tbuckley/cabot-search huggingface dataset:
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
Authors: Taku Inohara, Ying Xian, Li Liang, Roland A. Matsouaka, Jeffrey L. Saver, Eric E. Smith, Lee H. Schwamm, Mathew J. Reeves, Adrian F. Hernandez, Deepak L. Bhatt, Eric D. Peterson, Gregg C. Fonarow
Journal: JAMA (2018)

Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.In-hospital mortality.Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.
Metabolic Surgery
Authors: Manan Pareek, Philip R. Schauer, Lee M. Kaplan, Lawrence A. Leiter, Francesco Rubino, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2018)

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity. Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further examines their potential effects on cardiovascular outcomes and mortality and discusses future perspectives.
CCG criticises NHS England after being ordered to cut GP funding
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The head of a financially stricken clinical commissioning group (CCG) has launched an outspoken attack on NHS England after the group was ordered to cut GP funding to balance its books.

In a starkly written letter to local GPs sent on 12 January that was leaked to The BMJ , Paul Williams, chair of West Norfolk CCG, said that the group faced a “dire” financial situation, warning of “very unpleasant consequences” from decisions it was being forced to take.

Williams said that the CCG had been ordered by NHS England to cut local enhanced services payments to general practices, which fund work outside the core GP contract such as minor injury consultations, wound care, and phlebotomy. He wrote that “it …
PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL <sup>+</sup> human leukemia
Authors: Damian Lai, Min Chen, Jiechuang Su, Xiaohu Liu, Katharina Rothe, Kaiji Hu, Donna L. Forrest, Connie J. Eaves, Gregg B. Morin, Xiaoyan Jiang
Journal: Science Translational Medicine (2018)

PP2A inhibitors and BCR-ABL inhibitors synergize to kill drug-insensitive leukemia cells.
Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: <i>post-hoc</i> analysis of the Phase IIb MUSE trial of anifrolumab
Authors: Eric F Morand, Teodora Trasieva, Anna Berglind, Gabor G Illei, Raj Tummala
Journal: Annals of the Rheumatic Diseases (2018)

Objectives In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [ NCT01438489 ]) and then utilize LLDAS to discriminate between anifrolumab and placebo. Methods Patients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician’s Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored. Results LLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal p&lt;0.001). Only 74/159 (47%) of SRI(4) and 62/121 (51%) of BICLA responders reached LLDAS. Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, p&lt;0.001; 1,000 mg: 2.03, 95% CI 1.01 to 4.07, nominal p=0.046). Conclusions LLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint. Trial registration number NCT1438489 ; Post-results.
Health and social care, together at last?
Authors: Fiona Godlee
Journal: BMJ (2018)

How much of the rising pressure on the NHS could be relieved by proper funding and organisation of public health and social care? We are far from achieving either: cuts to public health are making people ill; failures of social care are keeping people in hospital when they could be at home.

Pressure on the NHS is nothing new. “Disseminating hyporesourcitis” was The BMJ ’s diagnosis back in the Thatcher 1980s (www.bmj.com/content/bmj/292/6529/1212.full.pdf). But the looming crisis is …
Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients
Authors: Sung Shine Shim, Mark L. Schiebler, Michael D. Evans, Nizar Jarjour, Ron L. Sorkness, Loren C. Denlinger, Alfonso Rodriguez, Sally Wenzel, Eric A. Hoffman, Ching-Long Lin, David S. Gierada, Mario Castro, Sean B. Fain
Journal: Journal of Allergy and Clinical Immunology (2018)
An unexpected protective role of low-affinity allergen-specific IgG through the inhibitory receptor FcγRIIb
Authors: Lisha Zha, Fabiana M.S. Leoratti, Lichun He, Mona O. Mohsen, Mark Cragg, Federico Storni, Monique Vogel, Martin F. Bachmann
Journal: Journal of Allergy and Clinical Immunology (2018)
Influence of Meibomian Gland Dysfunction and Friction-Related Disease on the Severity of Dry Eye
Authors: Chi Hoang Viet Vu, Motoko Kawashima, Masakazu Yamada, Kazuhisa Suwaki, Miki Uchino, Chika Shigeyasu, Yoshimune Hiratsuka, Norihiko Yokoi, Kazuo Tsubota
Journal: Ophthalmology (2018)
Abstract 15670: Implications of Surgical Parameters as Predictors of the Development of Postoperative Cardiac Events in Patients Undergoing Non-Cardiac Surgery
Authors: Myung Hwan Bae, Jae Hee Kim, Sun Hee Park, Se Yong Jang, Jang Hoon Lee, Dong Heon Yang, Hun Sik Park, Yongkeun Cho, Shung Chull Chae
Journal: Circulation (2013)

