tbuckley/cabot-search huggingface dataset:
PRO-BMI study: prognostic role of body mass index (BMI) in metastatic castration resistant prostate cancer (mCRPC) patients receiving chemotherapy.
Authors: Marcello Tucci, Stefania Eufemia Lutrino, Massimo Di Maio, Giuseppe Procopio, Francesco Massari, Nicola Calvani, Caterina Fontanella, Francesco Atzori, Sandro Barni, Chiara Caliolo, Francesca Vignani, Caterina Accettura, Annamaria Quaranta, Enrica Mazzoni, Maria D'amico, Claudio Scavelli, Maria Concetta Chetrì, Pasqualinda Ferrara, Saverio Cinieri
Journal: Journal of Clinical Oncology (2016)

e16543 Background: Limited data are available regarding the relationship between body mass index (BMI) and metastatic castration resistant prostate cancer (mCRPC). Pro-BMI trial is an Italian, observational, retrospective study designed to evaluate the correlation between BMI and outcome, in terms of progression-free survival (PFS) and overall survival (OS), of mCRPC patients (pts) treated with first-line chemotherapy. Methods: We analyzed 212 consecutive mCRPC pts who received docetaxel 75 mg/m2 every 3 weeks as first-line therapy in 10 Italian Institutions between 2003 and 2015. Data about baseline characteristics, treatment and outcome were collected in an anonymized dedicated database. Pts were stratified in 3 groups according to the World Health Organization BMI classification: normal weight (BMI < 25kg/m2), overweight (25 ≤ BMI < 30kg/m2), and obese (BMI ≥ 30kg/m2). PFS and OS were measured from the date of start of docetaxel: preplanned analyses aimed to compare obese vs. normal/overweight pts. Results: The median age at the time of start of docetaxel for mCRPC was 69 years (range 45-87). At baseline, 32% of pts were normal weight, 51% were overweight, and 17% were obese. 89% of obese pts had at least 1 co-morbidity versus 63% of overweight pts and 54% of normal weight pts (p = 0.002). PFS was not statistically different between obese (median 10.4 months) and normal/overweight pts (median 7.2 months, Hazard Ratio 0.84, 95%CI 0.58 – 1.22, p = 0.35). Similarly, OS was not statistically different between obese (median 27.7 months) and normal/overweight pts (median 24.4 months, Hazard Ratio 0.80, 95%CI 0.49 – 1.31, p = 0.38). Proportion of pts starting with full dose and needing dose reduction was slightly higher in obese pts (32.4%) vs. normal/overweight pts (21.5%), but this difference was not statistically significant (p = 0.17). Incidence of any hematologic toxicity was significantly higher in obese pts (69% vs 50%, p = 0.03). Conclusions: In this retrospective analysis, no significant association between BMI and outcome of pts receiving docetaxel for mCRPC was found. However, our results suggest that obesity could be associated with a lower tolerance to chemotherapy.
Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection
Authors: Hung-Yu Sun, Pin-Nan Cheng, Chiung-Ying Tseng, Wei-Jen Tsai, Yen-Cheng Chiu, Kung-Chia Young
Journal: Gut (2017)

Objective Lipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the clinical manifestation and mechanistic relevance of plasma triglyceride (TG), cholesterol (Chol), lipoproteins and apolipoproteins (apos) after DAA treatment. Design Twenty-four patients with chronic genotype 1 (GT1) HCV treated with elbasvir/grazoprevir or ledipasvir/sofosbuvir for 12 weeks, and followed-up thereafter, were recruited. Their TG, Chol, apoAI and apoB levels were quantified in plasma samples and individually fractionated lipoprotein of various classes. Liver fibrosis was evaluated using the FIB-4 Score. The TG and Chol loading capacities were calculated with normalisation to apoB, which represents per very low density lipoprotein (VLDL) and LDL particle unit Results DAA treatment achieved a sustained virological response rate of 91.7% and reduced the FIB-4 Score. Relative to the baseline, the plasma TG level was reduced but the Chol level increased gradually. Plasma apoB levels and apoB/apoAI ratio were transiently downregulated as early as the first 4 weeks of treatment. The TG and Chol loading capacities in VLDL were elevated by ~20% during the period of DAA treatment and had steadily increased by 100% at follow-up. Furthermore, the TG-to-Chol ratio in VLDL was increased, while the ratio in LDL was reduced, indicating an efficient catabolism. Conclusion The DAA treatment of patients with chronic hepatitis C might lead to efficient HCV eradication and hepatic improvement concomitantly evolving with favouring lipoprotein/apo metabolisms.
Large panel genomic profiling using CancerPlex to reveal candidates for HER2 targeted therapies in colorectal cancer.
Authors: Hiroshi Ichikawa, Yoshifumi Shimada, Masayuki Nagahashi, Hitoshi Kameyama, Jun Sakata, Takuma Okamura, Yosuke Tajima, Ryoma Yagi, Nobuaki Sato, Yasumasa Takii, Satoshi Maruyama, Hitoshi Nogami, Keiichi Honma, Takashi Kawasaki, Taro Inada, Shujiro Okuda, Alexei Protopopov, Stephen Lyle, Kazuaki Takabe, Toshifumi Wakai
Journal: Journal of Clinical Oncology (2016)

