tbuckley/cabot-search huggingface dataset:
Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality
Authors: Emil L. Fosbøl, Jawad H. Butt, Lauge Østergaard, Charlotte Andersson, Christian Selmer, Kristian Kragholm, Morten Schou, Matthew Phelps, Gunnar H. Gislason, Thomas A. Gerds, Christian Torp-Pedersen, Lars Køber
Journal: JAMA (2020)

It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19.To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.ACEI/ARB use was defined as prescription fillings 6 months prior to the index date.In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis.In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]).Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.
Heparin Infusion for Central Line Patency and Corrected Gestational Age May Affect Coagulation Studies in the Neonatal Intensive Care Unit
Authors: Kirk D. Wyatt, Vilmarie Rodriguez, Amulya A. Nageswara Rao, Stephanie Stoway, Dong Chen, Rajiv K. Pruthi, Deepti M. Warad
Journal: Blood (2017)
Overall, anti-malarial, and non-malarial effect of intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine on birthweight: a mediation analysis
Authors: Michelle E Roh, Feiko O ter Kuile, Francois Rerolle, M Maria Glymour, Stephen Shiboski, Roly Gosling, Julie Gutman, Abel Kakuru, Meghna Desai, Richard Kajubi, Anne L'Ianziva, Moses R Kamya, Grant Dorsey, R Matthew Chico
Journal: The Lancet Global Health (2020)

Trials of intermittent preventive treatment (IPTp) of malaria in pregnant women that compared dihydroartemisinin-piperaquine with the standard of care, sulfadoxine-pyrimethamine, showed dihydroartemisinin-piperaquine was superior at preventing malaria infection, but not at improving birthweight. We aimed to assess whether sulfadoxine-pyrimethamine shows greater non-malarial benefits for birth outcomes than does dihydroartemisinin-piperaquine, and whether dihydroartemisinin-piperaquine shows greater antimalarial benefits for birth outcomes than does sulfadoxine-pyrimethamine.We defined treatment as random assignment to sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine before pooling individual participant-level data from 1617 HIV-uninfected pregnant women in Kenya (one trial; n=806) and Uganda (two trials; n=811). We quantified the relative effect of treatment on birthweight (primary outcome) attributed to preventing placental malaria infection (mediator). We estimated antimalarial (indirect) and non-malarial (direct) effects of IPTp on birth outcomes using causal mediation analyses, accounting for confounders. We used two-stage individual participant data meta-analyses to calculate pooled-effect sizes.Overall, birthweight was higher among neonates of women randomly assigned to sulfadoxine-pyrimethamine compared with women assigned to dihydroartemisinin-piperaquine (mean difference 69 g, 95% CI 26 to 112), despite placental malaria infection being lower in the dihydroartemisinin-piperaquine group (relative risk [RR] 0·64, 95% CI 0·39 to 1·04). Mediation analyses showed sulfadoxine-pyrimethamine conferred a greater non-malarial effect than did dihydroartemisinin-piperaquine (mean difference 87 g, 95% CI 43 to 131), whereas dihydroartemisinin-piperaquine conferred a slightly larger antimalarial effect than did sulfadoxine-pyrimethamine (8 g, -9 to 26), although more frequent dosing increased the antimalarial effect (31 g, 3 to 60).IPTp with sulfadoxine-pyrimethamine appears to have potent non-malarial effects on birthweight. Further research is needed to evaluate monthly dihydroartemisinin-piperaquine with sulfadoxine-pyrimethamine (or another compound with non-malarial effects) to achieve greater protection against malarial and non-malarial causes of low birthweight.Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation, and Worldwide Antimalarial Resistance Network.
Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Authors: Simon Dujardin, Caitlin Commins, Aurelien Lathuiliere, Pieter Beerepoot, Analiese R. Fernandes, Tarun V. Kamath, Mark B. De Los Santos, Naomi Klickstein, Diana L. Corjuc, Bianca T. Corjuc, Patrick M. Dooley, Arthur Viode, Derek H. Oakley, Benjamin D. Moore, Kristina Mullin, Dinorah Jean-Gilles, Ryan Clark, Kevin Atchison, Renee Moore, Lori B. Chibnik, Rudolph E. Tanzi, Matthew P. Frosch, Alberto Serrano-Pozo, Fiona Elwood, Judith A. Steen, Matthew E. Kennedy, Bradley T. Hyman
Journal: Nature Medicine (2020)
Rapid Salivary Test suitable for a mass screening program to detect SARS-CoV-2: A diagnostic accuracy study
Authors: Lorenzo Azzi, Andreina Baj, Tiziana Alberio, Marta Lualdi, Giovanni Veronesi, Giulio Carcano, Walter Ageno, Cinzia Gambarini, Lorenzo Maffioli, Salomone Di Saverio, Daniela Dalla Gasperina, Angelo Paolo Genoni, Elias Premi, Simone Donati, Claudio Azzolini, Anna Maria Grandi, Francesco Dentali, Flavio Tangianu, Fausto Sessa, Vittorio Maurino, Lucia Tettamanti, Claudia Siracusa, Andrea Vigezzi, Elisa Monti, Valentina Iori, Domenico Iovino, Giuseppe Ietto, Paolo Antonio Grossi, Angelo Tagliabue, Mauro Fasano
Journal: Journal of Infection (2020)
Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients With Atrial Fibrillation
Authors: Pavel Osmancik, Dalibor Herman, Petr Neuzil, Pavel Hala, Milos Taborsky, Petr Kala, Martin Poloczek, Josef Stasek, Ludek Haman, Marian Branny, Jan Chovancik, Pavel Cervinka, Jiri Holy, Tomas Kovarnik, David Zemanek, Stepan Havranek, Vlastimil Vancura, Jan Opatrny, Petr Peichl, Petr Tousek, Veronika Lekesova, Jiri Jarkovsky, Martina Novackova, Klara Benesova, Petr Widimsky, Vivek Y. Reddy
Journal: Journal of the American College of Cardiology (2020)
Abstract 155: Effect of the 2010 CPR Guidelines for Patients With Out-of-Hospital Cardiac Arrest Due to Shockable Rhythm
Authors: Yoji Watanabe, Tsukasa Yagi, Ken Nagao, Shigemasa Tani, Eizo Tachibana, Nobutaka Chiba, Tadashi Ashida, Naohiro Yonemoto, Morimasa Takayama, Hiroshi Nonogi, Naoya Matsumoto, Yasuo Okumura
Journal: Circulation (2018)