Objectives:  Postoperative cardiac events are an important cause of morbidity and mortality in patients undergoing non-cardiac surgery. Predictive values of surgical parameters with respect to development of postoperative cardiac events have not been well investigated.   Methods and Results:  This study included 1,016 consecutive patients who underwent cardiac consultation prior to elective non-cardiac surgery. Clinical risk factors and surgical data, including types of surgery and anesthesia, surgical times, need for transfusion during surgery, and postoperative hemoglobin level, were evaluated. A major adverse cardiac event (MACE) was defined as a composite of all cause death, non-fatal myocardial infarction, and pulmonary edema within 30 days of surgery. There were 95 (9.4%) postoperative MACEs. Patients with postoperative MACE were significantly older, and had significantly higher RCRI than those without. ST-T change on ECG was significantly higher in patients with postoperative MACE. Of the surgical parameters, significant differences in surgical times (317±211 min versus 189±112 min, P Figure 1 ).   Conclusion:  Surgical parameters, including surgical time and transfusion, can strongly predict development of postoperative MACE in patients undergoing non-cardiac surgery.
Abstract 18931: CMTM3 Mediates Angiogenesis by Regulating Early Endocytosis of Ve-cadherin in Endothelial Cells
Authors: Ihsan Chrifi, Laura Louzao-Martinez, Maarten M Brandt, Christian G van Dijk, Petra Burgisser, Changbin Zhu, Johan M Kros, Dirk J Duncker, Caroline Cheng
Journal: Circulation (2016)

Introduction: Endocytosis plays a key role in regulating the vascular stability between endothelial cells (ECs) during angiogenesis and vascular homeostasis, by altering the bio-availability of Ve-...
A microRNA‐7/growth arrest specific 6/TYRO3 axis regulates the growth and invasiveness of sorafenib‐resistant cells in human hepatocellular carcinoma
Authors: Tasnuva D. Kabir, Clarissa Ganda, Rikki M. Brown, Dianne J. Beveridge, Kirsty L. Richardson, Vishal Chaturvedi, Patrick Candy, Michael Epis, Larissa Wintle, Felicity Kalinowski, Christina Kopp, Lisa M. Stuart, George C. Yeoh, Jacob George, Peter J. Leedman
Journal: Hepatology (2017)

Sorafenib remains the only approved drug for treating patients with advanced hepatocellular carcinoma (HCC). However, the therapeutic effect of sorafenib is transient, and patients invariably develop sorafenib resistance (SR). Recently, TYRO3, a member of the TYRO3‐AXL‐MER family of receptor tyrosine kinases, was identified as being aberrantly expressed in a significant proportion of HCC; however, its role in SR is unknown. In this study, we generated two functionally distinct sorafenib‐resistant human Huh‐7 HCC cell lines in order to identify new mechanisms to abrogate acquired SR as well as new potential therapeutic targets in HCC. Initially, we investigated the effects of a microRNA (miR), miR‐7‐5p (miR‐7), in both in vitro and in vivo preclinical models of human HCC and identified miR‐7 as a potent tumor suppressor of human HCC. We identified TYRO3 as a new functional target of miR‐7, which regulates proliferation, migration, and invasion of Huh‐7 cells through the phosphoinositide 3‐kinase/protein kinase B pathway and is markedly elevated with acquisition of SR. Furthermore, miR‐7 effectively silenced TYRO3 expression in both sorafenib‐sensitive and sorafenib‐resistant Huh‐7 cells, inhibiting TYRO3/growth arrest specific 6‐mediated cancer cell migration and invasion. Conclusion : We identified a mechanism for acquiring SR in HCC that is through the aberrant expression of the TYRO3/phosphoinositide 3‐kinase/protein kinase B signal transduction pathway, and that can be overcome by miR‐7 overexpression. Taken together, these data suggest a potential role for miR‐7 as an RNA‐based therapeutic to treat refractory and drug‐resistant HCC. (H epatology 2018;67:216‐231)
Abstract 17875: The Effects of Rapid Esophageal Cooling on Cardiac Outcomes After Cardiopulmonary Resuscitation in a Porcine Model
Authors: Jiefeng Xu, Mao Zhang, Qijiang Chen, Xiaohong Jin, Chunshuang Wu, Moli Wang, Zilong Li
Journal: Circulation (2017)