e13125 Background: Human epidermal growth receptor type 2 (HER2) overexpression/amplification is associated with the efficacy of HER2 targeted therapies in breast and gastric cancers, where candidates for its targeted therapies are selected by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) testing. However, the HER2 status in colorectal cancer (CRC) has not been fully investigated to date. CancerPlex is a comprehensive next-generation sequencing-based test that evaluates 400-plus genes for mutations and copy number changes, including HER2. In the present study, we aimed to clarify the association between HER2 status and HER2 gene alteration detected with CancerPlex in CRC. Methods: This retrospective study included 100 patients with Stage I-IV CRC, who were evaluated HER2 status and HER2 gene alteration. IHC for HER2 was classified as 4 grades according to the immunoreactivity. The patients with IHC2+ were further tested with FISH. IHC3+/IHC2+ and FISH positive patients were defined as HER2 positive. HER2 gene alteration was tested with CancerPlex, and the associations between HER2 status and HER2 gene alteration were analyzed using Fisher’s exact test. Results: HER2 positive cases were observed in 8% patients (IHC3+ in 6% and IHC2+ and FISH positive in 2% patients). CancerPlex results demonstrated that 6% had HER2 amplification, 15% had HER2 mutations, and 1% had both HER2 amplification and mutation. Additionally, CancerPlex detected the other mutations of MAPK pathway (KRAS, NRAS, HRAS, and BRAF). The Fisher’s exact test revealed a significant association between HER2 status and HER2 amplification detected with CancerPlex (P < 0.001), however, there was no significant association between HER2 status and HER2 mutation. Conclusions: We found 8 of 100 (8%) Japanese CRC cases are HER2 positive. There is a significant association between HER2 status and HER2 amplification detected with CancerPlex. CancerPlex is a comprehensive testing tool for detecting gene alterations including not only mutations of MAPK pathway (KRAS, NRAS, HRAS, and BRAF), but also HER2 amplification, which is a possible useful predictor of the candidates for HER2 targeted therapies in CRC.
Association of clinicopathological parameters with outcome in patients with metastatic breast cancer treated with eribulin in South East London.
Authors: Su Li, Antonios Agorastos, Hartmut Kristeleit
Journal: Journal of Clinical Oncology (2017)

e12567 Background: Eribulin is licensed for the ≥2-line treatment of patients with metastatic breast cancer. We assessed outcome of eribulin treatment in real world patients. Methods: We conducted a retrospective analysis of consecutive patients treated with eribulin for metastatic breast cancer at Guys Cancer Centre and affiliated units in South East London between Oct 2011 and Nov 2016. All data was extracted from electronic patient records. Results: We identified 158 patients with a median age of 55.8 years (range 30-94). Median WHO performance status (PS) was 1 (0-4). 68% were of white ethnicity, 23% black and 5% other. 67% were ER+, 13% Her2+ and 26% triple negative breast cancer (TNBC). 96% had visceral disease and 15% of patients had CNS involvement. Eribulin was given in 1% of patients as 1 st line, 10% as 2 nd , 51% as 3 rd , 21% as 4 th and 17% as 5 th line treatment or beyond. Patients received a median of 4 cycles of eribulin (range 1-35). Median overall survival (OS) was 9.3 months and progression free survival (PFS) 3.4 months. A response was seen in 34% of patients, disease stability in 19%. OS was significantly better for patients &gt; 60 years of age compared to &lt; 60 years (10.3 vs 8.3 months, HR 1.45, 95% CI 1.04-2.10). OS for ER+ was 10.2 vs 7.6 months for ER- and for TNBC. OS for white patients was 9.4 months vs 8 months for black ethnicity. Black patients were younger (median age 50.5 vs 59.9). We observed that amongst TNBC patients black ethnicity had a trend towards longer survival (9.1 months for black vs 7.7 months for white). Due to the retrospective nature of this study toxicity was not well documented. Dose reductions were required in 35% of patients and 3% experienced neutropenic fever. Conclusions: OS was inferior to documented outcome in the EMBRACE trial (9.3 vs 13.1 months). This is despite a lower median number of previous lines of chemotherapy. Our cohort had a poorer baseline PS (20% PS2, 3% PS3 and above vs 8% PS2 in EMBRACE) and a higher proportion of black patients (23% vs 4% in EMBRACE). 15% had known CNS disease. The observation that triple negative patients of black ethnicity fare better than white patients treated with eribulin warrants further exploration.
The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients
Authors: Jason L. Vassy, Kurt D. Christensen, Erica F. Schonman, Carrie L. Blout, Jill O. Robinson, Joel B. Krier, Pamela M. Diamond, Matthew Lebo, Kalotina Machini, Danielle R. Azzariti, Dmitry Dukhovny, David W. Bates, Calum A. MacRae, Michael F. Murray, Heidi L. Rehm, Amy L. McGuire, Robert C. Green
Journal: Annals of Internal Medicine (2017)

Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT01736566) Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years. Intervention: Patients were randomly assigned to receive a family history report alone (FH group) or in combination with an interpreted WGS report (FH + WGS group), which included monogenic disease risk (MDR) results (associated with Mendelian disorders), carrier variants, pharmacogenomic associations, and polygenic risk estimates for cardiometabolic traits. Each patient met with his or her PCP to discuss the report. Measurements: Clinical outcomes and health care use through 6 months were obtained from medical records and audio-recorded discussions between PCPs and patients. Patients' health behavior changes were surveyed 6 months after receiving results. A panel of clinician-geneticists rated the appropriateness of how PCPs managed MDR results. Results: Mean age was 55 years; 58% of patients were female. Eleven FH + WGS patients (22% [95% CI, 12% to 36%]) had new MDR results. Only 2 (4% [CI, 0.01% to 15%]) had evidence of the phenotypes predicted by an MDR result (fundus albipunctatus due to RDH5 and variegate porphyria due to PPOX). Primary care physicians recommended new clinical actions for 16% (CI, 8% to 30%) of FH patients and 34% (CI, 22% to 49%) of FH + WGS patients. Thirty percent (CI, 17% to 45%) and 41% (CI, 27% to 56%) of FH and FH + WGS patients, respectively, reported making a health behavior change after 6 months. Geneticists rated PCP management of 8 MDR results (73% [CI, 39% to 99%]) as appropriate and 2 results (18% [CI, 3% to 52%]) as inappropriate. Limitation: Limited sample size and ancestral and socioeconomic diversity. Conclusion: Adding WGS to primary care reveals new molecular findings of uncertain clinical utility. Nongeneticist providers may be able to manage WGS results appropriately, but WGS may prompt additional clinical actions of unclear value. Primary Funding Source: National Institutes of Health.
Ombudsman urges health professionals to listen to patients
Authors: Susan Mayor
Journal: BMJ (2000)

Inadequate supervision and support of doctors in training, poor record keeping, and mishandling of patients' complaints emerged as the three major problems in the latest investigations of the health service ombudsman in his role as health service commissioner for England, in a report published last week.

The report includes 35 investigations about health services in England completed by the ombudsman's office between 1 April and 30 July 2000. Most of the cases arose from events that occurred in 1999.

Three investigations involved …
Cosmetics, Regulations, and the Public Health
Authors: Robert M. Califf, Jonathan McCall, Daniel B. Mark
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Genomic complexity and prognosis of renal medullary carcinoma.
Authors: Hina Khan, Jeff Hall, A. Ari Hakimi, Kith Pradhan, Hongying Huang, Lawrence Cytryn, Caterina P. Minniti, Amit Verma, Benjamin Adam Gartrell
Journal: Journal of Clinical Oncology (2016)

