tbuckley/cabot-search huggingface dataset:
Fibronectin modulates formation of PF4/heparin complexes and is a potential factor for reducing risk of developing HIT
Authors: Krystin Krauel, Patricia Preuße, Theodore E. Warkentin, Catja Trabhardt, Sven Brandt, Inga Jensch, Martin Mandelkow, Elke Hammer, Sven Hammerschmidt, Andreas Greinacher
Journal: Blood (2018)
Two-Cohort Phase II Study in R/R CLL (COSMOS): First Preliminary Safety and Efficacy Results of Anti-CD19 MOR208 Treatment in Combination with Venetoclax in Patients Who Discontinued Prior BTK Inhibitor Therapy
Authors: Philipp Bernhard Staber, Asher A. Chanan-Khan, Talha Munir, Dietger Niederweiser, Johannes Schetelig, Jan Moritz Middeke, Maren Dirnberger-Hertweck, Peter Kelemen, Johannes Weirather, Sameer A. Parikh, Stephan Stilgenbauer, Clemens-Martin Wendtner, Jennifer A. Woyach
Journal: Blood (2018)
Worldwide Frequencies of <i>APOL1</i> Renal Risk Variants
Authors: Girish N Nadkarni, Christopher R Gignoux, Elena P Sorokin, Michelle Daya, Rayees Rahman, Kathleen C Barnes, Christina L Wassel, Eimear E Kenny
Journal: New England Journal of Medicine (2018)

To the Editor: Risk variants in the APOL1 gene on chromosome 22, which were first discovered in African Americans, confer a substantially increased risk of kidney disease, early-onset hypertension, and cardiovascular disease, although disease risk is modified by other genetic factors and by environmental factors. 1 This is an important discovery for genomic medicine and has improved our understanding of disparities among ethnic groups. 2 Efforts are under way to incorporate APOL1 testing in routine clinical settings, and APOL1 is under consideration as a therapeutic target for kidney disease. 3he APOL1 risk variants rose to high frequency in Western Africa in response to trypanosomal infection, 4 and most studies of APOL1 have involved populations of persons who self-report as African or African American.However, other populations who also share recent ancestry from Africa, such as Hispanic populations, may be at greater risk than expected for APOL1-driven disease.These persons may not undergo testing; however, they may still be at high risk because of the presence of APOL1 risk variants. 5Thus, it is important to understand more fully the global distribution of these variants on the basis of country of origin and genetic ancestry rather than self-reported race or ethnic group.We used linked genetic and demographic data from 111 populations in two large studies, the Population Architecture using Genomics and Epidemiology Study (https://pagestudy .org) and the Consortium on Asthma among African-ancestry Populations in the Americas (www .caapa -project .org), to determine the global frequencies of APOL1 risk variants (see the Supplementary Appendix, available with the full text of this letter at NEJM.org).We inferred risk-allele status using the two G1 alleles (rs60910145 and rs73885319) and the proxy single-nucleotide polymorphism commonly typed for G2 (rs12106505).The frequencies of the recessive risk genotypes
SAT0142 Efficacy analysis of low-energy laser therapy in treatment of fibromyalgia
Authors: M Terek, G Radunovic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of the study was to investigate the efficacy of low-energy laser therapy versus placebo in treatment of patients with fibromyalgia. <h3>Methods</h3> We followed 36 female patients (age from 31 to 51 years, mean age 41.94 years) with fibromyalgia according to latest American College of Rheumatology (ACR) criteria for diagnosis. The first group of 18 patients was treated with low-energy laser 10 times every other day by scanning each of tender points with single therapy doze of 40 J. Identical procedure was preformed in the second group of 18 patients, but low-energy laser diode was switched-off. All patients from both groups took similar drugs – NSAIDs and benzodiazepines, also had similar low-impact and stretching exercises. We measured the count of tender points, pain intensity with four-scale questionnaire; also sleep disturbance and malaise with similar four-scale questionnaire, before and after therapy procedure. Results were statistically analysed with Wilcoxon matched pairs test within groups of patients and with Mann-Whitney U test between groups. <h3>Results</h3> In both groups we found statistically significant lowering of count of tender points (p &lt; 0.001), pain intensity (p &lt; 0.001), sleep disturbance (p &lt; 0.001) and malaise (p &lt; 0.001 in the first group and p &lt; 0.05 in the second) after therapy procedure. Between groups we found that lowering of all followed disease parameters was more clearly in the first group and all differences were statistically significant (p &lt; 0.0001 for all parameters). <h3>Conclusion</h3> Treatment of patients with fibromyalgia with low-energy laser therapy improves symptoms of disease more than placebo. This statement suggests that low-energy laser therapy have prominent place in up to date treatment of patients with fibromyalgia, especially because of patient’s tolerance, no contraindications and simple applicability.
Making sense of cost-effectiveness analyses in respiratory medicine: a practical guide for non-health economists
Authors: Job F.M. van Boven, Susanne J. van de Hei, Mohsen Sadatsafavi
Journal: European Respiratory Journal (2018)

