tbuckley/cabot-search huggingface dataset:
A Phase II and Biomarker Study of Sorafenib Combined with Modified FOLFOX in Patients with Advanced Hepatocellular Carcinoma
Authors: Lipika Goyal, Hui Zheng, Thomas A. Abrams, Rebecca Miksad, Andrea J. Bullock, Jill N. Allen, Matthew B. Yurgelun, Jeffrey W. Clark, Avinash Kambadakone, Alona Muzikansky, Michelle Knowles, Aralee Galway, Anthony J. Afflitto, Caroline F. Dinicola, Eileen Regan, Tai Hato, Emilie Mamessier, Kohei Shigeta, Rakesh K. Jain, Dan G. Duda, Andrew X. Zhu
Journal: Clinical Cancer Research (2018)

Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma (HCC). The phase III SHARP trial showed a median time-to-progression (mTTP) of 5.5 months, overall response rate (ORR) of 2%, and median overall survival (mOS) of 10.7 months with sorafenib. FOLFOX4 has shown modest activity in advanced HCC. We evaluated the combination of sorafenib and modified (m)FOLFOX in a single-arm, multicenter phase II study.The study included Child-Pugh A patients with advanced HCC and no prior systemic therapies. Patients received sorafenib 400 mg twice a day for 2 weeks, followed by concurrent mFOLFOX [5-fluorouracil (5-FU) 1,200 mg/m2/day for 46 hours, leucovorin 200 mg/m2, and oxaliplatin 85 mg/m2 biweekly]. The primary endpoint was mTTP with an alternative hypothesis of 7 months, and secondary endpoints included ORR, mOS, and circulating biomarkers.The study enrolled 40 patients: HCV/EtOH/HBV, 43%/28%/13%; Child-Pugh A5, 70%. Notable grade 3/4 adverse events (AE) included AST/ALT elevation (28%/15%), diarrhea (13%), hyperbilirubinemia (10%), hand-foot syndrome (8%), and bleeding (8%). mTTP was 7.7 months [95% confidence interval (CI): 4.4-8.9], ORR 18%, and mOS 15.1 months (7.9-16.9). Sorafenib + mFOLFOX increased plasma PlGF, VEGF-D, sVEGFR1, IL12p70, and CAIX and CD4+ and CD8+ effector T lymphocytes and decreased plasma sVEGFR2 and s-c-KIT and regulatory T cells (Tregs). Shorter TTP was associated with high baseline sVEGFR1. Shorter TTP and OS were associated with increases in Tregs and CD56Dim natural killer (NK) cells after sorafenib alone and plasma sMET after combination treatment (all P < 0.05).Sorafenib + mFOLFOX met the prespecified endpoint with encouraging efficacy but moderate hepatotoxicity. Thus, this regimen may be effective in select patients with adequate liver reserve. Biomarker evaluations suggested a correlation between time-to-progression (TTP) and angiogenic biomarkers and circulating Tregs.
Immune Escape of Relapsed AML Cells after Allogeneic Transplantation
Authors: Matthew J. Christopher, Allegra A. Petti, Michael P. Rettig, Christopher A. Miller, Ezhilarasi Chendamarai, Eric J. Duncavage, Jeffery M. Klco, Nicole M. Helton, Michelle O’Laughlin, Catrina C. Fronick, Robert S. Fulton, Richard K. Wilson, Lukas D. Wartman, John S. Welch, Sharon E. Heath, Jack D. Baty, Jacqueline E. Payton, Timothy A. Graubert, Daniel C. Link, Matthew J. Walter, Peter Westervelt, Timothy J. Ley, John F. DiPersio
Journal: New England Journal of Medicine (2018)