1544 Background: Renal medullary carcinoma (RMC) is a rare and aggressive epithelial neoplasm seen in patients (pts) with sickle cell trait (SCT). Disease is often advanced at presentation and prognosis of RMC is presumed to be poor; though large studies are lacking due to the rarity of the disease and most of the data is based on isolated case reports. Data on molecular profiling of RMC is limited, and is needed due to chemorefractiveness of reported cases. Montefiore Medical Center serves a large population of patients with sickle cell anemia and we set out to study the clinical and molecular epidemiology of RMC at our center. Methods: After IRB approval, analysis of our large single center SCT cohort from 1995-2015 identified 12 pts of RMC with an approximate prevalence of 1 in 2500 SCT pts. Formalin-fixed paraffin-embedded tissues from 8 of these pts were retrieved and subjected to targeted sequencing of 150 genes at high depth. Results: Median age at presentation was 24.5 (13-79) years. RMC was male predominant (3:1), 10 pts were African American and 2 were Hispanic. Most pts presented with stage 4 disease (11/12). The median survival was 8.5 (1-77) mos with no objective responses to standard chemotherapy. Among the 8 archival specimens available for targeted genomic sequencing, 6 had ≥ 2 mutations. Notable mutations of pathogenic significance included TP53, SMARCB1, CDK4, JAK2 and TET2. SMARCB1, which has been implicated in previous case reports, was mutated with a frameshift insertion at ‘c.203dupA, p.H68Qfs*3’. Conclusions: We analyzed a large cohort of RMC pts and observed that this malignancy presents in young pts with sickle cell trait. RMC presents at advanced stages, is chemoresistant and has a dismal survival. Genetic profiling shows a complex mutational profile with novel alterations in TET2, CDK4 and SMARCB1. Age, sex Mutations Survival (months) 1 20, M CDH1 10 TP53 (pathogenic) EP300 (pathogenic) 2 28, M CDK4 (pathogenic) 15 TP53 (pathogenic) GATA1 JAK3 KDM5A LRP1B NSD1 PIK3R1 3 13, M ERBB4 77 TET2 4 79, M TET2 (pathogenic) 2.5 FAT1 KMT2A FLT3 MET (pathogenic) 5 15, F None 7 6 22, M MYD88 3 JAK2 (pathogenic) PTCH1 NF1 SMARCB1 (pathogenic) LOC100131635*BCL6* (pathogenic) 7 27, M None 16 8 34, M TSC2 (pathogenic) 1 PALB2 PLCG2
Palbociclib (PAL) in combination with fulvestrant (F) in pre-/peri-menopausal (PreM) women with metastatic breast cancer (MBC) and prior progression on endocrine therapy – results from Paloma-3.
Authors: Sibylle Loibl, Nicholas C. Turner, Jungsil Ro, Massimo Cristofanilli, Hiroji Iwata, Seock-Ah Im, Norikazu Masuda, Sherene Loi, Fabrice Andre, Nadia Harbeck, Sunil Verma, Elizabeth Folkerd, Kathy Puyana Theall, Ke Zhang, Cynthia Huang Bartlett, Mitch Dowsett
Journal: Journal of Clinical Oncology (2016)

524 Background: Standard endocrine therapy options for PreM women with MBC are limited and better options are needed. PALOMA-3 is the first large registrational study to include PreM women with HR+ MBC. Methods: In this double-blind phase 3 study, patients (pts) with HR+/HER2– MBC were randomized 2:1 to receive PAL (125 mg/d orally for 3 wk followed by 1 wk off) + F (500 mg) (PAL+F) or placebo (PLB)+F. PreM women received ovarian suppression starting ≥ 4 wk before randomization and throughout treatment (trt) with gosrelin. Reproductive biochemistry measurements (estradiol [E2] and FSH) were assessed using blood samples from day 15 of trt. Results: 108 (21%) of 521 enrolled pts were PreM (72, PAL+F; 36, PLB+F). Age groups were: ≤ 40 yrs (31%), > 40-50 yrs (46%), and > 50-59 yrs (23%). Of the 108 pts: 44 (41%) were Asian, 74 (69%) had ER+/PR+ disease, 27 (25%) were ER+/PR-, 68 (63%) had visceral disease, 55 (51%) had prior tamoxifen (TAM) only, and 50 (46%) had prior TAM + aromatase inhibitors. 27 (25%) of 108 pts had disease progression while on/within 12 mo of endocrine adjuvant trt. 46 (43%) of the PreM pts received one line of prior chemotherapy in the MBC setting. Median progression-free survival (PFS) among PreM women was 9.5 mo for PAL+F and 5.6 mo for PLB+F (HR, 0.50; 95% CI: 0.29-0.87; p = 0.006). Clinical benefit rate was 69% vs 44% (OR, 2.84; p = 0.01). In the PAL+F arm, the safety profile for PreM and PostM women was similar for all grade adverse event (AE) rate (99% each), grade 3/4 AEs (83% and 71%, respectively), and serious AEs (14% and 12%). The discontinuation rate due to AEs for PAL/PLB was 6% and 5%, respectively. E2 and FSH concentrations among PreM women for whom day 15 samples were available showed good suppression in both arms. PAL did not alter ovarian function suppression and plasma E2 levels were not significantly associated with the PFS results. Conclusions: The combination of PAL+F with goserelin is an effective and well-tolerated trt for PreM women who developed endocrine resistant MBC. The data on PAL plus F/goserelin support its use in HR+ MBC and expands the trt options for PreM women. Clinical trial information: NCT01942135.
Annals for Hospitalists Inpatient Notes - Research Highlights From Hospital Medicine 2017
Authors: Robert Burke, Andrew Auerbach
Journal: Annals of Internal Medicine (2017)