We live in a world of great advances in respiratory care, but at the same time, we are facing increasing budget constraints. In such a world, the use of any intervention is associated with "opportunity loss": the benefit forgone by not using alternative interventions. Take the example of biologicals for severe asthma ( e.g. mepolizumab) or lung cancer ( e.g. nivolumab), with annual costs of around EUR 15 000 and >EUR 100 000 per patient, respectively. The concept of opportunity loss applies whenever decisions are made, either by physicians in clinical practice who have to decide which treatment patients receive, or by health policymakers during the approval process of new interventions for market entrance. If resources are spent on these medications, it means that there will be less budget available for other interventions. In respiratory medicine, interventions could involve pharmacological treatments, but also new bronchoscopic procedures, biomarker tests, diagnostics or other health technologies [1–4]. Cost-effectiveness analyses explained: their current and future role in respiratory policy decision making and daily clinical practice <http://ow.ly/w0j630nuK72>
Salvage image-guided radiotherapy to the prostate after cryotherapy failure.
Authors: Austin B Hopper, John Paul Einck, Ajay Pal Sandhu
Journal: Journal of Clinical Oncology (2016)

e637 Background: Cryotherapy is used in increasing frequency for the primary treatment of localized prostate cancer. While it is known that local recurrence can occur in &gt; 20% of patients treated with primary cryotherapy there is a paucity of data on salvage treatments after failure. The use of external beam radiation therapy is an attractive option after cryotherapy failure but there is little data on efficacy and toxicity. We evaluate our data on a group of patients treated with image-guided dose-escalated radiotherapy (IGRT) at our institution. Methods: An IRB-approved database of patients treated with IGRT for prostate cancer from 2005 to 2013 was used to identify patients who underwent primary cryotherapy followed by salvage IGRT. Patients’ EMR were reviewed for age, cryotherapy-to-salvage interval, pre/post-salvage PSA and Gleason score (GS). All patients were treated with dose-escalated IGRT using standard treatment margins of 3 mm posterior and 7 mm in all other directions and daily CBCT or kv imaging to implanted fiducial markers. Narrative notes were used to identify GU/GI toxicity and scored according to CTCAE v4.03. The Phoenix definition of nadir + 2 was used to determine disease control following RT. Results: 5 patients were identified within the study period as having received salvage RT after primary cryotherapy. Mean age at the time of salvage RT was 74 (range 65-80). Median cryotherapy-salvage interval was 49 months (range 25-97) and prior to RT patients had GS of 7 (n = 3) or 8 (n = 2) and mean PSA of 8.1 ng/mL (range 4.2-14.38). Median total dose and follow-up were 76.7 Gy (range 75.6 – 81.0) and 52 months (range 6-63). One patient’s PSA did not decline post-RT and developed metastases while four patients responded post-RT with one experiencing biochemical recurrence after 30 months. No patients had acute GU/GI toxicities grade 2 or higher; one experienced late grade 2 GU toxicity (dysuria) which resolved with medication. There were no late grade 3 toxicities. Conclusions: High-dose radiotherapy as salvage treatment after cryotherapy failure is tolerated without significant GU or GI toxicities. Additionally, salvage IGRT is a viable option for long-term biochemical control in cases of local recurrence and warrants additional study.
Abstract 17856: Effect of Aspirin on the Cardiovascular, Gastrointestinal, and Renal Safety of Celecoxib, Naproxen, or Ibuprofen
Authors: Grant W Reed, Mouin Abdallah, Mingyuan Shao, Kathy Wolski, Venu Menon, A. Michael Lincoff, Steven E Nissen
Journal: Circulation (2017)