As consolidation therapy for acute myeloid leukemia (AML), allogeneic hematopoietic stem-cell transplantation provides a benefit in part by means of an immune-mediated graft-versus-leukemia effect. We hypothesized that the immune-mediated selective pressure imposed by allogeneic transplantation may cause distinct patterns of tumor evolution in relapsed disease.We performed enhanced exome sequencing on paired samples obtained at initial presentation with AML and at relapse from 15 patients who had a relapse after hematopoietic stem-cell transplantation (with transplants from an HLA-matched sibling, HLA-matched unrelated donor, or HLA-mismatched unrelated donor) and from 20 patients who had a relapse after chemotherapy. We performed RNA sequencing and flow cytometry on a subgroup of these samples and on additional samples for validation.On exome sequencing, the spectrum of gained and lost mutations observed with relapse after transplantation was similar to the spectrum observed with relapse after chemotherapy. Specifically, relapse after transplantation was not associated with the acquisition of previously unknown AML-specific mutations or structural variations in immune-related genes. In contrast, RNA sequencing of samples obtained at relapse after transplantation revealed dysregulation of pathways involved in adaptive and innate immunity, including down-regulation of major histocompatibility complex (MHC) class II genes ( HLA-DPA1, HLA-DPB1, HLA-DQB1, and HLA-DRB1) to levels that were 3 to 12 times lower than the levels seen in paired samples obtained at presentation. Flow cytometry and immunohistochemical analysis confirmed decreased expression of MHC class II at relapse in 17 of 34 patients who had a relapse after transplantation. Evidence suggested that interferon-γ treatment could rapidly reverse this phenotype in AML blasts in vitro.AML relapse after transplantation was not associated with the acquisition of relapse-specific mutations in immune-related genes. However, it was associated with dysregulation of pathways that may influence immune function, including down-regulation of MHC class II genes, which are involved in antigen presentation. These epigenetic changes may be reversible with appropriate therapy. (Funded by the National Cancer Institute and others.).
Monitoring film coalescence from aqueous polymeric dispersions using atomic force microscopy: Surface topographic and nano-adhesion studies
Authors: Ziyi Yang, Duncan Q.M. Craig
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The aim of the investigation was to develop the use of topographic and nano-adhesion atomic force microscopy (AFM) studies as a means of monitoring the coalescence of latex particles within films produced from a pharmaceutically relevant aqueous dispersion (EudragitⓇNE30D). Films were prepared via spin coating and analysed using AFM, initially via tapping mode for topographic assessment followed by force-distance measurements which allowed assessment of site-specific adhesion. The results showed that colloidal particles were clearly observed topographically in freshly prepared samples, with coalescence detected on curing via the disappearance of discernible surface features and a decrease in roughness indices. The effects of temperature and humidity on film curing were also studied, with the former having the most pronounced effect. AFM force measurements showed that the variation in adhesive force reduced with increasing curing time, suggesting a novel method of quantifying the rate of film formation upon curing. It was concluded that the AFM methods outlined in this study may be used as a means of qualitatively and quantitatively monitoring the curing of pharmaceutical films as a function of time and other variables, thereby facilitating rational design of curing protocols.
Changes in Prevalence of Health Care–Associated Infections in U.S. Hospitals
Authors: Shelley S. Magill, Erin O’Leary, Sarah J. Janelle, Deborah L. Thompson, Ghinwa Dumyati, Joelle Nadle, Lucy E. Wilson, Marion A. Kainer, Ruth Lynfield, Samantha Greissman, Susan M. Ray, Zintars Beldavs, Cindy Gross, Wendy Bamberg, Marla Sievers, Cathleen Concannon, Nicolai Buhr, Linn Warnke, Meghan Maloney, Valerie Ocampo, Janet Brooks, Tolulope Oyewumi, Shamima Sharmin, Katherine Richards, Jean Rainbow, Monika Samper, Emily B. Hancock, Denise Leaptrot, Eileen Scalise, Farzana Badrun, Ruby Phelps, Jonathan R. Edwards
Journal: New England Journal of Medicine (2018)

A point-prevalence survey that was conducted in the United States in 2011 showed that 4% of hospitalized patients had a health care–associated infection. We repeated the survey in 2015 to assess changes in the prevalence of health care–associated infections during a period of national attention to the prevention of such infections.
Increased Muscular MDP Activity in the Lower Extremities Caused by Multiple Arterial Thromboses
Authors: Fuqiang Shao, Na Li, Peng Xie, Yiman Li, Heng Zhang
Journal: Clinical Nuclear Medicine (2018)