Web Exclusives20 June 2017Annals for Hospitalists Inpatient Notes - Research Highlights From Hospital Medicine 2017Robert Burke, MD, MS and Andrew Auerbach, MD, MPHRobert Burke, MD, MSFrom Denver Veterans Affairs Medical Center, Denver, Colorado, and University of California, San Francisco, Francisco, California.Search for more papers by this author and Andrew Auerbach, MD, MPHFrom Denver Veterans Affairs Medical Center, Denver, Colorado, and University of California, San Francisco, Francisco, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-1243 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This year's Society of Hospital Medicine (SHM) Annual Meeting was the largest ever, with close to 5000 attendees from all over the world. Here are summaries of 5 of the best research posters from the meeting.Factors Associated With Excess Duration of Antibiotic Therapy for Patients Admitted With Pneumonia in Michigan Hospitals: A Cohort StudyVaughn VM, Flanders SA, Conlon A, Chopra V, Nielsen D, Malani A, Thyagarajan R, Hsaiky L, and Gandhi TQuestion: How often do non–intensive care unit medical patients receive excess antibiotic therapy for community-acquired pneumonia?Methods: In this retrospective cohort of about 2000 inpatients with pneumonia at 10 ... Author, Article, and Disclosure InformationAffiliations: From Denver Veterans Affairs Medical Center, Denver, Colorado, and University of California, San Francisco, Francisco, California.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1243.Requests for Single Reprints: Robert Burke, MD, MS, Denver Veterans Affairs Medical Center, 1055 Clermont Street, Denver, CO 80220; e-mail, Robert.[email protected]gov. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAnnals for Hospitalists - 20 June 2017 David H. Wesorick and Vineet Chopra Metrics Cited byCharacterizing pediatric inpatient sleep duration and disruptions 20 June 2017Volume 166, Issue 12Page: HO2-HO3KeywordsAntibioticsHospital medicineHospitalistsInpatientsMedical risk factorsPeripherally inserted central cathetersPneumoniaVenous thromboembolismVital signsWhite blood cells ePublished: 20 June 2017 Issue Published: 20 June 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impact de la réalisation précoce d'un examen par capsule endoscopique au cours d'une hémorragie digestive aigue inexpliquée extériorisée par voie basse
Authors: E Ben Soussan, S Sacher-Huvelin, V Maunoury, M Gaudric, P Jacob, MG Lapalus, J Mauillon, D Coumaros, S Herve, T Ponchon, D Heresbach, CE Sfed
Journal: Endoscopy (2006)

L'objectif principal de cette étude prospective multicentrique était d'évaluer l'impact diagnostique et thérapeutique de la capsule endoscopique (CE) effectuée précocement lors d'une hémorragie digestive aigue extériorisée par voie basse et inexpliquée par les examens endoscopiques conventionnels (HDAI).
Erratum: Airway mucosal blood flow in humans: Response to adrenergic agonists (American Journal of Respiratory and Critical Care Medicine (1994) 149 (1132-1137))
Authors: D. J. Onorato, M. C. Demirozu, A. Breitenbucher, N. D. Atkins, A. D. Chediak, A. Wanner
Journal: American Journal of Respiratory and Critical Care Medicine (1995)
Long-Term Outcomes Following CD19 CAR T Cell Therapy for B-ALL Are Superior in Patients Receiving a Fludarabine/Cyclophosphamide Preparative Regimen and Post-CAR Hematopoietic Stem Cell Transplantation
Authors: Daniel W. Lee, Maryalice Stetler-Stevenson, Constance M. Yuan, Nirali N Shah, Cindy Delbrook, Bonnie Yates, Hua Zhang, Ling Zhang, James N. Kochenderfer, Steven A. Rosenberg, Terry J Fry, David Stroncek, Crystal L. Mackall
Journal: Blood (2016)