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin are commonly used together, yet the safety of this is uncertain. Methods: In this analysis of the PRECISION trial on-treatmen...
A Phase I Study with an Expansion Cohort of the Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Trial of the ECOG-ACRIN Research Group (E4412: Arms G-I)
Authors: Catherine Diefenbach, Fangxin Hong, Richard F Ambinder, Jonathon B. Cohen, Michael Robertson, Kevin A. David, Ranjana H. Advani, Timothy S. Fenske, Stefan Klaus Barta, Neil Palmisano, Jakub Svoboda, David Morgan, Reem Karmali, Brad S Kahl, Stephen M. Ansell
Journal: Blood (2018)
Abstract 16870: Pharmacologically Induced Hypothermia With the Cannabinoid Receptor Agonist Win55, 212-2 Improves Microcirculation in a Rat Model of Cardiac Arrest
Authors: Yan Xiao, Nikki Duggal, Qinyue Guo, Jin Yang, Weiping Huang, Zhangle Hu, Jennifer Bradley, Mary Ann Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2017)

Introduction: We previously demonstrated that the cannabinoid receptor agonist WIN55, 212-2 (WIN) improves post-resuscitation neurological function. The mechanism of benefit is unclear. One mechani...
Addition of Venetoclax to Patients with Acute Myeloid Leukemia Relapsing after Treatment with Hypomethylating Agents. Multicenter Historical Prospective Study
Authors: Ron Ram, Odelia Amit, Tsila Zuckerman, Ronit Gurion, Pia Raanani, Yael Bar-On, Irit Avivi, Ofir Wolach
Journal: Blood (2018)
Venetoclax Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) Improves Outcomes in BCL2-Positive First-Line Diffuse Large B-Cell Lymphoma (DLBCL): First Safety, Efficacy and Biomarker Analyses from the Phase II CAVALLI Study
Authors: Franck Morschhauser, Pierre Feugier, Ian W. Flinn, Robin E Gasiorowski, Richard Greil, Árpád Illés, Nathalie A Johnson, Jean-Francois Larouche, Pieternella J Lugtenburg, Caterina Patti, Gilles Salles, Marek Trněný, Sven de Vos, Farheen Mir, Martin Kornacker, Elizabeth A Punnoose, Divya Samineni, Edith Szafer-Glusman, Adam Petrich, Arijit Sinha, Mehrdad Mobasher, Andrew D. Zelenetz
Journal: Blood (2018)
Abstract 14614: Limited Utilization of Fatty Acid With a Marked Increase in Glucose Uptake Exacerbates Cardiac Dysfunction During Pressure Overload in CD36 Deficient Mice
Authors: Yogi Umbarawan, Mas Rizky Anggun Syamsunarno, Norimichi Koitabashi, Masahiko Kurabayashi, Tatsuya Iso
Journal: Circulation (2017)

Background: Fatty acid (FA) is central energy substrate for the heart to generate adenosine triphosphate (ATP) while glucose utilization is dynamically regulated. CD36 is a transmembrane protein wh...
Cardiomyocyte-specific loss of RNA polymerase II subunit 5-mediating protein causes myocardial dysfunction and heart failure
Authors: Jian Zhang, Jingyi Sheng, Liwei Dong, Yinli Xu, Liming Yu, Yu Liu, Xiaoru Huang, Song Wan, Hui-Yao Lan, Huishan Wang
Journal: Cardiovascular Research (2018)