Introduction:  Numerous studies have confirmed that therapeutic hypothermia is beneficial to improve cardiac outcomes in post-cardiac arrest syndrome. A recent investigation demonstrated that the cooling via esophagus is an effective, easily-performed approach to induce rapid hypothermia. Here we investigated the effects of esophageal cooling on post-resuscitation cardiac outcomes in a porcine cardiac arrest model.   Hypothesis:  Therapeutic hypothermia induced by esophageal cooling would be superior to conventional surface cooling in alleviating cardiac dysfunction, tissue injury and inflammation after CPR.   Methods:  Ventricular fibrillation (VF) was induced in 27 male domestic pigs weighing between 35-41 kg. CPR was initiated after 7 mins of untreated VF. Defibrillation was attempted after 5 mins of CPR. The animals were randomized into 3 groups: 1) normothermia, 2) surface cooling, and 3) esophageal cooling. At 5 mins after resuscitation, blood temperature was reduced to target temperature of 33°C and then maintained until 24 hrs post-resuscitation in the hypothermic two groups.   Results:  Rapid hypothermia was observed in the esophageal cooling group, in which the cooling rate was significantly faster than the surface cooling group (2.8±0.7°C/h vs. 1.5±0.4°C/h,  p    Conclusion:  Rapid esophageal cooling was significantly better than surface cooling in improving post-resuscitation cardiac dysfunction, tissue injury and inflammation.
Hypothalamic loss of Snord116 and Prader-Willi syndrome hyperphagia: the buck stops here?
Authors: Juan A. Rodriguez, Jeffrey M. Zigman
Journal: Journal of Clinical Investigation (2018)

Hyperphagia and obesity are the best-known manifestations of Prader-Willi syndrome (PWS) and are responsible for most of the overall morbidity and mortality associated with the disease. Yet these PWS symptoms remain poorly understood and without effective pharmacologic therapies. Mouse models attempting to recapitulate both the genetic alterations and marked hyperphagia plus obesity of PWS have been enigmatic, leading to skepticism about the use of mouse models to investigate PWS. In this issue of the JCI, Polex-Wolf and colleagues challenge the skeptics by successfully inducing hyperphagia following bilateral mediobasal hypothalamic deletion of the Snord116 gene from adult mice. Obesity also resulted, although only in a subset of mice. While this approach represents an exciting advance, highlighting a pathologic effect of loss of mediobasal hypothalamic Snord116 expression on the development of PWS’s hallmark symptoms, the variability in the body-weight and body composition responses to this site-selective gene deletion raises several questions.
Infographic: Injury and illness, the 2016 Olympic Games
Authors: Torbjørn Soligard, Kathrin Steffen, Debbie Palmer, Juan Manuel Alonso, Roald Bahr, Alexandre Dias Lopes, Jiri Dvorak, Marie-Elaine Grant, Willem Meeuwisse, Margo Mountjoy, Leonardo O P Costa, Natalia Salmina, Richard Budgett, Lars Engebretsen
Journal: British Journal of Sports Medicine (2018)
Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine
Authors: Shuji Ogino, Jonathan A Nowak, Tsuyoshi Hamada, Amanda I Phipps, Ulrike Peters, Danny A Milner Jr, Edward L Giovannucci, Reiko Nishihara, Marios Giannakis, Wendy S Garrett, Mingyang Song
Journal: Gut (2018)

