY Queens Coll, Dept Psychol, New York, NY 11367 USA.
[Liu, Xun] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China.
[Ochsner, Kevin N.] Columbia Univ, Dept Psychol, New York, NY 10027 USA.
RP Koenigsberg, HW (reprint author), James J Peters VA Med Ctr, Mental Hlth Patient Care Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM HWarrenK@nyc.rr.com
RI Fan, Jin/A-6716-2009
OI Fan, Jin/0000-0001-9630-8330
FU National Institute of Mental Health; James J Peters VA Medical Center;
National Center for Advancing Translational Sciences (a component of the
National Institutes of Health)
FX This research was funded by the National Institute of Mental Health, the
James J Peters VA Medical Center, and the National Center for Advancing
Translational Sciences (a component of the National Institutes of
Health). This publication is solely the work of the authors. The study
sponsors had no role in the collection, analysis, or interpretation of
data, in the writing of the manuscript, or in the decision to submit the
manuscript for publication.
NR 36
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U1 2
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD FEB 1
PY 2015
VL 172
BP 1
EP 7
DI 10.1016/j.jad.2014.09.017
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AX0LD
UT WOS:000346643000001
PM 25451388
ER
PT J
AU Blanc, J
Bui, E
Mouchenik, Y
Derivois, D
Birmes, P
AF Blanc, Judite
Bui, Eric
Mouchenik, Yoram
Derivois, Daniel
Birmes, Philippe
TI Prevalence of post-traumatic stress disorder and depression in two
groups of children one year after the January 2010 earthquake in Haiti
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Depression; Children; Earthquake; Post-traumatic stress disorder
ID SYMPTOMS; SURVIVORS; VICTIMS
AB Background: More than 500 studies were conducted in Haiti following the January 12 of 2010 earthquake, yet few of them assessed mental health of the population. To our knowledge, none targeted the effectiveness of various methods used to treat survivors, whether adults or children
Method: Our study aimed to assess one year after the disaster, the effect of a specific psycho-social support offered to relocated children in Port-au-Prince compared with a control group.
Results: The two groups were homogeneous in the intensity of the peritraumatic distress they experienced. We were unable to show a significant difference between both in the average scores for PTSD, nor for depression, nor in three out of the four sub-scales of the Child Behavior Check-List. In case children, 68% and 40.9%, respectively, and 50% and 20.5% of the control group, reported severe levels of the symptoms of PTSD and depression. These surprising results can be explained by the absence of equivalence in the two groups from a socio-demographic point of view and because subjects were not randomly selected in the recruitment process.
Conclusion: This study has not made it possible to indicate the effectiveness of a specific psycho-social support offered to children in the aftermath of the disaster. On the other hand, the sample illustrates the high prevalence (more than 50% for PTSD) of severe post-traumatic stress in this group of school-age children, one year after the earthquake. These results indicate that serious attention should be paid to the mental health aspects in reconstruction program for the country. (C) 2014 Elsevier B.V. All rights reserved,
C1 [Blanc, Judite; Mouchenik, Yoram] Univ Paris 13, Lab UTRPP, F-93430 Villetaneuse, France.
[Blanc, Judite] Univ Toulouse, Lab Stress Traumat, Toulouse, France.
[Blanc, Judite] Univ Etat Haiti, FASCH, Port Au Prince, Haiti.
[Bui, Eric] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders,RSF MGH Ho, Boston, MA 02114 USA.
[Derivois, Daniel] Univ Lyon 2, Lab CRPPC, F-69365 Lyon 07, France.
[Birmes, Philippe] Univ Hosp Toulouse, LST, EA 4560, Toulouse, France.
[Birmes, Philippe] Univ Toulouse 3, F-31062 Toulouse, France.
RP Blanc, J (reprint author), Univ Paris 13, Lab UTRPP, 99 Ave Jean Baptiste Clement, F-93430 Villetaneuse, France.
EM juditeblanc@yahoo.fr
RI Bui, Eric/J-8347-2015
OI Bui, Eric/0000-0002-1413-6473
FU Agency Nationale de la Recherche in France
FX The translation of the manuscript front french to english was made
possible by ANR-10-HAIT-002 RECREAHVI project supported by Agency
Nationale de la Recherche in France
NR 25
TC 4
Z9 4
U1 3
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD FEB 1
PY 2015
VL 172
BP 121
EP 126
DI 10.1016/j.jad.2014.09.055
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AX0LD
UT WOS:000346643000018
PM 25451405
ER
PT J
AU Uchida, M
Serra, G
Zayas, L
Kenworthy, T
Hughes, B
Koster, A
Faraone, SV
Biederman, J
AF Uchida, Mai
Serra, Giulia
Zayas, Lazaro
Kenworthy, Tara
Hughes, Brittany
Koster, Ariana
Faraone, Stephen V.
Biederman, Joseph
TI Can manic switches be predicted in pediatric major depression? A
systematic literature review
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Review
DE Bipolar disorder; Major depressive disorder; Manic switch; Pediatric
ID BIPOLAR DISORDER; CLINICAL CHARACTERISTICS; CONDUCT DISORDER; FOLLOW-UP;
ADHD YOUTH; ADOLESCENTS; CHILDREN; BEHAVIOR; PROFILE; YOUNG
AB Background: The rate of switching from major depression to bipolar disorder is high in children. Predicting who is at risk for switching poses unique challenges and is of high clinical relevance. Our aim was to examine the existing scientific literature elucidating if certain clinical correlates predict ultimate bipolar switches in children initially presenting with a depressive episode.
Methods: We conducted a systematic literature search of studies assessing the risk factors for bipolar switching in youth. In all, seven studies fit our a priori criteria and were thus included in our qualitative review.
Results: Together, these papers found that manic switches in pediatric depression can be predicted by several risk factors, including positive family history of mood disorders, emotional and behavioral dysregulation, subthreshold mania, and psychosis.
Limitations: We identified only seven prospective informative studies for our review. The majority of subjects included in these studies were referred and Caucasian. Thus, the results may not generalize to other community samples and other ethnicities.
Conclusions: These findings can help alert clinicians of the risk of manic switches. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Uchida, Mai; Kenworthy, Tara; Hughes, Brittany; Koster, Ariana; Biederman, Joseph] Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA.
[Zayas, Lazaro] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Serra, Giulia] Univ Roma La Sapienza, NESMOS Dept, St Andrea Hosp, I-00185 Rome, Italy.
[Uchida, Mai; Serra, Giulia; Zayas, Lazaro; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA.
RP Uchida, M (reprint author), 55 Fruit St,Warren 625, Boston, MA 02114 USA.
EM muchida@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU Massachusetts General Hospital Pediatric Psychopharmacology Council Fund
FX This work was supported in part by the Massachusetts General Hospital
Pediatric Psychopharmacology Council Fund. The funding source had no
role in the study design; in the collection, analysis and interpretation
of data; in the writing of the report; or in the decision to submit the
article for publication.
NR 39
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U1 4
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD FEB 1
PY 2015
VL 172
BP 300
EP 306
DI 10.1016/j.jad.2014.10.046
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AX0LD
UT WOS:000346643000042
PM 25451429
ER
PT J
AU Pietrzak, RH
Rosenheck, RA
Cramer, JA
Vessichio, JC
Tsai, J
Southwick, SM
Krystal, JH
AF Pietrzak, Robert H.
Rosenheck, Robert A.
Cramer, Joyce A.
Vessichio, Jennifer C.
Tsai, Jack
Southwick, Steven M.
Krystal, John H.
CA VA CSP 504 Collaborative Grp
TI Elucidating the transdiagnostic dimensional structure of trauma-related
psychopathology: Findings from VA cooperative study 504-risperidone
treatment for military service related chronic post traumatic stress
disorder
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Posttraumatic stress disorder; Depression; Generalized anxiety disorder;
Veterans; Exploratory factor analysis; Functioning
ID RESEARCH DOMAIN CRITERIA; 5-FACTOR MODEL; SYMPTOMS; VETERANS; ANXIETY;
DEPRESSION; SCALE; PTSD; RDOC; DISTRESS
AB Background: Three of the most common trauma-related mental disorders posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD) are highly comorbid and share common transdiagnostic symptom dimensions of threat (i.e., fear) and loss (i.e., dysphoria) symptomatology. However, empirical evaluation of the dimensional structure of component aspects of these disorders is lacking.
Methods: Using structured clinical interview data from U.S. military veterans with chronic military related PTSD, we evaluated the transdiagnostic dimensional structure of PTSD, MDD, and GAD symptoms. We then examined the relationship between the best-fitting transdiagnostic model of these symptoms, and measures of physical and mental functioning, and life satisfaction and well-being.
Results: Exploratory factor analysis revealed that a 3-factor transdiagnostic model comprised of loss (i.e., dysphoria), threat (i.e., anxious arousal, re-experiencing, and avoidance symptoms), and somatic anxiety (i.e., physiological manifestations of anxiety) symptoms provided the best representation of trauma related PTSD, MDD, and GAD symptoms. Somatic anxiety symptoms were independently associated with physical functioning, while loss symptoms were independently associated with mental functioning and life satisfaction and well-being.
Limitations: Evaluation of study aims in a relatively homogeneous sample of veterans with chronic, military related PTSD.
Conclusions: Results of this study suggest that a 3-factor transdiagnostic model best characterizes the dimensional structure of PTSD, MDD, and GAD symptoms in military veterans with chronic military-related PTSD. This model evidenced external validity in demonstrating differential associations with measures of physical and mental functioning, and life satisfaction and well-being. Results provide support for emerging contemporary models of psychopathology, which emphasize transdiagnostic and dimensional conceptualizations of mental disorders. Such models may have utility in understanding the Functional status of trauma survivors. Published by Elsevier B.V.
C1 [Pietrzak, Robert H.; Southwick, Steven M.; Krystal, John H.] VA Connecticut Healthcare Syst, Clin Neurosci Div, US Dept Vet Affairs, Natl Ctr Posttraumat Stress Disorder, West Haven, CT USA.
[Pietrzak, Robert H.; Rosenheck, Robert A.; Cramer, Joyce A.; Vessichio, Jennifer C.; Tsai, Jack; Southwick, Steven M.; Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06516 USA.
[Rosenheck, Robert A.; Tsai, Jack; Krystal, John H.] New England Mental Illness Res Educ & Clin Ctr, US Dept Vet Affairs, West Haven, CT USA.
[Cramer, Joyce A.; Vessichio, Jennifer C.] VA Connecticut Healthcare Syst, Psychiat Serv, West Haven, CT USA.
[Krystal, John H.] Yale New Haven Med Ctr, Psychiat Serv, New Haven, CT 06504 USA.
RP Pietrzak, RH (reprint author), Yale Univ, Sch Med, US Dept Vet Affairs,Dept Psychiat, Natl Ctr Posttraumat Stress Disorder,VA Connectic, 950 Campbell Ave,151E, West Haven, CT 06516 USA.
EM robert.pietrzak@yale.edu
FU U.S. Department of Veterans Affairs [504]; National Institute on Alcohol
Abuse and Alcoholism [2P50AA012870-14]
FX This study was supported by the U.S. Department of Veterans Affairs
through its support of VA Cooperative Study #504, Clinical Neuroscience
Division of the VA National Center for PTSD, and the Consortium to
Alleviate PTSD. Johnson and Johnson provided medication and some
financial support to the U.S. Department of Veterans Affairs to
facilitate the initiation and conduct of the study. Additionally Dr.
Krystal received support from the National Institute on Alcohol Abuse
and Alcoholism grant (2P50AA012870-14) and the National Center for
Advancing Translational Science grants (UL1RR024139, PI: R. Sherwin,
UH2TR000960, PI: JHK).
NR 30
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Z9 0
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD FEB 1
PY 2015
VL 172
BP 331
EP 336
DI 10.1016/j.jad.2014.10.025
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AX0LD
UT WOS:000346643000047
PM 25451434
ER
PT J
AU Jacobsen, KK
Nievergelt, CM
Zayats, T
Greenwood, TA
Anttila, V
Akiskal, HS
Haavik, J
Fasmer, OB
Kelsoe, JR
Johansson, S
Oedegaard, KJ
AF Jacobsen, Kaya K.
Nievergelt, Caroline M.
Zayats, Tetyana
Greenwood, Tiffany A.
Anttila, Verneri
Akiskal, Hagop S.
Haavik, Jan
Fasmer, Ole Bernt
Kelsoe, John R.
Johansson, Stefan
Oedegaard, Ketil J.
CA BiGs Consortium IHG Consortium
TI Genome wide association study identifies variants in NBEA associated
with migraine in bipolar disorder
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Bipolar disorder; Migraine; Genetics; NBEA; Neurobeachin
ID RECEPTOR TRAFFICKING; SUSCEPTIBILITY LOCI; GENETIC ASSOCIATION;
NEUROBEACHIN; PREVALENCE; METAANALYSIS; POPULATION; GLUTAMATE; LINKAGE;
AUTISM
AB Background: Migraine is a common comorbidity among individuals with bipolar disorder, but the underlying mechanisms for this cooccurrence are poorly understood. The aim of this study was to investigate the genetic background of bipolar patients with and without migraine.
Methods: We performed a genome-wide association analysis contrasting 460 bipolar migraneurs with 914 bipolar patients without migraine from the Bipolar Genome Study (BiGS).
Results We identified one genome-wide significant association between migraine in bipolar disorder patients and rs1160720, an intronic single nucleotide polymorphism (SNP) in the NBEA gene (P=2.97 x 10(-8), OR: 1.82, 95% Cl: 1.47-225), although this was not replicated in a smaller sample of 289 migraine cases.
Limitations: Our study is based on self reported migraine.
Conclusions: NBEA encodes neurobeachin, a scaffolding protein primarily expressed in the brain and involved in trafficking of vesicles containing neurotransmitter receptors. This locus has not previously been implicated in migraine per se. We found no evidence of association in data from the GWAS migraine meta analysis consortium (n =118,710 participants) suggesting that the association might be specific to migraine co-morbid with bipolar disorder. (C) 2014 The Authors. Published by Elsevier B.V.
C1 [Jacobsen, Kaya K.; Zayats, Tetyana; Haavik, Jan; Johansson, Stefan] Univ Bergen, Dept Biomed, KG Jebsen Ctr Neurophyciatr Res, Bergen, Norway.
[Jacobsen, Kaya K.; Zayats, Tetyana; Johansson, Stefan] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway.
[Fasmer, Ole Bernt; Oedegaard, Ketil J.] Univ Bergen, Dept Clin Med, KG Jebsen Ctr Neurophyciatr Res, Bergen, Norway.
[Nievergelt, Caroline M.; Greenwood, Tiffany A.; Akiskal, Hagop S.; Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Anttila, Verneri] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Anttila, Verneri] Harvard Univ, Sch Med, Boston, MA USA.
[Anttila, Verneri] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Anttila, Verneri] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Akiskal, Hagop S.; Kelsoe, John R.] VA Hosp, Dept Psychiat, San Diego, CA USA.
[Haavik, Jan; Fasmer, Ole Bernt; Oedegaard, Ketil J.] Haukeland Hosp, Div Psychiat, N-5021 Bergen, Norway.
[Johansson, Stefan] Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway.
RP Jacobsen, KK (reprint author), Univ Bergen, Dept Biomed, N-5020 Bergen, Norway.
EM kja098@biomed.uib.no
RI Johansson, Stefan/C-4394-2011;
OI Johansson, Stefan/0000-0002-2298-7008; Nievergelt,
Caroline/0000-0001-5766-8923; Kaprio, Jaakko/0000-0002-3716-2455;
Wedenoja, Juho/0000-0002-6155-0378; Kaunisto, Mari/0000-0002-6946-9195;
Haavik, Jan/0000-0001-7865-2808
FU NIMH; NHGRI [MH68503, MH078151, MH081804, MH059567]; Genetic Association
Information Network (GAIN); UCSD General Clinical Research Center [M01
RR00827]; [R01 MH093500]; [U01 MH002758]; [K01 MH087889]
FX This work was supported by grants to JRK from the NIMH and NHGRI
(MH68503, MH078151, MH081804, MH059567 supplement) and by the Genetic
Association Information Network (GAIN) and the UCSD General Clinical
Research Center (M01 RR00827). CMN was supported by R01 MH093500 and U01
MH002758, TAG was funded by K01 MH087889.
NR 62
TC 1
Z9 1
U1 0
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD FEB 1
PY 2015
VL 172
BP 453
EP 461
PG 9
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AX0LD
UT WOS:000346643000063
PM 25451450
ER
PT J
AU Fava, M
Ramey, T
Pickering, E
Kinrys, G
Boyer, S
Altstiel, L
AF Fava, Maurizio
Ramey, Tanya
Pickering, Eve
Kinrys, Gustavo
Boyer, Stacey
Altstiel, Larry
TI A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the
Augmentation of a Nicotinic Acetylcholine Receptor Partial Agonist in
Depression Is There a Relationship to Leptin Levels?
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE CP-601,927; depression; MADRS score; leptin; BMI
ID OBESITY; ANTIDEPRESSANT; RESISTANCE; DISORDERS; CIGARETTE; CHOLINE;
SMOKING
AB This randomized, double-blind, placebo-controlled trial evaluated the efficacy of CP-601,927, an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist and an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to selective serotonin reuptake inhibitors (SSRIs). After open-label treatment with an SSRI for 8 weeks, subjects with a Hamilton Depression Scale 17 score greater than or equal to 16 were entered into a double-blind phase and randomized to CP-601,927 2 mg twice daily or placebo for 6 weeks. The primary end point was the change in Montgomery-Asberg Depression Rating Scale (MADRS) score from double-blind baseline to week 14. There was no significant difference in change from baseline to week 14 in the MADRS score for CP-610,927 versus placebo (least square mean difference [80% confidence interval], -1.30 [-3.32-0.71]). Post hoc analyses revealed that the drug-placebo difference in change from baseline (SE) to week 14 in MADRS score was greater in subjects with body mass index (BMI) less than or equal to 35 kg/m(2) (-3.43 [1.87], P = 0.069) than those with BMI greater than 35 kg/m(2) (3.37 [2.8], P = 0.230). Analysis of biomarkers associated with increased BMI suggests that baseline leptin had a significant effect on treatment outcome. P values for the effect of treatment on mean change in MADRS score for subjects with baseline leptin levels below and above the median were 0.055 and 0.0055, respectively. CP-601,927 was equivalent to placebo as an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to SSRIs. However, post hoc analyses suggest that BMI, particularly elevated leptin levels, may have affected the response to CP-601,927; however, further study may be needed to confirm these results.
C1 [Fava, Maurizio; Kinrys, Gustavo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Trials Network & Inst, Boston, MA USA.
[Pickering, Eve] Pfizer Res, Biostat, Cambridge, MA USA.
RP Fava, M (reprint author), Massachusetts Gen Hosp, Clin Trials Network & Inst, Bulfinch 351,55 Fruit St, Boston, MA 02114 USA.
EM MFAVA@PARTNERS.ORG
FU Pfizer Inc.
FX The study was funded by Pfizer Inc. Eve Pickering is an employee of
Pfizer Inc. Stacey Boyer is an employee of Biogen Idec. Tanya Ramey is
an employee of the National Institutes of Health. Maurizio Fava and
Gustavo Kinrys are employees of Harvard Medical School, Clinical Trials
Network and Institute at the Massachusetts General Hospital. Larry
Altstiel is an employee of Provectra Therapeutics.
NR 21
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U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD FEB
PY 2015
VL 35
IS 1
BP 51
EP 56
DI 10.1097/JCP.0000000000000245
PG 6
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA AX5QY
UT WOS:000346983200008
PM 25422883
ER
PT J
AU Monnelly, EP
Fonda, J
Gagnon, DR
Chittamooru, S
Lawler, EV
AF Monnelly, Edward P.
Fonda, Jennifer
Gagnon, David R.
Chittamooru, Subha
Lawler, Elizabeth V.
TI Weight Gain on Antipsychotic Medication Is Associated With Sustained Use
Among Veterans With Schizophrenia
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE schizophrenia; antipsychotic medications; weight change; persistence
ID THERAPEUTIC RESPONSE; RANDOMIZED-TRIAL; SERUM LEPTIN; CATIE;
RISPERIDONE; OLANZAPINE; ADHERENCE; DRUGS; EFFICACY; RISK
AB Objective: Continuous antipsychotic treatment is important in schizophrenia, and studies have shown that rates of discontinuation are high. Some studies suggest that weight gain may lead schizophrenic patients to discontinue treatment, whereas other studies show smaller effects of weight gain on medication discontinuation, and some find weight gain associated with symptom improvement. Our retrospective cohort study investigated the effect of weight change on the continued use for 1 year (persistence) of all antipsychotics, then among users of first-generation antipsychotics and second-generation antipsychotics (SGAs), and lastly subgroups of SGAs.
Methods: We identified 2130 patients with schizophrenia starting an antipsychotic that had not used 1 in the prior year. Using multivariable logistic regression adjusted for demographic and clinical variables, we determined the odds of remaining persistent on medication among patients who either gained weight or did not gain weight in the following year.
Results: For all antipsychotics combined, weight change was not associated with persistence. Among SGAs, weight gain was associated with a 23% increase in the adjusted odds ratio (OR) for persistence (OR, 1.23; 95% confidence interval [CI], 1.00-1.51), whereas there was a nonsignificant decrease in the adjusted odds of persistence among first-generation antipsychotic users (OR, 0.74; 95% CI, 0.43-1.28). When SGAs were divided into subgroups (clozapine/olanzapine, risperidone/quetiapine), both had increases in the likelihood of persistence, but only the association for clozapine/olanzapine was significant at a trend level (adjusted OR, 1.46; 95% CI, 0.99-2.16).
Conclusions: These findings are supportive of other research that shows weight gain does not invariably lead to medication discontinuation and may be associated with clinical improvement.
C1 [Monnelly, Edward P.; Fonda, Jennifer; Gagnon, David R.; Chittamooru, Subha; Lawler, Elizabeth V.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Monnelly, Edward P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Gagnon, David R.; Lawler, Elizabeth V.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lawler, Elizabeth V.] Harvard Univ, Sch Med, Boston, MA USA.
[Lawler, Elizabeth V.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
RP Monnelly, EP (reprint author), Jama Plain VA Med Ctr, Mental Hlth Serv, 150 S,Huntington Ave, Boston, MA 02130 USA.
EM Edward.monnelly@va.gov
FU Massachusetts Veterans Epidemiology Research and Information Center from
the Veterans Health Administration Cooperative Studies Program; Wyeth
Ayerst
FX This study was funded by the Massachusetts Veterans Epidemiology
Research and Information Center from the Veterans Health Administration
Cooperative Studies Program. Additional funding was provided by Wyeth
Ayerst.
NR 36
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD FEB
PY 2015
VL 35
IS 1
BP 57
EP 62
DI 10.1097/JCP.0000000000000262
PG 6
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA AX5QY
UT WOS:000346983200009
PM 25514067
ER
PT J
AU Bobo, WV
Reilly-Harrington, NA
Ketter, TA
Brody, BD
Kinrys, G
Kemp, DE
Shelton, RC
McElroy, SL
Sylvia, LG
Kocsis, JH
McInnis, MG
Friedman, ES
Singh, V
Tohen, M
Bowden, CL
Deckersbach, T
Calabrese, JR
Thase, ME
Nierenberg, AA
Rabideau, DJ
Schoenfeld, DA
Faraone, SV
Kamali, M
AF Bobo, William V.
Reilly-Harrington, Noreen A.
Ketter, Terence A.
Brody, Benjamin D.
Kinrys, Gustavo
Kemp, David E.
Shelton, Richard C.
McElroy, Susan L.
Sylvia, Louisa G.
Kocsis, James H.
McInnis, Melvin G.
Friedman, Edward S.
Singh, Vivek
Tohen, Mauricio
Bowden, Charles L.
Deckersbach, Thilo
Calabrese, Joseph R.
Thase, Michael E.
Nierenberg, Andrew A.
Rabideau, Dustin J.
Schoenfeld, David A.
Faraone, Stephen V.
Kamali, Masoud
TI Complexity of Illness and Adjunctive Benzodiazepine Use in Outpatients
With Bipolar I or II Disorder Results From the Bipolar CHOICE Study
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE benzodiazepines; bipolar disorder; patterns of practice; treatment
ID PSYCHOTROPIC-DRUG PRESCRIPTION; SEVERE MENTAL-ILLNESS; STEP-BD
PARTICIPANTS; DEPRESSIVE-ILLNESS; ANXIETY DISORDERS; MOOD DISORDERS;
COMORBIDITY; PATTERNS; LAMOTRIGINE; POPULATION
AB Benzodiazepines are widely prescribed for patients with bipolar disorders in clinical practice, but very little is known about the subtypes of patients with bipolar disorder or aspects of bipolar illness that contribute most to benzodiazepine use. We examined the prevalence of and factors associated with benzodiazepine use among 482 patients with bipolar I or II disorder enrolled in the Bipolar CHOICE study. Eighty-one subjects were prescribed benzodiazepines at study entry and were considered benzodiazepine users. Stepwise logistic regression was used to model baseline benzodiazepine use versus nonuse, using entry and exit criteria of P < 0.1. In bivariate analyses, benzodiazepine users were prescribed a significantly higher number of other psychotropic medications and were more likely to be prescribed lamotrigine or antidepressants as compared with benzodiazepine nonusers. Benzodiazepine users were more likely to have a diagnosis of bipolar I disorder and comorbid anxiety disorder, but not comorbid alcohol or substance use disorders. Benzodiazepine users also had experienced more anxiety and depressive symptoms and suicidality, but not irritability or manic symptoms, than did benzodiazepine nonusers. In the multivariate model, anxiety symptom level (regardless of diagnosis), lamotrigine use, number of concomitant psychotropic medications, college education, and high household income predicted benzodiazepine use. Benzodiazepine use in patients with bipolar disorders is associated with greater illness complexity as indicated by a higher number of concomitant psychotropic medications and higher anxiety symptom burden, regardless of a comorbid anxiety disorder diagnosis. Demographic factors were also important determinants of benzodiazepine use, which may be related to access to care and insurance coverage for benzodiazepines.
C1 [Bobo, William V.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN 55902 USA.
[Reilly-Harrington, Noreen A.; Kinrys, Gustavo; Sylvia, Louisa G.; Deckersbach, Thilo; Nierenberg, Andrew A.; Rabideau, Dustin J.; Schoenfeld, David A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Ketter, Terence A.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA.
[Ketter, Terence A.] Stanford Univ, Sch Med, Bipolar Disorders Clin, Stanford, CA 94305 USA.
[Brody, Benjamin D.; Kocsis, James H.] Cornell Univ, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10021 USA.
[Kemp, David E.; Calabrese, Joseph R.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Shelton, Richard C.] Univ Alabama Birmingham, Sch Med, Dept Psychiat, Birmingham, AL USA.
[McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA.
[McElroy, Susan L.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA.
[McInnis, Melvin G.; Kamali, Masoud] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[McInnis, Melvin G.; Kamali, Masoud] Univ Michigan, Depress Ctr, Ann Arbor, MI 48109 USA.
[Friedman, Edward S.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Singh, Vivek; Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Tohen, Mauricio] Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA.
[Thase, Michael E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
RP Bobo, WV (reprint author), Mayo Clin, Dept Psychiat & Psychol, 200 First St SW,Generose 2A, Rochester, MN 55902 USA.
EM bobo.william@mayo.edu
OI Faraone, Stephen/0000-0002-9217-3982
FU AstraZeneca Pharmaceuticals LP; Cephalon Inc; Eli Lilly and Company;
Pfizer Inc; Sunovion Pharmaceuticals; Allergan, Inc; Avanir
Pharmaceuticals; Bristol-Myers Squibb Company; Forest Pharmaceuticals;
Janssen Pharmaceutica Products, LP; Merck Co, Inc; Teva Pharmaceuticals;
Forest; Agency for Healthcare Research and Quality (AHRQ); Pritzker
Neuropsychiatric Disorders Research Consortium; AstraZeneca; Cephalon;
Elan Pharmaceuticals; Forest Pharmaceuticals Inc; GlaxoSmithKline;
Sanofi/Synthelabo; Sepracor Inc; UCB Pharma; Wyeth-Ayerst Laboratories;
Repligen; Roche; Takeda; Neosync; AHRQ; NIMH; NIDA; Burroughs Wellcome
Trust; Pritzker Consortium; Appian Labs; BristolMyers Squibb; Elan,
Corp; Euthymics Bioscience; Janssen Pharmaceutica; Naurex, Inc; Novartis
Pharmaceuticals; Otsuka Pharmaceuticals; Pamlab, Inc; RepligenRepligen,
Corp; Ridge Diagnostics; St Jude Medical, Inc; Takeda Pharmaceuticals;
Alkermes; Marriott Foundation; National Institute of Mental Health;
Orexigen Therapeutics, Inc; Pfizer; Shire; Takeda Pharmaceutical Company
Ltd; Transcept Pharmaceutical, Inc; Heinz C Prechter Research Fund;
Michigan Institute for Clinical Health Research (MICHR); Qatar National
Research Foundation; Merck Pharmaceuticals; Novartis; St Jude Medical;
Medtronics; NARSAD; TSA; OCF; Tufts University; NIH; NIA; Janssen
Pharmaceuticals; Forest Research Institute; Shire Development Inc;
Medtronic; Cyberonics; Northstar; Medacorp; MGH Psychiatry Academy;
BrainCells Inc; Systems Research and Applications Corporation; Boston
University; Catalan Agency for Health Technology Assessment and
Research; National Association of Social Workers Massachusetts;
Massachusetts Medical Society; Oxford University Press; Department of
Defense; Health Resources Services Administration; Cleveland Foundation;
Stanley Medical Research Institute; Abbott; Janssen; Eli Lilly;
Lundbeck; PharmaNeuroboost; Bristol-Myers Squibb; Cederroth; Elan;
Lichtwer Pharma; Pamlab; Stanley Foundation
FX Dr Reilly-Harrington receives royalties from Oxford University Press,
the American Psychological Association, and New Harbinger. She serves as
a consultant for United Biosource Corporation and was a shareholder in
Concordant Rater Systems. Dr Ketter, between May 14, 2010, and May 14,
2013, had the following financial interests/arrangements or affiliations
that could be perceived as real or apparent conflicts of interest:
grant/research support from AstraZeneca Pharmaceuticals LP, Cephalon
Inc, Eli Lilly and Company, Pfizer Inc, and Sunovion Pharmaceuticals;
consultant fees from Allergan, Inc, Avanir Pharmaceuticals,
Bristol-Myers Squibb Company, Cephalon Inc, Forest Pharmaceuticals,
Janssen Pharmaceutica Products, LP, Merck & Co, Inc, Sunovion
Pharmaceuticals, Teva Pharmaceuticals; lecture honoraria from Abbott
Laboratories, Inc, AstraZeneca Pharmaceuticals LP, GlaxoSmithKline, and
Otsuka Pharmaceuticals; and Publication Royalties from American
Psychiatric Publishing, Inc. In addition, Dr Ketter' s spouse is an
employee of and holds stock in Janssen Pharmaceuticals. Dr Brody has
received salary support over the past 3 years from grants funded by
Forest, Agency for Healthcare Research and Quality (AHRQ), and Pritzker
Neuropsychiatric Disorders Research Consortium. Dr Kinrys has received
research support from AstraZeneca, Bristol-Myers Squibb Company,
Cephalon, Elan Pharmaceuticals, Eli Lilly and Company, Forest
Pharmaceuticals Inc, GlaxoSmithKline, Sanofi/Synthelabo, Sepracor Inc,
Pfizer Inc, UCB Pharma, and Wyeth-Ayerst Laboratories. He has been an
advisor or consultant for AstraZeneca, Cephalon, Eli Lilly and Company,
Forest Pharmaceuticals Inc, GlaxoSmithKline, Janssen Pharmaceutica,
Pfizer Inc, Sepracor Inc, UCB Pharma, and Wyeth-Ayerst Laboratories. Dr
Kinrys has been a speaker for AstraZeneca, Forest Pharmaceuticals Inc,
GlaxoSmithKline, Sepracor Inc, and Wyeth-Ayerst Laboratories. Dr Sylvia
was a shareholder in Concordant Rater Systems and serves as a consultant
for Bracket Global, Inc and Clintara. She also receives royalties from
New Harbinger Publishers. Dr Friedman receives grant support from
Repligen, AstraZeneca, Roche, Takeda, and Neosync. He has been a
consultant for Pamlab. He receives royalties from Springer. He has
served as an expert forensic consultant for Thomson Rhodes & Cowie P. C.
and Berger and Zavesky Co. L. P. A. Dr Kocsis has received research
grants and contracts from AHRQ, NIMH, NIDA, Burroughs Wellcome Trust,
Pritzker Consortium, Takeda, Forest, AstraZeneca, and Roche. He is on
the speaker' s bureau at Pfizer and Merck and on the advisory board at
Corcept. Dr Kemp serves on the speaker's bureau for Pfizer and
AstraZeneca and is a consultant for Bristol-Myers Squibb, Teva, Corcept,
and Janssen. His spouse is a minor stockholder for Sanofi and Abbott. Dr
Shelton has served as a consultant to Bristol-Myers Squibb, Cyberonics,
Inc, Elan, Corp, Eli Lilly and Company, Euthymics Bioscience, Forest
Pharmaceuticals, Janssen Pharmaceutica, Medtronic, Inc, Otsuka
Pharmaceuticals, Pamlab, Inc, Pfizer, Inc, Ridge Diagnostics, and Takeda
Pharmaceuticals. Dr Shelton has received research grant support from
Appian Labs, BristolMyers Squibb, Elan, Corp, Eli Lilly and Company,
Euthymics Bioscience, Forest Pharmaceuticals, Janssen Pharmaceutica,
Naurex, Inc, Novartis Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab,
Inc, Repligen, Corp, Ridge Diagnostics, St Jude Medical, Inc, and Takeda
Pharmaceuticals.; Dr McElroy is a consultant to or member of the
scientific advisory boards of Alkermes, Bracket, Corcept, MedAvante,
Shire, Sunovian, and Teva. She is a principal or coinvestigator on
studies sponsored by the AHRQ, Alkermes, AstraZeneca, Cephalon, Eli
Lilly and Company, Forest, Marriott Foundation, National Institute of
Mental Health, Orexigen Therapeutics, Inc, Pfizer, Shire, Takeda
Pharmaceutical Company Ltd, and Transcept Pharmaceutical, Inc. She is
also an inventor onUnited States Patent no. 6,323,236 B2, Use of
Sulfamate Derivatives for Treating Impulse Control Disorders, and along
with the patent' s assignee, University of Cincinnati, Cincinnati, Ohio,
has received payments from Johnson & Johnson, which has exclusive rights
under the patent. Dr McInnis has received grants for research support
from NIMH, the Heinz C Prechter Research Fund, and the Michigan
Institute for Clinical Health Research (MICHR). He has received
consulting income from the Qatar National Research Foundation and Merck
Pharmaceuticals. Dr Friedman received grant support from NIMH, AHRQ,
Novartis, St Jude Medical, Medtronics, Repligen, AstraZeneca, Roche, and
Takeda. He receives royalties from Springer. He has been a consultant
for Pamlab. Dr Singh has been a speaker for Merck and Sunovion. He has
received research support from Novartis and AstraZeneca. Dr Tohen was an
employee of Lilly (1997-2008) and has received honoraria from or
consulted for AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Lilly,
Johnson & Johnson, Otsuka, Merck, Sunovion, Forest, Roche, Elan,
Lundbeck, Teva, Pamlab, Wyeth, and Wiley Publishing; his spouse is a
full-time employee and minor stockholder at Lilly. Dr Bowden is a
research collaborator with Elan and a consultant with Teva; he has no
participation with speaker bureaus, nor does he or his wife hold any
equity position in any biomedical or pharmaceutical corporation. Dr
Deckersbach has received research support from NIMH, NARSAD, TSA, OCF,
Tufts University, NIH, NIA, Janssen Pharmaceuticals, the Forest Research
Institute, Shire Development Inc, Medtronic, Cyberonics, and Northstar.
He has received honoraria, consultation fees, and/or royalties from the
following: Medacorp, MGH Psychiatry Academy, BrainCells Inc, Systems
Research and Applications Corporation, Boston University, Tufts
University, the Catalan Agency for Health Technology Assessment and
Research, the National Association of Social Workers Massachusetts, the
Massachusetts Medical Society, and Oxford University Press. Dr Calabrese
receives federal funding from the Department of Defense, Health
Resources Services Administration, and NIMH; he receives research
funding or grants from the following private industries or nonprofit
funds: Cleveland Foundation, NARSAD, and Stanley Medical Research
Institute; he receives research grants from Abbott, AstraZeneca,
Cephalon, GlaxoSmithKline, Janssen, Eli Lilly, and Lundbeck; he serves
on the advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb,
Dainippon Sumitomo Pharma, Forest, France Foundation, GlaxoSmithKline,
Janssen, NeuroSearch, OrthoMcNeil, Repligen, Schering-Plough, Servier,
Solvay/Wyeth, Takeda, and Supernus Pharmaceuticals; and he reports CME
activities with AstraZeneca, Bristol-Myers Squibb, France Foundation,
GlaxoSmithKline, Janssen, Johnson & Johnson, Schering-Plough, and
Solvay/Wyeth.; Dr Thase has been an advisor/consultant: to Alkermes,
AstraZeneca, BristolMyers Squibb, Eli Lilly, Forest Laboratories,
GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck, MedAvante, Merck,
Mylan, Neuronetics, Otsuka, Pamlab, PharmaNeuroboost, Pfizer, Rexahn,
Roche, Shire, Sunovion, Supernus, Takeda, and Teva, as well as the US
Food and Drug Administration and the National Institute of Mental
Health. During the same time frame, Dr Thase has received honoraria for
talks from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and
Pfizer and he has received research grants from Alkermes, AstraZeneca,
Eli Lilly, Forest, GlaxoSmithKline, Otsuka, PharmaNeuroboost, and Roche,
as well as the National Institute of Mental Health and the AHRQ. Dr
Nierenberg is a consultant for Abbott Laboratories, AstraZeneca,
Basilea, BrainCells Inc, Brandeis University, Bristol-Myers Squibb,
Cephalon, Corcept, Eli Lilly and Company, Forest, Genaissance,
GlaxoSmithKline, Innapharma, Janssen Pharmaceutica, Jazz
Pharmaceuticals, Lundbeck, Merck, Novartis, Pamlab, PGx Health, Pfizer,
Ridge Diagnostics, Roche, Sepracor, ScheringPlough, Shire, Somerset,
Sunovion, Takeda, Targacept, and Teva. He is a stakeholder in Appliance
Computing, Inc (MindSite); Brain Cells, Inc, InfoMed (potential share of
income). He receives research support from AHRQ, Bristol-Myers Squibb,
Cederroth, Cyberonics, Elan, Forest Pharmaceuticals, GlaxoSmithKline,
Janssen Pharmaceutica, Lichtwer Pharma, Eli Lilly, Mylin (formerly Dey
Pharmaceuticals), NARSAD, NIMH, Pamlab, Pfizer, Shire, Stanley
Foundation, and Wyeth-Ayerst. Honoraria include MGH Psychiatry Academy
in the past 3 years (prior to these, 3 years ago, he received honoraria
from Bristol-Myers Squibb, Cyberonics, Forest Pharmaceuticals,
GlaxoSmithKline, Eli Lilly, Shire, and WyethAyerst). Dr Nierenberg
receives other income from legal case reviews for CRICO, MBL Publishing
for past services as Editor-in-Chief of CNS Spectrums, Slack Inc for
services as Associate Editor of Psychiatric Annals, and Editorial Board,
Mind Mood Memory, Belvior Publications. He has copyright joint ownership
with MGH for Structured Clinical Interview for MADRS and Clinical
Positive Affect Scale and additional honoraria from ADURS, American
Society for Clinical Psychopharmacology and Zucker Hillside Hospital and
Forest and Janssen, Biomedical Development, Boston Center for the Arts,
University of Pisa, University of Wisconsin at Madison, University Texas
Southwest atDallas, Health New England and Harold Grinspoon Charitable
Foundation and Eli Lilly and AstraZeneca, Brandeis University,
International Society for Bipolar Disorder, 2nd East Asian Bipolar
Forum, MidAtlantic Permanente Research Institute, Up-to-Date. Dr
Schoenfeld has an ongoing consulting relationship with the following
pharmaceutical companies: Biogen, Neuronova, Cytokinetics, Edison
Pharmaceuticals, GlaxoSmithKline, Merck, Agennix, Alexion, and Pfizer.
He also has a consulting relationship with Aptiv, a contract research
organization. Dr Bobo, Mr Rabideau, and Dr Kamali report no competing
interests in the past 3 years.
NR 30
TC 2
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U1 4
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD FEB
PY 2015
VL 35
IS 1
BP 68
EP 74
DI 10.1097/JCP.0000000000000257
PG 7
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA AX5QY
UT WOS:000346983200011
PM 25514063
ER
PT J
AU Wijeakumar, S
Spencer, JP
Bohache, K
Boas, DA
Magnotta, VA
AF Wijeakumar, Sobanawartiny
Spencer, John P.
Bohache, Kevin
Boas, David A.
Magnotta, Vincent A.
TI Validating a new methodology for optical probe design and image
registration in fNIRS studies
SO NEUROIMAGE
LA English
DT Article
DE Functional near infrared spectroscopy; Probe geometry; Optode
co-registration; Visual working memory; AtlasViewerGUI
ID NEAR-INFRARED SPECTROSCOPY; WORKING-MEMORY; HEMODYNAMIC-RESPONSES;
BRAIN; STIMULI; INFANTS
AB Functional near-infrared spectroscopy (fNIRS) is an imaging technique that relies on the principle of shining near-infrared light through tissue to detect changes in hemodynamic activation. An important methodological issue encountered is the creation of optimized probe geometry for fNIRS recordings. Here, across three experiments, we describe and validate a processing pipeline designed to create an optimized, yet scalable probe geometry based on selected regions of interest (ROIs) from the functional magnetic resonance imaging (fMRI) literature. In experiment 1, we created a probe geometry optimized to record changes in activation from target ROIs important for visual working memory. Positions of the sources and detectors of the probe geometry on an adult head were digitized using a motion sensor and projected onto a generic adult atlas and a segmented head obtained from the subject's MRI scan. In experiment 2, the same probe geometry was scaled down to fit a child's head and later digitized and projected onto the generic adult atlas and a segmented volume obtained from the child's MRI scan. Using visualization tools and by quantifying the amount of intersection between target ROIs and channels, we show that out of 21 ROIs, 17 and 19 ROIs intersected with fNIRS channels from the adult and child probe geometries, respectively. Further, both the adult atlas and adult subject-specific MRI approaches yielded similar results and can be used interchangeably. However, results suggest that segmented heads obtained from MRI scans be used for registering children's data. Finally, in experiment 3, we further validated our processing pipeline by creating a different probe geometry designed to record from target ROIs involved in language and motor processing. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Wijeakumar, Sobanawartiny; Spencer, John P.; Bohache, Kevin] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA.
[Wijeakumar, Sobanawartiny; Spencer, John P.; Bohache, Kevin; Magnotta, Vincent A.] Univ Iowa, Delta Ctr, Iowa City, IA 52242 USA.
[Magnotta, Vincent A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
[Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA.
RP Wijeakumar, S (reprint author), Univ Iowa, Dept Psychol, E1 Seashore Hall, Iowa City, IA 52245 USA.
EM sobanawartiny-wijeakumar@uiowa.edu
FU NSF [HSD0527698]; NIH [P41 EB015896]
FX JPS acknowledges support from NSF HSD0527698.; DAB acknowledges support
from NIH P41 EB015896.
NR 34
TC 3
Z9 3
U1 0
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2015
VL 106
BP 86
EP 100
DI 10.1016/j.neuroimage.2014.11.022
PG 15
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AX7NG
UT WOS:000347101900008
PM 25705757
ER
PT J
AU Aganj, I
Reuter, M
Sabuncu, MR
Fischl, B
AF Aganj, Iman
Reuter, Martin
Sabuncu, Mert R.
Fischl, Bruce
TI Avoiding symmetry-breaking spatial non-uniformity in deformable image
registration via a quasi-volume-preserving constraint
SO NEUROIMAGE
LA English
DT Article
DE Deformable image registration; Volume-preserving constraints; Symmetry;
Inverse-consistency; Integral non-uniformity
ID LOCALLY ADAPTIVE REGULARIZATION; SURFACE-BASED ANALYSIS; FREE-FORM
DEFORMATION; NONRIGID REGISTRATION; DIFFEOMORPHIC REGISTRATION;
SEGMENTATION; ALGORITHM; DEMONS; BRAIN; CONSTRUCTION
AB The choice of a reference image typically influences the results of deformable image registration, thereby making it asymmetric. This is a consequence of a spatially non-uniform weighting in the cost function integral that leads to general registration inaccuracy. The inhomogeneous integral measure - which is the local volume change in the transformation, thus varying through the course of the registration - causes image regions to contribute differently to the objective function. More importantly, the optimization algorithm is allowed to minimize the cost function by manipulating the volume change, instead of aligning the images. The approaches that restore symmetry to deformable registration successfully achieve inverse-consistency, but do not eliminate the regional bias that is the source of the error. In this work, we address the root of the problem: the non-uniformity of the cost function integral. We introduce a new quasi-volume-preserving constraint that allows for volume change only in areas with well-matching image intensities, and show that such a constraint puts a bound on the error arising from spatial non-uniformity. We demonstrate the advantages of adding the proposed constraint to standard (asymmetric and symmetrized) demons and diffeomorphic demons algorithms through experiments on synthetic images, and real X-ray and 2D/3D brain MRI data. Specifically, the results show that our approach leads to image alignment with more accurate matching of manually defined neuroanatomical structures, better tradeoff between image intensity matching and registration-induced distortion, improved native symmetry, and lower susceptibility to local optima. In summary, the inclusion of this space-and time-varying constraint leads to better image registration along every dimension that we have measured it. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Aganj, Iman; Reuter, Martin; Sabuncu, Mert R.; Fischl, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Radiol De, Charlestown, MA 02129 USA.
[Reuter, Martin; Sabuncu, Mert R.; Fischl, Bruce] MIT, Dept Elect Engn & Comp Sci, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Fischl, Bruce] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Aganj, I (reprint author), 149,13th St,Room 2301, Charlestown, MA 02129 USA.
EM iman@nmr.mgh.harvard.edu; mreuter@nmr.mgh.harvard.edu;
msabuncu@nmr.mgh.harvard.edu; fischl@nmr.mgh.harvard.edu
RI Reuter, Martin/B-3456-2010
OI Reuter, Martin/0000-0002-2665-9693
FU National Center for Research Resources [U24 RR021382]; National
Institute for Biomedical Imaging and Bioengineering (NIBIB)
[P41-EB015896, R01EB006758]; National Institute on Aging [AG022381,
5R01AG008122-22, R01 AG016495-11]; National Center for Alternative
Medicine [RC1 AT005728-01]; National Institute for Neurological
Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963,
R01NS083534]; Autism & Dyslexia Project - Ellison Medical Foundation;
NIH Blueprint for Neuroscience Research [5U01-MH093765]; Massachusetts
Alzheimer's Disease Research Center [5 P50 AG005134]; Massachusetts
General Hospital (MGH) Neurology Clinical Trials Unit; Harvard
NeuroDiscovery Center; NIBIB K25 grant [1K25EB013649-01]; BrightFocus
Alzheimer's Disease Pilot grant [A2012333]; [1S10RR023401];
[1S10RR019307]; [1S10RR023043]
FX Support for this research was provided in part by the National Center
for Research Resources (U24 RR021382), the National Institute for
Biomedical Imaging and Bioengineering (NIBIB, P41-EB015896,
R01EB006758), the National Institute on Aging (AG022381,
5R01AG008122-22, R01 AG016495-11), the National Center for Alternative
Medicine (RC1 AT005728-01), the National Institute for Neurological
Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963,
R01NS083534), and was made possible by the resources provided by Shared
Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043.
Additional support was provided by The Autism & Dyslexia Project funded
by the Ellison Medical Foundation, and by the NIH Blueprint for
Neuroscience Research (5U01-MH093765), part of the multi-institutional
Human Connectome Project. IA was additionally supported by a grant from
the Massachusetts Alzheimer's Disease Research Center (5 P50 AG005134),
the Massachusetts General Hospital (MGH) Neurology Clinical Trials Unit,
and the Harvard NeuroDiscovery Center. MS received support from an NIBIB
K25 grant (1K25EB013649-01) and a BrightFocus Alzheimer's Disease Pilot
grant (A2012333). In addition, BF has a financial interest in
CorticoMetrics, a company whose medical pursuits focus on brain imaging
and measurement technologies. BF's interests were reviewed and are
managed by MGH and Partners HealthCare in accordance with their conflict
of interest policies.
NR 80
TC 2
Z9 3
U1 1
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2015
VL 106
BP 238
EP 251
DI 10.1016/j.neuroimage.2014.10.059
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AX7NG
UT WOS:000347101900022
PM 25449738
ER
PT J
AU De Winter, FL
Zhu, Q
Van den Stock, J
Nelissen, K
Peeters, R
de Gelder, B
Vanduffel, W
Vandenbulcke, M
AF De Winter, Francois-Laurent
Zhu, Qi
Van den Stock, Jan
Nelissen, Koen
Peeters, Ronald
de Gelder, Beatrice
Vanduffel, Wim
Vandenbulcke, Mathieu
TI Lateralization for dynamic facial expressions in human superior temporal
sulcus
SO NEUROIMAGE
LA English
DT Article
DE Lateralization; Dynamic facial expressions; Comparative; fMRI
ID FUSIFORM FACE AREA; CHIMPANZEES PAN-TROGLODYTES; HUMAN BRAIN; LANGUAGE
DOMINANCE; RIGHT-HEMISPHERE; FUNCTIONAL MRI; CEREBRAL LATERALIZATION;
MACAQUE CORTEX; PERCEPTION; FMRI
AB Most face processing studies in humans show stronger activation in the right compared to the left hemisphere. Evidence is largely based on studies with static stimuli focusing on the fusiform face area (FFA). Hence, the pattern of lateralization for dynamic faces is less clear. Furthermore, it is unclear whether this property is common to human and non-human primates due to predisposing processing strategies in the right hemisphere or that alternatively left sided specialization for language in humans could be the driving force behind this phenomenon. We aimed to address both issues by studying lateralization for dynamic facial expressions in monkeys and humans. Therefore, we conducted an event-related fMRI experiment in three macaques and twenty right handed humans. We presented human and monkey dynamic facial expressions (chewing and fear) as well as scrambled versions to both species. We studied lateralization in independently defined face-responsive and face-selective regions by calculating a weighted lateralization index (LIwm) using a bootstrapping method. In order to examine if lateralization in humans is related to language, we performed a separate fMRI experiment in ten human volunteers including a 'speech' expression (one syllable non-word) and its scrambled version.