Myocardial dysfunction is an important cause of heart failure (HF). RNA polymerase II subunit 5 (RPB5)-mediating protein (RMP) is a transcriptional mediating protein which co-ordinates cellular processes including gene expression, metabolism, proliferation, and genome stability. However, its role in cardiac disease remains unknown. We aimed to determine the role and regulatory mechanisms of RMP in cardiomyocyte function and the development of HF.Myocardial RMP expression was examined in human heart tissues from healthy controls and patients with advanced HF. Compared to normal cardiac tissues, RMP levels were significantly decreased in the myocardium of patients with advanced HF. To investigate the role of RMP in cardiac function, Cre-loxP recombinase technology was used to generate tamoxifen-inducible cardiomyocyte-specific Rmp knockout mice. Unexpectedly, cardiomyocyte-specific deletion of Rmp in mice resulted in contractile dysfunction, cardiac dilatation, and fibrosis. Furthermore, the lifespan of cardiac-specific Rmp-deficient mice was significantly shortened when compared with littermates. Mechanistically, we found that chronic HF in Rmp-deficient mice was associated with impaired mitochondrial structure and function, which may be mediated via a transforming growth factor-β/Smad3-proliferator-activated receptor coactivator1α (PGC1α)-dependent mechanism. PGC1α overexpression partially rescued chronic HF in cardiomyocyte-specific Rmp-deficient mice, and Smad3 blockade protected against the loss of PGC1α and adenosine triphosphate content that was induced by silencing RMP in vitro.RMP plays a protective role in chronic HF. RMP may protect cardiomyocytes from injury by maintaining PGC1α-dependent mitochondrial biogenesis and function. The results from this study suggest that RMP may be a potential therapeutic agent for treating HF.
No Added Benefit of Eight Versus Six Cycles of CHOP When Combined with Rituximab in Previously Untreated Diffuse Large B-Cell Lymphoma Patients: Results from the International Phase III GOYA Study
Authors: Laurie H Sehn, Angela Giovanna Congiu, Dominic J. Culligan, Mercedes Gironella, Dok Hyun Yoon, Michinori Ogura, Andras Rosta, Jun Zhu, Aino Launonen, Tina Nielsen, Gila Sellam, Marek Trněný, Umberto Vitolo, Maurizio Martelli
Journal: Blood (2018)
Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure
Authors: Mohit K. Turagam, Jalaj Garg, William Whang, Samantha Sartori, Jacob S. Koruth, Marc A. Miller, Noelle Langan, Aamir Sofi, Anthony Gomes, Subbarao Choudry, Srinivas R. Dukkipati, Vivek Y. Reddy
Journal: Annals of Internal Medicine (2018)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and are associated with increased morbidity and mortality risk. Purpose: To compare benefits and harms between catheter ablation and drug therapy in adult patients with AF and HF. Data Sources: ClinicalTrials.gov, PubMed, Web of Science (Clarivate Analytics), EBSCO Information Services, Cochrane Central Register of Controlled Trials, Google Scholar, and various scientific conference sessions from 1 January 2005 to 1 October 2018. Study Selection: Randomized controlled trials (RCTs) published in English that had at least 6 months of follow-up and compared clinical outcomes of catheter ablation versus drug therapy in adults with AF and HF. Data Extraction: 2 investigators independently extracted data and assessed study quality. Data Synthesis: 6 RCTs involving 775 patients met inclusion criteria. Compared with drug therapy, AF ablation reduced all-cause mortality (9.0% vs. 17.6%; risk ratio [RR], 0.52 [95% CI, 0.33 to 0.81]) and HF hospitalizations (16.4% vs. 27.6%; RR, 0.60 [CI, 0.39 to 0.93]). Ablation improved left ventricular ejection fraction (LVEF) (mean difference, 6.95% [CI, 3.0% to 10.9%]), 6-minute walk test distance (mean difference, 20.93 m [CI, 5.91 to 35.95 m]), peak oxygen consumption (Vo 2max) (mean difference, 3.17 mL/kg per minute [CI, 1.26 to 5.07 mL/kg per minute]), and quality of life (mean difference in Minnesota Living with Heart Failure Questionnaire score, −9.02 points [CI, −19.75 to 1.71 points]). Serious adverse events were more common in the ablation groups, although differences between the ablation and drug therapy groups were not statistically significant (7.2% vs. 3.8%; RR, 1.68 [CI, 0.58 to 4.85]). Limitation: Results driven primarily by 1 clinical trial, possible patient selection bias in the ablation group, lack of patient-level data, open-label trial designs, and heterogeneous follow-up length among trials. Conclusion: Catheter ablation was superior to conventional drug therapy in improving all-cause mortality, HF hospitalizations, LVEF, 6-minute walk test distance, Vo 2max, and quality of life, with no statistically significant increase in serious adverse events. Primary Funding Source: None.
Abstract 18539: Atrial Fibrillation and Sleep Apnea: Modulation of Response to Drug Therapy by Common Genetic Variants
Authors: Sandeep Goyal, Li Wang, Dawood Darbar, Ken Monahan
Journal: Circulation (2012)