Many reasons could lead to abnormal increased extraosseous tracer uptake on Tc-MDP bone scintigraphy. A 75-year-old man was referred a bone scintigraphy to evaluate his chest pain. The images revealed rib fractures. In addition, increased MDP activity in the muscle of the lower extremities was noted. The abnormal increased uptake in the muscles was likely related to the arterial thromboses revealed by vascular ultrasonography. The patient received interventional embolectomy.
Ectopic Papillary Thyroid Carcinoma Mimicking Esophageal Cancer in FDG PET
Authors: Rui Gao, Shan Gao, Xi Jia, Hongyan Wang, Guangjian Zhang
Journal: Clinical Nuclear Medicine (2018)

Ectopic papillary thyroid carcinoma (PTC) usually occurs along the cervical midline and was barely reported in FDG PET studies. We present a rare case of ectopic PTC within the esophagus with focal FDG activity on FDG PET in a 43-year-old woman who was previously diagnosed as having esophageal cancer based on the endoscopy and PET findings. Surgical pathology revealed the presence of PTC lesion within the muscular layer of the esophagus. Combining this with the negative imaging and laboratory results suggesting a normal thyroid gland led to a diagnosis of primary ectopic PTC.
Correction to: “Familial venoms”: a thallium intoxication cluster
Authors: Francesco Ratti, Alberto Facchini, Eduardo Beck, Sara Cazzaniga, Silvia Francesconi, Cecilia Tedesco, Alessandro Terrani, Gabriella Ciceri, Roberto Colombo, Maurizio Saini, Valeria Margherita Petrolini, Giuseppe Citerio
Journal: Intensive Care Medicine (2018)
Pericardial Solitary Fibrous Tumor on FDG PET/CT
Authors: Dan Shao, Shu-Xia Wang
Journal: Clinical Nuclear Medicine (2018)

Solitary fibrous tumor, which can occur in all parts of the body and is more frequently found in the visceral pleura, is a rare mesenchymal tissue-originating spindle cell tumor derived from CD34-positive dendriticmesenchymal cells, but it rarely occurs in the pericardium. We reported the FDG PET/CT findings of a pathologically confirmed benign pericardial solitary fibrous tumor in a 51-year-old woman.
Don’t blacklist surgery for common hand conditions, says royal college
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

NHS England should not restrict access to surgery for carpal tunnel syndrome, Dupuytren’s contracture, trigger finger, or wrist ganglion, the Royal College of Surgeons has urged.

In July, NHS England proposed cutting funding for 17 procedures it considered unnecessary, to save money and eliminate unwarranted clinical variation around the country.1 The list included a range of procedures, such as injections for non-specific low back pain without sciatica, knee arthroscopy for patients with osteoarthritis, breast reduction, and surgery for snoring.

NHS England said that these 17 …
Association between ambient temperature and mortality risk and burden: time series study in 272 main Chinese cities
Authors: Renjie Chen, Peng Yin, Lijun Wang, Cong Liu, Yue Niu, Weidong Wang, Yixuan Jiang, Yunning Liu, Jiangmei Liu, Jinlei Qi, Jinling You, Haidong Kan, Maigeng Zhou
Journal: BMJ (2018)