Both within face-responsive and selective regions, we found consistent lateralization for dynamic faces (chewing and fear) versus scrambled versions in the right human posterior superior temporal sulcus (pSTS), but not in FFA nor in ventral temporal cortex. Conversely, in monkeys no consistent pattern of lateralization for dynamic facial expressions was observed. Finally, LIwms based on the contrast between different types of dynamic facial expressions (relative to scrambled versions) revealed left-sided lateralization in human pSTS for speech-related expressions compared to chewing and emotional expressions.
To conclude, we found consistent laterality effects in human posterior STS but not in visual cortex of monkeys. Based on our results, it is tempting to speculate that lateralization for dynamic face processing in humans may be driven by left-hemispheric language specialization which may not have been present yet in the common ancestor of human and macaque monkeys. (C) 2014 Elsevier Inc. All rights reserved.
C1 [De Winter, Francois-Laurent; Van den Stock, Jan; de Gelder, Beatrice; Vandenbulcke, Mathieu] Katholieke Univ Leuven, Dept Neurosci, Res Grp Psychiat, B-3000 Leuven, Belgium.
[De Winter, Francois-Laurent; Van den Stock, Jan; Vandenbulcke, Mathieu] Univ Hosp Leuven, Dept Old Age Psychiat, B-3000 Leuven, Belgium.
[Zhu, Qi; Nelissen, Koen; Vanduffel, Wim] Katholieke Univ Leuven, Dept Neurosci, Lab Neuro & Psychophysiol, B-3000 Leuven, Belgium.
[Peeters, Ronald] UZ Leuven, Dept Radiol, B-3000 Leuven, Belgium.
[Peeters, Ronald] Katholieke Univ Leuven, Dept Imaging & Pathol, B-3000 Leuven, Belgium.
[de Gelder, Beatrice] Maastricht Univ, Dept Cognit Neurosci, NL-6200 MD Maastricht, Netherlands.
[de Gelder, Beatrice] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands.
[Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
RP De Winter, FL (reprint author), Katholieke Univ Leuven, Dept Neurosci, Res Grp Psychiat, Herestr 49,Box 1027, B-3000 Leuven, Belgium.
EM francoislaurent.dewinter@med.kuleuven.be
RI Van den Stock, Jan/F-1906-2014
OI Van den Stock, Jan/0000-0001-5756-3195
FU Fund for Scientific Research (Flanders) [G043912, G074609, G062208,
G083111]; Hercules II Funding; Inter University Attraction Pole [7/11]
FX We thank C. Fransen, C. Van Eupen and A. Coeman for animal training and
care; and D. Mantini, H. Kolster, W. Depuydt, G. Meulemans, P.
Kayenbergh, M. De Paep, S. Verstraeten, and I. Puttemans for technical
assistance. This work was supported by the Fund for Scientific Research
(Flanders) G043912, G074609, G062208, and G083111, Hercules II Funding,
Inter University Attraction Pole 7/11. Q.Z. and J.V.d.S. are
post-doctoral fellows of the FWO Vlaanderen.
NR 70
TC 17
Z9 17
U1 6
U2 33
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2015
VL 106
BP 340
EP 352
DI 10.1016/j.neuroimage.2014.11.020
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AX7NG
UT WOS:000347101900031
PM 25463458
ER
PT J
AU Iglesias, JE
Sabuncu, MR
Aganj, I
Bhatt, P
Casillas, C
Salat, D
Boxer, A
Fischl, B
Van Leemput, K
AF Eugenio Iglesias, Juan
Sabuncu, Mert Rory
Aganj, Iman
Bhatt, Priyanka
Casillas, Christen
Salat, David
Boxer, Adam
Fischl, Bruce
Van Leemput, Koen
TI An algorithm for optimal fusion of atlases with different labeling
protocols
SO NEUROIMAGE
LA English
DT Article
DE Segmentation; Label fusion
ID SPATIALLY VARYING PERFORMANCE; HUMAN-BRAIN; IMAGE SEGMENTATION;
HIPPOCAMPAL SUBFIELDS; STATISTICAL FUSION; ALZHEIMERS-DISEASE; MRI; AGE;
PROBABILITY; SELECTION
AB In this paper we present a novel label fusion algorithm suited for scenarios in which different manual delineation protocols with potentially disparate structures have been used to annotate the training scans (hereafter referred to as "atlases"). Such scenarios arise when atlases have missing structures, when they have been labeled with different levels of detail, or when they have been taken from different heterogeneous databases. The proposed algorithm can be used to automatically label a novel scan with any of the protocols from the training data. Further, it enables us to generate new labels that are not present in any delineation protocol by defining intersections on the underling labels. We first use probabilistic models of label fusion to generalize three popular label fusion techniques to the multi-protocol setting: majority voting, semi-locally weighted voting and STAPLE. Then, we identify some shortcomings of the generalized methods, namely the inability to produce meaningful posterior probabilities for the different labels (majority voting, semi-locally weighted voting) and to exploit the similarities between the atlases (all three methods). Finally, we propose a novel generative label fusion model that can overcome these drawbacks. We use the proposed method to combine four brain MRI datasets labeled with different protocols (with a total of 102 unique labeled structures) to produce segmentations of 148 brain regions. Using cross-validation, we show that the proposed algorithm outperforms the generalizations of majority voting, semi-locally weighted voting and STAPLE (mean Dice score 83%, vs. 77%, 80% and 79%, respectively). We also evaluated the proposed algorithm in an aging study, successfully reproducing some well-known results in cortical and subcortical structures. (C) 2014 The Authors. Published by Elsevier Inc.
C1 [Eugenio Iglesias, Juan] Basque Ctr Cognit Brain & Language BCBL, Gipuzkoa, Spain.
[Sabuncu, Mert Rory; Aganj, Iman; Salat, David; Fischl, Bruce; Van Leemput, Koen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Bhatt, Priyanka; Casillas, Christen; Boxer, Adam] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Sabuncu, Mert Rory; Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA.
[Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, Odense, Denmark.
[Van Leemput, Koen] Aalto Univ, Dept Informat & Comp Sci, Espoo, Finland.
[Van Leemput, Koen] Aalto Univ, Dept Biomed Engn & Computat Sci, Espoo, Finland.
RP Iglesias, JE (reprint author), Basque Ctr Cognit Brain & Language BCBL, Gipuzkoa, Spain.
EM e.iglesias@bcbl.eu
RI Van Leemput, Koen/A-9197-2009; Iglesias, Juan Eugenio/K-1184-2014
OI Van Leemput, Koen/0000-0001-6466-5309; Iglesias, Juan
Eugenio/0000-0001-7569-173X
FU National Center for Research Resources [U24 RR021382, P41-RR14075,
1KL2RR025757-01]; National Institute for Biomedical Imaging and
Bioengineering [P41-EB015896, R01EB006758, R01EB013565,
1K25EB013649-01]; National Institute on Aging [AG022381,
5R01AG008122-22, R01 AG016495-11]; National Center for Alternative
Medicine [RC1 AT005728-01]; National Institute for Neurological
Disorders and Stroke [R01 NS052585-01, 1R21NS 072652-01, 1R01NS070963,
R01NS083534]; Autism & Dyslexia Project - Ellison Medical Foundation;
NIH Blueprint for Neuroscience Research [5U01-MH093765]; TEKES
(ComBrain); Harvard Catalyst; Harvard; Gipuzkoako Foru Aldundia;
BrightFocus grant [AHAF-A2012333]; [1S10RR023401]; [1S10RR019307];
[1S10RR023043]
FX Support for this research was provided in part by the National Center
for Research Resources (U24 RR021382, P41-RR14075, 1KL2RR025757-01), the
National Institute for Biomedical Imaging and Bioengineering
(P41-EB015896, R01EB006758, R01EB013565, 1K25EB013649-01), the National
Institute on Aging (AG022381, 5R01AG008122-22, R01 AG016495-11), the
National Center for Alternative Medicine (RC1 AT005728-01), the National
Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS
072652-01, 1R01NS070963, R01NS083534), and was made possible by the
resources provided by Shared Instrumentation Grants 1S10RR023401,
1S10RR019307, and 1S10RR023043. Additional support was provided by The
Autism & Dyslexia Project funded by the Ellison Medical Foundation, and
by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of
the multi-institutional Human Connectome Project. This research was also
funded by TEKES (ComBrain), Harvard Catalyst, and financial
contributions from Harvard and affiliations. JEI was supported by the
Gipuzkoako Foru Aldundia (Fellows Gipuzkoa Program). MRS was partially
supported by a BrightFocus grant (AHAF-A2012333). In addition, BF has a
financial interest in CorticoMetrics, a company whose medical pursuits
focus on brain imaging and measurement technologies. BF's interests were
reviewed and are managed by Massachusetts General Hospital and Partners
HealthCare in accordance with their conflict of interest policies.
NR 42
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Z9 2
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2015
VL 106
BP 451
EP 463
DI 10.1016/j.neuroimage.2014.11.031
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AX7NG
UT WOS:000347101900041
PM 25463466
ER
PT J
AU Huang, SY
Nummenmaa, A
Witzel, T
Duval, T
Cohen-Adad, J
Wald, LL
Mcnab, JA
AF Huang, Susie Y.
Nummenmaa, Aapo
Witzel, Thomas
Duval, Tanguy
Cohen-Adad, Julien
Wald, Lawrence L.
McNab, Jennifer A.
TI The impact of gradient strength on in vivo diffusion MRI estimates of
axon diameter
SO NEUROIMAGE
LA English
DT Article
ID HUMAN CONNECTOME PROJECT; HUMAN CORPUS-CALLOSUM;
AMYOTROPHIC-LATERAL-SCLEROSIS; AUTISM SPECTRUM DISORDERS; BRAIN
WHITE-MATTER; WEIGHTED MR; FIBER COMPOSITION; MICROSTRUCTURE
SENSITIVITY; RESTRICTED DIFFUSION; WATER RELAXATION
AB Diffusion magnetic resonance imaging (MRI) methods for axon diameter mapping benefit from higher maximum gradient strengths than are currently available on commercial human scanners. Using a dedicated high-gradient 3 T human MRI scanner with a maximum gradient strength of 300 mT/m, we systematically studied the effect of gradient strength on in vivo axon diameter and density estimates in the human corpus callosum. Pulsed gradient spin echo experiments were performed in a single scan session lasting approximately 2 h on each of three human subjects. The data were then divided into subsets with maximum gradient strengths of 77, 145, 212, and 293 mT/m and diffusion times encompassing short (16 and 25 ms) and long (60 and 94 ms) diffusion time regimes. A three-compartment model of intra-axonal diffusion, extra-axonal diffusion, and free diffusion in cerebrospinal fluid was fitted to the data using a Markov chain Monte Carlo approach. For the acquisition parameters, model, and fitting routine used in our study, it was found that higher maximum gradient strengths decreased the mean axon diameter estimates by two to three fold and decreased the uncertainty in axon diameter estimates by more than half across the corpus callosum. The exclusive use of longer diffusion times resulted in axon diameter estimates that were up to two times larger than those obtained with shorter diffusion times. Axon diameter and density maps appeared less noisy and showed improved contrast between different regions of the corpus callosum with higher maximum gradient strength. Known differences in axon diameter and density between the genu, body, and splenium of the corpus callosum were preserved and became more reproducible at higher maximum gradient strengths. Our results suggest that an optimal q-space sampling scheme for estimating in vivo axon diameters should incorporate the highest possible gradient strength. The improvement in axon diameter and density estimates that we demonstrate from increasing maximum gradient strength will inform protocol development and encourage the adoption of higher maximum gradient strengths for use in commercial human scanners. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Huang, Susie Y.; Nummenmaa, Aapo; Witzel, Thomas; Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02138 USA.
[Duval, Tanguy; Cohen-Adad, Julien] Ecole Polytech, Inst Biomed Engn, Montreal, PQ H3C 3A7, Canada.
[Wald, Lawrence L.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[McNab, Jennifer A.] Stanford Univ, Dept Radiol, Radiol Sci Lab, Stanford, CA 94305 USA.
RP Huang, SY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02138 USA.
EM syhuang@nmr.mgh.harvard.edu
RI Witzel, Thomas/P-1402-2014; Wald, Lawrence/D-4151-2009
FU NIH Blueprint for Neuroscience Research Grant [U01MH093765]; NIH from
NCRR [P41EB015896]; NIBIB [R01EB006847, K99EB015445]; Canadian Institute
for Health Research; RSNA Research Resident Grant
FX This work was funded by an NIH Blueprint for Neuroscience Research
Grant: U01MH093765, as well as NIH funding from NCRR P41EB015896, NIBIB
R01EB006847, and NIBIB K99EB015445. Funding support was also received
from a fellowship from the Canadian Institute for Health Research and an
RSNA Research Resident Grant. We thank Eric Klawiter, Jonathan Polimeni,
and Bruce Rosen for helpful discussions on this material.
NR 72
TC 22
Z9 22
U1 3
U2 25
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 1
PY 2015
VL 106
BP 464
EP 472
DI 10.1016/j.neuroimage.2014.12.008
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AX7NG
UT WOS:000347101900042
PM 25498429
ER
PT J
AU Bredella, MA
Azevedo, DC
Oliveira, AL
Simeone, FJ
Chang, CY
Stubbs, AJ
Torriani, M
AF Bredella, Miriam A.
Azevedo, Debora C.
Oliveira, Adriana L.
Simeone, Frank J.
Chang, Connie Y.
Stubbs, Allston J.
Torriani, Martin
TI Pelvic morphology in ischiofemoral impingement
SO SKELETAL RADIOLOGY
LA English
DT Article
DE Ischiofemoral impingement; Hip; MRI; Quadratus femoris muscle
ID QUADRATUS FEMORIS MUSCLE; LESSER TROCHANTER; HIP PAIN; PELVIMETRY
AB To assess MRI measures to quantify pelvic morphology that may predispose to ischiofemoral impingement (IFI). We hypothesized that patients with IFI have a wider interischial distance and an increased femoral neck angle compared with normal controls.
The study was IRB-approved and complied with HIPAA guidelines. IFI was diagnosed based on clinical findings (hip or buttock pain) and ipsilateral edema of the quadratus femoris muscle on MRI. Control subjects did not report isolated hip/buttock pain and underwent MRI for surveillance of neoplasms or to exclude pelvic fractures. Two MSK radiologists measured the ischiofemoral (IF) and quadratus femoris (QF) distance, the ischial angle as a measure of inter-ischial distance, and the femoral neck angle. The quadratus femoris muscle was evaluated for edema. Groups were compared using ANOVA. Multivariate standard least-squares regression modeling was used to control for age and gender.
The study group comprised 84 patients with IFI (53 +/- 16 years, 73 female, 11 male) and 51 controls (52 +/- 16 years, 33 female, 18 male). Thirteen out of 84 patients (15 %) had bilateral IFI. Patients with IFI had decreased IF and QF distance (p < 0.0001), increased ischial angle (p = 0.004), and increased femoral neck angle (p = 0.02) compared with controls, independent of age and gender.
Patients with IFI have increased ischial and femoral neck angles compared with controls. These anatomical variations in pelvic morphology may predispose to IFI. MRI is a useful method of not only assessing the osseous and soft-tissue abnormalities associated with IFI, but also of quantifying anatomical variations in pelvic morphology that can predispose to IFI.
C1 [Bredella, Miriam A.; Azevedo, Debora C.; Oliveira, Adriana L.; Simeone, Frank J.; Chang, Connie Y.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA.
[Stubbs, Allston J.] Wake Forest Univ, Bowman Gray Sch Med, Div Sports Med, Dept Orthoped Surg, Winston Salem, NC USA.
RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol Musculoskeletal Imaging & Intervent, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA.
EM mbredella@partners.org
NR 14
TC 15
Z9 16
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2348
EI 1432-2161
J9 SKELETAL RADIOL
JI Skeletal Radiol.
PD FEB
PY 2015
VL 44
IS 2
BP 249
EP 253
DI 10.1007/s00256-014-2041-0
PG 5
WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging
GA AX4LQ
UT WOS:000346904500011
PM 25371087
ER
PT J
AU Arterburn, D
Wellman, R
Westbrook, EO
Ross, TR
McCulloch, D
Handley, M
Lowe, M
Cable, C
Zeliadt, SB
Hoffman, RM
AF Arterburn, David
Wellman, Robert
Westbrook, Emily O.
Ross, Tyler R.
McCulloch, David
Handley, Matt
Lowe, Marc
Cable, Chris
Zeliadt, Steven B.
Hoffman, Richard M.
TI Decision Aids for Benign Prostatic Hyperplasia and Prostate Cancer
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID CLINICAL-PRACTICE; MANAGEMENT; UPDATE; HEALTH; GUIDELINE; BARRIERS;
CARE; MEN
AB Objectives
To examine the relationships among implementing decision aids (DAs) for benign prostatic hyperplasia (BPH) and prostate cancer (PRCA), and treatment rates and costs.
Study Design
A pre-post observational evaluation of a quality improvement initiative in a healthcare system in Washington state.
Methods
Men with BPH seen in urology clinics and all men diagnosed with localized PRCA were identified for an intervention period, in which urologists were instructed to order a DA for every patient with those conditions, and a historical control period. Outcomes were 6-month rates of surgery for BPH, any active treatment (hormone therapy, radiation, or surgery) for PRCA, and total healthcare costs.
Results
During the intervention, DAs were delivered to 22% of men with recent BPH drug treatment, 24% of men with untreated BPH, and 56% of men with PRCA. DA implementation was associated with a 32% lower rate of surgery among men with treated BPH (rate ratio [RR], 0.68; 95% CI, 0.49-0.94) and a nonsignificant 22% lower rate of surgery among men with previously untreated BPH (RR, 0.78; 95% CI, 0.50-1.22). For PRCA, DA implementation was associated with a 27% lower rate of active treatment (RR, 0.73; 95% CI, 0.57-0.93). We found no significant associations between DA implementation and costs of care for either condition.
Conclusions
Implementing patient DAs was associated with lower rates of elective surgery for previously treated BPH and active treatment for localized PRCA; however, implementation of these DAs was not associated with lower costs of care.
C1 [Arterburn, David; Wellman, Robert; Westbrook, Emily O.; Ross, Tyler R.] Grp Hlth Res Inst, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA.
[McCulloch, David; Handley, Matt; Lowe, Marc; Cable, Chris] Grp Hlth Phys, Seattle, WA USA.
[Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Northwest HSR&D Ctr Excellence, Seattle, WA USA.
[Hoffman, Richard M.] Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA.
[Hoffman, Richard M.] New Mexico VA Hlth Care Syst, Med Serv, Albuquerque, NM USA.
RP Arterburn, D (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA.
EM arterburn.d@ghc.org
FU The Commonwealth Fund [20080479]; Informed Medical Decisions Foundation
[0103]; Group Health Foundation
FX This work was funded by The Commonwealth Fund (Grant #20080479), the
Informed Medical Decisions Foundation (Grant #0103), and the Group
Health Foundation. The decision aids used in this study were provided by
Health Dialog, Inc. The authors had full access to all of the data and
the funders did not have control over manuscript drafting or
publication.
NR 25
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Z9 1
U1 0
U2 0
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD FEB
PY 2015
VL 21
IS 2
BP E130
EP +
PG 13
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DR4XM
UT WOS:000379906800006
PM 25880488
ER
PT J
AU Grant, RW
Huang, ES
Wexler, DJ
Laiteerapong, N
Warton, EM
Moffet, HH
Karter, AJ
AF Grant, Richard W.
Huang, Elbert S.
Wexler, Deborah J.
Laiteerapong, Neda
Warton, E. Margaret
Moffet, Howard H.
Karter, Andrew J.
TI Patients Who Self-Monitor Blood Glucose and Their Unused Testing Results
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID TYPE-2 DIABETIC-PATIENTS; NORTHERN-CALIFORNIA; GLYCEMIC CONTROL;
PRIMARY-CARE; VALIDITY; RELIABILITY; HEALTH; TIME; COMMUNICATION;
VALIDATION
AB Objectives
To investigate the prevalence, predictors, and costs associated with unused results from self-monitoring of blood glucose (SMBG).
Study Design
Observational cohort study. Methods We studied 7320 patients with type 2 diabetes mellitus who were not prescribed insulin and who reported SMBG. Patients reported whether they used SMBG results to make adjustments to diet, exercise, or medicines; and whether their physician/provider reviewed their SMBG results. We categorized SMBG results as "used" (by patient and/or provider) or "unused" (not used by either patient or provider).
Results
SMBG results were unused by patient and provider in 15.2% of patients. In separate models adjusted for demographic and clinical differences, major predictors of SMBG without patient or physician using the results included a patient reporting that diabetes was not a high priority (relative risk [RR], 1.81; 95% CI, 1.58-2.07); the physician not engaging in shared decision making (RR, 1.66; 95% CI, 1.46-1.90); and no healthcare professional teaching the patient how to adjust diet/medicines based on SMBG results in the past year (RR, 2.27; 95% CI, 2.00-2.57). Patients with unused results were dispensed 171 +/- 191 test strips per year at an estimated annual cost of $168.
Conclusions
Nearly 1 in 6 non-insulin-treated patients practiced SMBG without either the patient or physician using the results. This represents a wasteful and ineffective practice for patients and health systems alike. Our results suggest that the decision to initiate and continue SMBG must be made in concert with the patient's own priorities, and, if prescribed, SMBG requires effective patient-provider communication and patient education.
C1 [Grant, Richard W.; Warton, E. Margaret; Moffet, Howard H.; Karter, Andrew J.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
[Huang, Elbert S.; Laiteerapong, Neda] Univ Chicago, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA.
[Wexler, Deborah J.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Wexler, Deborah J.] Harvard Med Sch, Boston, MA USA.
RP Grant, RW (reprint author), 2101 Webster St,20th Fl, Oakland, CA 94612 USA.
EM Richard.W.Grant@kp.org
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[R01-DK-081796, R01-DK080726, R01-DK-065664, R01-HD46113]; NIDDK Centers
for Diabetes Translation Research at Kaiser Permanente and University of
California, San Francisco [P30 DK092924]; University of Chicago [P30
DK092949]
FX This work was funded by the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) (R01-DK-081796, R01-DK080726, R01-DK-065664,
and R01-HD46113). Investigators were also supported by NIDDK Centers for
Diabetes Translation Research at Kaiser Permanente and University of
California, San Francisco (P30 DK092924) and the University of Chicago
(P30 DK092949).
NR 31
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Z9 5
U1 1
U2 1
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD FEB
PY 2015
VL 21
IS 2
BP E119
EP E129
PG 11
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DR4XM
UT WOS:000379906800005
PM 25880487
ER
PT J
AU Tsai, JN
Yu, EW
Derrico, N
Martinez-Betancourt, A
Bouxsein, ML
AF Tsai, J. N.
Yu, E. W.
Derrico, N.
Martinez-Betancourt, A.
Bouxsein, M. L.
TI IN VIVO CORTICAL BONE INDENTATION MEASUREMENTS ARE INDEPENDENT OF AGE,
BMD AND CORTICAL MORPHOLOGY IN POSTMENOPAUSAL WOMEN
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Meeting Abstract
CT WCO-IOF-ESCEO World Congress on Osteoporosis, Osteoarthritis and
Musculoskeletal Diseases (WCO-IOF-ESCEO)
CY MAR 26-29, 2015
CL Milan, ITALY
SP WCO, IOF, EsCEO
C1 [Tsai, J. N.; Yu, E. W.; Derrico, N.; Martinez-Betancourt, A.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Bouxsein, M. L.] Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD FEB
PY 2015
VL 26
SU 1
MA OC19
BP S46
EP S47
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DI8QX
UT WOS:000373767100028
ER
PT J
AU Bauer, MS
Lee, A
Miller, CJ
Bajor, L
Li, MF
Penfold, RB
AF Bauer, Mark S.
Lee, Austin
Miller, Christopher J.
Bajor, Laura
Li, Mingfei
Penfold, Robert B.
TI Effects of Diagnostic Inclusion Criteria on Prevalence and Population
Characteristics in Database Research
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; VS. UNSTRUCTURED INTERVIEWS;
NATIONAL-COMORBIDITY-SURVEY; BIPOLAR AFFECTIVE-DISORDER;
MENTAL-HEALTH-SERVICES; ADMINISTRATIVE DATA; 12-MONTH PREVALENCE;
SCHIZOPHRENIA; VETERANS; DEPRESSION
AB Objectives: Studies of serious mental illnesses that use administrative databases have employed various criteria to establish diagnoses of interest. Several studies have assessed the validity of diagnostic inclusion criteria against research diagnoses. However, no studies have examined the effect of diagnostic inclusion criteria on prevalence and population characteristics across such groups.
Methods: Administrative data for 2003-2010 from the Department of Veterans Affairs were used to calculate prevalence rates and assess effects of varying the diagnostic inclusion criteria on population composition for bipolar disorder, schizophrenia, and posttraumatic stress disorder (PTSD). Specifically, for each diagnosis, mutually exclusive sub-populations were compared on the basis of the following inclusion criteria for a given diagnosis: one treatment encounter, two outpatient encounters or one inpatient encounter, and any two encounters. For bipolar disorder and schizophrenia, effects of excluding individuals who had a competing diagnosis of, respectively, schizophrenia or bipolar disorder in the prior 12 months and since 2002 were also determined.
Results: In 2010, moving from the broadest definitions of bipolar disorder (N=120,382), schizophrenia (N=91,977), and PTSD (N=554,028) to the most restrictive definitions reduced prevalence rates by, respectively, 28.7%, 34.9%, and 25.7%, with temporal trends for 2003-2010 paralleling results in 2010. Population composition changes with changing diagnostic inclusion criteria were variable, with predominantly small odds ratios.
Conclusions: Population composition was relatively robust across common diagnostic inclusion criteria for each condition. Thus choice of criteria can focus on considerations of diagnostic validity and case-finding needs. Three mechanisms for the impact of diagnostic criteria on population composition in administrative data sets are discussed.
C1 [Bauer, Mark S.] Ctr Healthcare Org & Implementat Res, Dept Vet Affairs VA, Jamaica Plain, MA USA.
[Bauer, Mark S.; Bajor, Laura] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Lee, Austin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Miller, Christopher J.] Ctr Healthcare Org & Implementat Res, Jamaica Plain, MA USA.
[Bajor, Laura] Ctr Org Leadership & Management Res, London, England.
[Miller, Christopher J.; Bajor, Laura] VA Boston Healthcare Syst, Boston, MA USA.
[Li, Mingfei] Bentley Univ, Dept Math Sci, Waltham, MA USA.
[Penfold, Robert B.] Grp Hlth Res Ins, Dept Hlth Serv Res, Seattle, WA USA.
RP Bauer, MS (reprint author), Ctr Healthcare Org & Implementat Res, Dept Vet Affairs VA, Jamaica Plain, MA USA.
EM mark.bauer@va.gov
FU Health Services Research and Development grant from the Office of
Research and Development, Veterans Health Administration, U.S.
Department of Veterans Affairs [IIR-10-314]
FX This material is based on work supported by Health Services Research and
Development grant IIR-10-314 (to Dr. Bauer) from the Office of Research
and Development, Veterans Health Administration, U.S. Department of
Veterans Affairs. The funding organization provided competitive grant
support for these analyses but was not otherwise involved in the design
or conduct of the study or review or approval of the manuscript.
NR 37
TC 6
Z9 6
U1 4
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD FEB
PY 2015
VL 66
IS 2
BP 141
EP 148
DI 10.1176/appi.ps.201400115
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DE3TC
UT WOS:000370552100011
PM 25320943
ER
PT J
AU Kimerling, R
Bastian, LA
Bean-Mayberry, BA
Bucossi, MM
Carney, DV
Goldstein, KM
Phibbs, CS
Pomernacki, A
Sadler, AG
Yano, EM
Frayne, SM
AF Kimerling, Rachel
Bastian, Lori A.
Bean-Mayberry, Bevanne A.
Bucossi, Meggan M.
Carney, Diane V.
Goldstein, Karen M.
Phibbs, Ciaran S.
Pomernacki, Alyssa
Sadler, Anne G.
Yano, Elizabeth M.
Frayne, Susan M.
TI Patient-Centered Mental Health Care for Female Veterans
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID COLLABORATIVE CARE; WOMEN VETERANS; DEPRESSION; VALIDATION; DISORDERS;
SERVICES; QUALITY; VA; INTERVENTIONS; QUESTIONNAIRE
AB Objective: Mental health services for women vary widely across the Veterans Health Administration (VHA) system, without consensus on the need for, or organization of, specialized services for women. Understanding women's needs and priorities is essential to guide the implementation of patient-centered behavioral health services.
Methods: In a cross-sectional, multisite survey of female veterans using primary care, potential stakeholders were identified for VHA mental health services by assessing perceived or observed need for mental health services. These stakeholders (N=484) ranked priorities for mental health care among a wide range of possible services. The investigators then quantified the importance of having designated women's mental health services for each of the mental health services that emerged as key priorities.
Results: Treatment for depression, pain management, coping with chronic general medical conditions, sleep problems, weight management, and posttraumatic stress disorder (PTSD) emerged as women's key priorities. Having mental health services specialized for women was rated as extremely important to substantial proportions of women for each of the six prioritized services. Preference for primary care colocation was strongly associated with higher importance ratings for designated women's mental health services. For specific types of services, race, ethnicity, sexual orientation, PTSD symptoms, and psychiatric comorbidity were also associated with higher importance ratings for designated women's services.
Conclusions: Female veterans are a diverse population whose needs and preferences for mental health services vary along demographic and clinical factors. These stakeholder perspectives can help prioritize structural and clinical aspects of designated women's mental health care in the VHA.
C1 [Kimerling, Rachel] Vet Affairs VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA.
[Kimerling, Rachel; Bucossi, Meggan M.; Carney, Diane V.; Pomernacki, Alyssa; Frayne, Susan M.] Vet Affairs VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA.
[Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Stanford, CA 94305 USA.
[Bastian, Lori A.] VA Connecticut Healthcare Syst, Hlth Serv Res & Dev HSR&D Pain Res Informat Multi, West Haven, CT USA.
[Bastian, Lori A.] Univ Connecticut, Ctr Hlth, Div Gen Internal Med, Farmington, CT USA.
[Bean-Mayberry, Bevanne A.] VA Greater Los Angeles Healthcare Syst, HSR&D Ctr Study Healthcare Innovat Implementat &, Sepulveda, CA USA.
[Bean-Mayberry, Bevanne A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Health, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA.
[Goldstein, Karen M.] Durham VA Med Ctr, HSR&D Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Goldstein, Karen M.] Duke Univ, Dept Med, Durham, NC USA.
[Phibbs, Ciaran S.] VA Palo Alto Hlth Care Syst, HSR&D Hlth Econ Resource Ctr, Menlo Pk, CA USA.
[Phibbs, Ciaran S.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
[Sadler, Anne G.] Iowa City VA Hlth Care Syst, HSR&D Ctr Comprehens Access & Delivery Res & Eval, Iowa City, IA USA.
[Sadler, Anne G.] Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA.
RP Kimerling, R (reprint author), Vet Affairs VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA.
EM rachel.kimerling@va.gov
OI Kimerling, Rachel/0000-0003-0996-4212
FU VA HSRD grant [SDR 10-012]
FX This study was funded by VA HSR&D grant SDR 10-012 (Women's Health
Research Network). The authors thank Joanne Pavao, M.P.H., Deborah
Nazarian, Ph.D., Shannan Sonnicksen, L.C.S.W., M.P.H., Caitlin McLean,
M.S., and Julia Lin, Ph.D., of the VA Palo Alto Health Care System; Jill
Blakeney, R.N., of Durham VA Medical Center; Ruth Klap, Ph.D., and Julia
Yosef, M.S., R.N., of VA Greater Los Angeles Healthcare System; and
Brittany D. Martin, M.A., M. Litt., and Holly J. Erschens, B.A., of Iowa
City VA Health Care System. The views expressed in this article are
those of the authors and do not necessarily reflect the position or
policy of the VA or the U.S. government.
NR 41
TC 6
Z9 6
U1 1
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD FEB
PY 2015
VL 66
IS 2
BP 155
EP 162
DI 10.1176/appi.ps.201300551
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DE3TC
UT WOS:000370552100013
PM 25642611
ER
PT J
AU Fong, ZV
Fernandez-del Castillo, C
AF Fong, Zhi Ven
Fernandez-del Castillo, Carlos
TI Intraductal Papillary Mucinous Adenocarcinoma of the Pancreas: Clinical
Outcomes, Prognostic Factors, and the Role of Adjuvant Therapy
SO VISZERALMEDIZIN
LA English
DT Review
DE Intraductal papillary mucinous adenocarcinoma; Prognostic factors;
Adjuvant therapy
ID SINGLE-INSTITUTION EXPERIENCE; DUCTAL-ADENOCARCINOMA; SURGICAL
RESECTION; CLINICOPATHOLOGICAL CHARACTERISTICS; 1423
PANCREATICODUODENECTOMIES; SYMPTOMATIC PATIENTS; INVASIVE-CARCINOMA;
UPDATED EXPERIENCE; PREDICTIVE-FACTORS; NEOPLASM
AB Background: Intraductal papillary mucinous adenocarcinoma (IPMCs) occur more frequently in main-duct intraductal papillary mucinous neoplasms. Methods: Review of the literature. Results: The prognosis of IPMCs depends on its histopathological subtype: colloid IPMCs have superior survival rates mainly secondary to more favorable pathological features, whereas tubular IPMCs have survival outcomes similar to that of conventional pancreatic adenocarcinomas. The epithelial background plays an equally important role in defining the biology of IPMCs: gastric IPMC subtypes demonstrate an overall worse survival outcome when compared to intestinal, pancreatobiliary, and oncocytic subtypes. Lymph node involvement is one of the strongest predictors of survival in IPMC, with a decreasing overall survival as the lymph node ratio increases. There is little evidence to support adjuvant chemoradiation in patients with IPMC. Conclusion: Our current understanding of IPMC biology based on histopathological and epithelial background subtypes as well as clinicopathological predictors should influence patient counseling and selection for adjuvant therapy.
C1 [Fong, Zhi Ven; Fernandez-del Castillo, Carlos] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA.
EM cfernandez@partners.org
NR 38
TC 2
Z9 3
U1 0
U2 0
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1662-6664
EI 1662-6672
J9 VISZERALMEDIZIN
JI Viszeralmedizin
PD FEB
PY 2015
VL 31
IS 1
BP 43
EP 46
DI 10.1159/000373912
PG 4
WC Surgery
SC Surgery
GA DH8BO
UT WOS:000373018500007
PM 26288615
ER
PT J
AU Treadway, MT
Waskom, ML
Dillon, DG
Holmes, AJ
Park, MTM
Chakravarty, MM
Dutra, SJ
Polli, FE
Iosifescu, DV
Fava, M
Gabrieli, JDE
Pizzagalli, DA
AF Treadway, Michael T.
Waskom, Michael L.
Dillon, Daniel G.
Holmes, Avram J.
Park, Min Tae M.
Chakravarty, M. Mallar
Dutra, Sunny J.
Polli, Frida E.
Iosifescu, Dan V.
Fava, Maurizio
Gabrieli, John D. E.
Pizzagalli, Diego A.
TI Illness Progression, Recent Stress, and Morphometry of Hippocampal
Subfields and Medial Prefrontal Cortex in Major Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Dentate gyrus; Hippocampus; MAGeT brain; Major depression; mPFC; MRI
ID ANTERIOR CINGULATE CORTEX; CORTICAL SURFACE; DENDRITIC MORPHOLOGY;
MEMORY IMPAIRMENT; BIPOLAR-DISORDER; DECISION-MAKING; BRAIN; VOLUME;
AMYGDALA; SEGMENTATION
AB BACKGROUND: Longitudinal studies of illness progression in patients with major depressive disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in patients with MDD-especially in medial prefrontal cortex (mPFC) and the hippocampus-but few studies have investigated whether these changes are exacerbated by prior episodes.
METHODS: In a sample of 103 medication-free patients with depression and control subjects with no history of depression, structural magnetic resonance imaging was performed to examine relationships between number of prior episodes, current stress, hippocampal subfield volume and cortical thickness. Volumetric analyses of the hippocampus were performed using a recently validated subfield segmentation approach, and cortical thickness estimates were obtained using vertex-based methods. Participants were grouped on the basis of the number of prior depressive episodes and current depressive diagnosis.
RESULTS: Number of prior episodes was associated with both lower reported stress levels and reduced volume in the dentate gyrus. Cortical thinning of the left mPFC was associated with a greater number of prior depressive episodes but not current depressive diagnosis.
CONCLUSIONS: Collectively, these findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure and provide evidence for morphometric changes that are consistent with stress-sensitization models of recurrence in MDD.
C1 [Treadway, Michael T.; Dillon, Daniel G.; Pizzagalli, Diego A.] Harvard Univ, McLean Hosp, Sch Med, Ctr Depress Anxiety & Stress Res, Belmont, MA USA.
[Waskom, Michael L.] Stanford Univ, Dept Psychol, Palo Alto, CA 94304 USA.
[Holmes, Avram J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Holmes, Avram J.; Dutra, Sunny J.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Park, Min Tae M.; Chakravarty, M. Mallar] Ctr Addict & Mental Hlth, Kimel Family Imaging Genet Lab, Toronto, ON, Canada.
[Chakravarty, M. Mallar] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Chakravarty, M. Mallar] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada.
[Polli, Frida E.; Gabrieli, John D. E.] MIT, Cambridge, MA 02139 USA.
[Iosifescu, Dan V.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA.
RP Pizzagalli, DA (reprint author), McLean Hosp, Ctr Depress Anxiety & Stress Res, 115 Mill St, Belmont, MA 02478 USA.
EM dap@mclean.harvard.edu
OI Dillon, Daniel/0000-0002-1977-700X
FU National Institute of Mental Health (NIMH) [R01 MH068376]; National
Center for Complementary and Alternative Medicine (NCCAM) [R21
AT002974]; NCCAM [R01 AT001638]; NIMH [K01 MH099232, K99 MH094438]; W.
Garfield Weston Foundation; Icahn School of Medicine at Mount Sinai from
AstraZeneca; Brainsway; Euthymics Bioscience, Inc.; NeoSync; Roche;
Shire; Avanir Pharmaceuticals; CNS Response, Inc.; Otsuka; Servier;
Sunovion; Abbott Laboratories; Alkermes, Inc.; American Cyanamid; Aspect
Medical Systems; AstraZeneca; BioResearch; BrainCells, Inc.;
Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clintara LLC; Covance;
Covidien; Eli Lilly; Company; EnVivo Pharmaceuticals Inc.; Forest
Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Harvard
Clinical Research Institute; Hoffmann-La Roche; Icon Clinical Research;
i3 Innovus/Ingenix; Janssen RD LLC; Jed Foundation; Johnson & Johnson
Pharmaceutical Research Development; Lichtwer Pharma GmbH; Lorex
Pharmaceuticals; MedAvante; National Alliance for Research on
Schizophrenia and Depression; National Center for Complementary and
Alternative Medicine; National Institute of Drug Abuse; National
Institute of Mental Health, Neuralstem, Inc.; Novartis AG; Organon
Pharmaceuticals; Pamlab LLC; Pfizer, Inc.; Pharmacia-Upjohn;
Pharmaceutical Research Associates, Inc.; Pharmavite LLC; PharmoRx
Therapeutics; Photothera; RCT Logic LLC; Sanofi; Solvay Pharmaceuticals,
Inc.; Synthelabo; Wyeth-Ayerst Laboratories; Affectis Pharmaceuticals
AG; Amarin Pharma, Inc.; Auspex Pharmaceuticals; Bayer; Best Practice
Project Management, Inc.; BioMarin Pharmaceutical, Inc.; Biovail
Corporation; Cephalon, Inc.; Cerecor; Clinical Trials Solutions;
Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch
Life Sciences Pvt Ltd.; Dainippon Sumitomo Pharma Co., Inc.; DOV
Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai, Inc.; Eli
Lilly and Company; EnVivo Pharmaceuticals, Inc.; ePharmaSolutions; EPIX
Pharmaceuticals, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Genomind LLC;
Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz
Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research &
Development LLC; Knoll Pharmaceuticals Corp.; Labopharm, Inc.; Lundbeck,
Inc.; MedAvante Inc.; Merck Co., Inc.; MSI Methylation Sciences, Inc.;
Naurex, Inc.; Neuralstem, Inc.; Neuronetics, Inc.; NextWave
Pharmaceuticals; Nutrition 21; Orexigen Therapeutics, Inc.; Otsuka
Pharmaceuticals; PharmaStar; Precision Human Biolaboratory; Prexa
Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin
Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics,
Inc.; Sepracor, Inc.; Servier Laboratories; Schering-Plough Corporation;
Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals; Sunovion
Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Takeda Pharmaceutical
Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.;
TransForm Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda
Pharmaceuticals, Inc.; Advanced Neuro Technology North America; Ono
Pharma USA; Pfizer
FX This study was supported by National Institute of Mental Health (NIMH)
Grant R01 MH068376 awarded to DAP as well as National Center for
Complementary and Alternative Medicine (NCCAM) Grant R21 AT002974
awarded to DAP and NCCAM R01 AT001638 awarded to MF. AJH and DGD were
supported by NIMH Grants K01 MH099232 and K99 MH094438, respectively.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. MMC was supported by the W. Garfield Weston Foundation.; DVI has
received over the past 3 years funding through Icahn School of Medicine
at Mount Sinai from AstraZeneca, Brainsway, Euthymics Bioscience, Inc.,
NeoSync, Roche, and Shire and consulting fees from Avanir
Pharmaceuticals, CNS Response, Inc., Otsuka, Servier, and Sunovion.; MF
has received research support from Abbott Laboratories, Alkermes, Inc.,
American Cyanamid, Aspect Medical Systems, AstraZeneca, BioResearch,
BrainCells, Inc., Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon,
Clintara LLC, Covance, Covidien, Eli Lilly and Company, EnVivo
Pharmaceuticals Inc., Euthymics Bioscience, Inc., Forest
Pharmaceuticals, Inc., Ganeden Biotech, Inc., GlaxoSmithKline, Harvard
Clinical Research Institute, Hoffmann-La Roche, Icon Clinical Research,
i3 Innovus/Ingenix, Janssen R&D LLC, Jed Foundation, Johnson & Johnson
Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex
Pharmaceuticals, MedAvante, National Alliance for Research on
Schizophrenia and Depression, National Center for Complementary and
Alternative Medicine, National Institute of Drug Abuse, National
Institute of Mental Health, Neuralstem, Inc., Novartis AG, Organon
Pharmaceuticals, Pamlab LLC, Pfizer, Inc., Pharmacia-Upjohn,
Pharmaceutical Research Associates, Inc., Pharmavite LLC, PharmoRx
Therapeutics, Photothera, Roche, RCT Logic LLC (formerly Clinical Trials
Solutions LLC), Sanofi, Shire, Solvay Pharmaceuticals, Inc., Synthelabo,
Wyeth-Ayerst Laboratories; advisory/consulting fees from Abbott
Laboratories, Affectis Pharmaceuticals AG, Alkermes, Inc., Amarin
Pharma, Inc., Aspect Medical Systems, AstraZeneca, Auspex
Pharmaceuticals, Bayer, Best Practice Project Management, Inc., BioMarin
Pharmaceutical, Inc., Biovail Corporation, BrainCells, Inc.,
Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Inc., Cerecor,
Clinical Trials Solutions, CNS Response, Inc., Compellis
Pharmaceuticals, Cypress Pharmaceutical, Inc., DiagnoSearch Life
Sciences Pvt Ltd., Dainippon Sumitomo Pharma Co., Inc., DOV
Pharmaceuticals, Inc., Edgemont Pharmaceuticals, Inc., Eisai, Inc., Eli
Lilly and Company, EnVivo Pharmaceuticals, Inc., ePharmaSolutions, EPIX
Pharmaceuticals, Inc., Euthymics Bioscience, Inc., Fabre-Kramer
Pharmaceuticals, Inc., Forest Pharmaceuticals, Inc., Genomind LLC,
GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenis, Janssen
Pharmaceutica, Jazz Pharmaceuticals, Inc., Johnson & Johnson
Pharmaceutical Research & Development LLC, Knoll Pharmaceuticals Corp.,
Labopharm, Inc., Lorex Pharmaceuticals, Lundbeck, Inc., MedAvante Inc.,
Merck & Co., Inc., MSI Methylation Sciences, Inc., Naurex, Inc.,
Neuralstem, Inc., Neuronetics, Inc., NextWave Pharmaceuticals, Novartis
AG, Nutrition 21, Orexigen Therapeutics, Inc., Organon Pharmaceuticals,
Otsuka Pharmaceuticals, Pamlab LLC, Pfizer, Inc., PharmaStar, Pharmavite
LLC, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa
Pharmaceuticals, Inc., Puretech Ventures, PsychoGenics, Psylin
Neurosciences, Inc., Rexahn Pharmaceuticals, Inc., Ridge Diagnostics,
Inc., Roche, Sanofi, Sepracor, Inc., Servier Laboratories,
Schering-Plough Corporation, Solvay Pharmaceuticals, Inc., Somaxon
Pharmaceuticals, Inc., Somerset Pharmaceuticals, Sunovion
Pharmaceuticals, Supernus Pharmaceuticals, Inc., Synthelabo, Takeda
Pharmaceutical Company Limited, Tal Medical, Inc., Tetragenex
Pharmaceuticals, Inc., TransForm Pharmaceuticals, Inc., Transcept
Pharmaceuticals, Inc., and Vanda Pharmaceuticals, Inc.; and
speaking/publishing royalties from AdaMed, Advanced Meeting Partners,
American Psychiatric Association, American Society of Clinical
Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer
Ingelheim GmbH, BristolMyers Squibb, Cephalon, Inc., CME
Institute/Physicians Postgraduate Press, Inc., Eli Lilly and Company,
Forest Pharmaceuticals, Inc.; , GlaxoSmithKline, Imedex LLC, MGH
Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier,
Novartis AG, Organon Pharmaceuticals, Pfizer, Inc., PharmaStar, United
BioSource Corp., and Wyeth-Ayerst Laboratories. MF has equity holdings
in Compellis Pharmaceuticals and PsyBrain, Inc. and receives
royalty/patent or other income from patent for Sequential Parallel
Comparison Design, which is licensed by Massachusetts General Hospital
to RCT Logic LLC. He has a patent application for a combination of
scopolamine and ketamine in major depressive disorder and holds a
copyright for the Massachusetts General Hospital Cognitive & Physical
Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant
Treatment Response Questionnaire, Discontinuation-Emergent Signs &
Symptoms, and SAFER, Lippincott Williams & Wilkins, Wolters Kluwer,
World Scientific Publishing Co. Pte. Ltd.; DAP has received over the
past 3 years honoraria or consulting fees from Advanced Neuro Technology
North America, AstraZeneca, Ono Pharma USA, Pfizer, Servier, and Shire
for activities unrelated to this project.
NR 78
TC 38
Z9 41
U1 3
U2 27
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD FEB 1
PY 2015
VL 77
IS 3
BP 285
EP 294
DI 10.1016/j.biopsych.2014.06.018
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AX3NG
UT WOS:000346845500017
PM 25109665
ER
PT J
AU Mayeda, ER
Whitmer, RA
Yaffe, K
AF Mayeda, Elizabeth Rose
Whitmer, Rachel A.
Yaffe, Kristine
TI Diabetes and Cognition
SO CLINICS IN GERIATRIC MEDICINE
LA English
DT Article
DE Type 2 diabetes; Cognition; Cognitive decline; Dementia; Aging;
Epidemiology
ID VASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; DEMENTIA RISK; OLDER PERSONS;
SEVERE HYPOGLYCEMIA; OXIDATIVE DAMAGE; FOLLOW-UP; LATE-LIFE; MELLITUS;
DECLINE
AB Dementia is a major cause of disability and death among older adults. Those with type 2 diabetes (T2D) are 50-100% more likely to develop dementia than those without T2D, but it is unknown whether this association reflects a causal relationship. Proposed mechanisms through which T2D could cause dementia include the effects of insulin dysregulation and chronic hyperglycemia on features of Alzheimer's disease and macrovascular and microvascular disorders in the brain. More research is needed to elucidate the link between T2D and dementia and identify strategies to maintain cognitive function among people with T2D.
C1 [Mayeda, Elizabeth Rose] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA.
[Whitmer, Rachel A.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Mayeda, ER (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA.
EM elizabeth.mayeda@ucsf.edu
FU National Institute on Aging grant [K24 AG031155]; National Institute of
Diabetes and Digestive and Kidney Diseases grant [R01DK081796];
BrightFocus Foundation
FX The authors were supported by funding from National Institute on Aging
grant K24 AG031155, National Institute of Diabetes and Digestive and
Kidney Diseases grant R01DK081796, and grant support from the
BrightFocus Foundation.
NR 92
TC 15
Z9 16
U1 0
U2 24
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0749-0690
EI 1879-8853
J9 CLIN GERIATR MED
JI Clin. Geriatr. Med.
PD FEB
PY 2015
VL 31
IS 1
BP 101
EP +
DI 10.1016/j.cger.2014.08.021
PG 16
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA AX1CX
UT WOS:000346686900010
PM 25453304
ER
PT J
AU Agaram, NP
Chen, HW
Zhang, L
Sung, YS
Panicek, D
Healey, JH
Nielsen, GP
Fletcher, CDM
Antonescu, CR
AF Agaram, Narasimhan P.
Chen, Hsiao-Wei
Zhang, Lei
Sung, Yun-Shao
Panicek, David
Healey, John H.
Nielsen, G. Petur
Fletcher, Christopher D. M.
Antonescu, Cristina R.
TI EWSR1-PBX3: A Novel Gene Fusion in Myoepithelial Tumors
SO GENES CHROMOSOMES & CANCER
LA English
DT Article
ID SOFT-TISSUE; MALIGNANT MYOEPITHELIOMA; MODULAR FRAMEWORK; PRE-B; BONE;
RNA; REARRANGEMENTS; ORGANOGENESIS; EXPRESSION; CARCINOMA
AB The genetics of myoepithelial tumors (ME) of soft tissue and bone have recently been investigated, with EWSR1-related gene fusions being seen in approximately half of the tumors. The fusion partners of EWSR1 so far described include POU5F1, PBX1, ZNF444 and, in a rare case, ATF1. We investigated by RNA sequencing an index case of EWSR1-rearranged ME of the tibia, lacking a known fusion partner, and identified a novel EWSR1-PBX3 fusion. The fusion was further validated by reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH). To evaluate if this is a recurrent event, an additional cohort of 22 EWSR1-rearranged ME cases lacking a fusion partner were screened by FISH for abnormalities in PBX3 gene. Thus, two additional cases were identified showing an EWSR1-PBX3 gene fusion. One of them was also intraosseous involving the ankle, while the other occurred in the soft tissue of the index finger. The morphology of the EWSR1-PBX3 fusion positive cases showed similar findings, with nests or sheets of epithelioid to spindle cells in a partially myxoid to collagenous matrix. All three cases showed expression of S100 and EMA by immunohistochemistry. In summary, we report a novel EWSR1-PBX3 gene fusion in a small subset of ME, thereby expanding the spectrum of EWSR1-related gene fusions seen in these tumors. This gene fusion seems to occur preferentially in skeletal ME, with two of the three study cases occurring in intraosseous locations. (c) 2014 Wiley Periodicals, Inc.