Immunotherapy strategies targeting immune checkpoints such as the CTLA4 and CD274 (programmed cell death 1 ligand 1, PD-L1)/ PDCD1 (programmed cell death 1, PD-1) T-cell coreceptor pathways are revolutionising oncology. The approval of pembrolizumab use for solid tumours with high-level microsatellite instability or mismatch repair deficiency by the US Food and Drug Administration highlights promise of precision immuno-oncology. However, despite evidence indicating influences of exogenous and endogenous factors such as diet, nutrients, alcohol, smoking, obesity, lifestyle, environmental exposures and microbiome on tumour-immune interactions, integrative analyses of those factors and immunity lag behind. Immune cell analyses in the tumour microenvironment have not adequately been integrated into large-scale studies. Addressing this gap, the transdisciplinary field of molecular pathological epidemiology (MPE) offers research frameworks to integrate tumour immunology into population health sciences, and link the exposures and germline genetics (eg, HLA genotypes) to tumour and immune characteristics. Multilevel research using bioinformatics, in vivo pathology and omics (genomics, epigenomics, transcriptomics, proteomics and metabolomics) technologies is possible with use of tissue, peripheral blood circulating cells, cell-free plasma, stool, sputum, urine and other body fluids. This immunology-MPE model can synergise with experimental immunology, microbiology and systems biology. GI neoplasms represent exemplary diseases for the immunology-MPE model, given rich microbiota and immune tissues of intestines, and the well-established carcinogenic role of intestinal inflammation. Proof-of-principle studies on colorectal cancer provided insights into immunomodulating effects of aspirin, vitamin D, inflammatory diets and omega-3 polyunsaturated fatty acids. The integrated immunology-MPE model can contribute to better understanding of environment-tumour-immune interactions, and effective immunoprevention and immunotherapy strategies for precision medicine.
Less invasive than minimally invasive: peroral endoscopic myotomy with a slim scope in the treatment of esophageal achalasia
Authors: Antonio Coelho Conrado, Joao Guilherme Guerra, Claudio Hashimoto, Marcelo Averbach, Miguel Arcanjo dos Santos, Peter Draganov
Journal: Endoscopy (2018)

Peroral endoscopic myotomy (POEM) is an established therapy [1] [2] [3]. We describe a new technique for POEM using a slim/pediatric endoscope, which aims to provide a less-invasive approach compared with traditional POEM.
Risk of Synchronous Distant Recurrence at Time of Locoregional Recurrence in Patients With Stage II and III Breast Cancer (AFT-01)
Authors: Heather B. Neuman, Jessica R. Schumacher, Amanda B. Francescatti, Taiwo Adesoye, Stephen B. Edge, David J. Vanness, Menggang Yu, Daniel McKellar, David P. Winchester, Caprice C. Greenberg
Journal: Journal of Clinical Oncology (2018)

Purpose National Comprehensive Cancer Network guidelines recommend systemic staging imaging at the time of locoregional breast cancer recurrence. Limited data support this recommendation. We determined the rate of synchronous distant recurrence at the time of locoregional recurrence in high-risk patients and identified clinical factors associated with an increased risk of synchronous metastases. Methods A stage-stratified random sample of 11,046 patients with stage II to III breast cancer in 2006 to 2007 was selected from the National Cancer Database for participation in a Commission on Cancer special study. From medical record abstraction of imaging and recurrence data, we identified patients who experienced locoregional recurrence within 5 years of diagnosis. Synchronous distant metastases (within 30 days of locoregional recurrence) were determined. We used multivariable logistic regression to identify factors associated with synchronous metastases. Results Four percent experienced locoregional recurrence (n = 445). Synchronous distant metastases were identified in 27% (n = 120). Initial presenting stage ( P = .03), locoregional recurrence type ( P = .01), and insurance status ( P = .03) were associated with synchronous distant metastases. The proportion of synchronous metastases was highest for women with lymph node (35%), postmastectomy chest wall (30%), and in-breast (15%) recurrence; 54% received systemic staging imaging within 30 days of a locoregional recurrence. Conclusion These findings support current recommendations for systemic imaging in the setting of locoregional recurrence, particularly for patients with lymph node or chest wall recurrences. Because most patients with isolated locoregional recurrence will be recommended locoregional treatment, early identification of distant metastases through routine systemic imaging may spare them treatments unlikely to extend their survival.
Serum biomarker profiles suggest that atopic dermatitis is a systemic disease
Authors: Judith L. Thijs, Ian Strickland, Carla A.F.M. Bruijnzeel-Koomen, Stefan Nierkens, Barbara Giovannone, Edward F. Knol, Eszter Csomor, Bret R. Sellman, Tomas Mustelin, Matthew A. Sleeman, Marjolein S. de Bruin-Weller, Athula Herath, Julia Drylewicz, Richard D. May, DirkJan Hijnen
Journal: Journal of Allergy and Clinical Immunology (2018)