To examine the association between temperature and cause specific mortality, and to quantify the corresponding disease burden attributable to non-optimum ambient temperatures.Time series analysis.272 main cities in China.Non-accidental deaths in 272 cities covered by the Disease Surveillance Point System of China, from January 2013 to December 2015.Daily numbers of deaths from all non-accidental causes and main cardiorespiratory diseases. Potential effect modifiers included demographic, climatic, geographical, and socioeconomic characteristics. The analysis used distributed lag non-linear models to estimate city specific associations, and multivariate meta-regression analysis to obtain the effect estimates at national and regional levels.1 826 186 non-accidental deaths from total causes were recorded in the study period. Temperature and mortality consistently showed inversely J shaped associations. At the national average level, relative to the minimum mortality temperature (22.8°C, 79.1st centile), the mortality risk of extreme cold temperature (at -1.4°C, the 2.5th centile) lasted for more than 14 days, whereas the risk of extreme hot temperature (at 29.0°C, the 97.5th centile) appeared immediately and lasted for two to three days. 14.33% of non-accidental total mortality was attributable to non-optimum temperatures, of which moderate cold (ranging from -1.4 to 22.8°C), moderate heat (22.8 to 29.0°C), extreme cold (-6.4 to -1.4°C), and extreme heat (29.0 to 31.6°C) temperatures corresponded to attributable fractions of 10.49%, 2.08%, 1.14%, and 0.63%, respectively. The attributable fractions were 17.48% for overall cardiovascular disease, 18.76% for coronary heart disease, 16.11% for overall stroke, 14.09% for ischaemic stroke, 18.10% for haemorrhagic stroke, 10.57% for overall respiratory disease, and 12.57% for chronic obstructive pulmonary diseases. The mortality risk and burden were more prominent in the temperate monsoon and subtropical monsoon climatic zones, in specific subgroups (female sex, age ≥75 years, and ≤9 years spent in education), and in cities characterised by higher urbanisations rates and shorter durations of central heating.This nationwide study provides a comprehensive picture of the non-linear associations between ambient temperature and mortality from all natural causes and main cardiorespiratory diseases, as well as the corresponding disease burden that is mainly attributable to moderate cold temperatures in China. The findings on vulnerability characteristics can help improve clinical and public health practices to reduce disease burden associated with current and future abnormal weather.
An unusual outbreak of norovirus associated with a Halloween-themed swimming pool party in England, 2016
Authors: Karthik Paranthaman, Ellen Pringle, Alison Burgess, Neil Macdonald, James Sedgwick
Journal: Eurosurveillance (2018)

In October 2016, an outbreak of norovirus occurred among attendees of a Halloween-themed party at a public swimming pool in the south-east of England. Norovirus genogroup II was confirmed in 11 cases. In the retrospective cohort study of pool users, 68 individuals (37 female and 31 male), with a median age of 11 years (range: 0-50 years), met the case definition of developing diarrhoea or vomiting between 6 and 72 h after the pool visit. Multivariable analysis showed that increasing age was associated with a reduced risk of illness (odds ratio = 0.91; 95% confidence interval: 0.83-0.99). Pool behaviours (swallowing water) and the timing of visit (attending pool party after automatic dosing system was switched off) were independently associated with increased risk. Environmental investigations revealed that the automatic dosing system was switched off to reduce chlorine levels to an intended range of 0.5-1 parts per million to facilitate the use of a commercial red dye. There was a lack of compliance with the operator's own pool operating procedures, particularly on maintaining effective chlorine levels in pool water, recording of test results and recording of actions undertaken. This outbreak highlights the risks of lowering chlorine levels when using pool water colourants.
Medical supplies could be held up at border after Brexit, peers hear
Authors: Jacqui Wise
Journal: BMJ (2018)

Delays at the UK border resulting from a “no deal” Brexit could be a problem for supplies of medical products with a short shelf life, such as radioisotopes and some gene therapies, a House of Lords subcommittee has heard.1

Mark Dayan, policy and public affairs analyst at the health think tank the Nuffield Trust, told peers on the EU Home Affairs Sub-Committee on 31 October, “One of the biggest short term worries about a no deal Brexit for the NHS is the disruption in supplies caused by delays.” The subcommittee is charged with scrutinising proposed EU legislation on home …
Grandmaternal Diethylstilbestrol and Attention-Deficit/Hyperactivity Disorder in Children—Reply
Authors: Marianthi-Anna Kioumourtzoglou, Marc G. Weisskopf
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
Association Between Hospital Surgical Aortic Valve Replacement Volume and Transcatheter Aortic Valve Replacement Outcomes
Authors: Jialin Mao, Rita F. Redberg, John D. Carroll, Danica Marinac-Dabic, John Laschinger, Vinod Thourani, Michael Mack, Art Sedrakyan
Journal: JAMA Cardiology (2018)