C1 [Agaram, Narasimhan P.; Chen, Hsiao-Wei; Zhang, Lei; Sung, Yun-Shao; Antonescu, Cristina R.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Panicek, David] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA.
[Healey, John H.] Mem Sloan Kettering Canc Ctr, Dept Surg, Orthoped Serv, New York, NY 10065 USA.
[Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Fletcher, Christopher D. M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Agaram, NP (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA.
EM agaramn@mskcc.org; antonesc@mskcc.org
OI Panicek, David/0000-0003-0302-174X
FU Cycle for Survival [P01CA47179, P50 CA 140146-01]
FX Supported by: Cycle for Survival (C.R.A.) Grant Numbers: P01CA47179
(CRA), P50 CA 140146-01 (CRA).
NR 33
TC 14
Z9 14
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1045-2257
EI 1098-2264
J9 GENE CHROMOSOME CANC
JI Gene Chromosomes Cancer
PD FEB
PY 2015
VL 54
IS 2
BP 63
EP 71
DI 10.1002/gcc.22216
PG 9
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA AW5ZE
UT WOS:000346348600001
PM 25231231
ER
PT J
AU Naraghi, L
Peev, MP
Esteve, R
Chang, YC
Berger, DL
Thayer, SP
Rattner, DW
Lillemoe, KD
Kaafarani, H
Yeh, DD
de Moya, MA
Fagenholz, PJ
Velmahos, GS
King, DR
AF Naraghi, Leily
Peev, Miroslav P.
Esteve, Rogette
Chang, Yuchiao
Berger, David L.
Thayer, Sarah P.
Rattner, David W.
Lillemoe, Keith D.
Kaafarani, Haytham
Yeh, Daniel D.
de Moya, Marc A.
Fagenholz, Peter J.
Velmahos, George S.
King, David R.
TI The influence of anesthesia on heart rate complexity during elective and
urgent surgery in 128 patients
SO JOURNAL OF CRITICAL CARE
LA English
DT Article
DE Entropy; Surgery; SampEn; Elective; Variability; Complexity
ID DIMINISHED PHYSIOLOGICAL RESERVE; BEDSIDE MONITORING STRATEGY; 1,425
TRAUMA PATIENTS; RATE-VARIABILITY; LIFESAVING INTERVENTIONS;
GENERAL-ANESTHESIA; PREDICTS; MORTALITY; TOOL; VOLATILITY
AB Background: As an emerging "new vital sign," heart rate complexity (by sample entropy [SampEn]) has been shown to be a useful trauma triage tool by predicting occult physiologic compromise and need for life-saving interventions. Sample entropy may be confounded by anesthesia possibly limiting its value intraoperatively. We investigated the effects of anesthesia on SampEn during elective and urgent surgical procedures. We hypothesized that SampEn is reduced by general anesthesia.
Methods: With institutional review board-approved waiver of informed consent, 128 patients undergoing elective or urgent general surgery were prospectively enrolled. Real-time heart rate complexity was calculated using SampEn through electrocardiogram recordings of 200 consecutive beats in a continuous sliding-window fashion. We recorded SampEn starting 10 minutes before induction until 10 minutes after emergence from anesthesia. The time before induction of anesthesia was categorized as period 1, the time after induction and before emergence as period 2 (intraoperative), and the time after emergence as period 3. We analyzed SampEn changes as patients moved between the different periods and made 3 comparisons: from period 1 with period 2 (comparison A), from period 2 with period 3 (comparison B). We also compared period 1 with period 3 SampEn (comparison C).
Results: The mean SampEn value for all patients before induction of anesthesia was 1.55 +/- 0.58. In each 1 of the 3, comparisons there was a decline in SampEn. Comparison A had a mean decrease of 0.53 +/- 0.55 (P < .0001), comparison B had a decrease of 0.13 +/- 0.52 (P < .0051), and the mean SampEn difference for comparison C was 0.66 +/- 0.53 (P < .0001). Certain pharmacologics had significant effect on SampEn as did need for urgent surgery and American Society of Anesthesiologists class.
Conclusion: Sample entropy decreases after induction of anesthesia and continues to decrease even immediately after emergence in patients without any immediately life-threatening conditions. This finding may complicate interpretation low complexity as a predictor of life-saving interventions in patients in the perioperative period. (C) 2014 Elsevier Inc. All rights reserved.
C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02141 USA.
EM dking3@partners.org
OI King, David/0000-0003-1028-1478
NR 29
TC 0
Z9 0
U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0883-9441
EI 1557-8615
J9 J CRIT CARE
JI J. Crit. Care
PD FEB
PY 2015
VL 30
IS 1
BP 145
EP 149
DI 10.1016/j.jcrc.2014.08.008
PG 5
WC Critical Care Medicine
SC General & Internal Medicine
GA AW4GJ
UT WOS:000346238900025
PM 25239820
ER
PT J
AU Courtwright, AM
Brackett, S
Cadge, W
Krakauer, EL
Robinson, EM
AF Courtwright, Andrew M.
Brackett, Sharon
Cadge, Wendy
Krakauer, Eric L.
Robinson, Ellen M.
TI Experience with a hospital policy on not offering cardiopulmonary
resuscitation when believed more harmful than beneficial
SO JOURNAL OF CRITICAL CARE
LA English
DT Article
DE Cardiopulmonary resuscitation; Do not resuscitate; End of life; Ethics
consultation; Medical ethics; Medical futility
ID OF-LIFE CARE; MEDICAL FUTILITY; INTENSIVE-CARE; END; DECISIONS; ORDERS;
CONSENT; STATES; UNITS; CPR
AB Purpose: This study investigated the impact of age, race, and functional status on decisions not to offer cardiopulmonary resuscitation (CPR) despite patient or surrogate requests that CPR be performed.
Methods: This was a retrospective cohort study of all ethics committee consultations between 2007 and 2013 at a large academic hospital with a not offering CPR policy.
Results: There were 134 cases of disagreement over whether to provide CPR. In 45 cases (33.6%), the patient or surrogate agreed to a do-not-resuscitate (DNR) order after initial ethics consultation. In 67 (75.3%) of the remaining 89 cases, the ethics committee recommended not offering CPR. In the other 22 (24.7%) cases, the ethics committee recommended offering CPR. There was no significant relationship between age, race, or functional status and the recommendation not to offer CPR. Patients who were not offered CPR were more likely to be critically ill (61.2% vs 18.2%, P < .001). The 90-day mortality rate among patients who were not offered CPR was 90.2%.
Conclusions: There was no association between age, race, or functional status and the decision not to offer CPR made in consultation with an ethics committee. Orders to withhold CPR were more common among critically ill patients. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Courtwright, Andrew M.; Robinson, Ellen M.] Massachusetts Gen Hosp, Inst Patient Care, Patient Care Serv, Boston, MA 02114 USA.
[Courtwright, Andrew M.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Brackett, Sharon] Massachusetts Gen Hosp, Ellison Surg Intens Care Unit 4, Patient Care Serv, Boston, MA 02114 USA.
[Cadge, Wendy] Brandeis Univ, Dept Sociol, Waltham, MA USA.
[Krakauer, Eric L.] Massachusetts Gen Hosp, Div Palliat Care, Boston, MA 02114 USA.
[Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
[Robinson, Ellen M.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA.
RP Courtwright, AM (reprint author), Ctr Chest Dis, 15 Francis St, Boston, MA 02115 USA.
EM acourtwright@partners.org
FU Yvonne L. Munn Post Doctoral Research Fellowship; Yvonne L. Munn Center
for Nursing Research, Institute for Patient Care, MGH
FX Research support for E.R. was provided by the Yvonne L. Munn Post
Doctoral Research Fellowship and the Yvonne L. Munn Center for Nursing
Research, Institute for Patient Care, MGH.
NR 34
TC 5
Z9 6
U1 2
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0883-9441
EI 1557-8615
J9 J CRIT CARE
JI J. Crit. Care
PD FEB
PY 2015
VL 30
IS 1
BP 173
EP 177
DI 10.1016/j.jcrc.2014.10.003
PG 5
WC Critical Care Medicine
SC General & Internal Medicine
GA AW4GJ
UT WOS:000346238900030
PM 25457115
ER
PT J
AU Kwok, AC
Hu, YY
Dodgion, CM
Jiang, W
Ting, GV
Taback, N
Lipsitz, SR
Weeks, JC
Greenberg, CC
AF Kwok, Alvin C.
Hu, Yue-Yung
Dodgion, Christopher M.
Jiang, Wei
Ting, Gladys V.
Taback, Nathan
Lipsitz, Stuart R.
Weeks, Jane C.
Greenberg, Caprice C.
TI Invasive procedures in the elderly after stage IV cancer diagnosis
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Stage IV cancer; End-of-life; Procedure utilization
ID OF-LIFE DISCUSSIONS; CELL LUNG-CANCER; UNITED-STATES; CARE; END; TRENDS;
COST; SURVIVAL; EPIDEMIOLOGY; SURVEILLANCE
AB Background: Invasive procedures are resource intense and may be associated with substantial morbidity. These harms must be carefully balanced with the benefits gained in life expectancy and quality of life. Prior research has demonstrated an increasing aggressiveness of care in cancer patients at the end-of-life. To better characterize surgical care in this setting, we sought to examine trends in the use of invasive procedures in patients diagnosed with metastatic cancer on presentation.
Materials and methods: Using Surveillance Epidemiology and End Results -Medicare data, we identified invasive procedure claims from 1994-2009 for patients diagnosed with incident stage IV breast, colorectal, lung, and prostate cancer patients in 1995-2006. We grouped procedures into surgically relevant categories, using an adaptation of the Clinical Classifications Software, and measured utilization and relative changes over time.
Results: Of stage IV patients diagnosed in 2002-2006, 96% underwent a procedure during the course of their cancer care including 63% after the diagnostic period, and 25% in the last month of life. Between 1996 and 2006, minimal change was observed in utilization during the diagnostic period (+1.5%). However, there were significant increases during continuing care (+20.7%) and the last month of life (+21.5%). Procedures consistent with primary tumor resection decreased, whereas those with probable palliative intent and those unrelated to cancer increased.
Conclusions: Nearly all patients who present with metastatic cancer undergo invasive procedures. Although overall utilization is increasing, the specific procedure types indicate that it may be appropriate, enhancing the quality of life in this vulnerable population. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Kwok, Alvin C.; Hu, Yue-Yung; Dodgion, Christopher M.; Jiang, Wei; Lipsitz, Stuart R.; Greenberg, Caprice C.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Kwok, Alvin C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Kwok, Alvin C.] Univ Utah, Sch Med, Dept Plast & Reconstruct Surg, Salt Lake City, UT USA.
[Hu, Yue-Yung] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
[Dodgion, Christopher M.; Greenberg, Caprice C.] Univ Wisconsin Hosp & Clin, Dept Surg, Wisconsin Surg Outcomes Res WiSOR Program, Madison, WI 53792 USA.
[Ting, Gladys V.; Taback, Nathan; Weeks, Jane C.; Greenberg, Caprice C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
RP Hu, YY (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, 110 Francis St,Suite 9B, Boston, MA 02215 USA.
EM yhu@bidmc.harvard.edu
RI JIANG, WEI /F-3930-2015; Dodgion, Chris/A-2877-2016
OI Dodgion, Chris/0000-0002-5789-7731
FU National Institutes of Health [RC2CA148185-01, 2T32DK00754-12,
L30RR031458-01, L30CA123695-03]
FX This project was funded by the National Institutes of Health grants
#RC2CA148185-01 (J.C.W. and C.C.G.), #2T32DK00754-12 (Y.-Y.H.),
#L30RR031458-01 (Y.-Y.H.), and #L30CA123695-03 (C.C.G.).
NR 30
TC 4
Z9 4
U1 1
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD FEB
PY 2015
VL 193
IS 2
BP 754
EP 763
DI 10.1016/j.jss.2014.08.021
PG 10
WC Surgery
SC Surgery
GA AW4IK
UT WOS:000346244300033
PM 25234747
ER
PT J
AU Hobai, IA
Morse, JC
Siwik, DA
Colucci, WS
AF Hobai, Ion A.
Morse, Justin C.
Siwik, Deborah A.
Colucci, Wilson S.
TI Lipopolysaccharide and cytokines inhibit rat cardiomyocyte contractility
in vitro
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Sepsis; Sepsis-induced cardiomyopathy; Calcium; Excitation-contraction
coupling; L-type calcium channel; SERCA; Na+/Ca2+ exchange
ID NITRIC-OXIDE SYNTHASE; CARDIAC SARCOPLASMIC-RETICULUM;
NECROSIS-FACTOR-ALPHA; VENTRICULAR MYOCYTES; CA2+ TRANSIENTS; SEPTIC
SHOCK; MYOCARDIAL DYSFUNCTION; INDUCED DEPRESSION; CALCIUM CURRENT;
HEART-FAILURE
AB Background: Sepsis-induced cardiomyopathy (SIC) is thought to be the result of detrimental effects of inflammatory mediators on the cardiac muscle. Here we studied the effects of prolonged (24 +/- 4 h) exposure of adult rat ventricular myocytes (ARVM) to bacterial lipopolysaccharide (LPS) and inflammatory cytokines tumor necrosis factor (TNF) and interleukins-1 (IL-1) and IL-6.
Materials and methods: We measured sarcomere shortening (SS) and cellular calcium (Ca2+) transients (Delta Ca-i, with fura-2 AM) in isolated cardiomyocytes externally paced at 5 Hz at 37 degrees C.
Results: SS decreased after incubation with LPS (100 mu g/mL), IL-1 (100 ng/mL), and IL-6 (30 ng/mL), but not with lesser doses of these mediators, or TNF (10-100 ng/mL). A combination of LPS (100 mu g/mL), TNF, IL-1, and IL-6 (each 100 ng/mL; i.e., "Cytomix-100") induced a maximal decrease in SS and Delta Ca-i. Sarcoplasmic reticulum (SR) Ca2+ load (Ca-SR, measured with caffeine) was unchanged by Cytomix-100; however, SR fractional release (Delta Ca-i/Ca-SR) was decreased. Underlying these effects, Ca2+ influx into the cell (via L-type Ca2+ channels, LTCC) and Ca2+ extrusion via Na2+/Ca2+ exchange were decreased by Cytomix-100. SR Ca2+ pump (SERCA) (SR Ca2+ ATPase) was not affected.
Conclusions: Prolonged exposure of ARVM to a mixture of LPS and inflammatory cytokines inhibits cell contractility. The effect is mediated by the inhibition of Ca2+ influx via LTCC, and partially opposed by the inhibition of Na+/Ca2+ exchange. Because both mechanisms are commonly seen in animal models of SIC, we conclude that prolonged challenge with Cytomix-100 of ARVM may represent an accurate in vitro model for SIC. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Hobai, Ion A.; Morse, Justin C.; Siwik, Deborah A.; Colucci, Wilson S.] Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA.
[Hobai, Ion A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Hobai, IA (reprint author), Boston Univ, Med Ctr, Dept Med, Cardiovasc Med Sect, Evans Basic Res Bldg,650 Albany St,X740, Boston, MA 02118 USA.
EM ihobai@partners.org
FU National Institutes of Health [HL-061639, HL-064750]; National Heart,
Lung, and Blood Institute - Boston University Cardiovascular Proteomics
Center [N01-HV-28178]; National Institute of General Medical Sciences
[K08GM096082, T32GM00 7592]; Department of Anesthesia, Critical Care and
Pain Medicine, Massachusetts General Hospital
FX This work was supported by National Institutes of Health grants
HL-061639, HL-064750 (W.S.C.) and the National Heart, Lung, and Blood
Institute -sponsored Boston University Cardiovascular Proteomics Center
(Contract No. N01-HV-28178, W.S.C.). I.A.H. acknowledges support from
K08GM096082 and T32GM00 7592 (National Institute of General Medical
Sciences) and the Department of Anesthesia, Critical Care and Pain
Medicine, Massachusetts General Hospital. Other support includes Boston
University Student Research Awards for J.C.M.
NR 49
TC 4
Z9 4
U1 0
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD FEB
PY 2015
VL 193
IS 2
BP 888
EP 901
DI 10.1016/j.jss.2014.09.015
PG 14
WC Surgery
SC Surgery
GA AW4IK
UT WOS:000346244300049
PM 25439505
ER
PT J
AU Richard, MLL
Nowling, TK
Brandon, D
Watson, DK
Zhang, XK
AF Richard, Mara L. Lennard
Nowling, Tamara K.
Brandon, Danielle
Watson, Dennis K.
Zhang, Xian K.
TI Fli-1 controls transcription from the MCP-1 gene promoter, which may
provide a novel mechanism for chemokine and cytokine activation
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE Transcriptional factors; Gene regulation; Chemokines; Inflammation;
Fli-1; MCP-1
ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
NF-KAPPA-B; ETS FAMILY; RENAL-DISEASE; GROWTH-FACTOR; T-CELLS;
EXPRESSION; BINDING; MICE
AB Regulation of proinflammatory cytokines and chemokines is a primary role of the innate immune response. MCP-1 is a chemokine that recruits immune cells to sites of inflammation. Expression of MCP-1 is reduced in primary kidney endothelial cells from mice with a heterozygous knockout of the Fli-1 transcription factor. Fli-1 is a member of the Ets family of transcription factors, which are evolutionarily conserved across several organisms including Drosophilla, Xenopus, mouse and human. Ets family members bind DNA through a consensus sequence GGAA/T, or Ets binding site (EBS). Fli-1 binds to EBSs within the endogenous MCP-1 promoter by ChIP assay. In this study, transient transfection assays indicate that the Fli-1 gene actively promotes transcription from the MCP-1 gene promoter in a dose-dependent manner. Mutation of the DNA binding domain of Fli-1 demonstrated that Fli-1 activates transcription of MCP-1 both directly, by binding to the promoter, and indirectly, likely through interactions with other transcription factors.
Another-Ets-transcription-factor, Ets-1, was also tested, but failed to promote transcription. While Ets-1 failed to drive transcription independently, a weak synergistic activation of the MCP-1 promoter was observed between Ets-1 and FR-1. In addition, Fli-1 and the NF kappa B family member p65 were found to interact synergistically to activate transcription from the MCP-1 promoter, while Sp1 and p50 inhibit this interaction. Deletion studies identified that EBSs in the distal and proximal MCP-1 promoter are critical for Fli-1 activation from the MCP-1 promoter. Together, these results demonstrate that Fli-1 is a novel regulator of the proinflammatory chemokine MCP-1, that interacts with other transcription factors to form a complex transcriptional mechanism for the activation of MCP-1 and mediation of the inflammatory response. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Richard, Mara L. Lennard; Nowling, Tamara K.; Brandon, Danielle; Zhang, Xian K.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Nowling, Tamara K.; Zhang, Xian K.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29403 USA.
[Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Watson, Dennis K.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
RP Zhang, XK (reprint author), Div Rheumatol & Immunol, Suite 912,96 Jonathan Lucas St,MSC637, Charleston, SC 29425 USA.
EM zhangjo@musc.edu
OI Watson, Dennis/0000-0003-3448-7657
FU National Institute of Health (NIAMS) [AR056670]
FX This research study was supported by the National Institute of Health
grant (NIAMS, AR056670 to X.K.Z.). We would like to thank Dr. Jeremy
Boss from the Emory University School of Medicine for providing us with
the pJECAT2.6 vector and the p50, p65 and Sp1 expression constructs. We
would also like to thank Dr. Maria Trojanowska from the Boston
University School of Medicine Arthritis Center for the Fli-1 DNA binding
mutant expression construct.
NR 45
TC 3
Z9 3
U1 0
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD FEB
PY 2015
VL 63
IS 2
SI SI
BP 566
EP 573
DI 10.1016/j.molimm.2014.07.013
PG 8
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA AW8WT
UT WOS:000346540900053
ER
PT J
AU Ramly, E
Kaafarani, HMA
Velmahos, GC
AF Ramly, Elie
Kaafarani, Haytham M. A.
Velmahos, George C.
TI The Effect of Aging on Pulmonary Function Implications for Monitoring
and Support of the Surgical and Trauma Patient
SO SURGICAL CLINICS OF NORTH AMERICA
LA English
DT Article
DE Aging; Pulmonary function; Perioperative care; Postoperative pulmonary
complications
ID COLLEGE-OF-PHYSICIANS; RANDOMIZED CONTROLLED-TRIAL; MULTIFACTORIAL RISK
INDEX; POSITIVE AIRWAY PRESSURE; MAJOR NONCARDIAC SURGERY;
ABDOMINAL-SURGERY; NONCARDIOTHORACIC SURGERY; POSTOPERATIVE DELIRIUM;
ELDERLY-PATIENTS; CONTRACTILE PROPERTIES
AB Age-related anatomic, physiologic, and immunologic changes to the pulmonary system, as well as a high prevalence of chronic pulmonary diseases, puts the geriatric patient at an especially high risk for postoperative pulmonary complications. Successful perioperative respiratory care of the geriatric patient relies on careful risk assessment and optimization of pulmonary function and support. The success of such efforts aimed at preventing and/or mitigating pulmonary complications in the geriatric patient depends on a thorough, individualized, yet standardized and evidence-based approach to the care of every patient.
C1 [Ramly, Elie; Kaafarani, Haytham M. A.; Velmahos, George C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
RP Kaafarani, HMA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM hkaafarani@mgh.harvard.edu
NR 103
TC 8
Z9 8
U1 1
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0039-6109
EI 1558-3171
J9 SURG CLIN N AM
JI Surg. Clin.-North Am.
PD FEB
PY 2015
VL 95
IS 1
BP 53
EP +
DI 10.1016/j.suc.2014.09.009
PG 18
WC Surgery
SC Surgery
GA AW9AF
UT WOS:000346549500007
PM 25459542
ER
PT J
AU Scandrett, KG
Zuckerbraun, BS
Peitzman, AB
AF Scandrett, Karen G.
Zuckerbraun, Brian S.
Peitzman, Andrew B.
TI Operative Risk Stratification in the Older Adult
SO SURGICAL CLINICS OF NORTH AMERICA
LA English
DT Article
DE Geriatric; Frailty; Goals of care; Cognitive function
ID AMERICAN GERIATRICS SOCIETY; COLLEGE-OF-PHYSICIANS; SERVICES-TASK-FORCE;
ELDER LIFE PROGRAM; SURGICAL OUTCOMES; POSTOPERATIVE COMPLICATIONS;
NONCARDIOTHORACIC SURGERY; PULMONARY COMPLICATIONS; PREOPERATIVE
ASSESSMENT; ASPIRATION PNEUMONIA
AB As the population ages, the health care system must to adapt to the needs of the older population. Hospitalization risks are particularly significant in the frail geriatric patients, with costly and morbid consequences. Appropriate preoperative assessment can identify sources of increased risk and enable the surgical team to manage this risk, through "prehabilitation," intraoperative modification, and postoperative care. Geriatric preoperative assessment expands usual risk stratification and careful medication review to include screening for functional disability, cognitive impairment, nutritional deficiency, and frailty. The information gathered can also equip the surgeon to develop a patient-centered and realistic treatment plan.
C1 [Scandrett, Karen G.] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA.
[Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Zuckerbraun, Brian S.; Peitzman, Andrew B.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
RP Peitzman, AB (reprint author), UPMC Presbyterian, Dept Surg, F-1281, Pittsburgh, PA 15213 USA.
EM peitzmanab@upmc.edu
NR 84
TC 4
Z9 4
U1 6
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0039-6109
EI 1558-3171
J9 SURG CLIN N AM
JI Surg. Clin.-North Am.
PD FEB
PY 2015
VL 95
IS 1
BP 149
EP +
DI 10.1016/j.suc.2014.09.014
PG 26
WC Surgery
SC Surgery
GA AW9AF
UT WOS:000346549500014
PM 25459549
ER
PT J
AU Micheletti, RG
Werth, VP
AF Micheletti, Robert G.
Werth, Victoria P.
TI Small Vessel Vasculitis of the Skin
SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
DE Small vessel vasculitis of the skin; Cutaneous vasculitis;
Leukocytoclastic vasculitis; Hypersensitivity vasculitis; IgA
vasculitis; Henoch-Schonlein purpura
ID HENOCH-SCHONLEIN PURPURA; CUTANEOUS LEUKOCYTOCLASTIC VASCULITIS;
URTICARIAL-VASCULITIS; CLINICAL-FEATURES; HYPERSENSITIVITY VASCULITIS;
DIRECT IMMUNOFLUORESCENCE; LUPUS-ERYTHEMATOSUS; ETIOLOGIC FACTORS;
CONTROLLED-TRIAL; THERAPY
AB Small vessel vasculitis in the skin manifests with palpable purpura on the lower extremities. This clinical presentation prompts a complete physical examination, history, and review of systems, as well as biopsies for routine processing and direct immunofluorescence to confirm the diagnosis. The presence of vasculitis in other organs, associated underlying conditions, and the severity of cutaneous manifestations dictate management. The majority of cases are self-limited, and overall the prognosis is favorable. Still, a subset of patients can have serious complications and chronic or recurrent disease.
C1 [Micheletti, Robert G.; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
[Micheletti, Robert G.; Werth, Victoria P.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Dermatol, Philadelphia, PA 19104 USA.
[Werth, Victoria P.] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA.
RP Micheletti, RG (reprint author), Univ Penn, Perelman Sch Med, Dept Dermatol, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM Robert.Micheletti@uphs.upenn.edu
NR 43
TC 7
Z9 7
U1 2
U2 14
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-857X
EI 1558-3163
J9 RHEUM DIS CLIN N AM
JI Rheum. Dis. Clin. North Am.
PD FEB
PY 2015
VL 41
IS 1
BP 21
EP +
DI 10.1016/j.rdc.2014.09.006
PG 13
WC Rheumatology
SC Rheumatology
GA AW3XS
UT WOS:000346217100004
PM 25399937
ER
PT J
AU Miloslavsky, EM
Stone, JH
Unizony, SH
AF Miloslavsky, Eli M.
Stone, John H.
Unizony, Sebastian H.
TI Challenging Mimickers of Primary Systemic Vasculitis
SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
DE Mimicker; Vasculitis; IgG4-related disease; Livedoid vasculopathy;
Segmental arterial mediolysis; Lymphomatoid granulomatosis;
Fibromuscular dysplasia; Degos disease
ID SEGMENTAL ARTERIAL MEDIOLYSIS; MALIGNANT ATROPHIC PAPULOSIS; IDIOPATHIC
HYPEREOSINOPHILIC SYNDROME; PULMONARY LYMPHOMATOID GRANULOMATOSIS;
CEREBRAL VASOCONSTRICTION SYNDROMES; PRIMARY ANTIPHOSPHOLIPID SYNDROME;
CALCIFIC UREMIC ARTERIOLOPATHY; DIFFUSE ALVEOLAR HEMORRHAGE;
UNITED-STATES REGISTRY; FIBROMUSCULAR DYSPLASIA
AB The need to distinguish true primary systemic vasculitis from its multiple potential mimickers is one of the most challenging diagnostic conundrums in clinical medicine. This article reviews 9 challenging vasculitis mimickers: fibromuscular dysplasia, calciphylaxis, segmental arterial mediolysis, anti-phospholipid syndrome, hypereosinophilic syndrome, lymphomatoid granulomatosis, malignant atrophic papulosis, livedoid vasculopathy, and immunoglobulin G4-related disease.
C1 [Miloslavsky, Eli M.; Stone, John H.; Unizony, Sebastian H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA.
EM jhstone@mgh.harvard.edu
NR 113
TC 4
Z9 4
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-857X
EI 1558-3163
J9 RHEUM DIS CLIN N AM
JI Rheum. Dis. Clin. North Am.
PD FEB
PY 2015
VL 41
IS 1
BP 141
EP +
DI 10.1016/j.rdc.2014.09.011
PG 21
WC Rheumatology
SC Rheumatology
GA AW3XS
UT WOS:000346217100012
PM 25399945
ER
PT J
AU Psaros, C
Barinas, J
Robbins, GK
Bedoya, CA
Park, ER
Safren, SA
AF Psaros, Christina
Barinas, Jennifer
Robbins, Gregory K.
Bedoya, C. Andres
Park, Elyse R.
Safren, Steven A.
TI Reflections on living with HIV over time: exploring the perspective of
HIV-infected women over 50
SO AGING & MENTAL HEALTH
LA English
DT Article
DE women; coping; aging; HIV/AIDS; adjustment
ID RANDOMIZED CONTROLLED-TRIAL; MENTAL-HEALTH; OLDER-ADULTS; HIV/AIDS;
SUPPORT; RISK; LIFE; INTERVENTION; INDIVIDUALS; OUTCOMES
AB Objectives: Approximately 32.7% of people living with HIV/AIDS (PLWHA) in the USA are now over the age of 50. Women comprise a significant percentage of the US HIV epidemic and the percentage of women diagnosed with HIV continues to grow; however, little is known about women's experiences living and coping with HIV over time. The goal of this study was to explore the experiences of US women over 50 living with HIV to better understand how they make sense of their diagnosis and cope with their illness over time and during the aging process.
Method: Nineteen women (mean age = 56.79, SD = 4.63) referred from Boston-area organizations and hospitals completed one-time, in-depth individual interviews, out of which 47% of the participants were identified as Black/African Americans, and 37% as White. The average time since diagnosis was 16.32years (SD = 5.70). Inclusion criteria included: (1) female sex, (2) aged 50 or older, (3) HIV diagnosis, and (4) English speaking. Transcribed interviews were analyzed using a grounded theory approach and NVivo 9 software.
Results: Findings are described across the following themes: (1) experiences at diagnosis, (2) uncertainty of disease course, (3) acceptance, and (4) living 'well' with HIV. Participants appeared to be well adjusted to their HIV diagnosis and described a progression to acceptance and survivorship; they identified strategies to 'live well' in the context of HIV. For some, health-related uncertainty about the future remained. These findings were organized into a model of coping with HIV.
Conclusion: Themes and issues identified by this study may help guide interventions across the lifespan for women with HIV.
C1 [Psaros, Christina; Barinas, Jennifer; Bedoya, C. Andres; Park, Elyse R.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA.
RP Psaros, C (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM cpsaros@partners.org
FU Harvard University Center for AIDS Research (CFAR), an NIH [P30
AI060354]; NIAID; NCI; NICHD; NHLBI; NIDA; NIMH; NIA; NCCAM; FIC; OAR;
[K23 MH096651]
FX Dr Psaros' time was supported by the Harvard University Center for AIDS
Research (CFAR), an NIH funded program (P30 AI060354) which is supported
by the following NIH Co-Funding and Participating Institutes and
Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NCCAM, FIC, and OAR,
and K23 MH096651.
NR 29
TC 2
Z9 2
U1 0
U2 26
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1360-7863
EI 1364-6915
J9 AGING MENT HEALTH
JI Aging Ment. Health
PD FEB 1
PY 2015
VL 19
IS 2
BP 121
EP 128
DI 10.1080/13607863.2014.917608
PG 8
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AU1FB
UT WOS:000345365300003
PM 24903460
ER
PT J
AU Stewart, T
Sossi, V
Aasly, JO
Wszolek, ZK
Uitti, RJ
Hasegawa, K
Yokoyama, T
Zabetian, CP
Leverenz, JB
Stoessl, AJ
Wang, Y
Ginghina, C
Liu, CQ
Cain, KC
Auinger, P
Kang, UJ
Jensen, PH
Shi, M
Zhang, J
AF Stewart, Tessandra
Sossi, Vesna
Aasly, Jan O.
Wszolek, Zbigniew K.
Uitti, Ryan J.
Hasegawa, Kazuko
Yokoyama, Teruo
Zabetian, Cyrus P.
Leverenz, James B.
Stoessl, Alexander Jon
Wang, Yu
Ginghina, Carmen
Liu, Changqin
Cain, Kevin C.
Auinger, Peggy
Kang, Un Jung
Jensen, Poul Henning
Shi, Min
Zhang, Jing
TI Phosphorylated alpha-synuclein in Parkinson's disease: correlation
depends on disease severity
SO ACTA NEUROPATHOLOGICA COMMUNICATIONS
LA English
DT Article
DE Parkinson's disease; Cerebrospinal fluid; Biomarker; alpha-synuclein;
Phosphorylation; DATATOP
ID CEREBROSPINAL-FLUID; RAT MODEL; BLOOD-PLASMA; AMYLOID-BETA; IN-VIVO;
SER-129; DEMENTIA; NEURODEGENERATION; NEUROTOXICITY; PROGRESSION
AB Introduction: alpha a-Synuclein (alpha-syn) is a key protein in Parkinson's disease (PD), and one of its phosphorylated forms, pS129, is higher in PD patients than healthy controls. However, few studies have examined its levels in longitudinally collected cerebrospinal fluid (CSF) or in preclinical cases. In this study, CSF and clinical data were contributed by >300 subjects from three cohorts (the longitudinal DATATOP cohort, a large cross-sectional cohort, and a cohort of LRRK2 mutation carriers).
Results: Consistent with our previous observation that CSF pS129 positively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) scores, CSF pS129 in the DATATOP cohort increased over approximately two years of disease progression (mean change 5.60 pg/ml, p = 0.050). Intriguingly, in the DATATOP cohort, pS129 negatively correlated with UPDRS scores at the baseline (R = -0.244, p = 0.017), but not final point, suggesting that this association may depend on disease stage. Reanalysis of our previous cohort with stratification by PD stage, and addition of a cohort of LRRK2 mutation carriers with very early/preclinical PD, supported the idea that the relationship between CSF pS129 and disease severity over a wider range of PD stages might be represented with a U-shaped curve, in which lower pS129 levels correlated with worse clinical condition at early stages, but better condition at later stages.
Conclusion: The observation of a negative-to-positive transition of correlation of pS129 to disease severity as PD progresses could have profound impact on how pS129 is used as a biomarker clinically as well as in modeling PD experimentally.
C1 [Stewart, Tessandra; Ginghina, Carmen; Liu, Changqin; Shi, Min; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA.
[Sossi, Vesna] Univ British Columbia, Vancouver Hosp & Hlth Sci Ctr, Dept Phys & Astron, Vancouver, BC V5Z 1M9, Canada.
[Aasly, Jan O.] St Olavs Hosp, Dept Neurol, Trondheim, Norway.
[Wszolek, Zbigniew K.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Hasegawa, Kazuko; Yokoyama, Teruo] Sagamihara Natl Hosp, Natl Hosp Org, Dept Neurol, Kanagawa, Japan.
[Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr, Geriatr Res, Seattle, WA USA.
[Zabetian, Cyrus P.; Leverenz, James B.] Affairs Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA.
[Zabetian, Cyrus P.; Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98104 USA.
[Leverenz, James B.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA USA.
[Leverenz, James B.] Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr, Mental Illness Res, Seattle, WA USA.
[Stoessl, Alexander Jon] Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver Coastal Hlth, Vancouver, BC V5Z 1M9, Canada.
[Wang, Yu] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Neurosurg, Wuhan 430030, Hubei, Peoples R China.
[Liu, Changqin] Xiamen Univ, Affiliated Hosp 1, Dept Endocrinol & Metab, Xiamen, Peoples R China.
[Liu, Changqin] Xiamen Univ, Affiliated Hosp 1, Xiamen Diabet Inst, Xiamen, Peoples R China.
[Cain, Kevin C.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Auinger, Peggy] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Dept Neurol, Rochester, NY USA.
[Kang, Un Jung] Univ Chicago Med & Biol Sci, Dept Neurol, Chicago, IL USA.
[Jensen, Poul Henning] Aarhus Univ, Dept Biomed, DK-8000 Aarhus C, Denmark.
RP Zhang, J (reprint author), Univ Washington, Sch Med, Dept Pathol, 325 9th Ave,HMC Box 359635, Seattle, WA 98104 USA.
EM zhangj@uw.edu
FU NIA NIH HHS [R01 AG033398]; NIEHS NIH HHS [P30 ES007033-6364, R01
ES016873, P42 ES004696-5897, R01 ES019277, T32 ES007032, T32 ES015459];
NINDS NIH HHS [P50 NS072187, P50 NS062684-6221, R01 NS057567, R01
NS065070, U01 NS082137]
NR 35
TC 11
Z9 11
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-5960
J9 ACTA NEUROPATHOL COM
JI Acta Neuropathol. Commun.
PD JAN 31
PY 2015
VL 3
AR 7
DI 10.1186/s40478-015-0185-3
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CS6AI
UT WOS:000362159000003
PM 25637461
ER
PT J
AU Greaney, ML
Sprunck-Harrild, K
Ruddy, KJ
Ligibel, J
Barry, WT
Baker, E
Meyer, M
Emmons, KM
Partridge, AH
AF Greaney, Mary L.
Sprunck-Harrild, Kim
Ruddy, Kathryn J.
Ligibel, Jennifer
Barry, William T.
Baker, Emily
Meyer, Meghan
Emmons, Karen M.
Partridge, Ann H.
TI Study protocol for Young & Strong: a cluster randomized design to
increase attention to unique issues faced by young women with newly
diagnosed breast cancer
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Breast cancer; Oncology; Young women; Fertility; Exercise; Psychosocial
distress; Patient communication
ID QUALITY-OF-LIFE; FERTILITY CONCERNS; PRIMARY-CARE; SURVIVORS; HEALTH;
AGE; PREMENOPAUSAL; INTERVENTIONS; PRESERVATION; CHEMOTHERAPY
AB Background: Each year, approximately 11% of women diagnosed with breast cancer in the United States are 45 years of age or younger. These women have concerns specific to or accentuated by their age, including fertility-related concerns, and have higher rates of psychosocial distress than women diagnosed at older ages. Current guidelines recommend that fertility risks be considered early in all treatment plans; however, the extant research indicates that attention to fertility by the healthcare team is limited. Importantly, attention to fertility may be a proxy for whether or not other important issues warranting attention in younger women with breast cancer are addressed, including genetic risks, psychosocial distress, sexual functioning, and body image concerns. The Young & Strong study tests the efficacy of an intervention designed for young women recently diagnosed with breast cancer and their oncologists with the intention to: 1) increase attention to fertility as an important surrogate for other issues facing young women, 2) educate and support young women and their providers, and 3) reduce psychosocial distress among young women with breast cancer.
Methods/Design: The study employs a cluster randomized design including 14 academic institutions and 40 community sites across the U.S. assigned to either the study intervention arm or contact-time comparison intervention arm. Academic institutions enroll up to 15 patients per site while community sites enroll up to 10 patients. Patient eligibility requirements include: an initial diagnosis of stage I-III invasive breast cancer within three months prior, without a known recurrence or metastatic breast cancer; 18-45 years of age at diagnosis; ability to read and write in English. The primary outcome is oncologists' attention to fertility concerns as determined by medical record review. Secondary outcomes include differences in patient satisfaction with care and psychosocial distress between the two study arms.
Discussion: Study findings will provide valuable insight into how to increase attention to fertility and other issues specific to young women with breast cancer and how to improve doctor-patient communication around these issues, which may promote better quality of care for this population.
C1 [Greaney, Mary L.] Univ Rhode Isl, Kingston, RI 02881 USA.
[Sprunck-Harrild, Kim; Ligibel, Jennifer; Barry, William T.; Baker, Emily; Meyer, Meghan; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Ruddy, Kathryn J.] Mayo Clin, Rochester, MN USA.
[Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Ligibel, Jennifer; Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Greaney, ML (reprint author), Univ Rhode Isl, Kingston, RI 02881 USA.
EM mgreaney@uri.edu
FU ASCO Cancer Foundation/Susan G. Komen Improving Cancer Care Grant; NIH
[5 K05 CA124415-05]
FX This work was supported by an ASCO Cancer Foundation/Susan G. Komen
Improving Cancer Care Grant (PI: Partridge) and by NIH 5 K05 CA124415-05
(PI: K. Emmons). Study-related materials were developed in partnership
with the DF/HCC Health Communication Core, Boston, MA. We would like to
thank all the women who participated in the focus groups, key informant
interviews, and in the Young & Strong pilot and parent study, as well as
the oncologists, providers, site coordinators, and other study staff at
the sites.
NR 50
TC 1
Z9 1
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD JAN 31
PY 2015
VL 15
AR 37
DI 10.1186/s12889-015-1346-9
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CB1WN
UT WOS:000349418800002
PM 25636332
ER
PT J
AU Shen, HS
Liang, D
Luo, MY
Duan, CJ
Cai, WL
Zhu, SS
Qiu, JP
Li, WR
AF Shen, Hesong
Liang, Dan
Luo, Mingyue
Duan, Chaijie
Cai, Wenli
Zhu, Shanshan
Qiu, Jianping
Li, Wenru
TI Pilot Study on Image Quality and Radiation Dose of CT Colonography with
Adaptive Iterative Dose Reduction Three-Dimensional
SO PLOS ONE
LA English
DT Article
ID TUBE-CURRENT MODULATION; COLORECTAL LESIONS; MDCT COLONOGRAPHY;
RECONSTRUCTION; FEASIBILITY; CANCER; RISK; REIMBURSEMENT; COLONOSCOPY;
PERFORMANCE
AB Objective
To investigate image quality and radiation dose of CT colonography (CTC) with adaptive iterative dose reduction three-dimensional (AIDR3D).
Methods
Ten segments of porcine colon phantom were collected, and 30 pedunculate polyps with diameters ranging from 1 to 15 mm were simulated on each segment. Image data were acquired with tube voltage of 120 kVp, and current doses of 10 mAs, 20 mAs, 30 mAs, 40 mAs, 50 mAs, respectively. CTC images were reconstructed using filtered back projection (FBP) and AIDR3D. Two radiologists blindly evaluated image quality. Quantitative evaluation of image quality included image noise, signal-to-noise ratio (SNR), and contrast-tonoise ratio (CNR). Qualitative image quality was evaluated with a five-score scale. Radiation dose was calculated based on dose-length product. Ten volunteers were examined supine 50 mAs with FBP and prone 20 mAs with AIDR3D, and image qualities were assessed. Paired t test was performed for statistical analysis.
Results
For 20 mAs with AIDR3D and 50 mAs with FBP, image noise, SNRs and CNRs were (16.4 +/- 1.6) HU vs. (16.8 +/- 2.6) HU, 1.9 +/- 0.2 vs. 1.9 +/- 0.4, and 62.3 +/- 6.8 vs. 62.0 +/- 6.2, respectively; qualitative image quality scores were 4.1 and 4.3, respectively; their differences were all not statistically significant. Compared with 50 mAs with FBP, radiation dose (1.62 mSv) of 20 mAs with AIDR3D was decreased by 60.0%. There was no statistically significant difference in image noise, SNRs, CNRs and qualitative image quality scores between prone 20 mAs with AIDR3D and supine 50 mAs with FBP in 10 volunteers, the former reduced radiation dose by 61.1%.
Conclusion
Image quality of CTC using 20 mAs with AIDR3D could be comparable to standard 50 mAs with FBP, radiation dose of the former reduced by about 60.0% and was only 1.62 mSv.
C1 [Shen, Hesong; Liang, Dan; Luo, Mingyue; Zhu, Shanshan; Qiu, Jianping; Li, Wenru] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China.
[Duan, Chaijie] Tsinghua Univ, Grad Sch Shenzhen, Biomed Engn Res Ctr, Shenzhen 518057, Guangdong, Peoples R China.
[Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Cai, Wenli] Harvard Univ, Sch Med, Boston, MA USA.
RP Luo, MY (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China.
EM myluo720@163.com
RI Li, Wenjun/F-5634-2015
OI Li, Wenjun/0000-0001-5335-7386
FU National Natural Science Foundation of China [81230035]; Guangdong
Provincial Science and Technology Program [2011B031800182,
2013B051000016]
FX This study was supported by The National Natural Science Foundation of
China (81230035), http://www.nsfc.gov.cn/; and Guangdong Provincial
Science and Technology Program (2011B031800182, 2013B051000016),
http://pro.gdstc.gov.cn/. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 37
TC 1
Z9 1
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 30
PY 2015
VL 10
IS 1
AR e0117116
DI 10.1371/journal.pone.0117116
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CC9HX
UT WOS:000350680700070
PM 25635839
ER
PT J
AU Courties, G
Herisson, F
Sager, HB
Heidt, T
Ye, YX
Wei, Y
Sun, Y
Severe, N
Dutta, P
Scharff, J
Scadden, DT
Weissleder, R
Swirski, FK
Moskowitz, MA
Nahrendorf, M
AF Courties, Gabriel
Herisson, Fanny
Sager, Hendrik B.
Heidt, Timo
Ye, Yuxiang
Wei, Ying
Sun, Yuan
Severe, Nicolas
Dutta, Partha
Scharff, Jennifer
Scadden, David T.
Weissleder, Ralph
Swirski, Filip K.
Moskowitz, Michael A.
Nahrendorf, Matthias
TI Ischemic Stroke Activates Hematopoietic Bone Marrow Stem Cells
SO CIRCULATION RESEARCH
LA English
DT Article
DE bone marrow; hematopoietic stem cells; monocyte; stroke
ID FOCAL CEREBRAL-ISCHEMIA; INNATE IMMUNE-SYSTEM; MYOCARDIAL-INFARCTION;
POSTSTROKE INFECTION; INFLAMMATORY CELLS; BETA-BLOCKERS; BRAIN;
ATHEROSCLEROSIS; MACROPHAGES; NICHE
AB Rationale: The mechanisms leading to an expanded neutrophil and monocyte supply after stroke are incompletely understood.
Objective: To test the hypothesis that transient middle cerebral artery occlusion (tMCAO) in mice leads to activation of hematopoietic bone marrow stem cells.
Methods and Results: Serial in vivo bioluminescence reporter gene imaging in mice with tMCAO revealed that bone marrow cell cycling peaked 4 days after stroke (P<0.05 versus pre tMCAO). Flow cytometry and cell cycle analysis showed activation of the entire hematopoietic tree, including myeloid progenitors. The cycling fraction of the most upstream hematopoietic stem cells increased from 3.34%+/- 0.19% to 7.32%+/- 0.52% after tMCAO (P<0.05). In vivo microscopy corroborated proliferation of adoptively transferred hematopoietic progenitors in the bone marrow of mice with stroke. The hematopoietic system's myeloid bias was reflected by increased expression of myeloid transcription factors, including PU.1 (P<0.05), and by a decline in lymphocyte precursors. In mice after tMCAO, tyrosine hydroxylase levels in sympathetic fibers and bone marrow noradrenaline levels rose (P<0.05, respectively), associated with a decrease of hematopoietic niche factors that promote stem cell quiescence. In mice with genetic deficiency of the beta(3) adrenergic receptor, hematopoietic stem cells did not enter the cell cycle in increased numbers after tMCAO (naive control, 3.23 +/- 0.22; tMCAO, 3.74 +/- 0.33, P=0.51).
Conclusions: Ischemic stroke activates hematopoietic stem cells via increased sympathetic tone, leading to a myeloid bias of hematopoiesis and higher bone marrow output of inflammatory Ly6C(high) monocytes and neutrophils.
C1 [Courties, Gabriel; Sager, Hendrik B.; Heidt, Timo; Ye, Yuxiang; Sun, Yuan; Dutta, Partha; Scharff, Jennifer; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Courties, Gabriel; Sager, Hendrik B.; Heidt, Timo; Ye, Yuxiang; Sun, Yuan; Dutta, Partha; Scharff, Jennifer; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA.
[Herisson, Fanny; Wei, Ying; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA USA.
[Herisson, Fanny; Wei, Ying; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Neurol, Charlestown, MA USA.
[Severe, Nicolas; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
RP Nahrendorf, M (reprint author), Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.
EM mnahrendorf@mgh.harvard.edu
FU National Institutes of Health [R01-NS084863, R01-HL117829, R01-HL096576,
HHSN268201000044C]; MGH Research Scholar Award; American Heart
Association [13POST16580004]; German Research Foundation [HE6382/1-1,
SA1668/2-1]; Deutsche Herzstiftung [S/05/12]
FX This work was funded in part by grants from the National Institutes of
Health (R01-NS084863, R01-HL117829, R01-HL096576, HHSN268201000044C),
the MGH Research Scholar Award, the American Heart Association
(13POST16580004), the German Research Foundation (HE6382/1-1 and
SA1668/2-1), and the Deutsche Herzstiftung (S/05/12).
NR 52
TC 27
Z9 28
U1 2
U2 28
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD JAN 30
PY 2015
VL 116
IS 3
BP 407
EP +
DI 10.1161/CIRCRESAHA.116.305207
PG 19
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA CA3IJ
UT WOS:000348799500007
PM 25362208
ER
PT J
AU Newton, RH
Lu, Y
Papa, A
Whitcher, GH
Kang, YJ
Yan, C
Pandolfi, PP
Turka, LA
AF Newton, Ryan H.
Lu, Yu
Papa, Antonella
Whitcher, Greg H.
Kang, Youn-Jung
Yan, Catherine
Pandolfi, Pier Paolo
Turka, Laurence A.
TI Suppression of T-cell lymphomagenesis in mice requires PTEN phosphatase
activity
SO BLOOD
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR; GENOMIC INSTABILITY;
NEGATIVE REGULATION; NUCLEAR PTEN; PTEN/MMAC1; INACTIVATION; MANNER;
GENE
AB Mice with T-cell-specific loss of the tumor suppressor gene PTEN early in T-cell ontogeny develop thymic lymphomas that invariably harbor a reciprocal translocation involving the T-cell receptor alpha/delta locus and c-myc, t(14; 15). In addition to its known function as a lipid phosphatase opposing PI3K signaling, PTEN has also been described as playing a prominent role in promoting genomic stability. As a result, it has been uncertain which one(s) of these 2 separable features were required to block the development of lymphoma. Here, using a conditional model in which T cells selectively express 1 phosphatase-dead PTEN mutant (C124S) and maintain 1 null allele, we show that PTEN phosphatase activity is required for preventing the emergence of a malignant T-cell population harboring t(14; 15), thus constituting a critical function of PTEN in preventing lymphomagenesis.
C1 [Newton, Ryan H.; Whitcher, Greg H.; Turka, Laurence A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA.
[Newton, Ryan H.; Whitcher, Greg H.; Turka, Laurence A.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02129 USA.