Background: Severe obstructive sleep apnea (OSA) is associated with a decreased response of atrial fibrillation (AF) to anti-arrhythmic drugs (AADs). Whether common AF susceptibility alleles or common single nucleotide polymorphisms (SNPs) in the β1-adrenoreceptor (ADR) modulate response to AADs in patients with OSA is unknown. Hypothesis: Common genetic variants associated with AF decrease the efficacy of AADs to a greater degree in severe OSA as compared to non-severe OSA. Methods: We analyzed 84 individuals that had polysomnography, genotyping, and a comprehensive evaluation of AF status over time. Response to AADs was defined as a decrease in AF burden score by ≥ 75% on a validated symptom scoring tool or the combination of sinus rhythm on follow-up EKGs, stable AAD therapy, AF burden below the ASSERT threshold on device diagnostics or ambulatory monitoring, and the absence of non-pharmacologic therapies (cardioversion, nodal ablation, AF ablation). Severe OSA was defined as an apnea-hypopnea index (AHI) ≥ 30 events/hour. We analyzed common AF susceptibility alleles (rs2200733 and rs10033464 at 4q25, rs7193343 in ZFHX3, rs13376333 in KCNN3) and common SNPs in the β1-ADR (rs1801252 and rs1801253 at ADRB1). Results: Over an average follow-up period of 9.0 ± 4.5 months, 41 participants (49%) responded to AADs and 37 (44%) had severe OSA. For the β1-ADR SNP rs1801252, the AHI was higher in those with the variant compared to wild-type (37 ± 25 vs 23 ± 20 events/hour; p = 0.03 by Mann-Whitney test). Individuals with non-severe OSA and this variant were more likely to not respond to AADs when compared to wild-type allele (OR 2.0; 95% CI 0.5-7.8; Figure ). Conclusions: In a cohort receiving AAD therapy for AF, OSA severity was associated with a functional variant in the β1-ADR An unfavorable genotype may contribute to decreased response to AADs in those with AF and non-severe OSA. Genotype may play less of a role in the response to AADs in severe OSA.
Buprenorphine Deregulation and Mainstreaming Treatment for Opioid Use Disorder
Authors: Kevin Fiscella, Sarah E. Wakeman, Leo Beletsky
Journal: JAMA Psychiatry (2018)

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Influence of Donor Type, Stem Cell Source and Conditioning Regimen on Transplant Outcomes after Haploidentical Transplant with Post Transplant Cyclophosphamide for Lymphoma: A Report of the EBMT Lymphoma Working Party
Authors: Ali Bazarbachi, Ariane Boumendil, Hervé Finel, Luca Castagna, Alida Dominietto, Didier Blaise, Jose L. Diez-Martin, Johanna Tischer, Zafer Gülbas, Hélène Labussière, Lucia Lopez Corral, Mohamad Mohty, Yener Koc, Ibrahim Yakoub-Agha, Christoph Schmid, Jean Elcheikh, Mutlu Arat, Edouard Forcade, Peter Dreger, Vanderson G. Rocha, Gonzalo guiterez Garcia, Yves Chalandon, Christelle Ferra, Corentin Orvain, Stephen Robinson, Silvia Montoto, Anna Sureda
Journal: Blood (2018)
Women who become infertile through hospital negligence can seek surrogacy abroad, court rules
Authors: Clare Dyer
Journal: BMJ (2018)

Women whose fertility is destroyed by clinical negligence will have greater rights to damages covering the costs of surrogacy, after a landmark ruling by the Court of Appeal.1

Three judges have ruled that a High Court judge was wrong to hold that a trust which admitted negligently leaving a childless woman infertile need pay for surrogacy only in the UK and not abroad, with the woman’s own eggs and not those of a donor.

The unnamed woman, now 35, was diagnosed with invasive cervical cancer at the age of 29. Whittington Hospital NHS Trust in London had failed to detect cancer despite smear tests in 2008 …