The Centers for Medicare & Medicaid Services national coverage determination for transcatheter aortic valve replacement (TAVR) includes volume requirements for surgical aortic valve replacement (SAVR) for hospitals seeking to initiate or continue TAVR programs. Evidence regarding the association between SAVR volume and TAVR outcomes is limited.To examine the association of hospital SAVR and combined SAVR and TAVR volumes with patient outcomes of TAVR procedures performed within 1 year, 2 years, and for the entire period after initiation of TAVR programs.This observational cohort study included 60 538 TAVR procedures performed in 438 hospitals between October 1, 2011, and December 31, 2015, among Medicare beneficiaries.The associations between SAVR volume, SAVR and TAVR volumes, and risks of death, death or stroke, and readmissions within 30 days were determined using a hierarchical logistic regression model adjusting for patient and hospital characteristics. The association between SAVR and SAVR and TAVR volumes and 1-year and 2-year mortality after TAVR procedures was determined using a multivariable proportional hazard model with a robust variance estimator. The associations for procedures performed within 1 year, 2 years, and for the entire period after initiation of TAVR programs were examined.Among the 60 538 patients, 29 173 were women and 31 365 were men, with a mean (SD) age of 82.3 (8.0) years. Hospitals with high SAVR volume (mean annual volume, ≥97 per year) were more likely to adopt TAVR early and had a higher growth in TAVR volumes over time (median TAVR volume by hospitals with high SAVR volume and low SAVR volume: year 1, 32 vs 19; year 2, 48 vs 28; year 3, 82 vs 38; year 4, 118 vs 54; P < .001). In adjusted analysis, high hospital SAVR volume alone was not associated with better patient outcomes after TAVR. When hospital TAVR and SAVR volumes were jointly analyzed, patients treated in hospitals with high TAVR volume had lower 30-day mortality after TAVR (high TAVR and low SAVR vs low TAVR and low SAVR: odds ratio, 0.85; 95% CI, 0.72-0.99; high TAVR and high SAVR vs low TAVR and high SAVR: odds ratio, 0.81; 95% CI, 0.69-0.95), the effect of which was more pronounced when hospitals also had high SAVR volume. Patients treated in hospitals with high SAVR volume and high TAVR volume had the lowest 30-day mortality (vs hospitals with low SAVR volume and TAVR volume: odds ratio, 0.77; 95% CI, 0.66-0.89).Hospitals with high SAVR volume are most likely to be fast adopters of TAVR. Hospital SAVR volume alone is not associated with better TAVR outcomes. Accumulating high volumes of TAVR is associated with lower mortality after TAVR, particularly when hospitals have high SAVR volumes. Hospitals with high caseloads of both SAVR and TAVR are likely to achieve the best outcomes.
Electrical Alternans in Disguise—A Curious Case of Atrial Flutter
Authors: Emily R. Cedarbaum, Arun Padmanabhan, Nora Goldschlager
Journal: JAMA Internal Medicine (2018)

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
Tackling alcohol harm would make huge savings
Authors: Roger Williams
Journal: BMJ (2018)

The title of Oliver’s column in the 15 September issue sums up the UK government’s alcohol policy very well—an incoherent approach to alcohol harm.1 How can the government allow such continued health harm and such a high expenditure on treating it in the NHS when the causes are largely preventable?

Introduction of the 50p minimum unit pricing policy now …
The prothrombotic state in atrial fibrillation: pathophysiological and management implications
Authors: Ahsan A Khan, Gregory Y H Lip
Journal: Cardiovascular Research (2018)

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia and is associated with significant morbidity and mortality. There is plenty of evidence available to support the presence of a prothrombotic or hypercoagulable state in AF, but the contributory factors are multifactorial and cannot simply be explained by blood stasis. Abnormal changes in atrial wall (anatomical and structural, as 'vessel wall abnormalities'), the presence of spontaneous echo contrast to signify abnormal changes in flow and stasis ('flow abnormalities'), and abnormal changes in coagulation, platelet, and other pathophysiologic pathways ('abnormalities of blood constituents') are well documented in AF. The presence of these components therefore fulfils Virchow's triad for thrombogenesis. In this review, we present an overview of the established and professed pathophysiological mechanisms for thrombogenesis in AF and its management implications.