[Lu, Yu] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Papa, Antonella; Pandolfi, Pier Paolo] Beth Israel Deaconess Canc Ctr, Canc Res Inst, Boston, MA USA.
[Papa, Antonella; Pandolfi, Pier Paolo] Beth Israel Deaconess Med Ctr, Dept Pathol & Med, Boston, MA 02215 USA.
[Kang, Youn-Jung; Yan, Catherine] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Kang, Youn-Jung] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA.
RP Turka, LA (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, 149 13th St,Room 5101, Boston, MA 02129 USA.
EM lturka@partners.org
OI Papa, Antonella/0000-0001-8653-7121
NR 25
TC 4
Z9 4
U1 0
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JAN 29
PY 2015
VL 125
IS 5
BP 852
EP 855
DI 10.1182/blood-2014-04-571372
PG 4
WC Hematology
SC Hematology
GA CD1DR
UT WOS:000350814900019
PM 25477498
ER
PT J
AU Lawrence, MS
Sougnez, C
Lichtenstein, L
Cibulskisl, K
Lander, E
Gabriel, SB
Getz, G
Ally, A
Balasundaram, M
Birol, I
Bowlby, R
Brooks, D
Butterfield, YSN
Carlsen, R
Cheng, D
Chu, A
Dhalla, N
Guin, R
Holt, RA
Jones, SJM
Lee, D
Li, HYI
Marra, MA
Mayo, M
Moore, RA
Mungall, AJ
Robertson, AG
Schein, JE
Sipahimalan, P
Tam, A
Thiessen, N
Wong, T
Protopopov, A
Santoso, N
Lee, S
Parfenov, M
Zhang, JH
Mahadeshwar, HS
Tang, JB
Ren, XJ
Seth, S
Haseley, P
Zeng, D
Yang, LX
Xu, AW
Song, XZ
Pantazi, A
Bristow, CA
Hadjipanayis, A
Seidman, J
Chin, L
Park, PJ
Kucherlapati, R
Akbani, R
Casasent, T
Liu, WB
Le, Y
Mille, G
Motter, T
Weinstein, J
Diao, LX
Wang, J
Fan, YH
Lie, JZ
Wang, K
Auman, JT
Balu, S
Bodenheimer, T
Buda, E
Hayes, DN
Hoadley, KA
Hoyle, AP
Jefferys, SR
Jones, CD
Kimes, PK
Liu, YF
Marron, JS
Meng, SW
Mieczkowski, PA
Mose, LE
Parker, JS
Perou, CM
Prins, JF
Roach, J
Shi, Y
Simons, JV
Singh, D
Soloway, MG
Tan, DH
Veluvolu, U
Walter, V
Waring, S
Wilkerson, MD
Wu, JY
Zhao, N
Cherniack, AD
Hammerman, PS
Tward, AD
Pedamallu, CS
Saksena, G
Jung, J
Ojesina, AI
Carter, SL
Zack, TI
Schumacher, SE
Beroukhim, R
Freeman, SS
Meyerson, M
Cho, J
Chin, L
Getz, G
Noble, MS
DiCara, D
Zhang, H
Heiman, DI
Gehlenborg, N
Voet, D
Lin, P
Frazer, S
Stojanov, P
Liu, YC
Zou, LH
Kim, J
Sougnez, C
Gabriel, SB
Lawrence, MS
Muzny, D
Doddapaneni, H
Kovar, C
Reid, J
Morton, D
Han, Y
Hale, W
Chao, H
Chang, K
Drummond, JA
Gibbs, RA
Kakkar, N
Wheeler, D
Xi, L
Ciriello, G
Ladanyi, M
Lee, W
Ramirez, R
Sander, C
Shen, R
Sinhal, R
Weinhold, N
Taylor, BS
Aksoy, BA
Dresdner, G
Gao, JJ
Gross, B
Jacobsen, A
Reva, B
Schultz, N
Sumer, SO
Sun, YC
Chan, TA
Morris, LG
Stuart, J
Benz, S
Ng, S
Benz, C
Yau, C
Baylin, SB
Cope, L
Danilova, L
Herman, JG
Bootwalla, M
Maglinte, DT
Larid, PW
Triche, T
Weisenberger, DJ
Van den Berg, DJ
Agrawal, N
Bishop, J
Boutros, PC
Bruce, JP
Byers, LA
Califano, J
Carey, TE
Chen, Z
Cheng, H
Chiosea, SI
Cohen, E
Diergaarde, B
Egloff, AM
El-Naggar, AK
Ferris, RL
Frederick, MJ
Grandis, JR
Guo, Y
Haddad, RI
Hammerman, PS
Harris, T
Hayes, DN
Hui, ABY
Lee, JJ
Lippman, SM
Liu, FF
McHugh, JB
Myers, J
Ng, PKS
Perez-Ordonez, B
Pickering, CR
Prystowsky, M
Romkes, M
Saleh, AD
Sartor, MA
Seethala, R
Seiwert, TY
Si, H
Tward, AD
Van Waes, C
Waggott, DM
Wiznerowicz, M
Yarbrough, WG
Zhang, JX
Zuo, ZX
Burnett, K
Crain, D
Gardner, J
Lau, K
Mallery, D
Morris, S
Lauskis, JP
Penny, R
Shelton, C
Shelton, T
Sherman, M
Yena, P
Black, AD
Bowen, J
Frick, J
Gastier-Foster, JM
Harper, HA
Leraas, K
Lichtenberg, TM
Ramirez, NC
Wise, L
Zmuda, E
Baboud, J
Jensen, MA
Kahn, AB
Pihl, TD
Pot, DA
Srinivasan, D
Walton, JS
Wan, YH
Burton, RA
Davidsen, T
Demchok, JA
Eley, G
Ferguson, ML
Shaw, KRM
Ozenberger, BA
Sheth, M
Sofia, HJ
Tarnuzzer, R
Wang, ZN
Yang, LM
Zenklusen, JC
Saller, C
Tarvi, K
Chen, C
Bollag, R
Weinberger, P
Golusinski, W
Golusinski, P
Ibbs, M
Korski, K
Mackiewicz, A
Suchorska, W
Szybiak, B
Wiznerowicz, M
Burnett, K
Curley, E
Gardner, J
Mallery, D
Penny, R
Shelton, T
Yena, P
Beard, C
Mitchell, C
Sandusky, G
Agrawal, N
Ahn, J
Bishop, J
Califano, J
Khan, Z
Bruce, JP
Hui, ABY
Irish, J
Liu, FF
Perez-Ordonez, B
Waldron, J
Boutros, PC
Waggott, DM
Myers, J
William, WN
Lippman, SM
Egea, S
Gomez-Fernandez, C
Herbert, L
Bradford, CR
Carey, TE
Chepeha, DB
Haddad, AS
Jones, TR
Komarck, CM
Malakh, M
McHugh, JB
Moyer, JS
Nguyen, A
Peterson, LA
Prince, ME
Rozek, LS
Sartor, MA
Taylor, EG
Walline, HM
Wolf, GT
Boice, L
Chera, BS
Funkhouser, WK
Gulley, ML
Hackman, TG
Hayes, DN
Hayward, MC
Huang, M
Rathmell, WK
Salazar, AH
Shockley, WW
Shores, CG
Thorne, L
Weissler, MC
Wrenn, S
Zanation, AM
Chiosea, SI
Diergaarde, B
Egloff, AM
Ferris, RL
Romkes, M
Seethala, R
Brown, BT
Guo, Y
Pham, M
Yarbrough, WG
AF Lawrence, Michael S.
Sougnez, Carrie
Lichtenstein, Lee
Cibulskisl, Kristian
Lander, Eric
Gabriel, Stacey B.
Getz, Gad
Ally, Adrian
Balasundaram, Miruna
Birol, Inanc
Bowlby, Reanne
Brooks, Denise
Butterfield, Yaron S. N.
Carlsen, Rebecca
Cheng, Dean
Chu, Andy
Dhalla, Noreen
Guin, Ranabir
Holt, Robert A.
Jones, Steven J. M.
Lee, Darlene
Li, Haiyan I.
Marra, Marco A.
Mayo, Michael
Moore, Richard A.
Mungall, Andrew J.
Robertson, A. Gordon
Schein, Jacqueline E.
Sipahimalan, Payal
Tam, Angela
Thiessen, Nina
Wong, Tina
Protopopov, Alexei
Santoso, Netty
Lee, Semin
Parfenov, Michael
Zhang, Jianhua
Mahadeshwar, Harshad S.
Tang, Jiabin
Ren, Xiaojia
Seth, Sahil
Haseley, Psalm
Zeng, Dong
Yang, Lixing
Xu, Andrew W.
Song, Xingzhi
Pantazi, Angeliki
Bristow, Christopher A.
Hadjipanayis, Angela
Seidman, Jonathan
Chin, Lynda
Park, Peter J.
Kucherlapati, Raju
Akbani, Rehan
Casasent, Tod
Liu, Wenbin
Le, Yiling
Mille, Gordon
Motter, Thomas
Weinstein, John
Diao, Lixia
Wang, Jing
Fan, You Hong
Lie, Jinze
Wang, Kai
Auman, J. Todd
Balu, Saianand
Bodenheimer, Thomas
Buda, Elizabeth
Hayes, D. Neil
Hoadley, Katherine A.
Hoyle, Alan P.
Jefferys, Stuart R.
Jones, Corbin D.
Kimes, Patrick K.
Liu, Yufeng
Marron, J. S.
Meng, Shaowu
Mieczkowski, Piotr A.
Mose, Lisle E.
Parker, Joel S.
Perou, Charles M.
Prins, Jan F.
Roach, Jeffrey
Shi, Yan
Simons, Janae V.
Singh, Darshan
Soloway, Matthew G.
Tan, Donghui
Veluvolu, Umadevi
Walter, Vonn
Waring, Scot
Wilkerson, Matthew D.
Wu, Junyuan
Zhao, Ni
Cherniack, Andrew D.
Hammerman, Peter S.
Tward, Aaron D.
Pedamallu, Chandra Sekhar
Saksena, Gordon
Jung, Joonil
Ojesina, Akinyemi I.
Carter, Scott L.
Zack, Travis I.
Schumacher, Steven E.
Beroukhim, Rameen
Freeman, Samuel S.
Meyerson, Matthew
Cho, Juok
Chin, Lynda
Getz, Gad
Noble, Michael S.
DiCara, Daniel
Zhang, Hailei
Heiman, David I.
Gehlenborg, Nils
Voet, Doug
Lin, Pei
Frazer, Scott
Stojanov, Petar
Liu, Yingchun
Zou, Lihua
Kim, Jaegil
Sougnez, Carrie
Gabriel, Stacey B.
Lawrence, Michael S.
Muzny, Donna
Doddapaneni, HarshaVardhan
Kovar, Christie
Reid, Jeff
Morton, Donna
Han, Yi
Hale, Walker
Chao, Hsu
Chang, Kyle
Drummond, Jennifer A.
Gibbs, Richard A.
Kakkar, Nipun
Wheeler, David
Xi, Liu
Ciriello, Giovanni
Ladanyi, Marc
Lee, William
Ramirez, Ricardo
Sander, Chris
Shen, Ronglai
Sinhal, Rileen
Weinhold, Nils
Taylor, Barry S.
Aksoy, B. Arman
Dresdner, Gideon
Gao, Jianjiong
Gross, Benjamin
Jacobsen, Anders
Reva, Boris
Schultz, Nikolaus
Sumer, S. Onur
Sun, Yichao
Chan, Timothy A.
Morris, Luc G.
Stuart, Joshua
Benz, Stephen
Ng, Sam
Benz, Christopher
Yau, Christina
Baylin, Stephen B.
Cope, Leslie
Danilova, Ludmila
Herman, James G.
Bootwalla, Moiz
Maglinte, Dennis T.
Larid, Peter W.
Triche, Timothy, Jr.
Weisenberger, Daniel J.
Van den Berg, David J.
Agrawal, Nishant
Bishop, Justin
Boutros, Paul C.
Bruce, Jeff P.
Byers, Lauren Averett
Califano, Joseph
Carey, Thomas E.
Chen, Zhong
Cheng, Hui
Chiosea, Simion I.
Cohen, Ezra
Diergaarde, Brenda
Egloff, Ann Marie
El-Naggar, Adel K.
Ferris, Robert L.
Frederick, Mitchell J.
Grandis, Jennifer R.
Guo, Yan
Haddad, Robert I.
Hammerman, Peter S.
Harris, Thomas
Hayes, D. Neil
Hui, Angela B. Y.
Lee, J. Jack
Lippman, Scott M.
Liu, Fei-Fei
McHugh, Jonathan B.
Myers, Jeff
Ng, Patrick Kwok Shing
Perez-Ordonez, Bayardo
Pickering, Curtis R.
Prystowsky, Michael
Romkes, Marjorie
Saleh, Anthony D.
Sartor, Maureen A.
Seethala, Raja
Seiwert, Tanguy Y.
Si, Han
Tward, Aaron D.
Van Waes, Carter
Waggott, Daryl M.
Wiznerowicz, Maciej
Yarbrough, Wendell G.
Zhang, Jiexin
Zuo, Zhixiang
Burnett, Ken
Crain, Daniel
Gardner, Johanna
Lau, Kevin
Mallery, David
Morris, Scott
Lauskis, Joseph Pau
Penny, Robert
Shelton, Candace
Shelton, Troy
Sherman, Mark
Yena, Peggy
Black, Aaron D.
Bowen, Jay
Frick, Jessica
Gastier-Foster, Julie M.
Harper, Hollie A.
Leraas, Kristen
Lichtenberg, Tara M.
Ramirez, Nilsa C.
Wise, Lisa
Zmuda, Erik
Baboud, Julien
Jensen, Mark A.
Kahn, An B.
Pihl, Todd D.
Pot, David A.
Srinivasan, Deepak
Walton, Jessica S.
Wan, Yunhu
Burton, Robert A.
Davidsen, Tanja
Demchok, John A.
Eley, Greg
Ferguson, Martin L.
Shaw, Kenna R. Mills
Ozenberger, Bradley A.
Sheth, Margi
Sofia, Heidi J.
Tarnuzzer, Roy
Wang, Zhining
Yang, Liming
Zenklusen, Jean Claude
Saller, Charles
Tarvi, Katherine
Chen, Chu
Bollag, Roni
Weinberger, Paul
Golusinski, Wojciech
Golusinski, Pawel
Ibbs, Matthew
Korski, Konstanty
Mackiewicz, Andrzej
Suchorska, Wiktoria
Szybiak, Bartosz
Wiznerowicz, Maciej
Burnett, Ken
Curley, Erin
Gardner, Johanna
Mallery, David
Penny, Robert
Shelton, Troy
Yena, Peggy
Beard, Christina
Mitchell, Colleen
Sandusky, George
Agrawal, Nishant
Ahn, Julie
Bishop, Justin
Califano, Joseph
Khan, Zubair
Bruce, Jeff P.
Hui, Angela B. Y.
Irish, Jonathan
Liu, Fei-Fei
Perez-Ordonez, Bayardo
Waldron, John
Boutros, Paul C.
Waggott, Daryl M.
Myers, Jeff
William, William N., Jr.
Lippman, Scott M.
Egea, Sophie
Gomez-Fernandez, Carmen
Herbert, Lynn
Bradford, Carol R.
Carey, Thomas E.
Chepeha, Douglas B.
Haddad, Andrea S.
Jones, Tamara R.
Komarck, Christine M.
Malakh, Mayya
McHugh, Jonathan B.
Moyer, Jeffrey S.
Nguyen, Ariane
Peterson, Lisa A.
Prince, Mark E.
Rozek, Laura S.
Sartor, Maureen A.
Taylor, Evan G.
Walline, Heather M.
Wolf, Gregory T.
Boice, Lori
Chera, Bhishamjit S.
Funkhouser, William K.
Gulley, Margaret L.
Hackman, Trevor G.
Hayes, D. Neil
Hayward, Michele C.
Huang, Mei
Rathmell, W. Kimryn
Salazar, Ashley H.
Shockley, William W.
Shores, Carol G.
Thorne, Leigh
Weissler, Mark C.
Wrenn, Sylvia
Zanation, Adam M.
Chiosea, Simion I.
Diergaarde, Brenda
Egloff, Ann Marie
Ferris, Robert L.
Romkes, Marjorie
Seethala, Raja
Brown, Brandee T.
Guo, Yan
Pham, Michelle
Yarbrough, Wendell G.
CA Canc Genome Atlas Network
TI Comprehensive genomic characterization of head and neck squamous cell
carcinomas
SO NATURE
LA English
DT Article
ID NF-KAPPA-B; GROWTH-FACTOR-RECEPTOR; AJUBA FAMILY PROTEINS; CANCER
GROWTH; ACTIVATION; EXPRESSION; TRAF3; EGFR; CLASSIFICATION; RESISTANCE
AB The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.
C1 [Lichtenstein, Lee; Cibulskisl, Kristian; Lander, Eric; Gabriel, Stacey B.; Cherniack, Andrew D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalan, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
[Protopopov, Alexei; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Seth, Sahil; Zeng, Dong; Song, Xingzhi; Bristow, Christopher A.; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Le, Yiling; Mille, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Byers, Lauren Averett; El-Naggar, Adel K.; Frederick, Mitchell J.; Lee, J. Jack; Myers, Jeff; Ng, Patrick Kwok Shing; Pickering, Curtis R.; Zhang, Jiexin; William, William N., Jr.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Santoso, Netty; Lee, Semin; Parfenov, Michael; Ren, Xiaojia; Haseley, Psalm; Yang, Lixing; Xu, Andrew W.; Pantazi, Angeliki; Hadjipanayis, Angela; Seidman, Jonathan; Park, Peter J.; Kucherlapati, Raju; Beroukhim, Rameen; Meyerson, Matthew; Tward, Aaron D.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hadjipanayis, Angela; Park, Peter J.; Kucherlapati, Raju] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Park, Peter J.] Boston Childrens Hosp, Boston, MA 02115 USA.
[Lie, Jinze; Wang, Kai] Univ Kentucky, Lexington, KY 40506 USA.
[Auman, J. Todd; Balu, Saianand; Bodenheimer, Thomas; Buda, Elizabeth; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Liu, Yufeng; Marron, J. S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Boice, Lori; Chera, Bhishamjit S.; Funkhouser, William K.; Gulley, Margaret L.; Hackman, Trevor G.; Hayward, Michele C.; Huang, Mei; Rathmell, W. Kimryn; Salazar, Ashley H.; Shockley, William W.; Shores, Carol G.; Thorne, Leigh; Weissler, Mark C.; Wrenn, Sylvia; Zanation, Adam M.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Meyerson, Matthew; Stojanov, Petar; Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Zack, Travis I.] Harvard Univ, Boston, MA 02115 USA.
[Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu] Baylor Coll Med, Houston, TX 77030 USA.
[Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinhal, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timothy A.; Morris, Luc G.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Stuart, Joshua; Benz, Stephen; Ng, Sam; Benz, Christopher; Yau, Christina] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
[Baylin, Stephen B.; Cope, Leslie; Danilova, Ludmila; Herman, James G.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
[Bootwalla, Moiz; Maglinte, Dennis T.; Larid, Peter W.; Triche, Timothy, Jr.; Weisenberger, Daniel J.; Van den Berg, David J.] Univ So Calif, Los Angeles, CA 90033 USA.
[Agrawal, Nishant; Bishop, Justin; Califano, Joseph; Ahn, Julie; Khan, Zubair] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Boutros, Paul C.; Waggott, Daryl M.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Bruce, Jeff P.; Hui, Angela B. Y.] Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
[Carey, Thomas E.; McHugh, Jonathan B.; Sartor, Maureen A.; Bradford, Carol R.; Chepeha, Douglas B.; Haddad, Andrea S.; Jones, Tamara R.; Komarck, Christine M.; Malakh, Mayya; Moyer, Jeffrey S.; Nguyen, Ariane; Peterson, Lisa A.; Prince, Mark E.; Rozek, Laura S.; Taylor, Evan G.; Walline, Heather M.; Wolf, Gregory T.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Chen, Zhong; Cheng, Hui; Saleh, Anthony D.; Si, Han; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
[Chiosea, Simion I.; Diergaarde, Brenda; Egloff, Ann Marie; Ferris, Robert L.; Grandis, Jennifer R.; Romkes, Marjorie; Seethala, Raja] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
[Cohen, Ezra; Seiwert, Tanguy Y.; Zuo, Zhixiang] Univ Chicago, Chicago, IL 60637 USA.
[Guo, Yan; Brown, Brandee T.; Pham, Michelle] Vanderbilt Univ, Med Ctr, Med Ctr East 7209, Nashville, TN 37232 USA.
[Harris, Thomas; Prystowsky, Michael] Albert Einstein Coll Med, Bronx, NY 10461 USA.
[Lippman, Scott M.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Liu, Fei-Fei; Irish, Jonathan; Waldron, John] Univ Toronto, Toronto, ON M5G 2M9, Canada.
[Perez-Ordonez, Bayardo] Univ Hlth Network, Toronto, ON M5G 2C4, Canada.
[Wiznerowicz, Maciej; Golusinski, Wojciech; Golusinski, Pawel; Ibbs, Matthew; Korski, Konstanty; Mackiewicz, Andrzej; Suchorska, Wiktoria; Szybiak, Bartosz] Greater Poland Canc Ctr, PL-61866 Poznan, Poland.
[Yarbrough, Wendell G.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Burnett, Ken; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Lauskis, Joseph Pau; Shelton, Candace; Shelton, Troy; Sherman, Mark; Yena, Peggy; Curley, Erin] Int Genom Consortium, Phoenix, AZ 85004 USA.
[Black, Aaron D.; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M.; Harper, Hollie A.; Leraas, Kristen; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
[Baboud, Julien; Jensen, Mark A.; Kahn, An B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Walton, Jessica S.; Wan, Yunhu] SRA Int, Fairfax, VA 22033 USA.
[Burton, Robert A.] Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Davidsen, Tanja; Demchok, John A.; Ferguson, Martin L.; Shaw, Kenna R. Mills; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude] NCI, Bethesda, MD 20892 USA.
[Eley, Greg] Scimentis LLC, Atlanta, GA 30666 USA.
[Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Saller, Charles; Tarvi, Katherine] Analyt Biol Serv Inc, St Petersburg 198013, Russia.
[Chen, Chu] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Bollag, Roni; Weinberger, Paul] Georgia Regents Univ, Augusta, GA 30912 USA.
[Beard, Christina; Mitchell, Colleen; Sandusky, George] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46202 USA.
[Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
RP Hayes, DN (reprint author), Univ N Carolina, Chapel Hill, NC 27599 USA.
EM hayes@med.unc.edu; anaggar@mdanderson.org; grandisjr@upmc.edu
RI Schein, Jacquie/G-3674-2015; Weinberger, Paul/B-7007-2008; Holt,
Robert/C-3303-2009; Zhao, Ni/P-9086-2014; Marra, Marco/B-5987-2008;
Jones, Steven/C-3621-2009; Zuo, Zhixiang/M-4441-2016; Lee,
Semin/S-2629-2016; Birol, Inanc/G-5440-2011;
OI Schultz, Nikolaus/0000-0002-0131-4904; Diergaarde,
Brenda/0000-0002-3578-6547; Carey, Thomas/0000-0002-5202-7518; Seth,
Sahil/0000-0003-4579-3959; Pot, David/0000-0002-1480-9826; Jacobsen,
Anders/0000-0001-6847-4980; Sinha, Rileen/0000-0001-5497-5055; Perou,
Charles/0000-0001-9827-2247; Gehlenborg, Nils/0000-0003-0327-8297;
Weinberger, Paul/0000-0002-5885-2631; Zhao, Ni/0000-0002-7762-3949; Zuo,
Zhixiang/0000-0002-2492-2689; Lee, Semin/0000-0002-9015-6046; Birol,
Inanc/0000-0003-0950-7839; Ojesina, Akinyemi/0000-0003-0755-3639; Benz,
Stephen/0000-0002-4067-0602; Spence, Tara/0000-0001-7098-4103
FU National Institutes of Health (NIH) [P50CA097190, P50CA16672, U54
HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24
CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24
CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, RO1 CA
095419]; Bobby F. Garrett Fund for Head and Neck Cancer Research; NIDCD
Intramural Projects [ZIA-DC-000016, 73, 74]
FX This study was supported by National Institutes of Health (NIH) grants:
P50CA097190, P50CA16672, U54 HG003273, U54 HG003067, U54 HG003079, U24
CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24
CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24
CA143883, U24 CA144025 and RO1 CA 095419. Supported by The Bobby F.
Garrett Fund for Head and Neck Cancer Research and NIDCD Intramural
Projects ZIA-DC-000016, 73 and 74.
NR 45
TC 226
Z9 227
U1 27
U2 103
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 29
PY 2015
VL 517
IS 7536
BP 576
EP 582
DI 10.1038/nature14129
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA2ZL
UT WOS:000348775000035
ER
PT J
AU Norman, JM
Handley, SA
Baldridge, MT
Droit, L
Liu, CY
Keller, BC
Kambal, A
Monaco, CL
Zhao, G
Fleshner, P
Stappenbeck, TS
McGovern, DPB
Keshavarzian, A
Mutlu, EA
Sauk, J
Gevers, D
Xavier, RJ
Wang, D
Parkes, M
Virgin, HW
AF Norman, Jason M.
Handley, Scott A.
Baldridge, Megan T.
Droit, Lindsay
Liu, Catherine Y.
Keller, Brian C.
Kambal, Amal
Monaco, Cynthia L.
Zhao, Guoyan
Fleshner, Phillip
Stappenbeck, Thaddeus S.
McGovern, Dermot P. B.
Keshavarzian, Ali
Mutlu, Ece A.
Sauk, Jenny
Gevers, Dirk
Xavier, Ramnik J.
Wang, David
Parkes, Miles
Virgin, Herbert W.
TI Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel
Disease
SO CELL
LA English
DT Article
ID HUMAN GUT VIROME; FECAL MICROBIOTA TRANSPLANTATION; CROHNS-DISEASE;
STAPHYLOCOCCUS-AUREUS; METAGENOMIC ANALYSIS; BACTERIAL PATHOGENS;
ULCERATIVE-COLITIS; ANTIBIOTICS INDUCE; CYSTIC-FIBROSIS; SEQUENCING DATA
AB Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease and cohort specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases.
C1 [Norman, Jason M.; Handley, Scott A.; Baldridge, Megan T.; Droit, Lindsay; Liu, Catherine Y.; Keller, Brian C.; Kambal, Amal; Monaco, Cynthia L.; Zhao, Guoyan; Stappenbeck, Thaddeus S.; Wang, David; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Keller, Brian C.; Monaco, Cynthia L.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Zhao, Guoyan; Wang, David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Fleshner, Phillip] Cedars Sinai Med Ctr, Div Colorectal Surg, Los Angeles, CA 90048 USA.
[McGovern, Dermot P. B.] F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA.
[McGovern, Dermot P. B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Keshavarzian, Ali; Mutlu, Ece A.] Rush Univ, Med Ctr, Div Digest Dis & Nutr, Dept Med, Chicago, IL 60612 USA.
[Sauk, Jenny; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Sauk, Jenny; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Sauk, Jenny; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Gevers, Dirk; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Parkes, Miles] Univ Cambridge, Addenbrookes Hosp, Div Gastroenterol, Cambridge CB2 0QQ, England.
[Parkes, Miles] Univ Cambridge, Dept Med, Cambridge CB2 0QQ, England.
RP Virgin, HW (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM virgin@wustl.edu
RI Keller, Brian/E-2996-2016;
OI Keller, Brian/0000-0003-2997-6712; Baldridge, Megan/0000-0002-7030-6131
FU Crohn's and Colitis Foundation [R01 AI084887, R01 OD011170, 3132,
274415]; Broad Medical Foundation [IBD-0357]; NIH grant
[5T32AI007163-35, 5T32CA009547, T32 HL007317-36, 5T32AI007172-34];
European Union [305479]; Leona M. and Harry B. Helmsley Charitable
Trust; NIHR Biomedical Research Centre awards; University of Cambridge
School of Clinical Medicine; NIH Midwest Regional Center of Excellence
for Biodefense and Emerging Infectious Diseases Research grant [U54
AI057160]; NCI Cancer Center Support grant [P30 CA91842]; National
Center for Research Resources (NCRR) [UL1TR000448]; NIHR Biomedical
Research Centre award; Agency for Healthcare Research and Quality
[HS021747]; [R01 AT007143]; [DK071838]; [AT001628]; [DK062413];
[DK046763-19]; [AI067068]; [U54DE023789-01]; [U54 DE023798]; [R01
DK092405]
FX H.W.V., S.A.H., and J.M.N. were supported by R01 AI084887, R01 OD011170,
grants 3132 and 274415 from the Crohn's and Colitis Foundation, and
grant IBD-0357 from the Broad Medical Foundation. T.S.S. was supported
by grant 3132 from the Crohn's and Colitis Foundation. J.M.N. was
supported by NIH grant 5T32AI007163-35. M.T.B. was supported by NIH
grant 5T32CA009547. B.C.K. was supported by NIH grant T32 HL007317-36.
C.L.M. was supported by NIH grant 5T32AI007172-34. A. Keshavarzian and
E.A.M. were supported by R01 AT007143, DK071838, and AT001628. D.P.B.M.
was supported by DK062413, DK046763-19, AI067068, and U54DE023789-01,
grant HS021747 from the Agency for Healthcare Research and Quality,
grant 305479 from the European Union, and The Leona M. and Harry B.
Helmsley Charitable Trust. M.P. was supported by the NIHR Biomedical
Research Centre awards to Addenbrooke's Hospital and University of
Cambridge School of Clinical Medicine. D.W. was supported by the NIH
Midwest Regional Center of Excellence for Biodefense and Emerging
Infectious Diseases Research grant U54 AI057160. D.G. and R.J.X. were
supported by U54 DE023798 and R01 DK092405. We thank the Genome
Technology Access Center in the Department of Genetics at Washington
University School of Medicine for help with genomic analysis. The Center
is partially supported by NCI Cancer Center Support grant P30 CA91842 to
the Siteman Cancer Center and by ICTS/CTSA grant UL1TR000448 from the
National Center for Research Resources (NCRR), a component of the NIH,
and NIH Roadmap for Medical Research. This publication is solely the
responsibility of the authors and does not necessarily represent the
official view of NCRR or NIH. We would like to thank the patients and
relatives who contributed samples to this collection and the team of
research nurses and coordinators who supported this activity, including
Claire Dawson, Elizabeth Andersen, and Martina Lofthouse (Cambridge, UK)
and Gildardo Barron (Los Angeles, USA). We also acknowledge the NIHR
Biomedical Research Centre award to support research infrastructure at
Addenbrooke's Hospital/University of Cambridge School of Clinical
Medicine. We would also like to thank Jessica Hoisington-Lopez from the
Center for Genome Sciences and Systems Biology at Washington University
School of Medicine for her sequencing expertise.
NR 65
TC 108
Z9 109
U1 15
U2 64
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JAN 29
PY 2015
VL 160
IS 3
BP 447
EP 460
DI 10.1016/j.cell.2015.01.002
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CA8YX
UT WOS:000349208000011
PM 25619688
ER
PT J
AU Francis, PA
Regan, MM
Fleming, GF
Lang, I
Ciruelos, E
Bellet, M
Bonnefoi, HR
Climent, MA
Da Prada, GA
Burstein, HJ
Martino, S
Davidson, NE
Geyer, CE
Walley, BA
Coleman, R
Kerbrat, P
Buchholz, S
Ingle, JN
Winer, EP
Rabaglio-Poretti, M
Maibach, R
Ruepp, B
Giobbie-Hurder, A
Price, KN
Colleoni, M
Viale, G
Coates, AS
Goldhirsch, A
Gelber, RD
AF Francis, Prudence A.
Regan, Meredith M.
Fleming, Gini F.
Lang, Istvan
Ciruelos, Eva
Bellet, Meritxell
Bonnefoi, Herve R.
Climent, Miguel A.
Da Prada, Gian Antonio
Burstein, Harold J.
Martino, Silvana
Davidson, Nancy E.
Geyer, Charles E., Jr.
Walley, Barbara A.
Coleman, Robert
Kerbrat, Pierre
Buchholz, Stefan
Ingle, James N.
Winer, Eric P.
Rabaglio-Poretti, Manuela
Maibach, Rudolf
Ruepp, Barbara
Giobbie-Hurder, Anita
Price, Karen N.
Colleoni, Marco
Viale, Giuseppe
Coates, Alan S.
Goldhirsch, Aron
Gelber, Richard D.
CA SOFT Investigators
Int Breast Canc Study Grp
TI Adjuvant Ovarian Suppression in Premenopausal Breast Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID YOUNG-WOMEN; CHEMOTHERAPY; THERAPY; TRIALS; METAANALYSIS; AMENORRHEA;
TAMOXIFEN; GOSERELIN
AB BACKGROUND
Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.
METHODS
We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.
RESULTS
After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).
CONCLUSIONS
Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression.
C1 [Francis, Prudence A.] Univ Melbourne, St Vincents Hosp, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Francis, Prudence A.; Coates, Alan S.] Univ Newcastle, Australia & New Zealand Breast Canc Trials Grp, Newcastle, NSW 2300, Australia.
[Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia.
[Regan, Meredith M.; Giobbie-Hurder, Anita; Gelber, Richard D.] Dana Farber Canc Inst, IBCSG, Ctr Stat, Boston, MA 02115 USA.
[Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Burstein, Harold J.; Winer, Eric P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Susan F Smith Ctr Womens Canc, Boston, MA 02115 USA.
[Burstein, Harold J.; Winer, Eric P.] Alliance Clin Trials Oncol, Boston, MA USA.
[Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, IBCSG Stat Ctr, Boston, MA USA.
[Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Frontier Sci & Technol Res Fdn, Boston, MA 02115 USA.
[Fleming, Gini F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Fleming, Gini F.] Alliance Clin Trials Oncol, Chicago, IL USA.
[Lang, Istvan] Natl Inst Oncol, Budapest, Hungary.
[Lang, Istvan] Int Breast Canc Study Grp, Budapest, Hungary.
[Ciruelos, Eva] Univ Hosp 12 Octubre, Madrid, Spain.
[Bellet, Meritxell] Vall dHebron Inst Oncol, Barcelona, Spain.
[Bellet, Meritxell] Vall dHebron Univ Hosp, Barcelona, Spain.
[Ciruelos, Eva; Bellet, Meritxell; Climent, Miguel A.] SOLTI Grp, Barcelona, Spain.
[Climent, Miguel A.] Inst Valenciano Oncol, Valencia, Spain.
[Bonnefoi, Herve R.] Univ Bordeaux, Inst Bergonie Comprehens Canc Ctr, INSERM, U916, Bordeaux, France.
[Kerbrat, Pierre] Univ Rennes, Ctr Eugene Marquis, Rennes, France.
[Bonnefoi, Herve R.; Kerbrat, Pierre] European Org Res Treatment Canc, Brussels, Belgium.
[Da Prada, Gian Antonio] Salvatore Maugeri Fdn, Pavia, Italy.
[Da Prada, Gian Antonio] IBCSG, Pavia, Italy.
[Colleoni, Marco; Goldhirsch, Aron] Univ Milan, European Inst Oncol, Milan, Italy.
[Colleoni, Marco; Goldhirsch, Aron] Univ Milan, Int Breast Canc Study Grp, Milan, Italy.
[Viale, Giuseppe] Univ Milan, European Inst Oncol, IBCSG Cent Pathol Ctr, Milan, Italy.
[Martino, Silvana] Angeles Clin, Santa Monica, CA USA.
[Martino, Silvana] Res Inst, Santa Monica, CA USA.
[Martino, Silvana] SWOG, Santa Monica, CA USA.
[Davidson, Nancy E.] Univ Pittsburgh, Med Ctr, Inst Canc, Ctr Canc, Pittsburgh, PA USA.
[Davidson, Nancy E.] ECOG ACRIN Canc Res Grp, Pittsburgh, PA USA.
[Geyer, Charles E., Jr.] Virginia Commonwealth Univ, Massey Canc Ctr, Sch Med, Richmond, VA 23284 USA.
[Geyer, Charles E., Jr.] NRG Oncol, Richmond, VA USA.
[Walley, Barbara A.] Tom Baker Canc Clin, Calgary, AB, Canada.
[Walley, Barbara A.] Natl Canc Inst Canada, Clin Trials Grp, Calgary, AB, Canada.
[Coleman, Robert] Weston Pk Hosp, Sheffield, S Yorkshire, England.
[Coleman, Robert] Natl Inst Canc Res, Breast Canc Clin Studies Grp, London, England.
[Coleman, Robert] Inst Canc Res, Clin Trials & Stat Unit, London SW3 6JB, England.
[Buchholz, Stefan] Univ Med Ctr Regensburg, German Breast Grp, Regensburg, Germany.
[Buchholz, Stefan] Univ Med Ctr Regensburg, Dept Obstet & Gynecol, Regensburg, Germany.
[Ingle, James N.] Mayo Clin, Rochester, MN USA.
[Ingle, James N.] Alliance Clin Trials Oncol, Rochester, MN USA.
[Rabaglio-Poretti, Manuela] Univ Bern, Inselspital, Univ Hosp, CH-3010 Bern, Switzerland.
[Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara] IBCSG Coordinating Ctr, Bern, Switzerland.
RP Francis, PA (reprint author), Peter MacCallum Canc Ctr, Locked Bag 1,ABeckett St, Melbourne, Vic 8006, Australia.
EM ibcsgcc@ibcsg.org
OI Ciruelos, Eva /0000-0002-2796-1042
FU Pfizer
FX Funded by Pfizer and others; SOFT ClinicalTrials.gov number,
NCT00066690.
NR 19
TC 135
Z9 145
U1 7
U2 45
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 29
PY 2015
VL 372
IS 5
BP 436
EP 446
DI 10.1056/NEJMoa1412379
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA1CD
UT WOS:000348649700008
PM 25495490
ER
PT J
AU Cooper, CM
Baron, JM
AF Cooper, Cynthia M.
Baron, Jason M.
TI Case 4-2015: A 49-Year-Old Man with Obtundation Followed by Agitation
and Acidosis Ethylene glycol ingestion
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE MYOCARDIAL-INFARCTION; GAP
METABOLIC-ACIDOSIS; SUICIDAL IDEATION; RESPIRATORY RATE; ANION-GAP;
META-CHLOROPHENYLPIPERAZINE; PHARMACODYNAMIC PROFILE; VENLAFAXINE
OVERDOSE; OSMOLAL GAP
C1 [Cooper, Cynthia M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02163 USA.
[Baron, Jason M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Cooper, Cynthia M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Baron, Jason M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Cooper, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02163 USA.
NR 52
TC 1
Z9 1
U1 1
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 29
PY 2015
VL 372
IS 5
BP 465
EP 473
DI 10.1056/NEJMcpc1410940
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA1CD
UT WOS:000348649700012
PM 25629745
ER
PT J
AU Solomon, CG
Greene, MF
AF Solomon, Caren G.
Greene, Michael F.
TI Control of Hypertension in Pregnancy - If Some Is Good, Is More Worse?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Solomon, Caren G.; Greene, Michael F.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
RP Solomon, CG (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
NR 8
TC 4
Z9 5
U1 0
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 29
PY 2015
VL 372
IS 5
BP 475
EP 476
DI 10.1056/NEJMe1414836
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA1CD
UT WOS:000348649700013
PM 25629746
ER
PT J
AU Morris, H
DeWolf, S
Robins, H
Sprangers, B
LoCascio, SA
Shonts, BA
Kawai, T
Wong, WC
Yang, SX
Zuber, J
Shen, YF
Sykes, M
AF Morris, Heather
DeWolf, Susan
Robins, Harlan
Sprangers, Ben
LoCascio, Samuel A.
Shonts, Brittany A.
Kawai, Tatsuo
Wong, Waichi
Yang, Suxiao
Zuber, Julien
Shen, Yufeng
Sykes, Megan
TI Tracking donor-reactive T cells: Evidence for clonal deletion in
tolerant kidney transplant patients
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; MISMATCHED RENAL-TRANSPLANTATION;
MAINTENANCE IMMUNOSUPPRESSION; MEDIATED LYMPHOLYSIS; MIXED CHIMERISM;
IN-VIVO; INDUCTION; RECIPIENTS; REJECTION; REGIMEN
AB T cell responses to allogeneic major histocompatibility complex antigens present a formidable barrier to organ transplantation, necessitating long-term immunosuppression to minimize rejection. Chronic rejection and drug-induced morbidities are major limitations that could be overcome by allograft tolerance induction. Tolerance was first intentionally induced in humans via combined kidney and bone marrow transplantation (CKBMT), but the mechanisms of tolerance in these patients are incompletely understood. We now establish an assay to identify donor-reactive T cells and test the role of deletion in tolerance after CKBMT. Using high-throughput sequencing of the T cell receptor B chain CDR3 region, we define a fingerprint of the donor-reactive T cell repertoire before transplantation and track those clones after transplant. We observed posttransplant reductions in donor-reactive T cell clones in three tolerant CKBMT patients; such reductions were not observed in a fourth, nontolerant, CKBMT patient or in two conventional kidney transplant recipients on standard immunosuppressive regimens. T cell repertoire turnover due to lymphocyte-depleting conditioning only partially accounted for the observed reductions in tolerant patients; in fact, conventional transplant recipients showed expansion of circulating donor-reactive clones, despite extensive repertoire turnover. Moreover, loss of donor-reactive T cell clones more closely associated with tolerance induction than in vitro functional assays. Our analysis supports clonal deletion as a mechanism of allograft tolerance in CKBMT patients. The results validate the contribution of donor-reactive T cell clones identified before transplant by our method, supporting further exploration as a potential biomarker of transplant outcomes.
C1 [Morris, Heather; DeWolf, Susan; Sprangers, Ben; LoCascio, Samuel A.; Shonts, Brittany A.; Wong, Waichi; Yang, Suxiao; Zuber, Julien; Shen, Yufeng; Sykes, Megan] Columbia Univ, Med Ctr, New York, NY 10032 USA.
[Robins, Harlan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Kawai, Tatsuo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Shen, YF (reprint author), Columbia Univ, Med Ctr, New York, NY 10032 USA.
EM ys2411@columbia.edu; megan.sykes@columbia.edu
FU NIH grant ROI [AI084074]; NIH grant PO1 [P01 AI106697]; ITN [N01
AI15416]; Kidney Research Student Scholar Grant from the American
Society of Nephrology; NIH [S10RR027050]
FX The work was supported in part by NIH grants ROI #AI084074, PO1 grant
#P01 AI106697, and ITN contract N01 AI15416. S.D.W. was supported by a
Kidney Research Student Scholar Grant from the American Society of
Nephrology. FACS instrumentation was purchased with NIH grant
#S10RR027050.
NR 38
TC 34
Z9 34
U1 0
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JAN 28
PY 2015
VL 7
IS 272
AR 272ra10
DI 10.1126/scitranslmed.3010760
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CB1YA
UT WOS:000349422700001
PM 25632034
ER
PT J
AU Haridas, V
Pean, P
Jasenosky, LD
Madec, Y
Laureillard, D
Sok, T
Sath, S
Borand, L
Marcy, O
Chan, S
Tsitsikov, E
Delfraissy, JF
Blanc, FX
Goldfeld, AE
AF Haridas, Viraga
Pean, Polidy
Jasenosky, Luke D.
Madec, Yoann
Laureillard, Didier
Sok, Thim
Sath, Sun
Borand, Laurence
Marcy, Olivier
Chan, Sarin
Tsitsikov, Erdyni
Delfraissy, Jean-Francois
Blanc, Francois-Xavier
Goldfeld, Anne E.
CA CAPRI-T ANRS 121614 Study Team
TI TB-IRIS, T-cell activation, and remodeling of the T-cell compartment in
highly immunosuppressed HIV-infected patients with TB
SO AIDS
LA English
DT Article
DE activated T cells; antiretroviral therapy; CAMELIA trial; CCR5(+)CD4(+);
effector memory; HIV; immunosuppression; T cells; TB; TB-IRIS
ID RECONSTITUTION INFLAMMATORY SYNDROME; IMMUNE-RESTORATION-DISEASE;
ANTIRETROVIRAL THERAPY; TUBERCULOSIS; EXPRESSION; INITIATION; RESPONSES;
CCR5; LYMPHOCYTES; SUBSETS
AB Objective: To investigate the impact of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) upon immunological recovery and the T-cell compartment after initiation of TB and antiretroviral therapy (ART).
Design and methods: We prospectively evaluated T-cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n = 154) of highly immunosuppressed HIV-infected patients with TB from the Cambodian Early versus Late Introduction of Antiretrovirals randomized clinical trial. We compared findings from patients who developed TB-IRIS with findings from patients who did not develop TB-IRIS. Data were evaluated with mixed-effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank-sum tests, and q-values were calculated to control for multiple comparisons.
Results: Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DR(+)CD45RO(+)CD4(+), CCR5(+)CD4(+), OX40(+)CD4(+)and Fas(+) effector memory CD8(+) T cells, and significantly elevated levels of plasma interleukin (IL)-6, IL-1 beta, IL-8, and IL-10, and viral load. Post-ART initiation, effector memory CD4(+) and Fas(+) effector memory CD4(+) T-cell frequencies significantly expanded, and central memory CD4(+) T-cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, effector memory/central memory CD4(+) T-cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients.
Conclusions: A distinct pattern of pre-ART T-cell and cytokine markers appear to poise the immune response of certain patients to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4(+) T-cell memory compartment towards an effector memory-dominated phenotype. We speculate that these pre and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Haridas, Viraga; Jasenosky, Luke D.; Goldfeld, Anne E.] Harvard Univ, Boston Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Pean, Polidy] Inst Pasteur Cambodge, Phnom Penh, Cambodia.
[Madec, Yoann] Inst Pasteur, Emerging Dis Epidemiol Unit, Paris, France.
[Laureillard, Didier; Sok, Thim; Sath, Sun; Marcy, Olivier; Chan, Sarin; Goldfeld, Anne E.] Cambodian Hlth Comm, Phnom Penh, Cambodia.
[Borand, Laurence] Inst Pasteur Cambodge, Epidemiol & Publ Hlth Unit, Phnom Penh, Cambodia.
[Tsitsikov, Erdyni] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA USA.
[Delfraissy, Jean-Francois] French Natl Agcy Res AIDS & Viral Hepatitis ANRS, Paris, France.
[Delfraissy, Jean-Francois; Blanc, Francois-Xavier] Hop Bicetre, AP HP, Le Kremlin Bicetre, France.
RP Goldfeld, AE (reprint author), Harvard Univ, Boston Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA.
EM anne.goldfeld@childrens.harvard.edu
RI Blanc, Francois-Xavier/D-7425-2015
FU ANRS [12164]; NIH [R21AI076023]; Annenberg Foundation; AERAS; AmFAR;
NIAID/NIH-IeDEA [U01AI069907-07]
FX The authors are indebted to Wallis Annenberg whose generosity made this
study possible, and to John Moores for his generous gift. This work was
supported by grants from the ANRS (12164), the NIH (R21AI076023), the
Annenberg Foundation, AERAS, and AmFAR, with support from
NIAID/NIH-IeDEA (U01AI069907-07), and a gift from John Moores. We are
grateful to Francoise Barre-Sinoussi for her help, advice, and support
over the years. We thank Eric Nerrienet, Claire Rekacewicz, Daniel
Scott, Gianfranco Pancino, Jean-Louis Sarthou, and Charles Mayaud for
helpful discussions and advice as we began the study, and Jean-Louis
Sarthou for his long time support of the Harvard team's collaboration
with the Institut Pasteur du Cambodge. We thank the CAMELIA study team,
including the site nurses, doctors, and health workers, and Vincent
Deubel and the staff at the Institut Pasteur du Cambodge. We thank Larry
Fox, Rod Hoff, Jane Bupp, and Brigitte Bazin for their support and
helpful discussions from the beginning of CAMELIA onward and the staff
of the Cambodian Health Committee, especially Sam Sophan, for his
contributions to and support of the work. We thank Leslie Kalish of
Children's Hospital Boston and the Harvard Catalyst Biostatistical
Consulting program (NIH UL1 TR001102) for expert statistical advice and
help as we started the analysis. We also thank Jerry Sadoff for his
early support and Judy Lieberman for helpful comments on the manuscript.
Finally, we are deeply indebted to the patients who took part in this
study, who generously offered their participation to help the scientific
community find solutions to AIDS and TB.
NR 49
TC 6
Z9 6
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 28
PY 2015
VL 29
IS 3
BP 263
EP 273
DI 10.1097/QAD.0000000000000546
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AZ0SZ
UT WOS:000347956200002
PM 25486415
ER
PT J
AU Denison, JA
Koole, O
Tsui, S
Menten, J
Torpey, K
van Praag, E
Mukadi, YD
Colebunders, R
Auld, AF
Agolory, S
Kaplan, JE
Mulenga, M
Kwesigabo, GP
Wabwire-Mangen, F
Bangsberg, DR
AF Denison, Julie A.
Koole, Olivier
Tsui, Sharon
Menten, Joris
Torpey, Kwasi
van Praag, Eric
Mukadi, Ya Diul
Colebunders, Robert
Auld, Andrew F.
Agolory, Simon
Kaplan, Jonathan E.
Mulenga, Modest
Kwesigabo, Gideon P.
Wabwire-Mangen, Fred
Bangsberg, David R.
TI Incomplete adherence among treatment-experienced adults on
antiretroviral therapy in Tanzania, Uganda and Zambia
SO AIDS
LA English
DT Article
DE antiretroviral therapy; HIV/AIDS; medication adherence; sub-Saharan
Africa; Tanzania; Uganda; Zambia
ID SUB-SAHARAN AFRICA; SELF-REPORTED ADHERENCE; HIV-INFECTED PATIENTS;
HIGH-INCOME COUNTRIES; MEDICATION ADHERENCE; VIROLOGICAL RESPONSE;
CLINICAL-TRIALS; SOCIAL SUPPORT; NORTH-AMERICA; RURAL UGANDA
AB Objectives: To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa.
Design: A cross-sectional study.
Methods: Systematically selected ART clients (>= 18 years; on ART >= 6 months) attending 18facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index >= 48 consecutive hours of missed ART), healthcare provider estimates and the pharmacymedication possession ratio(MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors.
Results: A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma.
Conclusion: Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Denison, Julie A.; Tsui, Sharon; Torpey, Kwasi; van Praag, Eric; Mukadi, Ya Diul] FHI 360, Social & Behav Hlth Sci, Durham, NC USA.
[Denison, Julie A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
[Koole, Olivier; Menten, Joris; Colebunders, Robert] Inst Trop Med, B-2000 Antwerp, Belgium.
[Koole, Olivier] London Sch Hyg & Trop Med, London WC1, England.
[Colebunders, Robert] Univ Antwerp, B-2020 Antwerp, Belgium.
[Auld, Andrew F.; Agolory, Simon; Kaplan, Jonathan E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Mulenga, Modest] Trop Dis Res Ctr, Ndola, Zambia.
[Kwesigabo, Gideon P.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
[Wabwire-Mangen, Fred] Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda.
[Bangsberg, David R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Denison, JA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, 615 N Wolfe St,E5032, Baltimore, MD 21205 USA.
EM jdenison@jhu.edu
OI Auld, Andrew/0000-0001-5089-9163
FU President's Emergency Plan for AIDS Relief (PEPFAR) through the Centers
for Disease Control and Prevention (CDC); Health Resources & Services
Administration (HRSA) [2006-N-08428]; FHI [360]
FX This research has been supported by the President's Emergency Plan for
AIDS Relief (PEPFAR) through the Centers for Disease Control and
Prevention (CDC) and the Health Resources & Services Administration
(HRSA) under the terms of the contract no. 2006-N-08428 with FHI 360.
The findings and conclusions in this report are those of the author(s)
and do not necessarily represent the official position of CDC, HRSA or
any other federal agency or office.
NR 65
TC 10
Z9 10
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JAN 28
PY 2015
VL 29
IS 3
BP 361
EP 371
DI 10.1097/QAD.0000000000000543
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AZ0SZ
UT WOS:000347956200012
PM 25686684
ER
PT J
AU Friel, AM
Zhang, L
Pru, CA
Clark, NC
McCallum, ML
Blok, LJ
Shioda, T
Peluso, JJ
Rueda, BR
Pru, JK
AF Friel, Anne M.
Zhang, Ling
Pru, Cindy A.
Clark, Nicole C.
McCallum, Melissa L.
Blok, Leen J.
Shioda, Toshi
Peluso, John J.
Rueda, Bo R.
Pru, James K.
TI Progesterone receptor membrane component 1 deficiency attenuates growth
while promoting chemosensitivity of human endometrial xenograft tumors
SO CANCER LETTERS
LA English
DT Article
DE Cancer; Chemotherapy; Endometrial; PGRMC1; Progesterone; Xenograft
ID IMMORTALIZED GRANULOSA-CELLS; RNA-BINDING-PROTEIN; OVARIAN-CANCER;
ANTIAPOPTOTIC ACTION; HORMONAL-THERAPY; GENE-EXPRESSION; PGRMC1; BREAST;
CARCINOMA; VIABILITY
AB Endometrial cancer is the leading gynecologic cancer in women in the United States with 52,630 women predicted to be diagnosed with the disease in 2014. The objective of this study was to determine if progesterone (P4) receptor membrane component 1 (PGRMC1) influenced endometrial cancer cell viability in response to chemotherapy in vitro and in vivo. A lentiviral-based shRNA knockdown approach was used to generate stable PGRMC1-intact and PGRMC1-deplete Ishikawa endometrial cancer cell lines that also lacked expression of the classical progesterone receptor (PGR). Progesterone treatment inhibited mitosis of PGRMC1-intact, but not PGRMC1-deplete cells, suggesting that PGRMC1 mediates the anti-mitotic actions of P4. To test the hypothesis that PGRMC1 attenuates chemotherapy-induced apoptosis, PGRMC1-intact and PGRMC1-deplete cells were treated in vitro with vehicle, P4 (1 mu M), doxorubicin (Dox, 2 mu g/ml), or P4 + Dox for 48 h. Doxorubicin treatment of PGRMC1-intact cells resulted in a significant increase in cell death; however, co-treatment with P4 significantly attenuated Dox-induced cell death. This response to P-4 was lost in PGRMC1-deplete cells. To extend these observations in vivo, a xenograft model was employed where PGRMC1-intact and PGRMC1-deplete endometrial tumors were generated following subcutaneous and intraperitoneal inoculation of immunocompromised NOD/SCID and nude mice, respectively. Tumors derived from PGRMC1-deplete cells grew slower than tumors from PGRMC1-intact cells. Mice harboring endometrial tumors were then given three treatments of vehicle (1:1 cremophor EL: ethanol + 0.9% saline) or chemotherapy [Paditaxel (15 mg/kg, i.p.) followed after an interval of 30 minutes by CARBOplatin (50 mg/kg)] at five day intervals. In response to chemotherapy, tumor volume decreased approximately four-fold more in PGRMC1-deplete tumors when compared with PGRMC1-intact control tumors, suggesting that PGRMC1 promotes tumor cell viability during chemotherapeutic stress. In sum, these in Vitro and in vivo findings demonstrate that PGRMC1 plays a prominent role in the growth and chemoresistance of human endometrial tumors. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Friel, Anne M.; Zhang, Ling; Shioda, Toshi; Rueda, Bo R.] Harvard Univ, Sch Med, Vincent Ctr Reprod Biol,Ctr Canc Res, Dept Obstet & Gynecol,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pru, Cindy A.; McCallum, Melissa L.; Pru, James K.] Washington State Univ, Dept Anim Sci, Pullman, WA 99164 USA.
[Clark, Nicole C.; Pru, James K.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA.
[Blok, Leen J.] Erasmus Univ, Med Ctr, Josephine Nefkens Inst, Dept Obstet & Gynecol, Rotterdam, Netherlands.
[Rueda, Bo R.] Univ Connecticut, Ctr Hlth, Dept Obstet, Farmington, CT 06030 USA.
[Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Gynecol, Farmington, CT 06030 USA.
[Peluso, John J.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06030 USA.
RP Pru, JK (reprint author), Washington State Univ, Dept Anim Sci, Pullman, WA 99164 USA.
EM jpru@wsu.edu
FU Vincent Memorial Research Funds; Advanced Medical Research Foundation;
NIH [RR030264, OD016564]
FX This work was supported by Vincent Memorial Research Funds, the Advanced
Medical Research Foundation, and NIH RR030264 and OD016564.
NR 58
TC 10
Z9 10
U1 1
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD JAN 28
PY 2015
VL 356
IS 2
BP 434
EP 442
DI 10.1016/j.canlet.2014.09.036
PN B
PG 9
WC Oncology
SC Oncology
GA AZ1NL
UT WOS:000348005500013
PM 25304370
ER
PT J
AU Wong, WP
AF Wong, Wesley P.
TI Revealing the Mechanical Regulation of Hemostasis with Novel Approaches
in Single-Molecule Manipulation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
C1 [Wong, Wesley P.] Harvard Univ, Wyss Inst, Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA.
[Wong, Wesley P.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 27
PY 2015
VL 108
IS 2
SU 1
MA 35-Subg
BP 7A
EP 7A
PG 1
WC Biophysics
SC Biophysics
GA CO9DB
UT WOS:000359471700036
ER
PT J
AU Song, LK
Sun, ZYJ
Kim, M
Kaur, P
Wagner, G
Reinherz, EL
AF Song, Likai
Sun, Zhen-Yu J.
Kim, Mikyung
Kaur, Pavanjeet
Wagner, Gerhard
Reinherz, Ellis L.
TI HIV gp41-Antibody Interaction at the Viral Membrane Interface Defined by
EPR Spectroscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
C1 [Song, Likai; Kaur, Pavanjeet] Natl High Magnet Field Lab, Tallahassee, FL USA.
[Song, Likai; Kaur, Pavanjeet] Florida State Univ, Tallahassee, FL 32306 USA.
[Sun, Zhen-Yu J.; Kim, Mikyung; Wagner, Gerhard; Reinherz, Ellis L.] Harvard Univ, Sch Med, Boston, MA USA.
[Kim, Mikyung; Reinherz, Ellis L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 27
PY 2015
VL 108
IS 2
SU 1
MA 188-Plat
BP 38A
EP 39A
PG 2
WC Biophysics
SC Biophysics
GA CO9DB
UT WOS:000359471700189
ER
PT J
AU Kovacs-Bogdan, E
Sancak, Y
Kamer, KJ
Plovanich, M
Jambhekar, A
Huber, RJ
Myre, MA
Blower, MD
Mootha, VK
AF Kovacs-Bogdan, Erika
Sancak, Yasemin
Kamer, Kimberli J.
Plovanich, Molly
Jambhekar, Ashwini
Huber, Robert J.
Myre, Michael A.
Blower, Michael D.
Mootha, Vamsi K.
TI In vivo Reconstitution of the Mitochondrial Uniporter
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
C1 [Kovacs-Bogdan, Erika; Sancak, Yasemin; Kamer, Kimberli J.; Plovanich, Molly; Jambhekar, Ashwini; Blower, Michael D.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Mol Biol, Boston, MA 02114 USA.
[Huber, Robert J.; Myre, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 27
PY 2015
VL 108
IS 2
SU 1
MA 894-Plat
BP 177A
EP 178A
PG 2
WC Biophysics
SC Biophysics
GA CT5KR
UT WOS:000362849100104
ER
PT J
AU Kamer, KJ
Mootha, VK
AF Kamer, Kimberli J.
Mootha, Vamsi K.
TI MICU1 and MICU2 Operate Together to Regulate the Uniporter
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 59th Annual Meeting of the Biophysical-Society
CY FEB 07-11, 2015
CL Baltimore, MD
SP Biophys Soc
C1 [Kamer, Kimberli J.] Harvard Univ, Chem & Chem Biol, Cambridge, MA 02138 USA.
[Mootha, Vamsi K.] Massachusetts Gen Hosp, HHMI, Mol Biol, Boston, MA 02114 USA.
[Mootha, Vamsi K.] Harvard Univ, Sch Med, Syst Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JAN 27
PY 2015
VL 108
IS 2
SU 1
MA 2870-Pos
BP 567A
EP 567A
PG 1
WC Biophysics
SC Biophysics
GA CT5KV
UT WOS:000362849600478
ER
PT J
AU Zamani, P
Rawat, D
Shiva-Kumar, P
Geraci, S
Bhuva, R
Konda, P
Doulias, PT
Ischiropoulos, H
Townsend, RR
Margulies, KB
Cappola, TP
Poole, DC
Chirinos, JA
AF Zamani, Payman
Rawat, Deepa
Shiva-Kumar, Prithvi
Geraci, Salvatore
Bhuva, Rushik
Konda, Prasad
Doulias, Paschalis-Thomas
Ischiropoulos, Harry
Townsend, Raymond R.
Margulies, Kenneth B.
Cappola, Thomas P.
Poole, David C.
Chirinos, Julio A.
TI Effect of Inorganic Nitrate on Exercise Capacity in Heart Failure With
Preserved Ejection Fraction
SO CIRCULATION
LA English
DT Article
DE exercise; heart failure; nitrates; nitric oxide
ID NEAR-INFRARED SPECTROSCOPY; SOCIETY-OF-CARDIOLOGY; O-2 UPTAKE KINETICS;
DIETARY NITRATE; SKELETAL-MUSCLE; NITRIC-OXIDE; OXIDATIVE CAPACITY;
INTENSITY EXERCISE; OXYGEN-CONSUMPTION; WAVE REFLECTIONS
AB Background-Inorganic nitrate (NO3-), abundant in certain vegetables, is converted to nitrite by bacteria in the oral cavity. Nitrite can be converted to nitric oxide in the setting of hypoxia. We tested the hypothesis that NO3- supplementation improves exercise capacity in heart failure with preserved ejection fraction via specific adaptations to exercise.
Methods and Results-Seventeen subjects participated in this randomized, double-blind, crossover study comparing a single dose of NO3- rich beetroot juice (NO3-, 12.9 mmol) with an identical nitrate-depleted placebo. Subjects performed supine-cycle maximal-effort cardiopulmonary exercise tests, with measurements of cardiac output and skeletal muscle oxygenation. We also assessed skeletal muscle oxidative function. Study end points included exercise efficiency (total work/total oxygen consumed), peak Vo(2), total work performed, vasodilatory reserve, forearm mitochondrial oxidative function, and augmentation index (a marker of arterial wave reflections, measured via radial arterial tonometry). Supplementation increased plasma nitric oxide metabolites (median, 326 versus 10 mu mol/L; P=0.0003), peak (V) over doto(2) (12.6 +/- 3.7 versus 11.6 +/- 3.1 mL O-2.min(-1).kg(-1); P=0.005), and total work performed (55.6 +/- 35.3 versus 49.2 +/- 28.9 kJ; P=0.04). However, efficiency was unchanged. NO3- led to greater reductions in systemic vascular resistance (-42.4 +/- 16.6% versus -31.8 +/- 20.3%; P=0.03) and increases in cardiac output (121.2 +/- 59.9% versus 88.7 +/- 53.3%; P=0.006) with exercise. NO3- reduced aortic augmentation index (132.2 +/- 16.7% versus 141.4 +/- 21.9%; P=0.03) and tended to improve mitochondrial oxidative function.
Conclusions-NO3- increased exercise capacity in heart failure with preserved ejection fraction by targeting peripheral abnormalities. Efficiency did not change as a result of parallel increases in total work and (V)over doto(2). NO3- increased exercise vasodilatory and cardiac output reserves. NO3- also reduced arterial wave reflections, which are linked to left ventricular diastolic dysfunction and remodeling.
C1 [Zamani, Payman; Shiva-Kumar, Prithvi; Konda, Prasad; Margulies, Kenneth B.; Cappola, Thomas P.; Chirinos, Julio A.] Hosp Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
[Rawat, Deepa; Shiva-Kumar, Prithvi; Geraci, Salvatore; Bhuva, Rushik; Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Div Cardiol, Philadelphia, PA USA.
[Doulias, Paschalis-Thomas; Ischiropoulos, Harry] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA.
[Townsend, Raymond R.] Univ Penn, Perelman Sch Med, Div Nephrol Hypertens, Philadelphia, PA 19104 USA.
[Poole, David C.] Kansas State Univ, Dept Kinesiol, Manhattan, KS 66506 USA.
[Poole, David C.] Kansas State Univ, Dept Anat, Manhattan, KS 66506 USA.
[Poole, David C.] Kansas State Univ, Dept Physiol, Manhattan, KS 66506 USA.
RP Chirinos, JA (reprint author), 3800 Woodland Ave,Room 8B111, Philadelphia, PA 19104 USA.
EM Julio.Chirinos@uphs.upenn.edu
FU Gilead Life Sciences; Atcor Medical; Cardiodynamics; APC Cardiovascular;
National Institutes of Health [HL54926, HL105993, HL110338, HL113777];
Juventis Therapeutics; Celladon Corp; Thoratec Corp; Innolign
Biomedical, LLC
FX Dr Zamani performed prior research in HFpEF that was funded by Gilead
Life Sciences. Dr Chirinos is named as inventor in a patent application
for the use of inorganic nitrate in HFpEF. Dr Chirinos has received
minor support (equipment loans) from Atcor Medical, Cardiodynamics, and
APC Cardiovascular. Dr Ischiropoulos is the Gisela and Dennis Alter
Chair in Pediatric Neonatology at the Children's Hospital of
Philadelphia and is supported by National Institutes of Health grant
HL54926. Dr Margulies reports advisory committee membership for Novo
Nordisk and AstraZeneca, as well as research grant support from Juventis
Therapeutics, Celladon Corp, Thoratec Corp, Innolign Biomedical, LLC,
and the National Institutes of Health (HL105993, HL110338, HL113777).
The other authors report no conflicts.
NR 54
TC 57
Z9 59
U1 6
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 27
PY 2015
VL 131
IS 4
BP 371
EP U1184
DI 10.1161/CIRCULATIONAHA.114.012957
PG 17
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AZ7YR
UT WOS:000348432100014
PM 25533966
ER
PT J
AU Mozaffarian, D
Benjamin, EJ
Go, AS
Arnett, DK
Blaha, MJ
Cushman, M
de Ferranti, S
Despres, JP
Fullerton, HJ
Howard, VJ
Huffman, MD
Judd, SE
Kissela, BM
Lackland, DT
Lichtman, JH
Lisabeth, LD
Liu, SM
Mackey, RH
Matchar, DB
McGuire, DK
Mohler, ER
Moy, CS
Muntner, P
Mussolino, ME
Nasir, K
Neumar, RW
Nichol, G
Palaniappan, L
Pandey, DK
Reeves, MJ
Rodriguez, CJ
Sorlie, PD
Stein, J
Towfighi, A
Turan, TN
Virani, SS
Willey, JZ
Woo, D
Yeh, RW
Turner, MB
AF Mozaffarian, Dariush
Benjamin, Emelia J.
Go, Alan S.
Arnett, Donna K.
Blaha, Michael J.
Cushman, Mary
de Ferranti, Sarah
Despres, Jean-Pierre
Fullerton, Heather J.
Howard, Virginia J.
Huffman, Mark D.
Judd, Suzanne E.
Kissela, Brett M.
Lackland, Daniel T.
Lichtman, Judith H.
Lisabeth, Lynda D.
Liu, Simin
Mackey, Rachel H.
Matchar, David B.
McGuire, Darren K.
Mohler, Emile R., III
Moy, Claudia S.
Muntner, Paul
Mussolino, Michael E.
Nasir, Khurram
Neumar, Robert W.
Nichol, Graham
Palaniappan, Latha
Pandey, Dilip K.
Reeves, Mathew J.
Rodriguez, Carlos J.
Sorlie, Paul D.
Stein, Joel
Towfighi, Amytis
Turan, Tanya N.
Virani, Salim S.
Willey, Joshua Z.
Woo, Daniel
Yeh, Robert W.
Turner, Melanie B.
CA Amer Heart Assoc Stat Comm
Stroke Stat Subcomm
TI Executive Summary: Heart Disease and Stroke Statistics-2015 Update A
Report From the American Heart Association
SO CIRCULATION
LA English
DT Article
C1 [Mozaffarian, Dariush] Tufts Univ, Medford, MA 02155 USA.
[Arnett, Donna K.; Howard, Virginia J.; Judd, Suzanne E.; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Blaha, Michael J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA.
[de Ferranti, Sarah] Childrens Hosp Boston, Boston, MA USA.
[Despres, Jean-Pierre] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada.
[Fullerton, Heather J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Go, Alan S.] Kaiser Permanente, Oakland, CA USA.
[Huffman, Mark D.] Northwestern Univ, Evanston, IL 60208 USA.
[Kissela, Brett M.] Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH 45221 USA.
[Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA.
[Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Lisabeth, Lynda D.; Neumar, Robert W.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Liu, Simin] Brown Univ, Providence, RI 02912 USA.
[Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Matchar, David B.] Duke Univ, Durham, NC 27706 USA.
[McGuire, Darren K.] Univ Texas Southwestern Med Ctr, Houston, TX USA.
[Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA.
[Moy, Claudia S.; Mussolino, Michael E.] NIH, Washington, DC USA.
[Nasir, Khurram] Baptist Hlth Med Grp, New York, NY USA.
[Nichol, Graham] Univ Washington, Seattle, WA 98195 USA.
[Palaniappan, Latha] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Pandey, Dilip K.] Univ Illinois, Chicago, IL USA.
[Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA.
[Rodriguez, Carlos J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Sorlie, Paul D.] NHLBI, Washington, DC USA.
[Stein, Joel; Willey, Joshua Z.] Columbia Univ, New York, NY 10027 USA.
[Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA.
[Turner, Melanie B.] Amer Heart Assoc, Bethesda, MD USA.
[Virani, Salim S.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Innovat, Methodist DeBakey Heart & Vasc Ctr,Michael E DeBa, Houston, TX 77030 USA.
[Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Mozaffarian, D (reprint author), Tufts Univ, Medford, MA 02155 USA.
OI Mackey, Rachel/0000-0001-6088-2664; Turan, Tanya/0000-0001-5399-8845;
Huffman, Mark/0000-0001-7412-2519; Benjamin, Emelia/0000-0003-4076-2336;
Virani, Salim/0000-0001-9541-6954; Kissela, Brett/0000-0002-9773-4013
FU NIH/NHLBI; Canadian Institutes of Health Research (CIHR); European
Foundation for the Study of Diabetes (EFSD); Fondation de l'IUCPQ;
Canadian Partnership Against Cancer (CPAC); Heart & Stroke Foundation of
Canada (HSFC); Fonds de la recherche en sante du Quebec; Heart and
Stroke Foundation of Canada (HSFC); Diabete Quebec; Ministere de la
Sante et des Services sociaux du Quebec; Ministere des Finances et de
l'Economie du Quebec; Conseil franco-quebecois de cooperation
universitaire (CFQCU); Astra-Zeneca; NHLBI; National Institute of
Diabetes, Digestive and Kidney Diseases; Sanofi; World Heart Federation;
JR Alberts Foundation; Eisenberg Foundation; Stanford University;
GlaxoSmithKline; Takeda; Orexigen; Janssen; Eli Lilly; Bristol Myers
Squibb; AstraZeneca; Boehringer Ingelheim; Merck; Novo Nordisk; Lexicon;
Amgen Inc.; Nexstim; Tyromotion; Myomo; Department of Veterans Affairs;
American Heart Association; American Diabetes Association; NIH
FX Emelia J. Benjamin Boston University School of Medicine NIH/NHLBI dagger
None None None None AHA, Circulation Associate Editor dagger None;
Jean-Pierre Despres Centre de recherche de l'Institut universitaire de
cardiologie et de pneumologie de Quebec Canadian Institutes of Health
Research (CIHR)dagger; European Foundation for the Study of Diabetes
(EFSD)dagger; Fondation de l'IUCPQ dagger; Fondation de l'IUCPQ dagger;
Canadian Partnership Against Cancer (CPAC) and Heart & Stroke Foundation
of Canada (HSFC)dagger; Canadian Institutes of Health Research
(CIHR)dagger; Canadian Institutes of Health Research (CIHR)dagger;
Canadian Institutes of Health Research (CIHR)dagger; Fonds de la
recherche en sante du Quebec dagger; Canadian Institutes of Health
Research (CIHR)dagger; Canadian Institutes of Health Research
(CIHR)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger;
Canadian Institutes of Health Research (CIHR)dagger; Canadian Institutes
of Health Research (CIHR)dagger; Diabete Quebec*; Ministere de la Sante
et des Services sociaux du Quebec dagger; Ministere des Finances et de
l'Economie du Quebec dagger; Conseil franco-quebecois de cooperation
universitaire (CFQCU)dagger; Heart and Stroke Foundation of Canada
(HSFC)dagger; Heart and Stroke Foundation of Canada (HSFC)dagger; Heart
and Stroke Foundation of Canada (HSFC)dagger None Pfizer Canada dagger;
Merck dagger None None Abbott Laboratories dagger; Torrent
Pharmaceuticals dagger None; Alan S. Go Kaiser Permanente Astra-Zeneca
dagger; NHLBI dagger; National Institute of Diabetes, Digestive and
Kidney Diseases dagger; Sanofi dagger None None None None None None;
Mark D. Huffman Northwestern University World Heart Federation dagger;
JR Alberts Foundation dagger; Eisenberg Foundation dagger None None None
None None None; Simin Liu Brown University Stanford University dagger
None None None None None None; Darren K. McGuire University of
Texas-Southwestern Med Ctr GlaxoSmithKline*; Takeda*; Orexigen dagger;
Janssen dagger; Eli Lilly*; Bristol Myers Squibb dagger; AstraZeneca
dagger; Boehringer Ingelheim dagger; Merck dagger; Novo Nordisk dagger;
Lexicon dagger None None Takeda dagger None Novo Nordisk dagger;
Boehringer Ingelheim dagger; Merck*; Regeneron* None; Paul Muntner
University of Alabama at Birmingham Amgen Inc. (research grant to study
cardiovascular disease prevention, diagnosis and treatment)dagger None
None None None None None; Joel Stein Columbia University Nexstim*;
Tyromotion*; Myomo* None None None None Myomo* None; Salim S. Virani
Michael E. DeBakey VA Medical Center Health Services Research and
Development Center for Innovations, Baylor College of Medicine, Michael
E. DeBakey VAMC, Methodist DeBakey Heart and Vascular Center Department
of Veterans Affairs dagger; American Heart Association dagger; American
Diabetes Association dagger None None None None None None; Joshua Z.
Willey Columbia University NIH dagger None None None None None None
NR 0
TC 80
Z9 84
U1 5
U2 73
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 27
PY 2015
VL 131
IS 4
BP 434
EP 441
DI 10.1161/CIR.0000000000000157
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AZ7YR
UT WOS:000348432100023
ER
PT J
AU Mozaffarian, D
Benjamin, EJ
Go, AS
Arnett, DK
Blaha, MJ
Cushman, M
de Ferranti, S
Despres, JP
Fullerton, HJ
Howard, VJ
Huffman, MD
Judd, SE
Kissela, BM
Lackland, DT
Lichtman, JH
Lisabeth, LD
Liu, SM
Mackey, RH
Matchar, DB
McGuire, DK
Mohler, ER
Moy, CS
Muntner, P
Mussolino, ME
Nasir, K
Neumar, RW
Nichol, G
Palaniappan, L
Pandey, DK
Reeves, MJ
Rodriguez, CJ
Sorlie, PD
Stein, J
Towfighi, A
Turan, TN
Virani, SS
Willey, JZ
Woo, D
Yeh, RW
Turner, MB
AF Mozaffarian, Dariush
Benjamin, Emelia J.
Go, Alan S.
Arnett, Donna K.
Blaha, Michael J.
Cushman, Mary
de Ferranti, Sarah
Despres, Jean-Pierre
Fullerton, Heather J.
Howard, Virginia J.
Huffman, Mark D.
Judd, Suzanne E.
Kissela, Brett M.
Lackland, Daniel T.
Lichtman, Judith H.
Lisabeth, Lynda D.
Liu, Simin
Mackey, Rachel H.
Matchar, David B.
McGuire, Darren K.
Mohler, Emile R., III
Moy, Claudia S.
Muntner, Paul
Mussolino, Michael E.
Nasir, Khurram
Neumar, Robert W.
Nichol, Graham
Palaniappan, Latha
Pandey, Dilip K.
Reeves, Mathew J.
Rodriguez, Carlos J.
Sorlie, Paul D.
Stein, Joel
Towfighi, Amytis
Turan, Tanya N.
Virani, Salim S.
Willey, Joshua Z.
Woo, Daniel
Yeh, Robert W.
Turner, Melanie B.
CA Amer Heart Assoc Stat Comm
Stroke Stat Subcomm
TI Heart Disease and Stroke Statistics-2015 Update A Report From the
American Heart Association
SO CIRCULATION
LA English
DT Article
ID PERIPHERAL ARTERIAL-DISEASE; CHRONIC KIDNEY-DISEASE; BODY-MASS INDEX;
NUTRITION-EXAMINATION-SURVEY; ACUTE MYOCARDIAL-INFARCTION; SUDDEN
CARDIAC DEATH; CARDIOVASCULAR RISK-FACTORS; TYPE-2 DIABETES-MELLITUS;
TRANSIENT ISCHEMIC ATTACK; ALL-CAUSE MORTALITY
C1 [Mozaffarian, Dariush] Tufts Univ, Medford, MA 02155 USA.
[Arnett, Donna K.; Howard, Virginia J.; Judd, Suzanne E.; Muntner, Paul] Univ Alabama Birmingham, Birmingham, AL USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Blaha, Michael J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Cushman, Mary] Univ Vermont, Burlington, VT 05405 USA.
[de Ferranti, Sarah] Childrens Hosp Boston, Boston, MA USA.
[Despres, Jean-Pierre] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada.
[Fullerton, Heather J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Go, Alan S.] Kaiser Permanente, Oakland, CA USA.
[Huffman, Mark D.] Northwestern Univ, Evanston, IL 60208 USA.
[Kissela, Brett M.] Univ Cincinnati, Acad Hlth Ctr, Cincinnati, OH 45221 USA.
[Lackland, Daniel T.; Turan, Tanya N.] Med Univ S Carolina, Charleston, SC USA.
[Lichtman, Judith H.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Lisabeth, Lynda D.; Neumar, Robert W.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Liu, Simin] Brown Univ, Providence, RI 02912 USA.
[Mackey, Rachel H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Matchar, David B.] Duke Univ, Durham, NC 27706 USA.
[McGuire, Darren K.] Univ Texas Southwestern Med Ctr, Houston, TX USA.
[Mohler, Emile R., III] Univ Penn, Philadelphia, PA 19104 USA.
[Mussolino, Michael E.] NIH, Bethesda, MD USA.
[Nasir, Khurram] Baptist Hlth Med Grp, Houston, TX USA.
[Nichol, Graham] Univ Washington, Seattle, WA 98195 USA.
[Palaniappan, Latha] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Pandey, Dilip K.] Univ Illinois, Chicago, IL USA.
[Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA.
[Rodriguez, Carlos J.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Sorlie, Paul D.] NHLBI, Bethesda, MD USA.
[Stein, Joel; Willey, Joshua Z.] Columbia Univ, New York, NY 10027 USA.
[Towfighi, Amytis] Univ So Calif, Los Angeles, CA 90089 USA.
[Turner, Melanie B.] Amer Heart Assoc, Houston, TX USA.
[Virani, Salim S.] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Innovat, Methodist DeBakey Heart & Vasc Ctr,Michael E DeBa, Houston, TX 77030 USA.
[Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Mozaffarian, D (reprint author), Tufts Univ, Medford, MA 02155 USA.
OI Mackey, Rachel/0000-0001-6088-2664; Turan, Tanya/0000-0001-5399-8845;
Huffman, Mark/0000-0001-7412-2519; Benjamin, Emelia/0000-0003-4076-2336;
Virani, Salim/0000-0001-9541-6954; Kissela, Brett/0000-0002-9773-4013
FU NCATS NIH HHS [UL1 TR000077, UL1 TR001425]; NHLBI NIH HHS [R01
HL104199]; NINDS NIH HHS [K23 NS073104]
NR 1605
TC 1928
Z9 1977
U1 80
U2 324
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 27
PY 2015
VL 131
IS 4
BP E29
EP E322
DI 10.1161/CIR.0000000000000152
PG 294
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AZ7YR
UT WOS:000348432100002
PM 25520374
ER
PT J
AU Cong, J
Fan, TP
Yang, XQ
Squires, JW
Cheng, GM
Zhang, LL
Zhang, Z
AF Cong, Juan
Fan, Tingpan
Yang, Xiaoqian
Squires, Jared Wynn
Cheng, Guomei
Zhang, Linlin
Zhang, Zhan
TI Structural and functional changes in maternal left ventricle during
pregnancy: a three-dimensional speckle-tracking echocardiography study
SO CARDIOVASCULAR ULTRASOUND
LA English
DT Article
DE Pregnancy; Remodeling; Myocardial deformation; Three-dimension;
Speckle-tracking echocardiography
ID GLOBAL AREA STRAIN; QUANTIFICATION; DEFORMATION; VOLUMES; DISEASE;
MOTION; HEART
AB Background: Pregnancy represents a physiological adaptation to the transient load changes of maternal heart. This study aimed to investigate maternal left ventricle (LV) performance during normal pregnancy by three-dimensional speckle-tracking echocardiography (3D STE) parameters considering LV loading and shape.
Methods: Sequential two-dimensional echocardiography (2DE) and 3D STE were performed on 68 women during each pregnancy trimester and 6 to 9 weeks after delivery, while thirty age-matched, healthy, nonpregnant women served as controls. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and global radial strain (GRS) were measured.
Results: Increased cardiac index and progressive eccentric hypertrophy was detected, which subsequently recovered postpartum. In late pregnancy, GLS, GCS, GAS and GRS significantly decreased (P < 0.05) accompanied by a slight reduction of LV ejection fraction (EF) (P < 0.05), and these values returned postpartum to baseline level. All 3D strain indices correlated well with gestation age (P < 0.01), while compared to other components, GAS exhibited the strongest association with 3D EF (r = 0.549) and sphericity index (r = 0.328), and was the only parameter that correlated well with LV mass index (r = 0.22).
Conclusions: This study gives normal ranges of 3D STE indices in pregnancy. 3D STE demonstrated modified myocardial deformation and changes in maternal LV structure and function during the gestation period.
C1 [Cong, Juan; Fan, Tingpan] Zhengzhou Univ, Affiliated Hosp 3, Dept Ultrason Diag, Zhengzhou 450052, Henan Province, Peoples R China.
[Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan Province, Peoples R China.
[Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Linlin; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Henan Prov Engn Res Ctr Perinatal Med, Zhengzhou 450052, Henan Province, Peoples R China.
[Cong, Juan; Yang, Xiaoqian; Cheng, Guomei; Zhang, Linlin; Zhang, Zhan] Zhengzhou Univ, Affiliated Hosp 3, Henan Translat Med Engn Lab Maternal & Childrens, Zhengzhou 450052, Henan Province, Peoples R China.
[Squires, Jared Wynn] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA.
RP Zhang, Z (reprint author), Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou 450052, Henan Province, Peoples R China.
EM zhangzhanzdsfy@126.com
FU Henan Provincial Healthy Talents of Scientific and Technological
Innovative Program [ID_124200510005]
FX This work was supported by the Henan Provincial Healthy Talents of
Scientific and Technological Innovative Program (Grant ID_124200510005).
NR 26
TC 7
Z9 7
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-7120
J9 CARDIOVASC ULTRASOUN
JI Cardiovasc. Ultrasound
PD JAN 27
PY 2015
VL 13
AR 6
DI 10.1186/1476-7120-13-6
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CC0XM
UT WOS:000350063200002
PM 25626356
ER
PT J
AU Frakt, AB
AF Frakt, Austin B.
TI Hospital Consolidation Isn't the Key to Lowering Costs and Raising
Quality
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT News Item
C1 [Frakt, Austin B.] Boston VA Healthcare Syst, Boston, MA USA.
[Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Frakt, Austin B.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
RP Frakt, AB (reprint author), Boston VA Healthcare Syst, Boston, MA USA.
EM afrakt@gmail.com
NR 0
TC 3
Z9 3
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 27
PY 2015
VL 313
IS 4
BP 345
EP 345
DI 10.1001/jama.2014.17412
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7BS
UT WOS:000349072600003
PM 25626023
ER
PT J
AU Leroy, F
Cai, Q
Bogart, SL
Dubois, J
Coulon, O
Monzalvo, K
Fischer, C
Glasel, H
Van der Haegen, L
Benezita, A
Lin, CP
Kennedy, DN
Ihara, AS
Hertz-Pannier, L
Moutard, ML
Poupon, C
Brysbaert, M
Roberts, N
Hopkins, WD
Mangin, JF
Dehaene-Lambertz, G
AF Leroy, Francois
Cai, Qing
Bogart, Stephanie L.
Dubois, Jessica
Coulon, Olivier
Monzalvo, Karla
Fischer, Clara
Glasel, Herve
Van der Haegen, Lise
Benezita, Audrey
Lin, Ching-Po
Kennedy, David N.
Ihara, Aya S.
Hertz-Pannier, Lucie
Moutard, Marie-Laure
Poupon, Cyril
Brysbaert, Marc
Roberts, Neil
Hopkins, William D.
Mangin, Jean-Francois
Dehaene-Lambertz, Ghislaine
TI New human-specific brain landmark: The depth asymmetry of superior
temporal sulcus
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE brain; anatomy; asymmetry; human-specific; STS
ID SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; PLANUM TEMPORALE;
LANGUAGE LATERALIZATION; STRUCTURAL ASYMMETRIES; LEFT-HANDERS; AREA;
HANDEDNESS; INFANTS; FMRI
AB Identifying potentially unique features of the human cerebral cortex is a first step to understanding how evolution has shaped the brain in our species. By analyzing MR images obtained from 177 humans and 73 chimpanzees, we observed a human-specific asymmetry in the superior temporal sulcus at the heart of the communication regions and which we have named the "superior temporal asymmetrical pit" (STAP). This 45-mm-long segment ventral to Heschl's gyrus is deeper in the right hemisphere than in the left in 95% of typical human subjects, from infanthood till adulthood, and is present, irrespective of handedness, language lateralization, and sex although it is greater in males than in females. The STAP also is seen in several groups of atypical subjects including persons with situs inversus, autistic spectrum disorder, Turner syndrome, and corpus callosum agenesis. It is explained in part by the larger number of sulcal interruptions in the left than in the right hemisphere. Its early presence in the infants of this study as well as in fetuses and premature infants suggests a strong genetic influence. Because this asymmetry is barely visible in chimpanzees, we recommend the STAP region during midgestation as an important phenotype to investigate asymmetrical variations of gene expression among the primate lineage. This genetic target may provide important insights regarding the evolution of the crucial cognitive abilities sustained by this sulcus in our species, namely communication and social cognition.
C1 [Leroy, Francois; Dubois, Jessica; Monzalvo, Karla; Glasel, Herve; Benezita, Audrey; Dehaene-Lambertz, Ghislaine] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Cognit Neuroimaging Unit,U992, F-91191 Gif Sur Yvette, France.
[Fischer, Clara; Brysbaert, Marc; Mangin, Jean-Francois] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Anal & Proc Informat Unit, F-91191 Gif Sur Yvette, France.
[Hertz-Pannier, Lucie] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Clin & Translat Applicat Res Unit,U663, F-91191 Gif Sur Yvette, France.
[Poupon, Cyril] CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Nucl Magnet Resonance Imaging & Spect U, F-91191 Gif Sur Yvette, France.
[Cai, Qing] E China Normal Univ, Shanghai Key Lab Brain Funct Genom, Shanghai 200241, Peoples R China.
[Bogart, Stephanie L.; Hopkins, William D.] Emory Univ, Yerkes Reg Primate Res Ctr, Div Dev & Cognit Neurosci, Atlanta, GA 30322 USA.
[Coulon, Olivier] Aix Marseille Univ, UMR CNRS 7296, Lab Syst & Informat Sci, F-13284 Marseille, France.
[Van der Haegen, Lise] Univ Ghent, Dept Expt Psychol, B-9000 Ghent, Belgium.
[Lin, Ching-Po] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan.
[Kennedy, David N.] Massachusetts Gen Hosp, Ctr Neurosci, Ctr Morphometr Anal, Boston, MA 02114 USA.
[Ihara, Aya S.] Natl Inst Informat & Commun Technol, Ctr Informat & Neural Networks, Osaka 5650871, Japan.
[Moutard, Marie-Laure] Trousseau Hosp, AP HP, Neuropediat Dept, F-75012 Paris, France.
[Roberts, Neil] Univ Edinburgh, Coll Med & Vet Med, Clin Res Imaging Ctr, Edinburgh EH8 9YL, Midlothian, Scotland.
RP Leroy, F (reprint author), CEA, Off Atom Energy & Alternat Energies, INSERM, NeuroSpin,Cognit Neuroimaging Unit,U992, F-91191 Gif Sur Yvette, France.
EM francois.leroy@cea.fr
RI Dubois, Jessica/P-2461-2014;
OI Dubois, Jessica/0000-0003-4865-8111; Brysbaert, Marc/0000-0002-3645-3189
FU McDonnell Foundation; Bettencourt-Schueller Foundation
FX We thank the ABIDE initiative, the Laboratory for Neurocognitive and
Imaging Research (Kennedy Krieger Institute, Baltimore, MD), and Roberto
Toro for the dataset related to normally developing and autistic
children; specifically, from the Laboratory for Neurocognitive and
Imaging Research, we thank Anita Barber, Rebecca Buhlman, Brian Caffo,
Deana Crocetti, Suresh Joel, John Muschelli, Carrie Nettles, James
Pekar, Kristie Sweeney, Michelle Talley, Mary Beth Nebel, and Stewart
Mostofsky. We also thank Nicolas Molko and Stanislas Dehaene for the
dataset related to Turner syndrome. Finally, we are grateful to the
NeuroSpin teams for their help in the acquisition of infants and
children data. This work was supported by the McDonnell and
Bettencourt-Schueller Foundations.
NR 49
TC 15
Z9 15
U1 4
U2 27
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 27
PY 2015
VL 112
IS 4
BP 1208
EP 1213
DI 10.1073/pnas.1412389112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ7SB
UT WOS:000348417000064
PM 25583500
ER
PT J
AU Warren, HS
Tompkins, RG
Moldawer, LL
Seok, J
Xu, WH
Mindrinos, MN
Maier, RV
Xiao, WZ
Davis, RW
AF Warren, H. Shaw
Tompkins, Ronald G.
Moldawer, Lyle L.
Seok, Junhee
Xu, Weihong
Mindrinos, Michael N.
Maier, Ronald V.
Xiao, Wenzhong
Davis, Ronald W.
TI Mice are not men
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Letter
C1 [Warren, H. Shaw; Tompkins, Ronald G.; Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Warren, H. Shaw; Tompkins, Ronald G.; Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Warren, H. Shaw; Tompkins, Ronald G.; Xiao, Wenzhong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA.
[Moldawer, Lyle L.] Univ Florida, Dept Surg, Gainesville, FL 32608 USA.
[Seok, Junhee] Korea Univ, Sch Elect Engn, Seoul 136713, South Korea.
[Xu, Weihong; Mindrinos, Michael N.; Davis, Ronald W.] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94305 USA.
[Maier, Ronald V.] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98195 USA.
RP Xiao, WZ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
EM wenzhong.xiao@mgh.harvard.edu
FU NIGMS NIH HHS [R01 GM104481, R24 GM102656, U54 GM062119]
NR 2
TC 21
Z9 21
U1 1
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JAN 27
PY 2015
VL 112
IS 4
BP E345
EP E345
DI 10.1073/pnas.1414857111
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ7SB
UT WOS:000348417000003
PM 25540422
ER
PT J
AU Mehta, AJ
Kubzansky, LD
Coull, BA
Kloog, I
Koutrakis, P
Sparrow, D
Spiro, A
Vokonas, P
Schwartz, J
AF Mehta, Amar J.
Kubzansky, Laura D.
Coull, Brent A.
Kloog, Itai
Koutrakis, Petros
Sparrow, David
Spiro, Avron, III
Vokonas, Pantel
Schwartz, Joel
TI Associations between air pollution and perceived stress: the Veterans
Administration Normative Aging Study
SO ENVIRONMENTAL HEALTH
LA English
DT Article
DE Aged; Air pollution; Male; Particulate matter; Prospective studies;
Stress; Psychological
ID PARTICULATE MATTER; PSYCHOSOCIAL FACTORS; NOISE EXPOSURE; LUNG-FUNCTION;
OLDER-ADULTS; RISK-FACTOR; HEALTH; DEPRESSION; MORTALITY; INFLAMMATION
AB Background: There is mixed evidence suggesting that air pollution may be associated with increased risk of developing psychiatric disorders. We aimed to investigate the association between air pollution and non-specific perceived stress, often a precursor to development of affective psychiatric disorders.
Methods: This longitudinal analysis consisted of 987 older men participating in at least one visit for the Veterans Administration Normative Aging Study between 1995 and 2007 (n = 2,244 visits). At each visit, participants were administered the 14-item Perceived Stress Scale (PSS), which quantifies stress experienced in the previous week. Scores ranged from 0-56 with higher scores indicating increased stress. Differences in PSS score per interquartile range increase in moving average (1, 2, and 4-weeks) of air pollution exposures were estimated using linear mixed-effects regression after adjustment for age, race, education, physical activity, anti-depressant medication use, seasonality, meteorology, and day of week. We also evaluated effect modification by season (April-September and March-October for warm and cold season, respectively).
Results: Fine particles (PM2.5), black carbon (BC), nitrogen dioxide, and particle number counts (PNC) at moving averages of 1, 2, and 4-weeks were associated with higher perceived stress ratings. The strongest associations were observed for PNC; for example, a 15,997 counts/cm(3) interquartile range increase in 1-week average PNC was associated with a 3.2 point (95% CI: 2.1-4.3) increase in PSS score. Season modified the associations for specific pollutants; higher PSS scores in association with PM2.5, BC, and sulfate were observed mainly in colder months.
Conclusions: Air pollution was associated with higher levels of perceived stress in this sample of older men, particularly in colder months for specific pollutants.
C1 [Mehta, Amar J.; Koutrakis, Petros; Schwartz, Joel] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA.
[Kubzansky, Laura D.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA.
[Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Kloog, Itai] Ben Gurion Univ Negev, Dept Geog & Environm Dev, IL-84105 Beer Sheva, Israel.
[Sparrow, David; Spiro, Avron, III; Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA.
[Sparrow, David] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
[Vokonas, Pantel] Boston Univ, Sch Med, Dept Med, Boston, MA USA.
[Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
RP Mehta, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Landmark Ctr,West 415,401 Pk Dr, Boston, MA 02215 USA.
EM amehta@hsph.harvard.edu
FU National Institute of Environmental Health Sciences [ES014663-01A2, P01
ES09825]; U.S. Environmental Protection Agency [EPA R832416, R827353,
R83241601]; Cooperative Studies Program/Epidemiology Research and
Information Center of the US Department of Veterans Affairs and is a
component of the Massachusetts Veterans Epidemiology Research and
Information Center, Boston, Massachusetts; NIH [R01-AG018436]; VA
Research Career Scientist award; VA Senior Research Career Scientist
award; USEPA [R827353, R83241601, R832416]; USEPA (EPA Clean Air
Research Center grant) [RD83479801]
FX The authors thank the participants and staff of the VA Normative Aging
Study. This work was supported by the grants from the National Institute
of Environmental Health Sciences (ES014663-01A2 and P01 ES09825) and
from the U.S. Environmental Protection Agency (EPA R832416, R827353, and
R83241601). The Veterans Affairs (VA) Normative Aging Study is supported
by the Cooperative Studies Program/Epidemiology Research and Information
Center of the US Department of Veterans Affairs and is a component of
the Massachusetts Veterans Epidemiology Research and Information Center,
Boston, Massachusetts. Support was also provided by NIH grant
R01-AG018436. This research was also supported by a VA Research Career
Scientist award to David Sparrow and a VA Senior Research Career
Scientist award to Avron Spiro, III.; This publication was made possible
by USEPA grant (R832416, R827353, R83241601, and EPA Clean Air Research
Center grant RD83479801). Its contents are solely the responsibility of
the grantee and do not necessarily represent the official views of the
USEPA. Further, USEPA does not endorse the purchase of any commercial
products or services mentioned in the publication.
NR 65
TC 3
Z9 3
U1 6
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD JAN 27
PY 2015
VL 14
AR UNSP 10
DI 10.1186/1476-069X-14-10
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CA6RM
UT WOS:000349043200001
PM 25627872
ER
PT J
AU Singer, DE
Ezekowitz, MD
AF Singer, Daniel E.
Ezekowitz, Michael D.
TI Adding Rigor to Stroke Risk Prediction in Atrial Fibrillation
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE anticoagulation; atrial fibrillation; risk scores; stroke prevention
ID STRATIFICATION; GUIDELINES; MANAGEMENT; SCHEMES; ESC
C1 [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA.
[Ezekowitz, Michael D.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
RP Singer, DE (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
EM dsinger@partners.org
NR 13
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JAN 27
PY 2015
VL 65
IS 3
BP 233
EP 235
DI 10.1016/j.jacc.2014.11.013
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AZ2EA
UT WOS:000348046200002
PM 25614419
ER
PT J
AU Ho, PM
O'Donnell, CI
Bradley, SM
Grunwald, GK
Helfrich, C
Chapko, M
Liu, CF
Maddox, TM
Tsai, TT
Jesse, RL
Fihn, SD
Rumsfeld, JS
AF Ho, P. Michael
O'Donnell, Colin I.
Bradley, Steven M.
Grunwald, Gary K.
Helfrich, Christian
Chapko, Michael
Liu, Chuan-Fen
Maddox, Thomas M.
Tsai, Thomas T.
Jesse, Robert L.
Fihn, Stephan D.
Rumsfeld, John S.
TI 1-Year Risk-Adjusted Mortality and Costs of Percutaneous Coronary
Intervention in the Veterans Health Administration Insights From the VA
CART Program
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE costs; health care delivery; ischemic heart disease; PCI; outcomes;
value
ID CARDIOVASCULAR DATA REGISTRY; ACUTE MYOCARDIAL-INFARCTION; REPEAT
REVASCULARIZATION; QUALITY; PCI; PREDICTION; EFFICIENCY; OUTCOMES;
DISEASE; SURGERY
AB BACKGROUND There is significant interest in measuring health care value, but this concept has not been operationalized in specific patient cohorts. The longitudinal outcomes and costs for patients after percutaneous coronary intervention (PCI) provide an opportunity to measure an aspect of health care value.
OBJECTIVES This study evaluated variations in 1-year outcomes (risk-adjusted mortality) and risk-standardized costs of care for all patients undergoing PCI in the Veterans Affairs (VA) system from 2007 to 2010.
METHODS This retrospective cohort study evaluated all veterans undergoing PCI at any of 60 hospitals in the VA health care system, using data from the national VA Clinical Assessment, Reporting, and Tracking (CART) program. Primary outcomes were 1-year mortality and costs following PCI. Risk-standardized mortality and cost ratios were calculated, adjusting for cardiac and noncardiac comorbidities.
RESULTS A median of 261 PCIs were performed in the 60 hospitals during the study period. Median 1-year unadjusted hospital mortality rate was 6.13%. Four hospitals were significantly above the 1-year risk-standardized median mortality rate, with median mortality ratios ranging from 1.23 to 1.28. No hospitals were significantly below median mortality. Median 1-year total unadjusted hospital costs were $46,302 per patient. There were 16 hospitals above and 19 hospitals below the risk-standardized median cost, with risk-standardized ratios ranging from 0.45 to 2.09, reflecting a much larger magnitude of variability in costs than in mortality.
CONCLUSIONS There is much smaller variation in 1-year risk adjusted mortality than in risk-standardized costs after PCI in the VA. These findings suggest that there are opportunities to improve PCI value by reducing costs without compromising outcomes. This approach to evaluating outcomes and costs together may be a model for other health systems and accountable care organizations interested in operationalizing value measurement. (C) 2015 by the American College of Cardiology Foundation.
C1 [Ho, P. Michael; O'Donnell, Colin I.; Bradley, Steven M.; Grunwald, Gary K.; Maddox, Thomas M.; Tsai, Thomas T.; Rumsfeld, John S.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA.
[Ho, P. Michael; O'Donnell, Colin I.; Bradley, Steven M.; Grunwald, Gary K.; Maddox, Thomas M.; Tsai, Thomas T.; Rumsfeld, John S.] Univ Colorado, Div Cardiol, Denver, CO 80220 USA.
[Helfrich, Christian; Chapko, Michael; Liu, Chuan-Fen; Fihn, Stephan D.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Jesse, Robert L.] Dept Vet Affairs, Vet Hlth Adm, Washington, DC USA.
[Fihn, Stephan D.] Vet Affairs Off Analyt & Business Intelligence, Washington, DC USA.
RP Ho, PM (reprint author), Univ Colorado, Sect Cardiol, Denver Vet Affairs Med Ctr, 1055 Clermont St 111B, Denver, CO 80220 USA.
EM michael.ho@va.gov
RI Helfrich, Christian/D-2382-2016
OI Helfrich, Christian/0000-0002-9827-4768
FU Career Development Awards from VA Health Services Research and
Development
FX Drs. Bradley and Maddox are supported by Career Development Awards from
VA Health Services Research and Development. All other authors have
reported that they have no relationships relevant to the contents of
this paper to disclose.
NR 19
TC 6
Z9 6
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JAN 27
PY 2015
VL 65
IS 3
BP 236
EP 242
DI 10.1016/j.jacc.2014.10.048
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AZ2EA
UT WOS:000348046200003
PM 25614420
ER
PT J
AU Samarendra, P
Mangione, MP
AF Samarendra, Padmaraj
Mangione, Michael P.
TI Aortic Stenosis and Perioperative Risk With Noncardiac Surgery
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Review
DE clinical outcomes; heart failure; hypotension; intraoperative
monitoring; phenylephrine
ID CORONARY-ARTERY-DISEASE; LOW MORTALITY-RATES; VALVE-REPLACEMENT; CARDIAC
RISK; SURGICAL-PROCEDURES; PERFORM WELL; COMPLICATIONS; OUTCOMES;
HEMODYNAMICS; HOSPITALS
AB Aortic stenosis (AS) is characterized as a high-risk index for cardiac complications during noncardiac surgery. The American College of Cardiology/American Heart Association guidelines define severe AS as aortic valve area <= 1 cm(2), mean gradient of >= 40 mm Hg, and peak velocity of >= 4 m/s. As per current clinical practice, any of these characteristic features label a patient as at high risk for noncardiac surgery. However, these parameters appear inconsistent, particularly with respect to the aortic valve area cutoff value. The perioperative risk associated with AS during noncardiac surgery depends upon its severity (moderate vs. severe), clinical status, and the complexity of the surgical procedure (low to intermediate risk vs. high risk). A critical analysis of old and new data from published studies indicates that the significance of the presence of AS in patients undergoing noncardiac surgery is overemphasized in studies that predate the more recent advances in echocardiography and cardiac catheterization in assessment of aortic stenosis, anesthetic and surgical techniques, as well as post-operative patient care. (C) 2015 by the American College of Cardiology Foundation.
C1 [Samarendra, Padmaraj] VA Med Ctr, Noninvas Cardiol & Echocardiog Lab, Pittsburgh, PA 15240 USA.
[Samarendra, Padmaraj] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
[Mangione, Michael P.] VA Pittsburgh Hlth Care Syst, Dept Anesthesia, Pittsburgh, PA USA.
[Mangione, Michael P.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA.
RP Samarendra, P (reprint author), VA Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA.
EM Padmaraj@aol.com
NR 40
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JAN 27
PY 2015
VL 65
IS 3
BP 295
EP 302
DI 10.1016/j.jacc.2014.10.051
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AZ2EA
UT WOS:000348046200012
PM 25614427
ER
PT J
AU Boatin, AA
Wylie, B
Goldfarb, I
Azevedo, R
Pittel, E
Ng, C
Haberer, J
AF Boatin, Adeline A.
Wylie, Blair
Goldfarb, Ilona
Azevedo, Robin
Pittel, Elena
Ng, Courtney
Haberer, Jessica
TI Wireless Fetal Heart Rate Monitoring in Inpatient Full-Term Pregnant
Women: Testing Functionality and Acceptability
SO PLoS One
LA English
DT Article
AB We tested functionality and acceptability of a wireless fetal monitoring prototype technology in pregnant women in an inpatient labor unit in the United States. Women with full-term singleton pregnancies and no evidence of active labor were asked to wear the prototype technology for 30 minutes. We assessed functionality by evaluating the ability to successfully monitor the fetal heartbeat for 30 minutes, transmit this data to Cloud storage and view the data on a web portal. Three obstetricians also rated fetal cardiotocographs on ease of readability. We assessed acceptability by administering closed and open-ended questions on perceived utility and likeability to pregnant women and clinicians interacting with the prototype technology. Thirty-two women were enrolled, 28 of whom (87.5%) successfully completed 30 minutes of fetal monitoring including transmission of cardiotocographs to the web portal. Four sessions though completed, were not successfully uploaded to the Cloud storage. Six non-study clinicians interacted with the prototype technology. The primary technical problem observed was a delay in data transmission between the prototype and the web portal, which ranged from 2 to 209 minutes. Delays were ascribed to Wi-Fi connectivity problems. Recorded cardiotocographs received a mean score of 4.2/5 (+/- 1.0) on ease of readability with an interclass correlation of 0.81(95% CI 0.45, 0.96). Both pregnant women and clinicians found the prototype technology likable (81.3% and 66.7% respectively), useful (96.9% and 66.7% respectively), and would either use it again or recommend its use to another pregnant woman (77.4% and 66.7% respectively). In this pilot study we found that this wireless fetal monitoring prototype technology has potential for use in a United States inpatient setting but would benefit from some technology changes. We found it to be acceptable to both pregnant women and clinicians. Further research is needed to assess feasibility of using this technology in busy inpatient settings.
C1 [Boatin, Adeline A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02163 USA.
[Wylie, Blair; Goldfarb, Ilona] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Maternal Fetal Med,Dept Obstet & Gynecol, Boston, MA USA.
[Azevedo, Robin; Pittel, Elena] Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA.
[Ng, Courtney; Haberer, Jessica] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Global Hlth, Boston, MA USA.
RP Boatin, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02163 USA.
EM aboatin@partners.org
FU Gary and Mary West Health Institute
FX This study was conducted at the Massachusetts General Hospital with
support provided by the Gary and Mary West Health Institute, an
independent, not for profit medical research organization that works
with healthcare providers and research institutions to create new, more
effective ways of delivering care. The funders had no role in study
design, data collection and analysis, decision to publish or preparation
of the manuscript.
NR 9
TC 2
Z9 2
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 26
PY 2015
VL 10
IS 1
AR e0117043
DI 10.1371/journal.pone.0117043
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ8MR
UT WOS:000348470400016
PM 25622043
ER
PT J
AU Swerdlow, DI
Preiss, D
Kuchenbaecker, KB
Holmes, MV
Engmann, JEL
Shah, T
Sofat, R
Stender, S
Johnson, PCD
Scott, RA
Leusink, M
Verweij, N
Sharp, SJ
Guo, YR
Giambartolomei, C
Chung, C
Peasey, A
Amuzu, A
Li, K
Palmen, J
Howard, P
Cooper, JA
Drenos, F
Li, YR
Lowe, G
Gallacher, J
Stewart, MCW
Tzoulaki, I
Buxbaum, SG
Daphne, LV
Forouhi, NG
Onland-Moret, NC
van der Schouw, YT
Schnabel, RB
Hubacek, JA
Kubinova, R
Baceviciene, M
Tamosiunas, A
Pajak, A
Topor-Madry, R
Stepaniak, U
Malyutina, SA
Baldassarre, D
Sennblad, B
Tremoli, E
de Faire, U
Veglia, F
Ford, I
Jukema, JW
Westendorp, RGJ
de Borst, GJ
de Jong, PA
Algra, A
Spiering, W
Maitland-van der Zee, AH
Klungel, OH
de Boer, A
Doevendans, PA
Eaton, CB
Robinson, JG
Duggan, D
Kjekshus, J
Downs, JR
Gotto, AM
Keech, AC
Marchioli, R
Tognoni, G
Sever, PS
Poulter, NR
Waters, DD
Pedersen, TR
Amarenco, P
Nakamura, H
McMurray, JJV
Lewsey, JD
Chasman, DI
Ridker, PM
Maggioni, AP
Tavazzi, L
Ray, KK
Seshasai, SRK
Manson, JE
Price, JF
Whincup, PH
Morris, RW
Lawlor, DA
Smith, GD
Ben-Shlomo, Y
Schreiner, PJ
Fornage, M
Siscovick, DS
Cushman, M
Kumari, M
Wareham, NJ
Verschuren, WMM
Redline, S
Patel, SR
Whittaker, JC
Hamsten, A
Delaney, JA
Dale, C
Gaunt, TR
Wong, A
Kuh, D
Hardy, R
Kathiresan, S
Castillo, BA
van der Harst, P
Brunner, EJ
Tybjaerg-Hansen, A
Marmot, MG
Krauss, RM
Tsai, M
Coresh, J
Hoogeveen, RC
Psaty, BM
Lange, LA
Hakonarson, H
Dudbridge, F
Humphries, SE
Talmud, PJ
Kivimaki, M
Timpson, NJ
Langenberg, C
Asselbergs, FW
Voevoda, M
Bobak, M
Pikhart, H
Wilson, JG
Reiner, AP
Keating, BJ
Hingorani, AD
Sattar, N
AF Swerdlow, Daniel I.
Preiss, David
Kuchenbaecker, Karoline B.
Holmes, Michael V.
Engmann, Jorgen E. L.
Shah, Tina
Sofat, Reecha
Stender, Stefan
Johnson, Paul C. D.
Scott, Robert A.
Leusink, Maarten
Verweij, Niek
Sharp, Stephen J.
Guo, Yiran
Giambartolomei, Claudia
Chung, Christina
Peasey, Anne
Amuzu, Antoinette
Li, Kawah
Palmen, Jutta
Howard, Philip
Cooper, Jackie A.
Drenos, Fotios
Li, Yun R.
Lowe, Gordon
Gallacher, John
Stewart, Marlene C. W.
Tzoulaki, Ioanna
Buxbaum, Sarah G.
Daphne, L. van der A.
Forouhi, Nita G.
Onland-Moret, N. Charlotte
van der Schouw, Yvonne T.
Schnabel, Renate B.
Hubacek, Jaroslav A.
Kubinova, Ruzena
Baceviciene, Migle
Tamosiunas, Abdonas
Pajak, Andrzej
Topor-Madry, Roman
Stepaniak, Urszula
Malyutina, Sofi A.
Baldassarre, Damiano
Sennblad, Bengt
Tremoli, Elena
de Faire, Ulf
Veglia, Fabrizio
Ford, Ian
Jukema, J. Wouter
Westendorp, Rudi G. J.
de Borst, Gert Jan
de Jong, Pim A.
Algra, Ale
Spiering, Wilko
Maitland-van der Zee, Anke H.
Klungel, Olaf H.
de Boer, Anthonius
Doevendans, Pieter A.
Eaton, Charles B.
Robinson, Jennifer G.
Duggan, David
Kjekshus, John
Downs, John R.
Gotto, Antonio M.
Keech, Anthony C.
Marchioli, Roberto
Tognoni, Gianni
Sever, Peter S.
Poulter, Neil R.
Waters, David D.
Pedersen, Terje R.
Amarenco, Pierre
Nakamura, Haruo
McMurray, John J. V.
Lewsey, James D.
Chasman, Daniel I.
Ridker, Paul M.
Maggioni, Aldo P.
Tavazzi, Luigi
Ray, Kausik K.
Seshasai, Sreenivasa Rao Kondapally
Manson, Joann E.
Price, Jackie F.
Whincup, Peter H.
Morris, Richard W.
Lawlor, Debbie A.
Smith, George Davey
Ben-Shlomo, Yoav
Schreiner, Pamela J.
Fornage, Myriam
Siscovick, David S.
Cushman, Mary
Kumari, Meena
Wareham, Nick J.
Verschuren, W. M. Monique
Redline, Susan
Patel, Sanjay R.
Whittaker, John C.
Hamsten, Anders
Delaney, Joseph A.
Dale, Caroline
Gaunt, Tom R.
Wong, Andrew
Kuh, Diana
Hardy, Rebecca
Kathiresan, Sekar
Castillo, Berta A.
van der Harst, Pim
Brunner, Eric J.
Tybjaerg-Hansen, Anne
Marmot, Michael G.
Krauss, Ronald M.
Tsai, Michael
Coresh, Josef
Hoogeveen, Ronald C.
Psaty, Bruce M.
Lange, Leslie A.
Hakonarson, Hakon
Dudbridge, Frank
Humphries, Steve E.
Talmud, Philippa J.
Kivimaeki, Mika
Timpson, Nicholas J.
Langenberg, Claudia
Asselbergs, Folkert W.
Voevoda, Mikhail
Bobak, Martin
Pikhart, Hynek
Wilson, James G.
Reiner, Alex P.
Keating, Brendan J.
Hingorani, Aroon D.
Sattar, Naveed
CA DIAGRAM Consortium
MAGIC Consortium
InterAct Consortium
TI HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight:
evidence from genetic analysis and randomised trials
SO LANCET
LA English
DT Article
ID HIGH-DOSE ATORVASTATIN; BODY-MASS INDEX; STATIN THERAPY; MENDELIAN
RANDOMIZATION; ASSOCIATION ANALYSES; LDL CHOLESTEROL; METAANALYSIS;
RISK; PREVENTION; DISEASE
AB Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.
Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis.
Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0.06 mmol/L (95% CI 0.05-0.07) lower LDL cholesterol and higher body weight (0.30 kg, 0.18-0.43), waist circumference (0.32 cm, 0.16-0.47), plasma insulin concentration (1.62%, 0.53-2.72), and plasma glucose concentration (0.23%, 0.02-0.44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1.02, 95% CI 1.00-1.05); the rs12916-T allele association was consistent (1.06, 1.03-1.09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0.92 mmol/L (95% CI 0.18-1.67) at 1-year of follow-up, increased bodyweight by 0.24 kg (95% CI 0.10-0.38 in all trials; 0.33 kg, 95% CI 0.24-0.42 in placebo or standard care controlled trials and 0.15 kg, 95% CI 0.39 to 0.08 in intensive-dose vs moderate-dose trials) at a mean of 4. 2 years (range 1.9-6.7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1.12, 95% CI 1.06-1.18 in all trials; 1.11, 95% CI 1.03-1. 20 in placebo or standard care controlled trials and 1.12, 95% CI 1.04-1. 22 in intensive-dose vs moderate dose trials).
Interpretation The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition.
C1 [Swerdlow, Daniel I.; Holmes, Michael V.; Engmann, Jorgen E. L.; Shah, Tina; Asselbergs, Folkert W.; Hingorani, Aroon D.] UCL, UCL Inst Cardiovasc Sci & Farr Inst, London, England.
[Sofat, Reecha] UCL, UCL Dept Med, London, England.
[Chung, Christina; Peasey, Anne; Kumari, Meena; Brunner, Eric J.; Marmot, Michael G.; Kivimaeki, Mika; Bobak, Martin; Pikhart, Hynek] UCL, UCL Res Dept Epidemiol & Publ Hlth, London, England.
[Giambartolomei, Claudia] UCL, UCL Genet Inst, London, England.
[Morris, Richard W.] UCL, UCL Dept Primary Care & Populat Hlth, London, England.
[Li, Kawah; Palmen, Jutta; Howard, Philip; Cooper, Jackie A.; Drenos, Fotios; Humphries, Steve E.; Talmud, Philippa J.] UCL, Ctr Cardiovasc Genet, London, England.
[Wong, Andrew; Kuh, Diana; Hardy, Rebecca] UCL, MRCUnit Lifelong Hlth & Ageing, Inst Epidemiol & Hlth Care, London, England.
[Preiss, David; McMurray, John J. V.; Sattar, Naveed] Univ Glasgow, BHF Glasgow Cardiovascular Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
[Johnson, Paul C. D.; Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Lowe, Gordon] Univ Glasgow, Inst Cardiovasc & Med, Glasgow, Lanark, Scotland.
[Lewsey, James D.] Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
[Kuchenbaecker, Karoline B.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Kuchenbaecker, Karoline B.] Univ Penn, Dept Surg, Div Transplantat, Ctr Clin Epidemiol & Biostat,Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kuchenbaecker, Karoline B.] Univ Penn, Clin Epidemiol Unit, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Stender, Stefan; Tybjaerg-Hansen, Anne] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark.
[Scott, Robert A.; Sharp, Stephen J.; Forouhi, Nita G.; Wareham, Nick J.; Langenberg, Claudia] Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Leusink, Maarten; Maitland-van der Zee, Anke H.; Klungel, Olaf H.; de Boer, Anthonius] Univ Utrecht, Fac Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands.
[Verweij, Niek; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Guo, Yiran; Li, Yun R.; Castillo, Berta A.; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Dale, Caroline] Dept Noncommunicable Dis Epidemiol, London WC1, England.
[Amuzu, Antoinette; Dudbridge, Frank] London Sch Hyg & Trop Med, London WC1, England.
[Gallacher, John] Cardiff Univ, Sch Med, Dept Primary Care & Publ Hlth, Cardiff CF10 3AX, S Glam, Wales.
[Stewart, Marlene C. W.; Price, Jackie F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Tzoulaki, Ioanna] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.
[Sever, Peter S.; Poulter, Neil R.] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London, England.
[Buxbaum, Sarah G.] Jackson State Univ, Jackson, MS USA.
[Daphne, L. van der A.; Verschuren, W. M. Monique] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.; Algra, Ale] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[de Borst, Gert Jan] Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands.
[de Jong, Pim A.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
[Algra, Ale] Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Utrecht, Netherlands.
[Spiering, Wilko] Univ Med Ctr Utrecht, Dept Vasc Med, Utrecht, Netherlands.
[Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
[Schnabel, Renate B.] Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany.
[Hubacek, Jaroslav A.] Ctr Med Expt, Inst Clin & Expt Med, Prague, Czech Republic.
[Kubinova, Ruzena] Natl Inst Publ Hlth, Prague, Czech Republic.
[Tamosiunas, Abdonas] Inst Cardiol, Kaunas, Lithuania.
[Baceviciene, Migle] Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
[Pajak, Andrzej; Topor-Madry, Roman; Stepaniak, Urszula] Jagiellonian Univ, Coll Med, Fac Hlth Sci, Dept Epidemiol & Populat Studies,Inst Publ Hlth, Krakow, Poland.
[Malyutina, Sofi A.; Voevoda, Mikhail] Russian Acad Med Sci, Inst Internal & Prevent Med, Siberian Branch, Novosibirsk, Russia.
[Voevoda, Mikhail] Russian Acad Med Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk, Russia.
[Baldassarre, Damiano; Tremoli, Elena] Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy.
[Sennblad, Bengt] Karolinska Inst, Sci Life Lab, Stockholm, Sweden.
[de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden.
[Veglia, Fabrizio] IRCCS, Biostat Unit, Milan, Italy.
[Baldassarre, Damiano; Tremoli, Elena] IRCCS, Ctr Cardiol Monzino, Milan, Italy.
[Jukema, J. Wouter] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
[Westendorp, Rudi G. J.] Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.
[Eaton, Charles B.] Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA.
[Robinson, Jennifer G.] Univ Iowa, Iowa City, IA 52242 USA.
[Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA.
[Kjekshus, John] Univ Oslo, Rikshosp, Dept Cardiol, N-0027 Oslo, Norway.
[Pedersen, Terje R.] Univ Oslo, Rikshosp, Ctr Preventat Med, N-0027 Oslo, Norway.
[Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Downs, John R.] VERDICT, South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Gotto, Antonio M.] Weill Cornell Med Coll, New York, NY USA.
[Keech, Anthony C.] Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW 2006, Australia.
[Marchioli, Roberto] Quintiles, Hematol & Oncol Therapeut Delivery Unit, Milan, Italy.
[Tognoni, Gianni] Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Chieti, Italy.
[Waters, David D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Amarenco, Pierre] Denis Diderot Univ, Paris, France.
[Nakamura, Haruo] Mitsukoshi Hlth & Welf Fdn, Tokyo, Japan.
[Chasman, Daniel I.; Ridker, Paul M.; Manson, Joann E.] Harvard Univ, Div Prevent Med, Sch Med, Boston, MA USA.
[Patel, Sanjay R.] Harvard Univ, Div Sleep Med, Sch Med, Boston, MA USA.
[Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy.
[Tavazzi, Luigi] Maria Cecilia Hosp, GVM Care & Res, ES Hlth Sci Fdn, Cotignola, RA, Italy.
[Ray, Kausik K.; Seshasai, Sreenivasa Rao Kondapally] Cardiac & Cell Sci Res Inst, London, England.
[Whincup, Peter H.] St Georges Univ, London, England.
[Lawlor, Debbie A.; Smith, George Davey; Gaunt, Tom R.; Timpson, Nicholas J.] Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
[Lawlor, Debbie A.; Smith, George Davey; Ben-Shlomo, Yoav; Timpson, Nicholas J.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Tsai, Michael] Univ Minnesota, Minneapolis, MN USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Med, Dept Epidemiol, Cardiovascular Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Delaney, Joseph A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Cushman, Mary] Univ Vermont, Dept Med, Colchester, VT USA.
[Cushman, Mary] Univ Vermont, Dept Pathol, Colchester, VT USA.
[Whittaker, John C.] GlaxoSmithKline, Stevenage, Herts, England.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kathiresan, Sekar] Broad Inst, Program Med & Populat Gent, Cambridge, MA USA.
[Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hoogeveen, Ronald C.] Baylor Coll Med, Dept Med, Div Atherosclerosis & Vasc Med, Houston, TX 77030 USA.
[Lange, Leslie A.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA.
[Asselbergs, Folkert W.] Durrer Ctr Cardiogenet Res, ICIN Netherlands Heart Inst, Utrecht, Netherlands.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
RP Preiss, D (reprint author), Univ Glasgow, BHF Glasgow Cardiovascular Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
EM d.swerdlow@ucl.ac.uk; david.preiss@glasgow.ac.uk
RI Gaunt, Tom/O-3918-2014; Guo, Yiran/H-4120-2011; de Jong,
Pim/G-7220-2014; Onland-Moret, N. Charlotte/G-9185-2011; Fox, Laura
/C-6249-2016; Klungel, Olaf/I-9563-2016; Verweij, Niek/A-4499-2017;
Davey Smith, George/A-7407-2013; Baldassarre, Damiano/J-3295-2016;
OI Maggioni, Aldo Pietro/0000-0003-2764-6779; mcmurray,
john/0000-0002-6317-3975; Lawlor, Debbie A/0000-0002-6793-2262; Morris,
Richard/0000-0001-7240-4563; Pikhart, Hynek/0000-0001-5277-4049;
TREMOLI, ELENA/0000-0002-0929-6106; Whincup, Peter/0000-0002-5589-4107;
Johnson, Paul/0000-0001-6663-7520; Humphries, Stephen
E/0000-0002-8221-6547; Patel, Sanjay/0000-0002-9142-5172; Kumari,
Meena/0000-0001-9716-1035; Verweij, Niek/0000-0002-4303-7685; Forouhi,
Nita/0000-0002-5041-248X; Timpson, Nicholas/0000-0002-7141-9189; Marmot,
Michael/0000-0002-2431-6419; Gaunt, Tom/0000-0003-0924-3247; Guo,
Yiran/0000-0002-6549-8589; de Jong, Pim/0000-0003-4840-6854; Davey
Smith, George/0000-0002-1407-8314; Baldassarre,
Damiano/0000-0002-2766-8882; Talmud, Philippa/0000-0002-5560-1933;
Swerdlow, Daniel/0000-0002-7946-3459; Preiss, David/0000-0003-3139-1836
FU Medical Research Council (MRC) Doctoral Training Award; Rosetrees Trust;
MRC Population Health Scientist Fellowship [G0802432]; National
Institutes of Health (NIH); British Heart Foundation (Schillingford)
Clinical Training Fellowship [FS/07/011]; Danish MRC [10-083788];
Research Fund at Rigshospitalet; Copenhagen University Hospital; Chief
Physician Johan Boserup and Lise Boserup's Fund; Wellcome Trust
[064947/Z/01/Z, 081081/Z/06/Z]; National Institute on Aging [1R01
AG23522-01]; MacArthur Foundation; National Institute on Minority
Health; Health Disparities of the NIH [P20MD006899]; MRC; Ministry of
Health, Czech Republic [00023001]; Magnus Bergvall Foundation;
Foundation for Old Servants; National Institute for Healthy Ageing
[05060810]; British Heart Foundation; Chest, Heart and Stroke Scotland;
Wellcome Trust; British Heart Foundation [RG/13/2/30098]; MooDFOOD
Collaborative Project (FP7) [613598]; NIH [NIH U19 HL065797, NHLBI
33014]; British Heart Foundation (BHF) [RG 08/008, PG/07/133/24260];
EMIF [115372]
FX DIS is supported by a Medical Research Council (MRC) Doctoral Training
Award and a grant from the Rosetrees Trust. MVH is supported by a MRC
Population Health Scientist Fellowship (G0802432). JELL is supported by
grants from the National Institutes of Health (NIH) and the MRC. RS has
been supported by a British Heart Foundation (Schillingford) Clinical
Training Fellowship (FS/07/011). SS is supported by the Danish MRC
(grant no. 10-083788), the Research Fund at Rigshospitalet, Copenhagen
University Hospital, and Chief Physician Johan Boserup and Lise
Boserup's Fund. CC and APe are supported by grants from the Wellcome
Trust (064947/Z/01/Z and 081081/Z/06/Z), a grant from the National
Institute on Aging (1R01 AG23522-01), and a grant from MacArthur
Foundation. SGB was supported by an award from the National Institute on
Minority Health and Health Disparities of the NIH (award number
P20MD006899). NGF is supported by a grant from the MRC. JAH is supported
by the project (Ministry of Health, Czech Republic) for the development
of research organisation 00023001 (IKEM, Prague, Czech Republic). APa is
supported by grants from the Wellcome Trust (064947/Z/01/Z and
081081/Z/06/Z) and National Institute on Aging (1R01 AG23522-01). BS is
supported by the Magnus Bergvall Foundation and the Foundation for Old
Servants. RGJW is supported by the National Institute for Healthy Ageing
(Grant 05060810). JFP is supported by the British Heart Foundation;
Chest, Heart and Stroke Scotland; the Wellcome Trust; and the MRC. DAL,
GDS, and NJT work in a unit that receives funding from the MRC and
University of Bristol. EJB's research is supported by a British Heart
Foundation programme grant (RG/13/2/30098) and the MooDFOOD
Collaborative Project (FP7 grant 613598). RMK is supported by the NIH
(grant NIH U19 HL065797). SEH and PJT are supported by the British Heart
Foundation (BHF RG 08/008, PG/07/133/24260), MRC, and NIH (grant NHLBI
33014). MKi is supported by the National Institute on Aging (AG034454);
the M RC (K013351); the National Heart, Lung and Blood Institute
(HL036310); and the Academy of Finland. NJT is supported by the MRC
(grant G0600705). FWA is supported by a clinical fellowship from the
Netherlands Organisation for Health Research and Development (ZonMw
grant 90700342). ADH is supported by University College London NIHR
Biomedical Research Centre. NS's research is supported by the British
Heart Foundation, Diabetes UK, and the EU/EF PIA Innovative Medicines
Initiative Joint Undertaking (EMIF grant 115372). We thank Merck and
Novartis for contributing data to the statin trials analysis. Details of
grants or other support for included studies are provided in the
appendix.
NR 40
TC 123
Z9 126
U1 11
U2 51
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JAN 24
PY 2015
VL 385
IS 9965
BP 351
EP 361
DI 10.1016/S0140-6736(14)61183-1
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA AZ9CN
UT WOS:000348509000028
PM 25262344
ER
PT J
AU Ursea, R
De Castro, D
Bowen, TJ
Chan, CC
AF Ursea, Roxana
De Castro, Dawn
Bowen, Trent J.
Chan, Chi-Chao
TI The role of conjunctival biopsy in the diagnosis of granulomatosis with
polyangiitis
SO JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION
LA English
DT Article
DE Conjunctivitis; Cornea; Ulceration; Biopsy; Granulomatosis with
polyangiitis
ID WEGENERS-GRANULOMATOSIS; PRESENTING FEATURE; LIMITED FORMS;
MANIFESTATIONS
AB Background: The purpose of this study is to describe a patient who was diagnosed with granulomatosis with polyangiitis based on conjunctival biopsy. This study is a case report and review of the literature.
Findings: A 48-year-old Caucasian woman presented with a 2-week history of a left eye peripheral corneal ulcer with adjacent conjunctivitis and a 4-month history of a non-resolving productive cough. Given her elevated serum perinuclear antineutrophil cytoplasmic antibody (P-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as a chest computed topography (CT) that showed bilateral patchy infiltrates, suspicion of limited granulomatosis with polyangiitis with lung and ocular involvement was high. Because bronchoalveolar lavage was nondiagnostic for granulomatous disease, conjunctival biopsy was initially attempted in order to avoid a more invasive lung biopsy. The conjunctival biopsy revealed mixed subacute inflammatory mediators and vasculitis consistent with granulomatosis with polyangiitis.
Conclusions: Conjunctival biopsy may be a valuable, minimally invasive method for diagnosing systemic granulomatosis with polyangiitis.
C1 [Ursea, Roxana] Univ Arizona, Dept Ophthalmol & Vis Sci, Coll Med, Tucson, AZ 85711 USA.
[De Castro, Dawn] Massachusetts Eye & Ear Infirm, Oculoplast Serv, Boston, MA 02114 USA.
[Bowen, Trent J.] Univ Arizona, Coll Med, Tucson, AZ 85711 USA.
[Chan, Chi-Chao] NEI, Immunopathol Sect, Bethesda, MD 20892 USA.
RP Ursea, R (reprint author), Univ Arizona, Dept Ophthalmol & Vis Sci, Coll Med, Tucson, AZ 85711 USA.
EM roxanaursea@hotmail.com
NR 26
TC 2
Z9 2
U1 0
U2 8
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1869-5760
J9 J OPHTHALMIC INFLAMM
JI J. Ophthalmic Inflamm. Infect.
PD JAN 23
PY 2015
VL 5
AR 1
DI 10.1186/s12348-014-0033-9
PG 5
WC Ophthalmology
SC Ophthalmology
GA CZ2JP
UT WOS:000366931600001
PM 25632308
ER
PT J
AU Hori, Y
Takeda, S
Cho, H
Wegmann, S
Shoup, TM
Takahashi, K
Irimia, D
Elmaleh, DR
Hyman, BT
Hudry, E
AF Hori, Yukiko
Takeda, Shuko
Cho, Hansang
Wegmann, Susanne
Shoup, Timothy M.
Takahashi, Kazue
Irimia, Daniel
Elmaleh, David R.
Hyman, Bradley T.
Hudry, Eloise
TI A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts
Amyloid beta in the Brain in a Transgenic Model of Alzheimer Disease
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LONG-TERM POTENTIATION; FIBRIL FORMATION; PRECURSOR PROTEIN; IN-VIVO;
MUTANT PRESENILIN-1; SYNAPTIC PLASTICITY; SECRETED OLIGOMERS; COGNITIVE
FUNCTION; FLAVONOID FISETIN; OXIDATIVE STRESS
AB Interfering with the assembly of Amyloid beta (A beta) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-A beta-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of A beta monomers into higher-order oligomers and fibrils in vitro without affecting A beta production. In vivo, the levels of soluble A beta are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble A beta in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on A beta economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease.
C1 [Hori, Yukiko; Takeda, Shuko; Wegmann, Susanne; Hyman, Bradley T.; Hudry, Eloise] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA.
[Cho, Hansang; Irimia, Daniel] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02129 USA.
[Shoup, Timothy M.; Elmaleh, David R.] Harvard Univ, Med Sch Charlestown, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02129 USA.
[Takahashi, Kazue] Harvard Univ, Med Sch Charlestown, Serv Pediat, Boston, MA 02129 USA.
RP Hudry, E (reprint author), MA Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Alzheimers Dis Res Lab, Bldg 114,16th St, Charlestown, MA 02129 USA.
EM ehudry@partners.org
FU AZ Therapies Inc.; Uehara Memorial Foundation; Japan Society for the
Promotion of Science; Dreyfoos Fund Against Alzheimer's Disease
FX This study was supported by AZ Therapies Inc., by a postdoctoral
fellowship from the Uehara Memorial Foundation (to Y. H.), by the
Postdoctoral Fellowship for Research Abroad from the Japan Society for
the Promotion of Science (to S. T.), and by the Dreyfoos Fund Against
Alzheimer's Disease.
NR 50
TC 1
Z9 1
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 23
PY 2015
VL 290
IS 4
BP 1966
EP 1978
DI 10.1074/jbc.M114.586602
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CA0EH
UT WOS:000348588000006
PM 25468905
ER
PT J
AU Sea, K
Sohn, SH
Durazo, A
Sheng, YW
Shaw, BF
Cao, XH
Taylor, AB
Whitson, LJ
Holloway, SP
Hart, PJ
Cabelli, DE
Gralla, EB
Valentine, JS
AF Sea, Kevin
Sohn, Se Hui
Durazo, Armando
Sheng, Yuewei
Shaw, Bryan F.
Cao, Xiaohang
Taylor, Alexander B.
Whitson, Lisa J.
Holloway, Stephen P.
Hart, P. John
Cabelli, Diane E.
Gralla, Edith Butler
Valentine, Joan Selverstone
TI Insights into the Role of the Unusual Disulfide Bond in Copper-Zinc
Superoxide Dismutase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU,ZN-SUPEROXIDE DISMUTASE;
SACCHAROMYCES-CEREVISIAE; ATOMIC-RESOLUTION; PULSE-RADIOLYSIS; REDUCED
FORM; METAL; AGGREGATION; YEAST; ALS
AB The functional and structural significance of the intrasubunit disulfide bond in copper-zinc superoxide dismutase (SOD1) was studied by characterizing mutant forms of human SOD1 (hSOD) and yeast SOD1 lacking the disulfide bond. We determined x-ray crystal structures of metal-bound and metal-deficient hC57S SOD1. C57S hSOD1 isolated from yeast contained four zinc ions per protein dimer and was structurally very similar to wild type. The addition of copper to this four-zinc protein gave properly reconstituted 2Cu, 2Zn C57S hSOD, and its spectroscopic properties indicated that the coordination geometry of the copper was remarkably similar to that of holo wild type hSOD1. In contrast, the addition of copper and zinc ions to apo C57S human SOD1 failed to give proper reconstitution. Using pulse radiolysis, we determined SOD activities of yeast and human SOD1s lacking disulfide bonds and found that they were enzymatically active at similar to 10% of the wild type rate. These results are contrary to earlier reports that the intrasubunit disulfide bonds in SOD1 are essential for SOD activity. Kinetic studies revealed further that the yeast mutant SOD1 had less ionic attraction for superoxide, possibly explaining the lower rates. Saccharomyces cerevisiae cells lacking the sod1 gene do not grow aerobically in the absence of lysine, but expression of C57S SOD1 increased growth to 30-50% of the growth of cells expressing wild type SOD1, supporting that C57S SOD1 retained a significant amount of activity.
C1 [Sea, Kevin; Sohn, Se Hui; Durazo, Armando; Sheng, Yuewei; Shaw, Bryan F.; Gralla, Edith Butler; Valentine, Joan Selverstone] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
[Sea, Kevin] Santa Rosa Jr Coll, Dept Wine Studies, Santa Rosa, CA 95401 USA.
[Sohn, Se Hui] LG Chem Ltd, Taejon 305380, South Korea.
[Durazo, Armando] Univ Arizona, Dept Chem & Environm Engn, Tucson, AZ 85721 USA.
[Cabelli, Diane E.] Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA.
[Shaw, Bryan F.] Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA.
[Cao, Xiaohang; Taylor, Alexander B.; Whitson, Lisa J.; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Hart, P. John] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA.
[Valentine, Joan Selverstone] Ewha Womans Univ, Dept Bioinspired Sci, Seoul 120750, South Korea.
RP Sea, K (reprint author), Santa Rosa Jr Coll, Dept Wine Studies, 1501 Mendocino Ave, Santa Rosa, CA 95401 USA.
EM kevinsea@yahoo.com; jsv@chem.ucla.edu
RI Shaw, Bryan/A-7001-2008
FU National Institutes of Health [DK46828, GM28222, GM08496, NS39112];
Veterans Affairs [VA 101 BX00506]; U.S. Department of Energy Division of
Chemical Sciences, Geosciences, and Biosciences [DE-AC02-98CH10886]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK46828 and GM28222 (to J. S. V.), GM08496 (to K. S.), and
NS39112 (to P. J. H.). This work was also supported by Veterans Affairs
Grant VA 101 BX00506 (to P. J. H.) and Contract DE-AC02-98CH10886 from
the U.S. Department of Energy Division of Chemical Sciences,
Geosciences, and Biosciences (to Brookhaven National Laboratory).
NR 63
TC 6
Z9 6
U1 3
U2 27
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JAN 23
PY 2015
VL 290
IS 4
BP 2405
EP 2418
DI 10.1074/jbc.M114.588798
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CA0EH
UT WOS:000348588000043
PM 25433341
ER
PT J
AU Goroll, AH
Hunt, DP
AF Goroll, Allan H.
Hunt, Daniel P.
TI Bridging the Hospitalist-Primary Care Divide through Collaborative Care
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Goroll, Allan H.; Hunt, Daniel P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
RP Goroll, AH (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
NR 5
TC 7
Z9 7
U1 1
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 22
PY 2015
VL 372
IS 4
BP 308
EP 309
DI 10.1056/NEJMp1411416
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AZ4PJ
UT WOS:000348204500005
PM 25607426
ER
PT J
AU Ansell, SM
Lesokhin, AM
Borrello, I
Halwani, A
Scott, EC
Gutierrez, M
Schuster, SJ
Millenson, MM
Cattry, D
Freeman, GJ
Rodig, SJ
Chapuy, B
Ligon, AH
Zhu, LL
Grosso, JF
Kim, SY
Timmerman, JM
Shipp, MA
Armand, P
AF Ansell, Stephen M.
Lesokhin, Alexander M.
Borrello, Ivan
Halwani, Ahmad
Scott, Emma C.
Gutierrez, Martin
Schuster, Stephen J.
Millenson, Michael M.
Cattry, Deepika
Freeman, Gordon J.
Rodig, Scott J.
Chapuy, Bjoern
Ligon, Azra H.
Zhu, Lili
Grosso, Joseph F.
Kim, Su Young
Timmerman, John M.
Shipp, Margaret A.
Armand, Philippe
TI PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's
Lymphoma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; T-CELLS; LYMPHOPROLIFERATIVE DISORDERS;
ANTI-PD-1 ANTIBODY; RESPONSE CRITERIA; PHASE-II; CANCER; SAFETY;
THERAPEUTICS; PIDILIZUMAB
AB BACKGROUND
Preclinical studies suggest that Reed-Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin's lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1-blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma.
METHODS
In this ongoing study, 23 patients with relapsed or refractory Hodgkin's lymphoma that had already been heavily treated received nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks until they had a complete response, tumor progression, or excessive toxic effects. Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 (also called CD274 and PDCD1LG2, respectively) loci and PD-L1 and PD-L2 protein expression.
RESULTS
Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands. Reed-Sternberg cells showed nuclear positivity of phosphorylated STAT3, indicative of active JAK-STAT signaling.
CONCLUSIONS
Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma.
C1 [Ansell, Stephen M.] Mayo Clin, Rochester, MN 55905 USA.
[Lesokhin, Alexander M.; Cattry, Deepika] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Lesokhin, Alexander M.] Weill Cornell Med Coll, New York, NY 10021 USA.
[Borrello, Ivan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Borrello, Ivan] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Halwani, Ahmad] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Scott, Emma C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Scott, Emma C.] Knight Canc Inst, Portland, OR USA.
[Gutierrez, Martin] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Zhu, Lili; Grosso, Joseph F.; Kim, Su Young] Bristol Myers Squibb Co, Lawrenceville, NJ USA.
[Schuster, Stephen J.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Millenson, Michael M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Freeman, Gordon J.; Chapuy, Bjoern; Shipp, Margaret A.; Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Rodig, Scott J.; Ligon, Azra H.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Freeman, Gordon J.; Rodig, Scott J.; Chapuy, Bjoern; Ligon, Azra H.; Shipp, Margaret A.; Armand, Philippe] Harvard Univ, Sch Med, Boston, MA USA.
[Timmerman, John M.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
RP Ansell, SM (reprint author), Mayo Clin, 200 First St SW, Rochester, MN 55905 USA.
EM ansell.stephen@mayo.edu; philippe_armand@dfci.harvard.edu
OI Halwani, Ahmad/0000-0001-6183-6491
FU Bristol-Myers Squibb; National Institutes of Health [U54CA163125,
P01AI056299, R01CA161026]; Miller Fund; Seattle Genetics; Celldex
Therapeutics; Millennium; Idera; Regeneron; Kyowa Hakko Kirin; AbbVie;
Genentech; Ventana/Roche; Bayer; Gilead; Merck; Pharmacyclics; Janssen;
Sanofi Aventis
FX Supported by Bristol-Myers Squibb, by grants from the National
Institutes of Health (U54CA163125 and P01AI056299, to Dr. Freeman; and
R01CA161026, to Dr. Shipp), and by a grant from the Miller Fund (to Dr.
Shipp).; Dr. Ansell reports receiving grant support from Seattle
Genetics, Celldex Therapeutics, Millennium, Idera, and Regeneron; Dr.
Lesokhin, receiving consulting fees and grant support from Bristol-Myers
Squibb; Dr. Halwani, receiving grant support from Seattle Genetics,
Millennium, Kyowa Hakko Kirin, AbbVie, Genentech, and Bristol-Myers
Squibb; Dr. Freeman, receiving royalties from patents related to PD-1,
PD-L1, and PD-L2 pathways (US 6808710, US 6936704, US 7038013,
US7101550, US 7432059, US 7635757, US 7638492, US 7700301, US 7709214,
US 8552154, and US 8652465), which are licensed to Bristol-Myers Squibb,
Roche, Merck, EMD Serono, Boehringer Ingelheim, Amplimmune, and
Novartis; Dr. Rodig, receiving grant support from Bristol-Myers Squibb
and Ventana/Roche and having a pending patent application related to
anti-PD-L1 monoclonal antibodies and fragments (US 61/895,543); Ms. Zhu,
Dr. Grosso, and Dr. Kim, being employees of Bristol-Myers Squibb; Dr.
Timmerman, receiving grant support from Bristol-Myers Squibb; Dr. Shipp,
receiving fees for serving on advisory boards from Bristol-Myers Squibb,
Bayer, Gilead, Merck, Pharmacyclics, and Janssen and receiving grant
support from Bristol-Myers Squibb, Sanofi Aventis, and Bayer; and Dr.
Armand, receiving consulting fees from Merck. No other potential
conflict of interest relevant to this article was reported.
NR 26
TC 595
Z9 622
U1 28
U2 101
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 22
PY 2015
VL 372
IS 4
BP 311
EP 319
DI 10.1056/NEJMoa1411087
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AZ4PJ
UT WOS:000348204500006
PM 25482239
ER
PT J
AU David, WS
Temin, ES
Kraeft, JJ
Hooper, DC
AF David, William S.
Temin, Elizabeth S.
Kraeft, Jessica J.
Hooper, David C.
TI Case 3-2015: A 60-Year-Old Woman with Abdominal Pain, Dyspnea, and
Diplopia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SUCCINYLCHOLINE-INDUCED HYPERKALEMIA; STATES
C1 [David, William S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Temin, Elizabeth S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Kraeft, Jessica J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hooper, David C.] Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA.
[David, William S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Temin, Elizabeth S.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA.
[Kraeft, Jessica J.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Hooper, David C.] Harvard Univ, Sch Med, Dept Infect Dis, Boston, MA USA.
RP David, WS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 6
TC 0
Z9 0
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JAN 22
PY 2015
VL 372
IS 4
BP 364
EP 372
DI 10.1056/NEJMcpc1410936
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AZ4PJ
UT WOS:000348204500012
PM 25607430
ER
PT J
AU Xu, J
Shao, Z
Li, D
Xie, HF
Kim, W
Huang, JL
Taylor, JE
Pinello, L
Glass, K
Jaffe, JD
Yuan, GC
Orkin, SH
AF Xu, Jian
Shao, Zhen
Li, Dan
Xie, Huafeng
Kim, Woojin
Huang, Jialiang
Taylor, Jordan E.
Pinello, Luca
Glass, Kimberly
Jaffe, Jacob D.
Yuan, Guo-Cheng
Orkin, Stuart H.
TI Developmental Control of Polycomb Subunit Composition by GATA Factors
Mediates a Switch to Non-Canonical Functions
SO MOLECULAR CELL
LA English
DT Article
ID HISTONE METHYLTRANSFERASE ACTIVITY; HEMATOPOIETIC STEM-CELLS;
PROSTATE-CANCER; GENE-EXPRESSION; GROUP PROTEINS; LYSINE 27; IN-VIVO;
EZH2; CHROMATIN; COMPLEX
AB Polycomb repressive complex 2 (PRC2) plays crucial roles in transcriptional regulation and stem cell development. However, the context-specific functions associated with alternative subunits remain largely unexplored. Here we show that the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during blood cell development. An erythroid-specific enhancer mediates transcriptional activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental EZH1/2 switch by differential association with EZH1 enhancers. We further examine the in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence of an EZH1-SUZ12 subcomplex lacking EED. EZH1 together with SUZ12 form a non-canonical PRC2 complex, occupy active chromatin, and positively regulate gene expression. Loss of EZH2 expression leads to repositioning of EZH1 to EZH2 targets. Thus, the lineage-and developmental stage-specific regulation of PRC2 subunit composition leads to a switch from canonical silencing to non-canonical functions during blood stem cell specification.
C1 [Xu, Jian; Shao, Zhen; Xie, Huafeng; Kim, Woojin; Huang, Jialiang; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Xu, Jian; Shao, Zhen; Xie, Huafeng; Kim, Woojin; Huang, Jialiang; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Li, Dan] Harvard Univ, Cambridge, MA 02138 USA.
[Huang, Jialiang; Pinello, Luca; Glass, Kimberly; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Taylor, Jordan E.; Jaffe, Jacob D.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Xu, Jian] Univ Texas SW Med Ctr Dallas, Dept Pediat, Childrens Res Inst, Dallas, TX 75390 USA.
[Shao, Zhen] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Computat Biol, CAS MPG Partner Inst Computat Biol, Shanghai 200031, Peoples R China.
RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
EM stuart_orkin@dfci.harvard.edu
FU NIH; NIDDK [K01DK093543, R03DK101665]
FX We thank Sidinh Luc, Cong Peng, Matthew Canver, Daniel Bauer, and
members of the S.H.O. laboratory for assistance and discussion; Ross
Tomaino and Steven Gygi for assistance with proteomics analysis; and
John Stamatoyannopoulos for assistance with DNase-seq. We thank Kambiz
Mousavi and Vittorio Sartorelli for providing the EZH1 antibody, and Ben
van Handel and Hanna Mikkola for providing the fetal liver CD34+ cells.
This work was supported by funding from the NIH (G.-C.Y. and S.H.O.).
S.H.O. is an Investigator of the Howard Hughes Medical Institute (HHMI).
J.X. is supported by NIDDK Career Development Awards K01DK093543 and
R03DK101665.
NR 48
TC 24
Z9 24
U1 2
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD JAN 22
PY 2015
VL 57
IS 2
BP 304
EP 316
DI 10.1016/j.molcel.2014.12.009
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AZ9CC
UT WOS:000348507800010
PM 25578878
ER
PT J
AU Kung, JT
Kesner, B
An, JY
Ahn, JY
Cifuentes-Rojas, C
Colognori, D
Jeon, Y
Szanto, A
del Rosario, BC
Pinter, SF
Erwin, JA
Lee, JT
AF Kung, Johnny T.
Kesner, Barry
An, Jee Young
Ahn, Janice Y.
Cifuentes-Rojas, Catherine
Colognori, David
Jeon, Yesu
Szanto, Attila
del Rosario, Brian C.
Pinter, Stefan F.
Erwin, Jennifer A.
Lee, Jeannie T.
TI Locus-Specific Targeting to the X Chromosome Revealed by the RNA
Interactome of CTCF
SO MOLECULAR CELL
LA English
DT Article
ID BINDING PROTEINS; CHROMATIN INTERACTIONS; GENE-EXPRESSION; SEQ
EXPERIMENTS; INACTIVATION; GENOME; CLIP; DNA; IDENTIFICATION;
TRANSCRIPTION
AB CTCF is a master regulator that plays important roles in genome architecture and gene expression. How CTCF is recruited in a locus-specific manner is not fully understood. Evidence from epigenetic processes, such as X chromosome inactivation (XCI), indicates that CTCF associates functionally with RNA. Using genome-wide approaches to investigate the relationship between its RNA interactome and epigenomic landscape, here we report that CTCF binds thousands of transcripts in mouse embryonic stem cells, many in close proximity to CTCF's genomic binding sites. CTCF is a specific and high-affinity RNA-binding protein (K-d < 1 nM). During XCI, CTCF differentially binds the active and inactive X chromosomes and interacts directly with Tsix, Xite, and Xist RNAs. Tsix and Xite RNAs target CTCF to the X inactivation center, thereby inducing homologous X chromosome pairing. Our work elucidates one mechanism by which CTCF is recruited in a locus-specific manner and implicates CTCF-RNA interactions in long-range chromosomal interactions.
C1 [Kung, Johnny T.; Kesner, Barry; An, Jee Young; Ahn, Janice Y.; Cifuentes-Rojas, Catherine; Colognori, David; Jeon, Yesu; Szanto, Attila; del Rosario, Brian C.; Pinter, Stefan F.; Erwin, Jennifer A.; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Kung, Johnny T.; Kesner, Barry; An, Jee Young; Ahn, Janice Y.; Cifuentes-Rojas, Catherine; Colognori, David; Jeon, Yesu; Szanto, Attila; del Rosario, Brian C.; Pinter, Stefan F.; Erwin, Jennifer A.; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Kung, Johnny T.; Kesner, Barry; An, Jee Young; Ahn, Janice Y.; Cifuentes-Rojas, Catherine; Colognori, David; Jeon, Yesu; Szanto, Attila; del Rosario, Brian C.; Pinter, Stefan F.; Erwin, Jennifer A.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ahn, Janice Y.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu
OI Pinter, Stefan/0000-0003-4750-1403; Ahn, Janice/0000-0003-3625-9906
FU Natural Sciences and Engineering Research Council of Canada; Michael and
Anna Vranos Fellowship for the Life Sciences; NSF; NIH [F32-GM101828,
RO1-GM58839]
FX We thank all lab members for helpful advice and many important
discussions. We also give special thanks to C.T. Wu, S. Buratowski, R.
Reed, W. Bender, M. Blower, and P. Garrity for valuable advice during
the thesis work of J.T.K, and C.T. Wu, R. Losick, and N. Francis during
the thesis work of J.Y. Ahn. We acknowledge Exiqon Corporation for
design of LNA oligonucleotides. This work was supported by a
Postgraduate Scholarship from the Natural Sciences and Engineering
Research Council of Canada (to J.T.K), a Michael and Anna Vranos
Fellowship for the Life Sciences (to J.Y. Ahn), an NSF graduate
fellowship (to J.A.E.), and NIH grants F32-GM101828 (to C.C.R.) and
RO1-GM58839 (to J.T.L.). J.T.L. is an Investigator of the Howard Hughes
Medical Institute.
NR 61
TC 27
Z9 27
U1 1
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD JAN 22
PY 2015
VL 57
IS 2
BP 361
EP 375
DI 10.1016/j.molcel.2014.12.006
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AZ9CC
UT WOS:000348507800015
PM 25578877
ER
PT J
AU Savar, A
Acin, S
Gonzalez, CL
El-Sawy, T
Mejia, O
Li, Z
Esmaeli, B
Lacy-Hulbert, A
El-Naggar, AK
McCarty, JH
Caulin, C
AF Savar, A.
Acin, S.
Gonzalez, C. L.
El-Sawy, T.
Mejia, O.
Li, Z.
Esmaeli, B.
Lacy-Hulbert, A.
El-Naggar, A. K.
McCarty, J. H.
Caulin, C.
TI Loss of epithelial p53 and alpha v integrin cooperate through Akt to
induce squamous cell carcinoma yet prevent remodeling of the tumor
microenvironment
SO ONCOGENE
LA English
DT Article
DE p53; squamous cell carcinoma; mouse model; integrins; tumor
microenvironment
ID GAIN-OF-FUNCTION; ONCOGENIC K-RAS; SKIN-CANCER; ORGAN-TRANSPLANTATION;
MOUSE MODEL; EXPRESSION; MUTATIONS; KERATINOCYTES; DIFFERENTIATION;
INACTIVATION
AB Most of the squamous cell carcinomas (SCCs) of the skin and head and neck contain p53 mutations. The presence of p53 mutations in premalignant lesions suggests that they represent early events during tumor progression and additional alterations may be required for SCC development. Here we show that codeletion of the p53 and alpha v integrin genes in mouse stratified epithelia induced SCCs in 100% of the mice, more frequently and with much shorter latency than deletion of either gene alone. The SCCs that lacked p53 and alpha v in the epithelial tumor cells exhibited high Akt activity, lacked multiple types of infiltrating immune cells, contained a defective vasculature and grew slower than tumors that expressed p53 or alpha v. These results reveal that loss of alpha v in epithelial cells that lack p53 promotes SCC development, but also prevents remodeling of the tumor microenvironment and delays tumor growth. We observed that Akt inactivation in SCC cells that lack p53 and alpha v promoted anoikis. Thus, tumors may arise in these mice as a result of the increased cell survival induced by Akt activation triggered by loss of alpha v and p53, and by the defective recruitment of immune cells to these tumors, which may allow immune evasion. However, the defective vasculature and lack of a supportive stroma create a restrictive microenvironment in these SCCs that slows their growth. These mechanisms may underlie the rapid onset and slow growth of SCCs that lack p53 and alpha v.
C1 [Savar, A.; Acin, S.; Gonzalez, C. L.; El-Sawy, T.; Mejia, O.; Li, Z.; Esmaeli, B.; Caulin, C.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
[Lacy-Hulbert, A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[El-Naggar, A. K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[McCarty, J. H.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA.
[Caulin, C.] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
RP Caulin, C (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Unit 123, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM ccaulin@mdanderson.org
FU National Institutes of Health [DE015344]; Pilot Project grant from the
American Cancer Society Institutional Research Grant Program; National
Institutes of Health through Cancer Center Support Grant [CA16672]
FX We thank Dennis Roop for the K14.CrePR1 mice, Anton Berns for the floxed
p53 mice and Sarah Bronson and Dawn Chalaire for editorial assistance.
This study was supported by the National Institutes of Health through
Grant DE015344 (C Caulin) and a Pilot Project grant from the American
Cancer Society Institutional Research Grant Program (JH McCarty).
Veterinary services and core facilities at The University of Texas MD
Anderson Cancer Center were supported in part by the National Institutes
of Health through Cancer Center Support Grant CA16672.
NR 41
TC 4
Z9 4
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JAN 22
PY 2015
VL 34
IS 4
BP 516
EP 524
DI 10.1038/onc.2013.585
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AZ8FU
UT WOS:000348451300012
PM 24469034
ER
PT J
AU Korn, D
AF Korn, David
TI Indirect costs: cash is no gravy train
SO NATURE
LA English
DT Letter
C1 [Korn, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Korn, David] Harvard Univ, Sch Med, Boston, MA USA.
RP Korn, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM david_korn@harvard.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JAN 22
PY 2015
VL 517
IS 7535
BP 438
EP 438
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ4MU
UT WOS:000348196500017
PM 25612045
ER
PT J
AU Tasnim, M
Ma, SN
Yang, EW
Jiang, T
Li, W
AF Tasnim, Masruba
Ma, Shining
Yang, Ei-Wen
Jiang, Tao
Li, Wei
TI Accurate inference of isoforms from multiple sample RNA-Seq data
SO BMC GENOMICS
LA English
DT Article
ID FUNCTIONAL ELEMENTS; SPLICE JUNCTIONS; IDENTIFICATION; REVEALS; GENOME;
QUANTIFICATION; TRANSCRIPTOMES; PROJECT; READS
AB Background: RNA-Seq based transcriptome assembly has become a fundamental technique for studying expressed mRNAs (i.e., transcripts or isoforms) in a cell using high-throughput sequencing technologies, and is serving as a basis to analyze the structural and quantitative differences of expressed isoforms between samples. However, the current transcriptome assembly algorithms are not specifically designed to handle large amounts of errors that are inherent in real RNA-Seq datasets, especially those involving multiple samples, making downstream differential analysis applications difficult. On the other hand, multiple sample RNA-Seq datasets may provide more information than single sample datasets that can be utilized to improve the performance of transcriptome assembly and abundance estimation, but such information remains overlooked by the existing assembly tools.
Results: We formulate a computational framework of transcriptome assembly that is capable of handling noisy RNA-Seq reads and multiple sample RNA-Seq datasets efficiently. We show that finding an optimal solution under this framework is an NP-hard problem. Instead, we develop an efficient heuristic algorithm, called Iterative Shortest Path (ISP), based on linear programming (LP) and integer linear programming (ILP). Our preliminary experimental results on both simulated and real datasets and comparison with the existing assembly tools demonstrate that (i) the ISP algorithm is able to assemble transcriptomes with a greatly increased precision while keeping the same level of sensitivity, especially when many samples are involved, and (ii) its assembly results help improve downstream differential analysis.
C1 [Tasnim, Masruba; Ma, Shining; Yang, Ei-Wen; Jiang, Tao; Li, Wei] Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92507 USA.
[Ma, Shining; Jiang, Tao] Tsinghua Univ, MOE Key Lab Bioinformat, TNLIST, Dept Automat, Beijing 100084, Peoples R China.
[Ma, Shining] Tsinghua Univ, Bioinformat Div, TNLIST, Dept Automat, Beijing 100084, Peoples R China.
[Jiang, Tao] Tsinghua Univ, Bioinformat Div, TNLIST, Dept Comp Sci & Technol, Beijing 100084, Peoples R China.
[Li, Wei] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Li, Wei] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Jiang, T (reprint author), Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92507 USA.
EM jiang@cs.ucr.edu; wli@jimmy.harvard.edu
FU National Science Foundation [DBI-1262107]
FX The research was partially supported by National Science Foundation
grant DBI-1262107.
NR 31
TC 2
Z9 2
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JAN 21
PY 2015
VL 16
SU 2
AR S15
DI 10.1186/1471-2164-16-S2-S15
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CH4CL
UT WOS:000353978900015
PM 25708199
ER
PT J
AU Hu, ZT
Vashlishan-Murray, AB
Kaplan, JM
AF Hu, Zhitao
Vashlishan-Murray, Amy B.
Kaplan, Joshua M.
TI NLP-12 Engages Different UNC-13 Proteins to Potentiate Tonic and Evoked
Release
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE C. elegans; CCK; Munc13; neuropeptide; NLP-12; UNC-13
ID ELEGANS NEUROMUSCULAR-JUNCTION; SHORT-TERM PLASTICITY; NEUROTRANSMITTER
RELEASE; CAENORHABDITIS-ELEGANS; SYNAPTIC-TRANSMISSION; C-ELEGANS;
VESICLE DOCKING; ACTIVE ZONES; G(Q)ALPHA; MUNC13-1
AB A neuropeptide (NLP-12) and its receptor (CKR-2) potentiate tonic and evoked ACh release at Caenorhabditis elegans neuromuscular junctions. Increased evoked release is mediated by a presynaptic pathway (egl-30 G alpha(q) and egl-8 PLC beta) that produces DAG, and by DAG binding to short and long UNC-13 proteins. Potentiation of tonic ACh release persists in mutants deficient for egl-30 G alpha(q) and egl-8 PLC beta and requires DAG binding to UNC-13L (but not UNC-13S). Thus, NLP-12 adjusts tonic and evoked release by distinct mechanisms.
C1 [Hu, Zhitao; Vashlishan-Murray, Amy B.; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Hu, Zhitao; Vashlishan-Murray, Amy B.; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Vashlishan-Murray, Amy B.] Emerson Coll, Dept Commun Sci & Disorders, Boston, MA 02116 USA.
RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg,7th Floor,185 Cambridge St, Boston, MA 02114 USA.
EM kaplan@molbio.mgh.harvard.edu
FU National Institutes of Health [GM54728]
FX This work was supported by a National Institutes of Health research
grant (GM54728 to J.K.). We thank members of the Kaplan lab for critical
comments on this manuscript. Some strains were provided by the C.
elegans Genetics Stock Center.
NR 44
TC 1
Z9 1
U1 0
U2 0
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 21
PY 2015
VL 35
IS 3
BP 1038
EP 1042
DI 10.1523/JNEUROSCI.2825-14.2015
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA CB1TU
UT WOS:000349411700017
PM 25609620
ER
PT J
AU Lee, HG
Milner, PJ
Placzek, MS
Buchwald, SL
Hooker, JM
AF Lee, Hong Geun
Milner, Phillip J.
Placzek, Michael S.
Buchwald, Stephen L.
Hooker, Jacob M.
TI Virtually Instantaneous, Room-Temperature [C-11]-Cyanation Using Biaryl
Phosphine Pd(0) Complexes
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PALLADIUM-CATALYZED CYANATION; RECEPTOR ANTAGONIST; PET; C-11
AB A new radiosynthetic protocol for the preparation of [C-11]aryl nitriles has been developed. This process is based on the direct reaction of in situ prepared L Pd(Ar)X complexes (L = biaryl phosphine) with [C-11]HCN. The strategy is operationally simple, exhibits a remarkably wide substrate scope with short reaction times, and demonstrates superior reactivity compared to previously reported systems. With this procedure, a variety of [C-11]nitrile-containing pharmaceuticals were prepared with high radiochemical efficiency.
C1 [Lee, Hong Geun; Milner, Phillip J.; Buchwald, Stephen L.] MIT, Cambridge, MA 02139 USA.
[Placzek, Michael S.; Hooker, Jacob M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Placzek, Michael S.; Hooker, Jacob M.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Hooker, Jacob M.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
RP Buchwald, SL (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM sbuchwal@mit.edu; hooker@nmr.mgh.harvard.edu
FU National Institutes of Health [GM46059]; National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health [P41EB015896]; National Institutes of Health Shared
Instrumentation Grant Program; High-End Instrumentation Grant Program
[S10RR017208, S10RR026666]; National Science Foundation [2010094243];
NIH-NIDA [2T32DA015036]
FX Research reported in this publication was supported by the National
Institutes of Health (GM46059). A portion of this research was carried
out at the Athinoula A. Martinos Center for Biomedical Imaging at the
Massachusetts General Hospital, using resources provided by the Center
for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional
Resource supported by the National Institute of Biomedical Imaging and
Bioengineering (NIBIB), National Institutes of Health. This work also
involved the use of instrumentation supported by the National Institutes
of Health Shared Instrumentation Grant Program and/or High-End
Instrumentation Grant Program (S10RR017208 and S10RR026666). The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
P.J.M. thanks the National Science Foundation for a predoctoral
fellowship (2010094243). We also thank Amgen for an educational
donation. M.S.P. thanks NIH-NIDA for a postdoctoral fellowship
(2T32DA015036). Technical assistance from Nathaniel Schauer, Judit Sore,
and Dr. Ramesh Neelamegam (MGH/HST) is appreciated. We are grateful to
Dr. Todd Senecal (MIT) for performing preliminary experiments.
NR 18
TC 6
Z9 6
U1 1
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JAN 21
PY 2015
VL 137
IS 2
BP 648
EP 651
DI 10.1021/ja5121155
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8RX
UT WOS:000348483400025
PM 25565277
ER
PT J
AU Santillan-Hernandez, Y
Almanza-Miranda, E
Xin, WW
Goss, K
Vera-Loaiza, A
Gorraez-de la Mora, MT
Pina-Aguilar, RE
AF Santillan-Hernandez, Yuritzi
Almanza-Miranda, Enory
Xin, Winnie W.
Goss, Kendrick
Vera-Loaiza, Aurea
Gorraez-de la Mora, Maria T.
Pina-Aguilar, Raul E.
TI Novel LIPA mutations in Mexican siblings with lysosomal acid lipase
deficiency
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Cholesteryl ester storage disease; Liver fibrosis; Dyslipidemia; Liver
steatosis; Wolman disease
ID ESTER STORAGE DISEASE
AB Lysosomal acid lipase (LAL) deficiency is an under-recognized lysosomal disease caused by deficient enzymatic activity of LAL. In this report we describe two affected female Mexican siblings with early hepatic complications. At two months of age, the first sibling presented with alternating episodes of diarrhea and constipation, and later with hepatomegaly, elevated transaminases, high levels of total and low-density lipoprotein cholesterol, and low levels of high-density lipoprotein. Portal hypertension and grade 2 esophageal varices were detected at four years of age. The second sibling presented with hepatomegaly, elevated transaminases and mildly elevated low-density lipoprotein and low high-density lipoprotein at six months of age. LAL activity was deficient in both patients. Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4: c. 253C>A and c. 294C>G. These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease, and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.
C1 [Santillan-Hernandez, Yuritzi; Vera-Loaiza, Aurea] ISSSTE, Ctr Med Nacl Noviembre 20, Dept Med Genet, Mexico City 03100, DF, Mexico.
[Almanza-Miranda, Enory] ISSSTE, Ctr Med Nacl Noviembre 20, Dept Pediat Gastroenterol, Mexico City 03229, DF, Mexico.
[Xin, Winnie W.; Goss, Kendrick] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA.
[Gorraez-de la Mora, Maria T.] ISSSTE, Ctr Med Nacl Noviembre 20, Dept Pathol, Mexico City 03100, DF, Mexico.
[Pina-Aguilar, Raul E.] ISSSTE, Ctr Med Nacl Noviembre 20, Med Genom Div, Mexico City 03100, DF, Mexico.
RP Pina-Aguilar, RE (reprint author), ISSSTE, Ctr Med Nacl Noviembre 20, Med Genom Div, San Lorenzo 502D,Col Valle, Mexico City 03100, DF, Mexico.
EM rpina.a@hotmail.com
OI Pina-Aguilar, Raul/0000-0002-2043-4282
NR 21
TC 0
Z9 0
U1 0
U2 0
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1007-9327
EI 2219-2840
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD JAN 21
PY 2015
VL 21
IS 3
BP 1001
EP 1008
DI 10.3748/wjg.v21.i3.1001
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AZ7TA
UT WOS:000348419400031
PM 25624737
ER
PT J
AU Hurwitz, M
Williams, CL
Mishra, P
Rottmann, J
Dhou, S
Wagar, M
Mannarino, EG
Mak, RH
Lewis, JH
AF Hurwitz, Martina
Williams, Christopher L.
Mishra, Pankaj
Rottmann, Joerg
Dhou, Salam
Wagar, Matthew
Mannarino, Edward G.
Mak, Raymond H.
Lewis, John H.
TI Generation of fluoroscopic 3D images with a respiratory motion model
based on an external surrogate signal
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE respiration; lung motion; radiation therapy planning
ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; GATED RADIOTHERAPY;
RADIATION-THERAPY; XCAT PHANTOM; PATIENT DATA; TUMOR SIZE;
RECONSTRUCTION; ACQUISITION; SIMULATION; PROJECTION
AB Respiratory motion during radiotherapy can cause uncertainties in definition of the target volume and in estimation of the dose delivered to the target and healthy tissue. In this paper, we generate volumetric images of the internal patient anatomy during treatment using only the motion of a surrogate signal. Pre-treatment four-dimensional CT imaging is used to create a patient-specific model correlating internal respiratory motion with the trajectory of an external surrogate placed on the chest. The performance of this model is assessed with digital and physical phantoms reproducing measured irregular patient breathing patterns. Ten patient breathing patterns are incorporated in a digital phantom. For each patient breathing pattern, the model is used to generate images over the course of thirty seconds. The tumor position predicted by the model is compared to ground truth information from the digital phantom. Over the ten patient breathing patterns, the average absolute error in the tumor centroid position predicted by the motion model is 1.4 mm. The corresponding error for one patient breathing pattern implemented in an anthropomorphic physical phantom was 0.6 mm. The global voxel intensity error was used to compare the full image to the ground truth and demonstrates good agreement between predicted and true images. The model also generates accurate predictions for breathing patterns with irregular phases or amplitudes.
C1 [Hurwitz, Martina] Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Hurwitz, M (reprint author), Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA.
EM martinah@gmail.com; jhlewis@lroc.harvard.edu
FU Varian Medical Systems, Inc.; Radiological Society of North America
Research Scholar Grant [RSCH1206]
FX The authors would like to thank Dr S Nishioka of the Department of
Radiology, NTT Hospital, Sapporo, Japan, Dr H Shirato of the Department
of Radiation Medicine, Hokkaido University School of Medicine, Sapporo,
Japan, and Dr R Berbeco of Brigham and Women's Hospital, Boston, MA for
sharing the patient tumor motion dataset with us. This project was
supported, in part, through a Master Research Agreement with Varian
Medical Systems, Inc. and Radiological Society of North America Research
Scholar Grant #RSCH1206.
NR 28
TC 2
Z9 2
U1 1
U2 1
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JAN 21
PY 2015
VL 60
IS 2
BP 521
EP 535
DI 10.1088/0031-9155/60/2/521
PG 15
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA AY6KL
UT WOS:000347675100006
PM 25548999
ER
PT J
AU Grassberger, C
Lomax, A
Paganetti, H
AF Grassberger, C.
Lomax, Anthony
Paganetti, H.
TI Characterizing a proton beam scanning system for Monte Carlo dose
calculation in patients
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE active scanning proton therapy; Monte Carlo simulation; patient dose
calculation
ID RANGE UNCERTAINTIES; THERAPY; TOPAS
AB The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI).
Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction.
To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.
C1 [Grassberger, C.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Grassberger, C.; Lomax, Anthony] Harvard Univ, Sch Med, Boston, MA 02114 USA.
Paul Scherrer Inst, Ctr Proton Radiotherapy, CH-5232 Villigen, Switzerland.
RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
EM Grassberger.Clemens@mgh.harvard.edu
FU National Cancer Institute Grant [R01CA111590]
FX The authors would like to acknowledge Dr Ben Clasie for sharing his
knowledge about active scanning proton delivery systems, Dr Thomas
Bortfeld for fruitful discussions concerning his analytical Bragg peak
model and Dr Jon Jackson and Partners Research Computing for maintenance
of the computing cluster. This work was supported by National Cancer
Institute Grant R01CA111590.
NR 20
TC 10
Z9 10
U1 1
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JAN 21
PY 2015
VL 60
IS 2
BP 633
EP 645
DI 10.1088/0031-9155/60/2/633
PG 13
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA AY6KL
UT WOS:000347675100012
PM 25549079
ER
PT J
AU Copik, AJ
Baldys, A
Nguyen, K
Sahdeo, S
Ho, H
Kosaka, A
Dietrich, PJ
Fitch, B
Raymond, JR
Ford, APDW
Button, D
Milla, ME
AF Copik, Alicja J.
Baldys, Aleksander
Nguyen, Khanh
Sahdeo, Sunil
Ho, Hoangdung
Kosaka, Alan
Dietrich, Paul J.
Fitch, Bill
Raymond, John R.
Ford, Anthony P. D. W.
Button, Donald
Milla, Marcos E.
TI Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that
Selectively Activates the MAPK/ERK Pathway
SO PLOS ONE
LA English
DT Article
ID PROTEIN-KINASE PATHWAYS; PAROTID ACINAR-CELLS; ALPHA(1)-ADRENERGIC
RECEPTOR SUBTYPES; BETA-ADRENERGIC-RECEPTORS; TRANSFECTED PC12 CELLS;
BETA(2)-ADRENERGIC RECEPTOR; ALPHA(1A)-ADRENERGIC RECEPTORS;
INTERNALIZATION PROPERTIES; SYMPATHOMIMETIC AMINES; FUNCTIONAL
SELECTIVITY
AB The alpha(1A)-AR is thought to couple predominantly to the G alpha(q)/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with G alpha(q) coupling-defective variants of alpha(1A)-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between alpha(1A)-AR and beta(2)-AR that leads to potentiation of a G alpha(q)-independent signaling cascade in response to alpha(1A)-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as beta-AR-selective agonist, was examined with respect to activation of alpha(1A)-AR. alpha(1A)-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at alpha(1A)-AR. Iso induced signaling at alpha(1A)-AR was further interrogated by probing steps along the G alpha(q)/PLC, G alpha(s) and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with alpha(1A)-AR, and CHO_alpha(1A)-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by alpha(1A)-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical G alpha(q)-mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of alpha(1A)-AR partial agonist with signaling bias toward MAPK/ERK signaling cascade that is likely independent of coupling to G alpha(q).
C1 [Copik, Alicja J.; Sahdeo, Sunil; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.] Roche Palo Alto LLC, Biochem Pharmacol Inflammat Discovery, Palo Alto, CA 94304 USA.
[Nguyen, Khanh; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill] Roche Palo Alto LLC, Discovery Technol, Palo Alto, CA 94304 USA.
[Baldys, Aleksander; Raymond, John R.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
[Baldys, Aleksander; Raymond, John R.] Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29425 USA.
RP Milla, ME (reprint author), Roche Palo Alto LLC, Biochem Pharmacol Inflammat Discovery, 3401 Hillview Dr, Palo Alto, CA 94304 USA.
EM mmilla22@its.jnj.com
FU Department of Veterans Affairs Merit and Research Enhancement Award
Program grants; National Institutes of Health [DK052448, GM063909];
Medical University of South Carolina Division of Nephrology, and
Dialysis Clinics, Inc.; Roche Palo Alto LLC
FX Most of this work was performed at Roche Palo Alto LLC.
Immunofluorescence microscopy studies were performed with support from
the Department of Veterans Affairs Merit and Research Enhancement Award
Program grants, by National Institutes of Health Grants DK052448 and
GM063909, by laboratory endowment jointly supported by the Medical
University of South Carolina Division of Nephrology, and Dialysis
Clinics, Inc. (to JRR). Roche Palo Alto LLC, the funder, provided
support in the form of salaries for authors AJC, KN, SS, HH, AK, PJD,
BF, APDWF, DB and MEM, but did not have any additional role in the study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. The specific roles of these authors are
articulated in the 'author contributions' section.
NR 69
TC 2
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U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 21
PY 2015
VL 10
IS 1
AR e0115701
DI 10.1371/journal.pone.0115701
PG 31
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ4PR
UT WOS:000348205300018
PM 25606852
ER
PT J
AU Penagarikano, O
Lazaro, MT
Lu, XH
Gordon, A
Dong, HM
Lam, HA
Peles, E
Maidment, NT
Murphy, NP
Yang, XW
Golshani, P
Geschwind, DH
AF Penagarikano, Olga
Lazaro, Maria T.
Lu, Xiao-Hong
Gordon, Aaron
Dong, Hongmei
Lam, Hoa A.
Peles, Elior
Maidment, Nigel T.
Murphy, Niall P.
Yang, X. William
Golshani, Peyman
Geschwind, Daniel H.
TI Exogenous and evoked oxytocin restores social behavior in the Cntnap2
mouse model of autism
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID RECEPTOR GENE OXTR; SPECTRUM DISORDER; PLASMA OXYTOCIN; PRAIRIE VOLES;
AFFILIATIVE BEHAVIOR; MICROTUS-OCHROGASTER; HYPERPHAGIC OBESITY; MICE;
VASOPRESSIN; RELEASE
AB Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the para-ventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit.
C1 [Penagarikano, Olga; Lazaro, Maria T.; Dong, Hongmei; Golshani, Peyman; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA.
[Penagarikano, Olga; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Autism Res & Treament, Los Angeles, CA 90095 USA.
[Penagarikano, Olga; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Lu, Xiao-Hong; Yang, X. William; Geschwind, Daniel H.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Gordon, Aaron; Peles, Elior] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Lam, Hoa A.; Maidment, Nigel T.; Murphy, Niall P.] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Golshani, Peyman] Univ Calif Los Angeles, Integrat Ctr Learning & Memory, Los Angeles, CA 90095 USA.
[Golshani, Peyman] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA.
RP Geschwind, DH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Program Neurogenet, Dept Neurol, Los Angeles, CA 90095 USA.
EM dhg@ucla.edu
OI Penagarikano, Olga/0000-0001-8153-8221
FU NIH/National Institute of Mental Health (NIMH) [R01 MH081754-02R,
NIH/NS50220]; NIH Autism Centers of Excellence (ACE) (Project II)
[1P50-HD055784-01]; Simons Foundation Autism Research Initiative; UCLA
Center for Autism Research and Treatment (CART) Pilot Grant; Autism
Speaks grant in translational research [7657]; NIH/National Institute of
Neurological Disorders and Stroke (NINDS) [R01 NS049501, R01 NS074312];
McKnight Foundation; [5R01-MH081754-04]
FX This work was supported by grants NIH/National Institute of Mental
Health (NIMH) R01 MH081754-02R to D.H.G., NIH/NS50220 to E.P., NIH
Autism Centers of Excellence (ACE) 1P50-HD055784-01 to D.H.G. (Project
II), Network grant 5R01-MH081754-04 to D.H.G., Simons Foundation Autism
Research Initiative to E.P. and D.H.G., UCLA Center for Autism Research
and Treatment (CART) Pilot Grant to N.T.M. and N.P.M., and Autism Speaks
grant in translational research 7657 to O.P. X.W.Y. is supported by the
NIH/National Institute of Neurological Disorders and Stroke (NINDS)
grants R01 NS049501 and R01 NS074312, and the Brain Disorder Award from
McKnight Foundation.
NR 76
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U1 4
U2 32
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JAN 21
PY 2015
VL 7
IS 271
AR 271ra8
DI 10.1126/scitranslmed.3010257
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AZ6TS
UT WOS:000348353900002
PM 25609168
ER
PT J
AU Chen, XQ
Wales, P
Quinti, L
Zuo, FX
Moniot, S
Herisson, F
Rauf, NA
Wang, H
Silverman, RB
Ayata, C
Maxwell, MM
Steegborn, C
Schwarzschild, MA
Outeiro, TF
Kazantsev, AG
AF Chen, Xiqun
Wales, Pauline
Quinti, Luisa
Zuo, Fuxing
Moniot, Sebastien
Herisson, Fanny
Rauf, Nazifa Abdul
Wang, Hua
Silverman, Richard B.
Ayata, Cenk
Maxwell, Michelle M.
Steegborn, Clemens
Schwarzschild, Michael A.
Outeiro, Tiago F.
Kazantsev, Aleksey G.
TI The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson's
Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia
SO PLOS ONE
LA English
DT Article
ID MOUSE MODEL; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; SIRT2; DEACETYLASE;
ALS; PROTEIN; NEURODEGENERATION; POLYMORPHISM; GENERATION
AB Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkinson's disease, amyotrophic lateral sclerosis and cerebral ischemia. Our results demonstrate that AK7 is neuroprotective in models of Parkinson's disease; it ameliorates alpha-synuclein toxicity in vitro and prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion and dopaminergic neuron loss in vivo. The compound does not show beneficial effects in mouse models of amyotrophic lateral sclerosis and cerebral ischemia. These findings underscore the specificity of protective effects observed here in models of Parkinson's disease, and previously in Huntington's disease, and support the development of SIRT2 inhibitors as potential therapeutics for the two neurodegenerative diseases.
C1 [Chen, Xiqun; Quinti, Luisa; Zuo, Fuxing; Herisson, Fanny; Rauf, Nazifa Abdul; Ayata, Cenk; Maxwell, Michelle M.; Schwarzschild, Michael A.; Kazantsev, Aleksey G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA.
[Wales, Pauline; Outeiro, Tiago F.] Univ Med Ctr Goettingen, Ctr Nanoscale Microscopy & Mol Physiol Brain, Dept NeuroDegenerat & Restorat Res, D-37073 Gottingen, Germany.
[Moniot, Sebastien; Steegborn, Clemens] Univ Bayreuth, Dept Biochem, D-95447 Bayreuth, Germany.
[Wang, Hua; Silverman, Richard B.] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Chem,Dept Mol Biosci, Evanston, IL 60208 USA.
RP Chen, XQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA.
EM xchen17@mgh.harvard.edu; AKAZANTSEV@mgh.harvard.edu
FU NIH [U01-NS066912]; RJG foundation [2011D004473]; DFG Center of
Excellence on Nanoscale Microscopy and Molecular Physiology of the Brain
FX This work was supported by grants from the NIH U01-NS066912
(http://grants.nih.gov/grants/funding/ac_search_results.htm?text_curr =
u01), RJG foundation 2011D004473 (no website), and DFG Center of
Excellence on Nanoscale Microscopy and Molecular Physiology of the Brain
(http://grc.unigoettingen.de/89.html). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 39
TC 19
Z9 19
U1 3
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 21
PY 2015
VL 10
IS 1
AR UNSP e0116919
DI 10.1371/journal.pone.0116919
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ4PR
UT WOS:000348205300044
ER
PT J
AU Bendell, JC
Powderly, JD
Lieu, CH
Eckhardt, SG
Hurwitz, H
Hochster, HS
Murphy, JE
Funke, RP
Rossi, C
Wallin, J
Waterkamp, D
Pishvaian, MJ
AF Bendell, Johanna C.
Powderly, John D.
Lieu, Christopher Hanyoung
Eckhardt, S. Gail
Hurwitz, Herbert
Hochster, Howard S.
Murphy, Janet E.
Funke, Roel Peter
Rossi, Cheryl
Wallin, Jeffrey
Waterkamp, Daniel
Pishvaian, Michael J.
TI Safety and efficacy of MPDL3280A (anti-PDL1) in combination with
bevacizumab (bev) and/or FOLFOX in patients (pts) with metastatic
colorectal cancer (mCRC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA.
Carolina BioOncol Inst, Huntersville, NC USA.
Univ Colorado, Denver, CO 80202 USA.
Univ Colorado, Sch Med, Aurora, CO USA.
Duke Univ, Med Ctr, Durham, NC USA.
Yale Univ, Sch Med, Dept Med Oncol, New Haven, CT USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Genentech Inc, San Francisco, CA 94080 USA.
F Hoffmann La Roche Ltd, Basel, Switzerland.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 704
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800699
ER
PT J
AU Castillo, JJ
Glezerman, I
Boklage, S
Chiodo, J
Schulman, KL
AF Castillo, Jorge J.
Glezerman, Ilya
Boklage, Susan
Chiodo, Joseph
Schulman, Kathy L.
TI Incidence of hyponatremia in a cohort of patients with colorectal cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Weill Cornell Med Coll, New York, NY USA.
Otsuka Amer Pharmaceut Inc, Princeton, NJ USA.
Outcomes Res Solutions Inc, Shrewsbury, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 545
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800542
ER
PT J
AU Chong, DQ
Mehta, R
Song, MY
Kedrin, D
Meyerhardt, JA
Ng, K
Wu, K
Ogino, S
Fuchs, CS
Giovannucci, EL
Chan, AT
AF Chong, Dawn Q.
Mehta, Raaj
Song, Mingyang
Kedrin, Dmitriy
Meyerhardt, Jeffrey A.
Ng, Kimmie
Wu, Kana
Ogino, Shuji
Fuchs, Charles S.
Giovannucci, Edward L.
Chan, Andrew T.
TI Prediagnostic plasma adiponectin and survival among patients with
colorectal cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Natl Canc Ctr, Singapore, Singapore.
Harvard Univ, Sch Med, Boston, MA USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Channing Labs, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, TH Chan Sch Publ Hlth, Sch Med, Boston, MA 02115 USA.
RI Song, Mingyang/M-6701-2013
OI Song, Mingyang/0000-0002-1324-0316
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 526
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800523
ER
PT J
AU Coart, E
Saad, ED
Shi, Q
Sommeijer, DW
Zalcberg, JR
Maughan, T
Goldberg, RM
Schmoll, HJ
Punt, CJA
Van Cutsem, E
Douillard, JY
Hoff, PM
Tebbutt, NC
Fuchs, CS
Falcone, A
Tournigand, C
De Gramont, A
Sargent, DJ
Burzykowski, T
Buyse, ME
AF Coart, Elisabeth
Saad, Everardo D.
Shi, Qian
Sommeijer, Dirkje Willemien
Zalcberg, John Raymond
Maughan, Tim
Goldberg, Richard M.
Schmoll, Hans-Joachim
Punt, Cornelis J. A.
Van Cutsem, Eric
Douillard, Jean-Yves
Hoff, Paulo Marcelo
Tebbutt, Niall C.
Fuchs, Charles S.
Falcone, Alfredo
Tournigand, Christophe
De Gramont, Aimery
Sargent, Daniel J.
Burzykowski, Tomasz
Buyse, Marc E.
CA ARCAD Grp
TI Trial-level association between response-based endpoints (RBEs) and
progression-free (PFS)/overall survival (OS) in first-line therapy for
metastatic colorectal cancer (mCRC) in the ARCAD database.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Int Inst Drug Dev, Louvain, Belgium.
Dendrix Res, Sao Paulo, Brazil.
Mayo Clin, Rochester, MN USA.
Univ Amsterdam, Acad Med Ctr, NHMRC Clin Trials Ctr, Flevohosp, NL-1105 AZ Amsterdam, Netherlands.
Monash Univ, Sch Publ Hlth, Melbourne, Vic 3004, Australia.
CRUK MRC Oxford Inst Radiat Oncol, Oxford, England.
Ohio State Univ Wexner Med Ctr, Columbus, OH USA.
Univ Clin Halle Saale, Dept Internal Med 4, Halle, Germany.
Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
Univ Hosp Gasthuisberg Leuven, Leuven, Belgium.
Ctr Rene Gauducheau, Dept Med Oncol, F-44035 Nantes, France.
Univ Sao Paulo, Hosp Sirio Libanes, Sao Paulo, Brazil.
Univ Sao Paulo, Inst Canc Estado Sao Paulo, Sao Paulo, Brazil.
Austin Hlth, Melbourne, Vic, Australia.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Azienda Osped Univ Pisana Ist Toscano Tumori, UO Oncol Med 2, Pisa, Italy.
Hop Henri Mondor, UPEC, F-94010 Creteil, France.
Hosp St Antoine, Paris, France.
Int Inst Drug Dev, Leuven, Belgium.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 666
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800661
ER
PT J
AU Demetri, GD
Reichardt, P
Kang, YK
Blay, JY
Joensuu, H
Schaefer, KB
Kuss, I
Kappeler, C
Casali, PG
AF Demetri, George D.
Reichardt, Peter
Kang, Yoon-Koo
Blay, Jean-Yves
Joensuu, Heikki
Schaefer, Klaus Bernd
Kuss, Iris
Kappeler, Christian
Casali, Paolo Giovanni
TI An updated overall survival analysis with correction for
protocol-planned crossover of the international, phase III, randomized,
placebo-controlled trial of regorafenib in advanced gastrointestinal
stromal tumors after failure of imatinib and sunitinib (GRID).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
HELIOS Klinikum Berlin Buch, Berlin, Germany.
Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea.
Ctr Leon Berard, F-69373 Lyon, France.
Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland.
Bayer Pharma AG, Berlin, Germany.
Bayer HealthCare Pharmaceut, Berlin, Germany.
Fdn IRCCS Ist Nazl Tumori, Milan, Italy.
RI Blay, Jean-Yves/N-3966-2016
OI Blay, Jean-Yves/0000-0001-7190-120X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 110
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800108
ER
PT J
AU Fuentes, E
Ahmad, R
Hong, TS
Clark, JW
Kwak, EL
Rattner, DW
Mullen, JT
AF Fuentes, Eva
Ahmad, Rima
Hong, Theodore S.
Clark, Jeffrey W.
Kwak, Eunice Lee
Rattner, David W.
Mullen, John Thomas
TI The impact of neoadjuvant therapy for gastroesophageal adenocarcinoma on
postoperative morbidity and mortality
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 156
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800154
ER
PT J
AU Goyal, L
Yurgelun, MB
Abrams, TA
Kwak, EL
Cleary, JM
Knowles, M
Regan, E
Gisondi, A
Sheehan, S
Zheng, H
Zhu, AX
AF Goyal, Lipika
Yurgelun, Matthew B.
Abrams, Thomas Adam
Kwak, Eunice Lee
Cleary, James M.
Knowles, Michelle
Regan, Eileen
Gisondi, Amy
Sheehan, Susan
Zheng, Hui
Zhu, Andrew X.
TI A phase II trial of cabozantinib (XL-184) in patients with advanced
cholangiocarcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
MGH Canc Ctr, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 800
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800795
ER
PT J
AU Hatziapostolou, M
Koutsioumpa, M
Kottakis, F
Iliopoulos, D
Polytarchou, C
AF Hatziapostolou, Maria
Koutsioumpa, Marina
Kottakis, Filippos
Iliopoulos, Dimitrios
Polytarchou, Christos
TI Targeting colon cancer metabolism through a long noncoding RNA.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Syst Biomed, Div Digest Dis, Los Angeles, CA 90095 USA.
Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 604
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800601
ER
PT J
AU Isakoff, SJ
Saleh, MN
Lugovskoy, A
Mathews, S
Czibere, AG
Shields, AF
Bahleda, R
Soria, JC
Arnedos, M
AF Isakoff, Steven J.
Saleh, Mansoor N.
Lugovskoy, Alexey
Mathews, Sara
Czibere, Akos Gabor
Shields, Anthony Frank
Bahleda, Rastislav
Soria, Jean-Charles
Arnedos, Monica
TI First-in-human study of MM-141: A novel tetravalent monoclonal antibody
targeting IGF-1R and ErbB3.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Georgia Canc Specialists PC, Atlanta, GA USA.
Merrimack Pharmaceut Inc, Cambridge, MA USA.
Karmanos Canc Inst, Detroit, MI USA.
Inst Gustave Roussy, Drug Dev Dept, Villejuif, France.
Inst Gustave Roussy, Villejuif, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 384
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800382
ER
PT J
AU Kwak, EL
LoRusso, P
Hamid, O
Janku, F
Kittaneh, M
Catenacci, DVT
Chan, E
Bekaii-Saab, TS
Amore, B
Hwang, YC
Tang, R
Ngarmchamnanrith, G
Hong, DS
AF Kwak, Eunice Lee
LoRusso, Patricia
Hamid, Omid
Janku, Filip
Kittaneh, Muaiad
Catenacci, Daniel Virgil Thomas
Chan, Emily
Bekaii-Saab, Tanios S.
Amore, Benny
Hwang, Yuying C.
Tang, Rui
Ngarmchamnanrith, Gataree
Hong, David S.
TI Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult
patients (pts) with MET-amplified gastroesophageal junction (GEJ),
gastric (G), or esophageal (E) cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Yale Canc Ctr, New Haven, CT USA.
Angeles Clin & Res Inst, Los Angeles, CA USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Karmanos Canc Inst, Detroit, MI USA.
Univ Chicago, Chicago, IL 60637 USA.
Vanderbilt Univ, Med Ctr, Nashville, TN USA.
Ohio State Univ, Ctr Comprehens Canc, Arthur G James Canc Hosp, Columbus, OH 43210 USA.
Richard J Solove Res Inst, Columbus, OH USA.
Amgen Inc, Seattle, WA USA.
Amgen Inc, Thousand Oaks, CA 91320 USA.
NR 0
TC 8
Z9 8
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 1
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800002
ER
PT J
AU Olszanski, AJ
Wang-Gillam, A
Kwak, EL
Nazzal, K
Mehdi, F
Borad, MJ
AF Olszanski, Anthony J.
Wang-Gillam, Andrea
Kwak, Eunice Lee
Nazzal, Kamal
Mehdi, Fazal
Borad, Mitesh J.
TI A phase I dose-escalation trial of TH-302 with nab-paclitaxel and
gemcitabine in patients with locally advanced or metastatic pancreatic
adenocarcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Temple Hlth, Fox Chase Canc Ctr, Philadelphia, PA USA.
Washington Univ, St Louis, MO USA.
Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
EMD Serono, Billerica, MA USA.
Mayo Clin, Scottsdale, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA TPS505
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800503
ER
PT J
AU Tabernero, J
Ohtsu, A
Muro, K
Van Cutsem, E
Oh, SC
Bodoky, G
Shimada, Y
Hironaka, S
Ajani, JA
Tomasek, J
Safran, H
Chandrawansa, K
Hsu, YZ
Heathman, M
Khan, AZ
Ni, L
Melemed, AS
Gao, L
Ferry, D
Fuchs, CS
AF Tabernero, Josep
Ohtsu, Atsushi
Muro, Kei
Van Cutsem, Eric
Oh, Sang Cheul
Bodoky, Gyorgy
Shimada, Yasuhiro
Hironaka, Shuichi
Ajani, Jaffer A.
Tomasek, Jiri
Safran, Howard
Chandrawansa, Kumari
Hsu, Yanzhi
Heathman, Michael
Khan, Azhar Z.
Ni, Lan
Melemed, Allen S.
Gao, Ling
Ferry, David
Fuchs, Charles S.
TI Exposure-response (E-R) relationship of ramucirumab (RAM) from two
global, randomized, double-blind, phase 3 studies of patients (Pts) with
advanced second-line gastric cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Vall dHebron Univ Hosp, Barcelona, Spain.
Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Kashiwa, Chiba, Japan.
Aichi Canc Ctr Hosp, Dept Clin Oncol, Nagoya, Aichi 464, Japan.
Univ Hosp Gasthuisberg Leuven, Leuven, Belgium.
Korea Univ, Guro Hosp, Seoul, South Korea.
Szent Laszlo Hosp, Budapest, Hungary.
Natl Canc Ctr, Tokyo, Japan.
Chiba Canc Ctr, Clin Trial Promot Dept, Chiba 2608717, Japan.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Masaryk Univ, Fac Med, Masaryk Mem Canc Inst, Brno, Czech Republic.
Brown Univ, Oncol Res Grp, Providence, RI 02912 USA.
Eli Lilly & Co, Bridgewater, NJ USA.
Eli Lilly & Co, Indianapolis, IN 46285 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 2
Z9 2
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 121
PG 2
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800119
ER
PT J
AU Yao, JC
Buzzoni, R
Carnaghi, C
Fazio, N
Singh, S
Wolin, EM
Tomasek, J
Raderer, M
Lahner, H
Lam, DH
Cauwel, H
Valle, JW
Delle Fave, G
Van Cutsem, E
Strosberg, JR
Tesselaar, ME
Shimada, Y
Oh, DY
Kulke, M
Pavel, ME
AF Yao, James C.
Buzzoni, Roberto
Carnaghi, Carlo
Fazio, Nicola
Singh, Simron
Wolin, Edward M.
Tomasek, Jiri
Raderer, Markus
Lahner, Harald
Lam, Du Hung
Cauwel, Helene
Valle, Juan W.
Delle Fave, Gianfranco
Van Cutsem, Eric
Strosberg, Jonathan R.
Tesselaar, Margot Et
Shimada, Yasuhiro
Oh, Do-Youn
Kulke, Matthew
Pavel, Marianne E.
CA Fourth Trial RADIANT-4 Study Grp
TI Baseline demographics of the randomized, placebo-controlled,
double-blind, phase III RADIANT-4 study of everolimus in nonfunctional
gastrointestinal (GI) or lung neuroendocrine tumors (NET).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Fdn IRCCS Ist Nazl Tumori, Milan, Italy.
IRCCS Ist Clin Humanitas, Rozzano, Italy.
Ist Europeo Oncol, Milan, Italy.
Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
Univ Kentucky, Markey Canc Ctr, Lexington, KY USA.
Masaryk Univ, Masaryk Mem Canc Inst, Fac Med, Brno, Czech Republic.
AKH, Univ Klin Innere Med 1, Vienna, Austria.
Univ Klinikum Essen, Zentrum Innere Med, Essen, Germany.
Novartis Pharmaceut, E Hanover, NJ USA.
Novartis Pharma AG, Basel, Switzerland.
Univ Manchester, Manchester Acad Hlth Sci Ctr, Dept Med Oncol, Christie NHS Fdn Trust, Manchester, Lancs, England.
Univ Roma La Sapienza, Azienda Osped St Andrea, Rome, Italy.
Univ Hosp Gasthuisberg Leuven, Leuven, Belgium.
Univ S Florida, H Lee Moffitt Canc Ctr, Dept Med, Tampa, FL 33682 USA.
Netherlands Canc Inst, Amsterdam, Netherlands.
Natl Canc Ctr, Tokyo, Japan.
Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Charite, Campus Virchow Klinikum, D-13353 Berlin, Germany.
RI Valle, Juan/J-3571-2015
OI Valle, Juan/0000-0002-1999-0863
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 276
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800274
ER
PT J
AU Zhu, AX
Ryoo, BY
Yen, CJ
Kudo, M
Poon, RTP
Pastorelli, D
Blanc, JF
Chung, HC
Baron, AD
Pfiffer, TEF
Okusaka, T
Kubackova, K
Trojan, J
Sastre, J
Chau, I
Chang, SC
Abada, P
Yang, L
Hsu, Y
Park, JO
AF Zhu, Andrew X.
Ryoo, Baek-Yeol
Yen, Chia-Jui
Kudo, Masatoshi
Poon, Ronnie Tung-Ping
Pastorelli, Davide
Blanc, Jean-Frederic
Chung, Hyun Cheol
Baron, Ari David
Pfiffer, Tulio Eduardo Flesch
Okusaka, Takuji
Kubackova, Katerina
Trojan, Jorg
Sastre, Javier
Chau, Ian
Chang, Shao-Chun
Abada, Paolo
Yang, Ling
Hsu, Yanzhi
Park, Joon Oh
TI Ramucirumab (RAM) as second-line treatment in patients (pts) with
advanced hepatocellular carcinoma (HCC): Analysis of patients with
elevated alpha-fetoprotein (AFP) from the randomized phase III REACH
study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 15-17, 2015
CL San Francisco, CA
C1 Massachusetts Gen Hosp Canc Ctr, Boston, MA USA.
Univ Ulsan Coll Med, Dept Oncol, Asan Med Ctr, Seoul, South Korea.
Natl Cheng Kung Univ Hosp, Internal Med, Tainan 70428, Taiwan.
Kinki Univ Sch Med, Dept Gastroenterol & Hepatol, Osaka, Japan.
Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China.
IRCCS, Oncol Med 1, Ist Oncol Veneto, Padua, Italy.
Hop St Andre, Bordeaux, France.
Yonsei Univ Coll Med, Yonsei Canc Ctr, Canc Metastasis Res Ctr, Shinchon Dong, South Korea.
Pacific Hematol Oncol Associates, San Francisco, CA USA.
Inst Canc Estado Sao Paulo, Sao Paulo, Brazil.
Natl Canc Ctr, Div Hepatobiliary & Pancreat Oncol, Tokyo, Japan.
Charles Univ Prague, Univ Hosp Motol, Dept Oncol, Prague, Czech Republic.
Goethe Univ Frankfurt, D-60054 Frankfurt, Germany.
Hosp Clin San Carlos, Madrid, Spain.
Royal Marsden NHS Fdn Trust, London, England.
Royal Marsden NHS Fdn Trust, Surrey, England.
Eli Lilly & Co, Indianapolis, IN 46285 USA.
Eli Lilly & Co, Bridgewater, NJ USA.
Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea.
NR 0
TC 3
Z9 3
U1 1
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
SU S
MA 232
PG 1
WC Oncology
SC Oncology
GA CL3WY
UT WOS:000356883800230
ER
PT J
AU Munoz, JL
Rodriguez-Cruz, V
Ramkissoon, SH
Ligon, KL
Greco, SJ
Rameshwar, P
AF Munoz, Jessian L.
Rodriguez-Cruz, Vivian
Ramkissoon, Shakti H.
Ligon, Keith L.
Greco, Steven J.
Rameshwar, Pranela
TI Temozolomide resistance in glioblastoma occurs by miRNA-9-targeted
PTCH1, independent of sonic hedgehog level
SO ONCOTARGET
LA English
DT Article
DE glioblastoma; MicroRNA-9; PTCH; Temozolomide; P-gp
ID BREAST-CANCER CELLS; STEM-CELLS; EXPRESSION; MICRORNAS; INHIBITION;
DELIVERY; DIFFERENTIATION; NEUROGENESIS; ACTIVATION; MUTATIONS
AB Glioblastoma Multiforme (GBM), the most common and lethal adult primary tumor of the brain, showed a link between Sonic Hedgehog (SHH) pathway in the resistance to temozolomide (TMZ). PTCH1, the SHH receptor, can tonically represses signaling by endocytosis. We asked how the decrease in PTCH1 in GBM cells could lead to TMZ-resistance. TMZ resistant GBM cells have increased PTCH1 mRNA and reduced protein. Knockdown of Dicer, a Type III RNAase, indicated that miRNAs can explain the decreased PTCH1 in TMZ resistant cells. Computational studies, real-time PCR, reporter gene studies, western blots, target protector oligos and ectopic expression identified miR-9 as the target of PTCH1 in resistant GBM cells with concomitant activation of SHH signaling. MiR-9 mediated increases in the drug efflux transporters, MDR1 and ABCG2. MiR-9 was increased in the tissues from GBM patients and in an early passage GBM cell line from a patient with recurrent GBM but not from a naive patient. Pharmacological inhibition of SHH signaling sensitized the GBM cells to TMZ. Taken together, miR-9 targets PTCH1 in GBM cells by a SHH-independent method in GBM cells for TMZ resistance. The identified pathways could lead to new strategies to target GBM with combinations of drugs.
C1 [Munoz, Jessian L.; Greco, Steven J.; Rameshwar, Pranela] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA.
[Munoz, Jessian L.; Rameshwar, Pranela] Rutgers Sch Biomed Hlth Sci, Grad Sch Biomed Sci, Newark, NJ USA.
[Rodriguez-Cruz, Vivian] Univ Puerto Rico, Dept Chem, Cayey, PR USA.
[Ramkissoon, Shakti H.; Ligon, Keith L.] Boston Childrens Hosp, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA.
[Ramkissoon, Shakti H.; Ligon, Keith L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Rameshwar, P (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, 185 S Orange Ave, Newark, NJ 07103 USA.
EM rameshwa@njms.rutgers.edu
FU F.M Kirby
FX This work was supported by F.M Kirby to PR.
NR 36
TC 12
Z9 14
U1 1
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JAN 20
PY 2015
VL 6
IS 2
BP 1190
EP 1201
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CF4AE
UT WOS:000352489800048
PM 25595896
ER
PT J
AU Berg, A
Hoivik, EA
Mjos, S
Holst, F
Werner, HMJ
Tangen, IL
Taylor-Weiner, A
Gibson, WJ
Kusonmano, K
Wik, E
Trovik, J
Halle, MK
Oyan, AM
Kalland, KH
Cherniack, AD
Beroukhim, R
Stefansson, I
Mills, GB
Krakstad, C
Salvesen, HB
AF Berg, Anna
Hoivik, Erling A.
Mjos, Siv
Holst, Frederik
Werner, Henrica M. J.
Tangen, Ingvild L.
Taylor-Weiner, Amaro
Gibson, William J.
Kusonmano, Kanthida
Wik, Elisabeth
Trovik, Jone
Halle, Mari K.
Oyan, Anne M.
Kalland, Karl-Henning
Cherniack, Andrew D.
Beroukhim, Rameen
Stefansson, Ingunn
Mills, Gordon B.
Krakstad, Camilla
Salvesen, Helga B.
TI Molecular profiling of endometrial carcinoma precursor, primary and
metastatic lesions suggests different targets for treatment in obese
compared to non-obese patients
SO ONCOTARGET
LA English
DT Article
DE endometrial carcinoma; endometrial hyperplasia; metastasis; body mass
index; PI3Kinase
ID GYNECOLOGIC-ONCOLOGY-GROUP; PTEN EXPRESSION; ATYPICAL HYPERPLASIA;
PIK3CA MUTATIONS; HIGH-FREQUENCY; CANCER; GENE; WOMEN; RISK;
AMPLIFICATION
AB Obesity is linked to increased incidence of endometrioid endometrial cancer (EEC) and complex atypical hyperplasia (CAH). We here explore pattern and sequence of molecular alterations characterizing endometrial carcinogenesis in general and related to body mass index (BMI), to improve diagnostic stratification and treatment strategies. We performed molecular characterization of 729 prospectively collected EEC and CAH. Candidate biomarkers were identified in frozen samples by whole-exome and Sanger sequencing, oligonucleotide gene expression and Reverse Phase Protein Arrays (investigation cohort) and further explored in formalin fixed tissues by immunohistochemistry and Fluorescent in Situ Hybridization (validation cohort). We here demonstrate that PIK3CA mutations, PTEN loss, PI3K and KRAS activation are early events in endometrial carcinogenesis. Molecular changes related to KRAS activation and inflammation are more common in obese CAH patients, suggesting different prevention and systemic treatment strategies in obese and non-obese patients. We also found that oncoprotein Stathmin might improve preoperative diagnostic distinction between premalignant and malignant endometrial lesions.
C1 [Berg, Anna; Hoivik, Erling A.; Mjos, Siv; Holst, Frederik; Werner, Henrica M. J.; Tangen, Ingvild L.; Kusonmano, Kanthida; Trovik, Jone; Halle, Mari K.; Oyan, Anne M.; Kalland, Karl-Henning; Krakstad, Camilla; Salvesen, Helga B.] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway.
[Berg, Anna; Hoivik, Erling A.; Mjos, Siv; Holst, Frederik; Werner, Henrica M. J.; Tangen, Ingvild L.; Kusonmano, Kanthida; Trovik, Jone; Halle, Mari K.; Krakstad, Camilla; Salvesen, Helga B.] Haukeland Hosp, Dept Gynecol & Obstet, Bergen, Norway.
[Kusonmano, Kanthida] Univ Bergen, Computat Biol Unit, N-5020 Bergen, Norway.
[Wik, Elisabeth; Stefansson, Ingunn] Haukeland Hosp, Dept Pathol, Bergen, Norway.
[Wik, Elisabeth; Stefansson, Ingunn] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Med, N-5020 Bergen, Norway.
[Oyan, Anne M.; Kalland, Karl-Henning] Haukeland Hosp, Dept Microbiol, Bergen, Norway.
[Taylor-Weiner, Amaro; Gibson, William J.; Cherniack, Andrew D.; Beroukhim, Rameen] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Taylor-Weiner, Amaro; Gibson, William J.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Taylor-Weiner, Amaro; Gibson, William J.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Taylor-Weiner, Amaro; Gibson, William J.; Beroukhim, Rameen] Harvard Univ, Sch Med, Boston, MA USA.
[Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
RP Salvesen, HB (reprint author), Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway.
EM Helga.salvesen@k2.uib.no
RI Kalland, Karl-Henning/B-9445-2017; salvesen, Helga/C-1187-2017
OI Kalland, Karl-Henning/0000-0003-4486-2334; salvesen,
Helga/0000-0002-4438-8831
FU Helse Vest; University of Bergen; Norwegian Cancer Society; Research
Council of Norway; Bergen Medisinske Forskningsstiftelse; MD Anderson
Cancer Center Support Grant (CCSG) from the National Cancer Institute
[CA016672]; [P50 CA098258]
FX HBS was supported by Helse Vest, the University of Bergen, the Norwegian
Cancer Society (Harald Andersen Legat), and the Research Council of
Norway, KC by Bergen Medisinske Forskningsstiftelse, GBM by P50
CA098258. RPPA analysis was supported by MD Anderson Cancer Center
Support Grant (CCSG) CA016672 from the National Cancer Institute.
NR 72
TC 13
Z9 13
U1 0
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JAN 20
PY 2015
VL 6
IS 2
BP 1327
EP 1339
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CF4AE
UT WOS:000352489800058
PM 25415225
ER
PT J
AU Stearns, V
Chapman, JAW
Ma, CX
Ellis, MJ
Ingle, JN
Pritchard, KI
Budd, GT
Rabaglio, M
Sledge, GW
Le Maitre, A
Kundapur, J
Liedke, PER
Shepherd, LE
Goss, PE
AF Stearns, Vered
Chapman, Judith-Anne W.
Ma, Cynthia X.
Ellis, Matthew J.
Ingle, James N.
Pritchard, Kathleen I.
Budd, G. Thomas
Rabaglio, Manuela
Sledge, George W.
Le Maitre, Aurelie
Kundapur, Jessica
Liedke, Pedro E. R.
Shepherd, Lois E.
Goss, Paul E.
TI Treatment-Associated Musculoskeletal and Vasomotor Symptoms and
Relapse-Free Survival in the NCIC CTG MA.27 Adjuvant Breast Cancer
Aromatase Inhibitor Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ADVERSE EVENTS; POSTMENOPAUSAL WOMEN; RISK; DISCONTINUATION; MANAGEMENT;
EXEMESTANE; THERAPY
AB Purpose
Treatment-emergent symptoms with adjuvant tamoxifen and aromatase inhibitors (AIs) have been associated with superior recurrence-free survival (RFS). We hypothesized that MA. 27 anastrozoleor exemestane-treated patients with new or worsening vasomotor and/or joint symptoms would have improved RFS.
Patients and Methods
MA. 27 randomly assigned 7,576 postmenopausal women with breast cancer to 5 years of anastrozole or exemestane. Patient-reported symptoms were collected using the Common Terminology Criteria for Adverse Events version 3.0 at protocol-specified baseline and 6-and 12-month clinical visits. Symptoms were considered present with either vasomotor and/or joint complaints. Associations between symptoms and baseline patient characteristics were examined with chi(2) and Fisher's exact tests. Subsequent effects of new or worsening symptoms on RFS were examined with landmark analyses and stratified univariable and multivariable Cox models. We examined the effects of 3-month symptoms arising from unplanned clinic visits as a result of severe toxicity.
Results
Patients were assessable if eligible for the MA. 27 trial, received some trial therapy, and had no disease recurrence at the end of a symptom assessment period; 96% of patients (n = 7,306 patients) were included at 6 months, and 96% (n = 7,246) were included at 12 months. Thirty-four percent of patients had baseline symptoms. For patients without baseline symptoms, 25% and 52% had new symptoms by 6 and 12 months, respectively. Neither treatment-emergent nor baseline symptoms significantly impacted RFS (P >.10) in patients with or without baseline symptoms.
Conclusion
In MA. 27, anastrozole or exemestane treatment-emergent symptoms were not associated with improved RFS. Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms. (C) 2014 by American Society of Clinical Oncology
C1 [Stearns, Vered] Kimmel Canc Ctr, Baltimore, MD USA.
[Chapman, Judith-Anne W.; Le Maitre, Aurelie; Kundapur, Jessica; Shepherd, Lois E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada.
[Pritchard, Kathleen I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Pritchard, Kathleen I.] Univ Toronto, Toronto, ON, Canada.
[Ma, Cynthia X.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA.
[Ellis, Matthew J.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Ingle, James N.] Mayo Clin, Rochester, MN USA.
[Budd, G. Thomas] Cleveland Clin, Cleveland, OH 44106 USA.
[Sledge, George W.] Stanford Univ, San Francisco, CA USA.
[Liedke, Pedro E. R.; Goss, Paul E.] Harvard Univ, Cambridge, MA 02138 USA.
[Goss, Paul E.] Massachusetts Gen Hosp, Avon Int Breast Canc Res Program, Boston, MA 02114 USA.
[Rabaglio, Manuela] Inselspital Univ Hosp, Bern, Switzerland.
[Rabaglio, Manuela] Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland.
[Liedke, Pedro E. R.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Liedke, Pedro E. R.] Inst Canc Mae Deus, Oncol, Porto Alegre, RS, Brazil.
RP Goss, PE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Lawrence House,LRH 302, Boston, MA 02114 USA.
EM pgoss@partners.org
FU NCI NIH HHS [U10 CA180888, P30 CA015083, U10 CA180833]
NR 20
TC 10
Z9 10
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
BP 265
EP U163
DI 10.1200/JCO.2014.57.6926
PG 13
WC Oncology
SC Oncology
GA CF3BC
UT WOS:000352421400011
PM 25512454
ER
PT J
AU Shulman, LN
Berry, DA
Cirrincione, CT
Hudis, CA
Winer, EP
AF Shulman, Lawrence N.
Berry, Donald A.
Cirrincione, Constance T.
Hudis, Clifford A.
Winer, Eric P.
TI Reply to V. Amoroso et al
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID POSITIVE BREAST-CANCER; ADJUVANT THERAPY
C1 [Shulman, Lawrence N.; Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Cirrincione, Constance T.] Duke Univ, Durham, NC USA.
[Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Shulman, LN (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 5
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JAN 20
PY 2015
VL 33
IS 3
BP 291
EP 291
DI 10.1200/JCO.2014.59.1875
PG 1
WC Oncology
SC Oncology
GA CF3BC
UT WOS:000352421400019
PM 25512457
ER
PT J
AU Katz, IT
Leister, E
Kacanek, D
Hughes, MD
Bardeguez, A
Livingston, E
Stek, A
Shapiro, DE
Tuomala, R
AF Katz, Ingrid T.
Leister, Erin
Kacanek, Deborah
Hughes, Michael D.
Bardeguez, Arlene
Livingston, Elizabeth
Stek, Alice
Shapiro, David E.
Tuomala, Ruth
TI Factors Associated With Lack of Viral Suppression at Delivery Among
Highly Active Antiretroviral Therapy-Naive Women With HIV A Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXPOSED UNINFECTED INFANTS; INFECTED
PREGNANT-WOMEN; TO-CHILD TRANSMISSION; HIV-1-INFECTED WOMEN;
UNITED-STATES; RISK-FACTORS; PERINATAL TRANSMISSION; HEALTH LITERACY;
LOAD
AB Background: A high delivery maternal plasma HIV-1 RNA level (viral load [VL]) is a risk factor for mother-to-child transmission and poor maternal health.
Objective: To identify factors associated with detectable VL at delivery despite initiation of highly active antiretroviral therapy (HAART) during pregnancy.
Design: Multicenter observational study. (ClinicalTrial.gov: NCT00028145)
Setting: 67 U.S. AIDS clinical research sites.
Patients: Pregnant women with HIV who initiated HAART during pregnancy.
Measurements: Descriptive summaries and associations among sociodemographic, HIV disease, and treatment characteristics; pregnancy-related risk factors; and detectable VL (>400 copies/mL) at delivery.
Results: Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had detectable VL at delivery. Factors associated with detectable VL included multiparity (16.4% vs. 8.0% nulliparity; P = 0.002), black ethnicity (17.6% vs. 6.6% Hispanic and 6.6% white; P < 0.001), 11th grade education or less (17.6% vs. 12.1% had a high school diploma; P = 0.013), initiation of HAART in the third trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P = 0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0% during the current pregnancy; P = 0.051), and having the first prenatal visit in the third trimester (33.3% vs. 14.3% and 10.5% in the second and third trimesters, respectively; P = 0.002). Women who had treatment interruptions or reported poor medication adherence were more likely to have detectable VL at delivery.
Limitation: Data on many covariates were incomplete because women entered the study at varying times during pregnancy.
Conclusion: A total of 13.1% of women who initiated HAART during pregnancy had detectable VL at delivery. The timing of HAART initiation and prenatal care, along with medication adherence during pregnancy, were associated with detectable VL at delivery. Social factors, including ethnicity and education, may help identify women who could benefit from focused efforts to promote early HAART initiation and adherence.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp,Ctr Global Hlth, Boston, MA USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
Duke Univ, Sch Med, Durham, NC USA.
Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
RP Katz, IT (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA.
EM ikatz2@partners.org
FU U.S. Department of Health and Human Services
FX U.S. Department of Health and Human Services.
NR 48
TC 9
Z9 9
U1 1
U2 6
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JAN 20
PY 2015
VL 162
IS 2
BP 90
EP +
DI 10.7326/M13-2005
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA CC1NB
UT WOS:000350106600015
PM 25599347
ER
PT J
AU Ghatalia, P
Je, Y
Kaymakcalan, MD
Sonpavde, G
Choueiri, TK
AF Ghatalia, P.
Je, Y.
Kaymakcalan, M. D.
Sonpavde, G.
Choueiri, T. K.
TI QTc interval prolongation with vascular endothelial growth factor
receptor tyrosine kinase inhibitors
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE vascular endothelial growth factor receptor; tyrosine kinase inhibitors;
approved; QTc interval prolongation; meta-analysis; cardiac toxicity
ID RENAL-CELL CARCINOMA; PHASE-III TRIAL; VANDETANIB PLUS DOCETAXEL;
DOUBLE-BLIND; LUNG-CANCER; CLINICAL-TRIALS; TREATMENT PATTERNS;
CARDIOVASCULAR SAFETY; THYROID-CANCER; BREAST-CANCER
AB Background: Multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are known to cause cardiac toxicity, but the relative risk (RR) of QTc interval prolongation and serious arrhythmias associated with them are not reported.
Methods: We conducted a trial-level meta-analysis of randomised phase II and III trials comparing arms with and without a US Food and Drug Administration-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib and regorafenib). A total of 6548 patients from 18 trials were selected. Statistical analyses were conducted to calculate the summary incidence, RR and 95% CIs.
Results: The RR for all-grade and high-grade QTc prolongation for the TKI vs no TKI arms was 8.66 (95% CI 4.92-15.2, P < 0.001) and 2.69 (95% CI 1.33-5.44, P = 0.006), respectively, with most of the events being asymptomatic QTc prolongation. Respectively, 4.4% and 0.83% of patients exposed to VEGFR TKI had all-grade and high-grade QTc prolongation. On subgroup analysis, only sunitinib and vandetanib were associated with a statistically significant risk of QTc prolongation, with higher doses of vandetanib associated with a greater risk. The rate of serious arrhythmias including torsades de pointes did not seem to be higher with high-grade QTc prolongation. The risk of QTc prolongation was independent of the duration of therapy.
Conclusions: In the largest study to date, we show that VEGFR TKI can be associated with QTc prolongation. Although most cases were of low clinical significance, it is unclear whether the same applies to patients treated off clinical trials.
C1 [Ghatalia, P.] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL USA.
[Je, Y.] Kyung Hee Univ, Dept Food & Nutr, Seoul, South Korea.
[Kaymakcalan, M. D.; Choueiri, T. K.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Kaymakcalan, M. D.; Choueiri, T. K.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Sonpavde, G.] UAB Med Ctr Birmingham, Sect Med Oncol, Dept Internal Med, Birmingham, AL USA.
RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA.
EM toni_choueiri@dfci.harvard.edu
NR 51
TC 13
Z9 14
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JAN 20
PY 2015
VL 112
IS 2
BP 296
EP 305
DI 10.1038/bjc.2014.564
PG 10
WC Oncology
SC Oncology
GA AZ5SY
UT WOS:000348281100012
PM 25349964
ER
PT J
AU Norden, AD
Ligon, KL
Hammond, SN
Muzikansky, A
Reardon, DA
Kaley, TJ
Batchelor, TT
Plotkin, SR
Raizer, JJ
Wong, ET
Drappatz, J
Lesser, GJ
Haidar, S
Beroukhim, R
Lee, EQ
Doherty, L
Lafrankie, D
Gaffey, SC
Gerard, M
Smith, KH
McCluskey, C
Phuphanich, S
Wen, PY
AF Norden, Andrew D.
Ligon, Keith L.
Hammond, Samantha N.
Muzikansky, Alona
Reardon, David A.
Kaley, Thomas J.
Batchelor, Tracy T.
Plotkin, Scott R.
Raizer, Jeffrey J.
Wong, Eric T.
Drappatz, Jan
Lesser, Glenn J.
Haidar, Sam
Beroukhim, Rameen
Lee, Eudocia Q.
Doherty, Lisa
Lafrankie, Debra
Gaffey, Sarah C.
Gerard, Mary
Smith, Katrina H.
McCluskey, Christine
Phuphanich, Surasak
Wen, Patrick Y.
TI Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or
progressive meningioma
SO NEUROLOGY
LA English
DT Article
ID SOMATOSTATIN ANALOG; IN-VITRO; THERAPY; OCTREOTIDE; MUTATIONS;
MECHANISM; SST(2A); AKT1; SMO
AB Objective: A subset of meningiomas recur after surgery and radiation therapy, but no medical therapy for recurrent meningioma has proven effective.
Methods: Pasireotide LAR is a long-acting somatostatin analog that may inhibit meningioma growth. This was a phase II trial in patients with histologically confirmed recurrent or progressive meningioma designed to evaluate whether pasireotide LAR prolongs progression-free survival at 6 months (PFS6). Patients were stratified by histology (atypical [World Health Organization grade 2] and malignant [grade 3] meningiomas in cohort A and benign [grade 3] in cohort B).
Results: Eighteen patients were accrued in cohort A and 16 in cohort B. Cohort A had median age 59 years, median Karnofsky performance status 80, 17 (94%) had previous radiation therapy, and 11 (61%) showed high octreotide uptake. Cohort B had median age 52 years, median Karnofsky performance status 90, 11 (69%) had previous radiation therapy, and 12 (75%) showed high octreotide uptake. There were no radiographic responses to pasireotide LAR therapy in either cohort. Twelve patients (67%) in cohort A and 13 (81%) in cohort B achieved stable disease. In cohort A, PFS6 was 17% and median PFS 15 weeks (95% confidence interval: 8-20). In cohort B, PFS6 was 50% and median PFS 26 weeks (12-43). Treatment was well tolerated. Octreotide uptake and insulin-like growth factor-1 levels did not predict outcome. Expression of somatostatin receptor 3 predicted favorable PFS and overall survival.
Conclusions: Pasireotide LAR has limited activity in recurrent meningiomas. The finding that somatostatin receptor 3 is associated with favorable outcomes warrants further investigation. Classification of evidence: This study provides Class IV evidence that in patients with recurrent or progressive meningioma, pasireotide LAR does not significantly increase the proportion of patients with PFS at 6 months.
C1 [Norden, Andrew D.; Lee, Eudocia Q.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, Boston, MA 02115 USA.
[Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Norden, Andrew D.; Hammond, Samantha N.; Reardon, David A.; Beroukhim, Rameen; Lee, Eudocia Q.; Doherty, Lisa; Lafrankie, Debra; Gerard, Mary; Smith, Katrina H.; McCluskey, Christine; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Norden, Andrew D.; Ligon, Keith L.; Reardon, David A.; Batchelor, Tracy T.; Plotkin, Scott R.; Wong, Eric T.; Beroukhim, Rameen; Lee, Eudocia Q.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Ligon, Keith L.; Haidar, Sam] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Kaley, Thomas J.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA.
[Batchelor, Tracy T.; Plotkin, Scott R.] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Raizer, Jeffrey J.] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Wong, Eric T.] Beth Israel Deaconess Med Ctr, Brain Tumor Ctr, Boston, MA 02215 USA.
[Drappatz, Jan] Univ Pittsburgh, Med Ctr, Adult Neurooncol Program, Pittsburgh, PA USA.
[Lesser, Glenn J.] Wake Forest Univ, Ctr Comprehens Canc, Baptist Med Ctr, Winston Salem, NC 27109 USA.
[Phuphanich, Surasak] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA.
[Phuphanich, Surasak] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA.
RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Canc Neurol, 75 Francis St, Boston, MA 02115 USA.
EM pwen@partners.org
OI Kaley, Thomas/0000-0002-2540-8518
FU Novartis
FX This study was supported by Novartis.
NR 24
TC 11
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JAN 20
PY 2015
VL 84
IS 3
BP 280
EP 286
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA CA1XQ
UT WOS:000348702600014
PM 25527270
ER
PT J
AU Arora, P
Song, YN
Dusek, J
Plotnikoff, G
Sabatine, MS
Cheng, S
Valcour, A
Swales, H
Taylor, B
Carney, E
Guanaga, D
Young, JR
Karol, C
Torre, M
Azzahir, A
Strachan, SM
O'Neill, DC
Wolf, M
Harrell, F
Newton-Cheh, C
Wang, TJ
AF Arora, Pankaj
Song, Yanna
Dusek, Jeffery
Plotnikoff, Gregory
Sabatine, Marc S.
Cheng, Susan
Valcour, Andre
Swales, Heather
Taylor, Beth
Carney, Erin
Guanaga, Derek
Young, Joseph R.
Karol, Courtney
Torre, Michael
Azzahir, Atum
Strachan, Semerit M.
O'Neill, Dillon C.
Wolf, Myles
Harrell, Frank
Newton-Cheh, Christopher
Wang, Thomas J.
TI Vitamin D Therapy in Individuals With Prehypertension or Hypertension
The DAYLIGHT Trial
SO CIRCULATION
LA English
DT Article
DE blood pressure; dietary supplements; hypertension; vitamin D deficiency
ID RANDOMIZED CONTROLLED-TRIAL; D-BINDING PROTEIN; BLOOD-PRESSURE; D
SUPPLEMENTATION; CARDIOVASCULAR-DISEASE; PARATHYROID-HORMONE; D
DEFICIENCY; RISK; RECOMMENDATIONS; ASSOCIATION
AB Background-A large body of epidemiological and experimental evidence suggests that vitamin D deficiency may promote hypertension. This raises the possibility that vitamin D supplementation could be a simple intervention to reduce blood pressure, but data from prospective, randomized trials are limited.
Methods and Results-A double-blind, randomized, controlled trial was conducted at 4 sites in the United States. We enrolled 534 individuals 18 to 50 years of age with low vitamin D status (25-hydroxyvitamin D levels <= 25 ng/mL) and systolic blood pressure of 120 to 159 mm Hg. Participants were randomized to high-dose (4000 IU/d) versus low-dose (400 IU/d) oral vitamin D 3 for 6 months. The primary end point was change in mean 24-hour systolic blood pressure. Secondary end points included change in ambulatory diastolic blood pressure and clinic systolic and diastolic blood pressures. The median age was 38 years, and 62% of participants were men. Forty-six percent of participants were white, and 48% were black. The median 25-hydroxyvitamin D level at baseline was 15.3 ng/mL. Four-hundred fifty-ive participants (85%) had at least 1 follow-up blood pressure measurement; 383 participants (72%) completed the full 6-month study. At the end of the study, there was no significant difference in the primary end point (change in mean 24-hour systolic blood pressure, -0.8 versus -1.6 mm Hg in the high-dose and low-dose arms; P=0.71) or in any of the secondary end points. Furthermore, there was no evidence of association between change in 25-hydroxyvitamin D and change in 24-hour systolic blood pressure at 6 months (Spearman correlation coefficient, -0.05, P=0.34). Results were consistent across prespecified subgroups.
Conclusions-Vitamin D supplementation did not reduce blood pressure in individuals with prehypertension or stage I hypertension and vitamin D deficiency. Our findings suggest that the association between vitamin D status and elevated blood pressure noted in observational studies is not causal.
C1 [Arora, Pankaj] Univ Alabama Birmingham, Div Cardiol, Dept Med, Birmingham, AL USA.
[Song, Yanna; Harrell, Frank] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA.
[O'Neill, Dillon C.; Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Dept Med, Nashville, TN 37232 USA.
[Dusek, Jeffery; Plotnikoff, Gregory] Abbott NW Hosp, Integrat Hlth Res Ctr, Minneapolis, MN 55407 USA.
[Sabatine, Marc S.; Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA.
[Valcour, Andre] LabCorp, Esoterix Clin Lab Serv, Res Triangle Pk, NC USA.
[Swales, Heather; Taylor, Beth] Hartford Hosp, Div Cardiol, Dept Med, Hartford, CT 06115 USA.
[Carney, Erin; Guanaga, Derek; Young, Joseph R.; Karol, Courtney; Torre, Michael; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA.
[Azzahir, Atum; Strachan, Semerit M.] Cultural Wellness Ctr, Div Cardiol, Minneapolis, MN USA.
[Wolf, Myles] Northwestern Univ, Dept Med, Feinberg Sch Med, Div Nephrol, Chicago, IL 60611 USA.
RP Wang, TJ (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 2220 Pierce Ave,383 PRB, Nashville, TN 37232 USA.
EM thomas.j.wang@vanderbilt.edu
OI Arora, Pankaj/0000-0003-2420-3550
FU DiaSorin Inc.
FX The study was funded by an investigator-initiated grant from DiaSorin
Inc. Additional assay support was provided by LabCorp Inc. DiaSorin Inc
was not involved in the design or conduct of the study; the collection,
management, analysis, and interpretation of the data; or the preparation
of the manuscript for publication.
NR 28
TC 27
Z9 29
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 20
PY 2015
VL 131
IS 3
BP 254
EP +
DI 10.1161/CIRCULATIONAHA.114.011732
PG 17
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AZ3KT
UT WOS:000348126800010
PM 25359163
ER
PT J
AU Delling, FN
Rong, J
Larson, MG
Lehman, B
Osypiuk, E
Stantchev, P
Slaugenhaupt, SA
Benjamin, EJ
Levine, RA
Vasan, RS
AF Delling, Francesca N.
Rong, Jian
Larson, Martin G.
Lehman, Birgitta
Osypiuk, Ewa
Stantchev, Plamen
Slaugenhaupt, Susan A.
Benjamin, Emelia J.
Levine, Robert A.
Vasan, Ramachandran S.
TI Familial Clustering of Mitral Valve Prolapse in the Community
SO CIRCULATION
LA English
DT Article
DE echocardiography; epidemiology; genetics; mitral valve prolapse
ID LATE SYSTOLIC MURMUR; MIDSYSTOLIC CLICK; NATURAL-HISTORY; REGURGITATION;
HEART; DIAGNOSIS; LEAFLET; LOCUS; DETERMINANTS; INHERITANCE
AB Background-Knowledge of mitral valve prolapse (MVP) inheritance is based on pedigree observation and M-mode echocardiography. The extent of familial clustering of MVP among unselected individuals in the community using current, more specific echocardiographic criteria is unknown. In addition, the importance of nondiagnostic MVP morphologies (NDMs; first described in large pedigrees) has not been investigated in the general population. We hypothesized that parental MVP and NDMs increase the risk of offspring MVP.
Methods and Results-Study participants were 3679 Generation 3 individuals with available parental data in the Offspring or the New Offspring Spouse cohorts. MVP and NDMs were distinguished by leaflet displacement >2 versus <= 2 mm beyond the mitral annulus, respectively. We compared MVP prevalence in Generation 3 participants with at least 1 parent with MVP (n=186) with that in individuals without parental MVP (n=3493). Among 3679 participants (53% women; mean age, 40 +/- 9 years), 49 (1%) had MVP. Parental MVP was associated with a higher prevalence of MVP in Generation 3 participants (10 of 186, 5.4%) compared with no parental MVP (39 of 3493, 1.1%; adjusted odds ratio, 4.51; 95% confidence interval, 2.13-9.54; P<0.0001). When parental NDMs were examined alone, the prevalence of Generation 3 MVP remained higher (12 of 484, 2.5%) compared with those without parental MVP or NDMs (27 of 3009, 0.9%; adjusted odds ratio, 2.52; 95% confidence interval, 1.25-5.10; P=0.01).
Conclusions-Parental MVP and NDMs are associated with increased prevalence of offspring MVP, highlighting the genetic substrate of MVP and the potential clinical significance of NDMs in the community.
C1 [Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Framingham, MA USA.
[Delling, Francesca N.; Rong, Jian; Larson, Martin G.; Lehman, Birgitta; Osypiuk, Ewa; Stantchev, Plamen; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Delling, Francesca N.] Harvard Univ, Sch Med, Dept Med, Cardiovasc Div,Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Rong, Jian] Boston Univ, Sch Med, Dept Med, Neurol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Sect Math & Stat, Boston, MA 02215 USA.
[Slaugenhaupt, Susan A.] Univ Hartford, Ctr Human Genet Res, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Levine, Robert A.] Univ Hartford, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Dept Med,Med Sch, Boston, MA USA.
RP Delling, FN (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Div, 330 Brookline Ave,E-SH-458, Boston, MA 02215 USA.
EM fdelling@bidmc.harvard.edu
OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU Founders Affiliate American Heart Association Clinical Research Program;
National Heart, Lung, and Blood Institute FHS [N01-HC-25195];
[R01HL080124]; [RO1HL0107385]; [K23HL116652]
FX This work was supported by the Founders Affiliate American Heart
Association Clinical Research Program (Dr Delling), National Heart,
Lung, and Blood Institute FHS contract No. N01-HC-25195, and research
grants R01HL080124, RO1HL0107385 (Dr Vasan), and K23HL116652 (Dr
Delling).
NR 39
TC 7
Z9 8
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JAN 20
PY 2015
VL 131
IS 3
BP 263
EP +
DI 10.1161/CIRCULATIONAHA.114.012594
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AZ3KT
UT WOS:000348126800011
PM 25361552
ER
PT J
AU Nelson, RW
Beisang, D
Tubo, NJ
Dileepan, T
Wiesner, DL
Nielsen, K
Wuthrich, M
Klein, BS
Kotov, DI
Spanier, JA
Fife, BT
Moon, JJ
Jenkins, MK
AF Nelson, Ryan W.
Beisang, Daniel
Tubo, Noah J.
Dileepan, Thamotharampillai
Wiesner, Darin L.
Nielsen, Kirsten
Wuethrich, Marcel
Klein, Bruce S.
Kotov, Dmitri I.
Spanier, Justin A.
Fife, Brian T.
Moon, James J.
Jenkins, Marc K.
TI T Cell Receptor Cross-Reactivity between Similar Foreign and Self
Peptides Influences Naive Cell Population Size and Autoimmunity
SO IMMUNITY
LA English
DT Article
ID CLASS-II; PRECURSOR FREQUENCIES; REPERTOIRE DIVERSITY; RESPONSE
MAGNITUDE; H-2(B) MICE; IN-VIVO; EPITOPE; INFECTION; COMPLEX; BINDING
AB T cell receptor (TCR) cross-reactivity between major histocompatibility complex II (MHCII)-binding self and foreign peptides could influence the naive CD4(+) T cell repertoire and autoimmunity. We found that nonamer peptides that bind to the same MHCII molecule only need to share five amino acids to cross-react on the same TCR. This property was biologically relevant because systemic expression of a self peptide reduced the size of a naive cell population specific for a related foreign peptide by deletion of cells with cross-reactive TCRs. Reciprocally, an incompletely deleted naive T cell population specific for a tissue-restricted self peptide could be triggered by related microbial peptides to cause autoimmunity. Thus, TCR cross-reactivity between similar self and foreign peptides can reduce the size of certain foreign peptide-specific T cell populations and might allow T cell populations specific for tissue-restricted self peptides to cause autoimmunity after infection.
C1 [Nelson, Ryan W.; Tubo, Noah J.; Dileepan, Thamotharampillai; Kotov, Dmitri I.; Spanier, Justin A.; Fife, Brian T.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA.
[Nelson, Ryan W.; Beisang, Daniel; Tubo, Noah J.; Dileepan, Thamotharampillai; Wiesner, Darin L.; Nielsen, Kirsten; Kotov, Dmitri I.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA.
[Wuethrich, Marcel; Klein, Bruce S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53706 USA.
[Spanier, Justin A.; Fife, Brian T.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA.
[Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA.
[Moon, James J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02129 USA.
[Moon, James J.] Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Jenkins, MK (reprint author), Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA.
EM jenki002@umn.edu
OI Fife, Brian/0000-0001-9826-5637; Jenkins, Marc/0000-0001-8009-7655;
Kotov, Dmitri/0000-0001-7843-1503
FU NIH [T32 GM008244, F30 DK093242, UL1 TR000114, R01 AI107020, R01
AI080275, R01 AI105816, R01 AI040996, R01 AI093553, P01 AI035296, R37
AI027998, R01 AI039614, R01 AI103760]; William F. Milton Fund
FX We thank J. Walter and A. Quade for technical assistance, S. McSorley
for the Aasf:I-Ab, RplF:I-Ab, and
PmpG1:I-Ab tetramers, and all members of the Jenkins
Laboratory for helpful discussions. Grants from the NIH (T32 GM008244
and F30 DK093242 to R.W.N., UL1 TR000114 to D. B., R01 AI107020 to J. J.
M., R01 AI080275 to K.N., R01 AI105816 and R01 AI040996 to B. S. K., R01
AI093553 to M. W., P01 AI035296 to B. T. F., and R37 AI027998, R01
AI039614, P01 AI035296, and R01 AI103760 to M. K. J.) and the William F.
Milton Fund (to J. J. M.) supported this work.
NR 51
TC 36
Z9 36
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JAN 20
PY 2015
VL 42
IS 1
BP 95
EP 107
DI 10.1016/j.immuni.2014.12.022
PG 13
WC Immunology
SC Immunology
GA AZ4NC
UT WOS:000348197500014
PM 25601203
ER
PT J
AU Corrales-Medina, VF
Alvarez, KN
Weissfeld, LA
Angus, DC
Chirinos, JA
Chang, CCH
Newman, A
Loehr, L
Folsom, AR
Elkind, MS
Lyles, MF
Kronmal, RA
Yende, S
AF Corrales-Medina, Vicente F.
Alvarez, Karina N.
Weissfeld, Lisa A.
Angus, Derek C.
Chirinos, Julio A.
Chang, Chung-Chou H.
Newman, Anne
Loehr, Laura
Folsom, Aaron R.
Elkind, Mitchell S.
Lyles, Mary F.
Kronmal, Richard A.
Yende, Sachin
TI Association Between Hospitalization for Pneumonia and Subsequent Risk of
Cardiovascular Disease
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; HEART-DISEASE; INFLAMMATORY MARKERS;
ATHEROSCLEROSIS RISK; OLDER AMERICANS; ACUTE INFECTION; SEVERE SEPSIS;
SURVIVAL; MORTALITY; STROKE
AB IMPORTANCE The risk of cardiovascular disease (CVD) after infection is poorly understood.
OBJECTIVE To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD.
DESIGN, SETTINGS, AND PARTICIPANTS We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, >= 65 years; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15 792; enrollment age, 45-64 years; enrollment period, 1987-1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status.
EXPOSURES Hospitalization for pneumonia.
MAIN OUTCOMES AND MEASURES Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease).
RESULTS Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. Compared with controls, CVD risk among pneumonia cases was highest during the first year after hospitalization and remained significantly higher than among controls through 10 years. In ARIC, of 680 pneumonia cases, 112 had CVD events over 10 years after hospitalization. After the second year, CVD risk among pneumonia cases was not significantly higher than among controls.
[GRAPHICS]
CONCLUSIONS AND RELEVANCE Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD.
C1 [Corrales-Medina, Vicente F.] Univ Ottawa, Dept Med, Ottawa, ON, Canada.
[Corrales-Medina, Vicente F.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada.
[Alvarez, Karina N.; Weissfeld, Lisa A.; Angus, Derek C.; Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness CRI, Pittsburgh, PA 15261 USA.
[Weissfeld, Lisa A.; Chang, Chung-Chou H.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
[Chirinos, Julio A.] Univ Penn, Philadelphia, PA 19104 USA.
[Chirinos, Julio A.] Philadelphia Vet Affairs Med Ctr, Div Cardiol, Philadelphia, PA USA.
[Chang, Chung-Chou H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA.
[Newman, Anne] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Loehr, Laura] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Elkind, Mitchell S.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA.
[Elkind, Mitchell S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Lyles, Mary F.] Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA.
[Kronmal, Richard A.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Yende, Sachin] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Yende, S (reprint author), Univ Pittsburgh, Dept Crit Care Med, Clin Res Invest & Syst Modeling Acute Illness CRI, 606D Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.
EM angusdc@upmc.edu; yendes@upmc.edu
RI Newman, Anne/C-6408-2013; Angus, Derek/E-9671-2012;
OI Newman, Anne/0000-0002-0106-1150; Corrales-Medina,
Vicente/0000-0002-9691-491X
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C,
HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086, HL080295]; National Institute on
Aging (NIA) [AG023629]; NHLBI [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Department of
Medicine of The Ottawa Hospital; Ottawa Hospital Research Institute in
Ottawa, Ontario, Canada; National Institute of General Medical Sciences
[K23GM083215, R01GM097471]
FX The Cardiovascular Health Study (CHS) was supported by contracts
HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant
HL080295 from the National Heart, Lung, and Blood Institute (NHLBI),
with additional contribution from the National Institute of Neurological
Disorders and Stroke (NINDS). Additional support was provided by grant
AG023629 from the National Institute on Aging (NIA). A full list of
principal CHS investigators and institutions can be found at CHS- NHLBI.
org. The Atherosclerosis Risk in Communities study was supported by
contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, and HHSN268201100012C from the NHLBI. This article is
also supported by a Junior Investigator Award from the Department of
Medicine of The Ottawa Hospital and the Ottawa Hospital Research
Institute in Ottawa, Ontario, Canada (Dr Corrales- Medina) and by
K23GM083215 and R01GM097471 from the National Institute of General
Medical Sciences (Dr Yende).
NR 41
TC 49
Z9 49
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 20
PY 2015
VL 313
IS 3
BP 264
EP 274
DI 10.1001/jama.2014.18229
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA AZ3RS
UT WOS:000348145000018
PM 25602997
ER
PT J
AU Malhotra, R
Burke, MF
Martyn, T
Shakartzi, HR
Thayer, TE
O'Rourke, C
Li, PC
Derwall, M
Spagnolli, E
Kolodziej, SA
Hoeft, K
Mayeur, C
Jiramongkolchai, P
Kumar, R
Buys, ES
Yu, PB
Bloch, KD
Bloch, DB
AF Malhotra, Rajeev
Burke, Megan F.
Martyn, Trejeeve
Shakartzi, Hannah R.
Thayer, Timothy E.
O'Rourke, Caitlin
Li, Pingcheng
Derwall, Matthias
Spagnolli, Ester
Kolodziej, Starsha A.
Hoeft, Konrad
Mayeur, Claire
Jiramongkolchai, Pawina
Kumar, Ravindra
Buys, Emmanuel S.
Yu, Paul B.
Bloch, Kenneth D.
Bloch, Donald B.
TI Inhibition of Bone Morphogenetic Protein Signal Transduction Prevents
the Medial Vascular Calcification Associated with Matrix Gla Protein
Deficiency
SO PLOS ONE
LA English
DT Article
ID CORONARY-ARTERY CALCIFICATION; SMOOTH-MUSCLE-CELLS; IN-VIVO;
MOLECULAR-MECHANISMS; VULNERABLE PLAQUE; ENDOTHELIAL-CELLS;
KEUTEL-SYNDROME; ATHEROSCLEROSIS; RUNX2; HYDROXYAPATITE
AB Objective
Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice.
Approach and Results
MGP-deficient mice (MGP(-/-)) were treated with one of two BMP signaling inhibitors, LDN-193189 or ALK3-Fc, beginning one day after birth. Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by staining tissue sections with Alizarin red. Aortic calcification was 80% less in MGP(-/-) mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control animals (P < 0.001 for both). LDN-193189-treated MGP(-/-) mice survived longer than vehicle-treated MGP(-/-) mice. Levels of phosphorylated Smad1/5 and Id1 mRNA (markers of BMP signaling) did not differ in the aortas from MGP(-/-) and wild-type mice. Markers of EndMT and osteogenesis were increased in MGP(-/-) aortas, an effect that was prevented by LDN-193189. Calcification of isolated VSMCs was also inhibited by LDN-193189.
Conclusions
Inhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP(-/-) mice. The EndMT and osteogenic transdifferentiation associated with MGP deficiency is dependent upon BMP signaling. These results suggest that BMP signal transduction has critical roles in the development of vascular calcification in MGP-deficient mice.
C1 [Malhotra, Rajeev; Burke, Megan F.; Thayer, Timothy E.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA.
[Malhotra, Rajeev; Burke, Megan F.; Thayer, Timothy E.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02115 USA.
[Martyn, Trejeeve; Shakartzi, Hannah R.; O'Rourke, Caitlin; Li, Pingcheng; Derwall, Matthias; Spagnolli, Ester; Kolodziej, Starsha A.; Hoeft, Konrad; Mayeur, Claire; Jiramongkolchai, Pawina; Buys, Emmanuel S.; Bloch, Kenneth D.; Bloch, Donald B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res,Dept Anesthesia Crit, Boston, MA 02115 USA.
[Derwall, Matthias] Rhein Westfal TH Aachen, Uniklin Aachen, Dept Anesthesiol, Aachen, Germany.
[Kumar, Ravindra] Acceleron Pharma Inc, Cambridge, MA USA.
[Yu, Paul B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Bloch, Donald B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02115 USA.
[Bloch, Donald B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02115 USA.
RP Malhotra, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA.
EM rmalhotra@partners.org
OI Yu, Paul/0000-0003-2145-4944; Malhotra, Rajeev/0000-0003-0120-4630
FU American Heart Association [11FTF7290032]; National Heart, Lung, and
Blood Institute [K08HL111210]; Howard Hughes Medical Institute; Sarnoff
Cardiovascular Research Foundation; START-Program of the Faculty of
Medicine at RWTH Aachen (MD); Leducq Foundation; National Institute of
Arthritis and Musculoskeletal and Skin Diseases [R01AR057374]; National
Institute of Diabetes and Digestive and Kidney Diseases [R01DK082971]
FX This work was supported by the American Heart Association
Fellow-to-Faculty Award # 11FTF7290032 (RM); the National Heart, Lung,
and Blood Institute (K08HL111210, RM); the Howard Hughes Medical
Institute (TM and PJ); the Sarnoff Cardiovascular Research Foundation
(MFB and TET); the START-Program of the Faculty of Medicine at RWTH
Aachen (MD); the Leducq Foundation (Multidisciplinary Program to
Elucidate the Role of Bone Morphogenetic Protein Signaling in the
Pathogenesis of Pulmonary and Systemic Vascular Diseases, PBY and KDB);
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases (R01AR057374, PBY); and the National Institute of Diabetes and
Digestive and Kidney Diseases (R01DK082971, KDB). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 54
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U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JAN 20
PY 2015
VL 10
IS 1
AR e0117098
DI 10.1371/journal.pone.0117098
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AZ4OZ
UT WOS:000348203500042
PM 25603410
ER
PT J
AU Walters, DL
Raffel, OC
Jang, IK
AF Walters, Darren L.
Raffel, O. Christopher
Jang, Ik-Kyung
TI Are the findings of optical coherence tomography sufficient for the
evaluation of the safety and efficacy of the next generation of drug
eluting stents?
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Editorial Material
DE Optical coherence tomography; Coronary stent; Neointima
ID COMPLETE NEOINTIMAL COVERAGE; INTRAVASCULAR ULTRASOUND;
CLINICAL-APPLICATIONS; IMPLANTATION; THROMBOSIS; TERMINOLOGY;
METHODOLOGY; APPOSITION; DOCUMENT; LIGHT
C1 [Walters, Darren L.; Raffel, O. Christopher] Prince Charles Hosp, Brisbane, Qld 4032, Australia.
[Walters, Darren L.; Raffel, O. Christopher] Univ Queensland, St Lucia, Qld, Australia.
[Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jang, Ik-Kyung] Harvard Univ, Med Sch Boston, Cambridge, MA 02138 USA.
RP Walters, DL (reprint author), Prince Charles Hosp, Dept Cardiol, Rode Rd, Brisbane, Qld 4032, Australia.
EM darren.walters@health.qld.gov.au
NR 25
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Z9 0
U1 1
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JAN 20
PY 2015
VL 179
BP 127
EP 128
DI 10.1016/j.ijcard.2014.10.146
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AW2AC
UT WOS:000346089400043
PM 25464431
ER
PT J
AU Goto, T
Gibo, K
Hagiwara, Y
Morita, H
Brown, DFM
Brown, CA
Hasegawa, K
AF Goto, Tadahiro
Gibo, Koichiro
Hagiwara, Yusuke
Morita, Hiroshi
Brown, David F. M.
Brown, Calvin A., III
Hasegawa, Kohei
CA Japanese Emergency Med Network Inv
TI Multiple failed intubation attempts are associated with decreased
success rates on the first rescue intubation in the emergency
department: a retrospective analysis of multicentre observational data
SO SCANDINAVIAN JOURNAL OF TRAUMA RESUSCITATION & EMERGENCY MEDICINE
LA English
DT Article
DE Intubation; Failed intubation; Rescue intubation; Success rate;
Emergency department
ID UNANTICIPATED DIFFICULT AIRWAY; RAPID-SEQUENCE INTUBATION; HOSPITAL
CARDIAC-ARREST; TRACHEAL INTUBATION; ENDOTRACHEAL INTUBATION;
MANAGEMENT; PATIENT; RECOMMENDATIONS; LARYNGOSCOPE; VENTILATION
AB Background: Although the international guidelines emphasize early and systematic use of rescue intubation techniques, there is little evidence to support this notion. We aimed to test the hypothesis that preceding multiple failed intubation attempts are associated with a decreased success rate on the first rescue intubation in emergency departments (EDs).
Methods: We analysed data from two multicentre prospective registries designed to characterize current ED airway management in Japan between April 2010 and June 2013. All patients who underwent a rescue intubation after a failed attempt or a series of failed attempts were included for the analysis. Multiple failed intubation attempts were defined as >= 2 consecutive failed intubation attempts before a rescue intubation. Primary outcome measure was success rate on the first rescue intubation attempt.
Results: Of 6,273 consecutive patients, 1,151 underwent a rescue intubation. The success rate on the first rescue intubation attempt declined as the number of preceding failed intubation attempts increased (81% [95% CI, 79%-84%] after one failed attempt; 71% [95% CI, 66%-76%] after two failed attempts; 67% [95% CI, 55%-78%] after three or more failed attempts; P-trend < 0.001). In the multivariable analysis adjusting for age, sex, principal indication, change in methods, devices, and intubator specialty, and clustering of patients within EDs, success rate on the first rescue intubation after two failed attempts was significantly lower (OR, 0.56; 95% CI, 0.41-0.77) compared to that after one failed attempt. Similarly, success rate on the first rescue intubation attempt after three or more failed attempts was significantly lower (OR, 0.49; 95% CI, 0.25-0.94) compared to that after one failed attempt.
Conclusion: Preceding multiple failed intubation attempts was independently associated with a decreased success rate on the first rescue intubation in the ED.
C1 [Goto, Tadahiro; Morita, Hiroshi] Univ Fukui Hosp, Dept Emergency Med, Yoshida, Fukui 9101193, Japan.
[Gibo, Koichiro] Okinawa Prefectural Chubu Hosp, Dept Emergency Med, Uruma, Okinawa 9042293, Japan.
[Hagiwara, Yusuke] Tokyo Metropolitan Childrens Med Ctr, Dept Pediat Emergency & Crit Care Med, Div Pediat Emergency Med, Fuchu, Tokyo 1838561, Japan.
[Brown, David F. M.; Hasegawa, Kohei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
[Brown, Calvin A., III] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
RP Goto, T (reprint author), Univ Fukui Hosp, Dept Emergency Med, 23-3 Shimoaiduki, Yoshida, Fukui 9101193, Japan.
EM qq_gto@yahoo.co.jp
FU St. Luke's Life Science Institute; Massachusetts General Hospital;
Brigham and Women's Hospital (PI, Hasegawa)
FX This study was supported by a grant from St. Luke's Life Science
Institute and a grant from Massachusetts General Hospital and Brigham
and Women's Hospital (PI, Hasegawa). The study sponsors have no
involvement in the study design, in the collection, analysis and
interpretation of data; in the writing of the manuscript; and in the
decision to submit the manuscript for publication
NR 37
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Z9 5
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-7241
J9 SCAND J TRAUMA RESUS
JI Scand. J. Trauma Resusc. Emerg. Med.
PD JAN 16
PY 2015
VL 23
DI 10.1186/s13049-014-0085-8
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA CD1OX
UT WOS:000350845300001
PM 25700237
ER
PT J
AU Cheng, C
Gao, NX
Yu, CJ
Wang, ZY
Wang, J
Hao, EH
Wei, Y
Mu, XL
Tian, YL
Ran, CZ
Jiao, LJ
AF Cheng, Chi
Gao, Naixun
Yu, Changjiang
Wang, Zhaoyun
Wang, Jun
Hao, Erhong
Wei, Yun
Mu, Xiaolong
Tian, Yanli
Ran, Chongzhao
Jiao, Lijuan
TI Diversity-Oriented Facile Access to Highly Fluorescent
Membrane-Permeable Benz[c,d]indole N-Heteroarene BF2 Dyes
SO ORGANIC LETTERS
LA English
DT Article
ID BORON DIFLUORIDE DYES; BODIPY DYES; BORATE COMPLEXES; GFP-CHROMOPHORE;
FAR-RED; PROBES; ANALOGS; DESIGN; DERIVATIVES; STRATEGIES
AB A diversity-oriented one-pot synthesis of a series of membrane-permeable BF2-rigidified benz[c,d]indole N-heteroarene BBN and BBC dyes has been achieved from the condensation of two commercial components (benz[c,d]indol-2-one and a set of N-heteroarene derivatives that can be selected from thousands of commercially available sources) and the subsequent in situ BF2