Background: The 2010 guidelines have stressed that systematic post-cardiac arrest care after return of spontaneous circulation (ROSC) can improve the likelihood of patient survival with good neurological outcome. Especially, the 2010 guidelines recommended that comatose adult patients with ROSC after out-of-hospital ventricular fibrillation (VF) cardiac arrest should be induced therapeutic hypothermia (Class I). However, it is unknown whether the post-cardiac arrest care which was recommended by the 2010 guidelines contributed to favorable neurological outcome. The aim of the present study was to clarify the effects of the 2010 guidelines in patients with ROSC after cardiac arrest due to shockable rhythm, using the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital cardiac arrest (OHCA). Methods: From the data of this registry between 2005 and 2015, we included adult patients with ROSC after out-of-hospital shockable cardiac arrest due to cardiac etiology. Study patients were divided into three groups based on the different CPR guidelines; the era of the 2000 guidelines (2000G), the era of the 2005 guidelines (2005G), and the era of the 2010 guidelines (2010G). The primary endpoint was favorable neurological outcome at 30 days after OHCA. Results: The 30,518 patients who met the inclusion criteria comprised 24,729 with ROSC before arrival at the hospital and 5,789 with ROSC after hospital arrival without prehospital ROSC. Figure showed favorable neurological outcome at 30 days in the three groups. Moreover, multivariable analysis showed that the 2010 guidelines were an independent predictor of favorable neurological outcome at 30 days after OHCA, respectively (Figure). Conclusion: In the patients with ROSC after out-of-hospital shockable cardiac arrest, the 2010 guidelines were superior to the 2005 guidelines and the 2000 guidelines, in terms of neurological benefits.
Response to: ‘Treatment adherence behaviours in rheumatic diseases during pandemic COVID-19: a Latin American experience’ by Pineda-Sic <i>et al</i>
Authors: Hendrik Schulze-Koops, Klaus Krueger, Christof Specker
Journal: Annals of the Rheumatic Diseases (2020)

With great interest but also some concerns we read the study of Dr Pineda-Sic et al 1 on treatment adherence of patients with inflammatory rheumatic diseases (IRD) during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 pandemic in Latin America. In an anonymous electronic survey of consecutive patients at the rheumatology outpatient clinic of the university hospital in Monterrey, Mexico, the authors requested information about treatment adherence from patients with IRD. From the 345 patients who responded between 14 and 25 May 2020, 293 (85%) had not changed their medication. Importantly, 91.3% of all patients indicated that they knew about the benefits of their treatment.

These data are reassuring, as current guidelines, for example by the German Society of Rheumatology (DGRh eV),2 the European League Against Rheumatism3 or the American College of Rheumatology,4 …
Efficacy and Safety Exposure–Response Relationships of Apalutamide in Patients with Nonmetastatic Castration-Resistant Prostate Cancer
Authors: Carlos Perez-Ruixo, Oliver Ackaert, Daniele Ouellet, Caly Chien, Hiroji Uemura, David Olmos, Paul Mainwaring, Ji Youl Lee, Margaret K. Yu, Juan Jose Perez-Ruixo, Matthew R. Smith, Eric J. Small
Journal: Clinical Cancer Research (2020)

Abstract Purpose: To evaluate the relationship between exposure of apalutamide and its active metabolite, N-desmethyl-apalutamide, and selected clinical efficacy and safety parameters in men with high-risk nonmetastatic castration-resistant prostate cancer. Patients and Methods: An exploratory exposure–response analysis was undertaken using data from the 1,207 patients (806 apalutamide and 401 placebo) enrolled in the SPARTAN study, including those who had undergone dose reductions and dose interruptions. Univariate and multivariate Cox regression models evaluated the relationships between apalutamide and N-desmethyl-apalutamide exposure, expressed as area under the concentration–time curve at steady state, and metastasis-free survival (MFS). Univariate and multivariate logistic regression models assessed the relationship between apalutamide and N-desmethyl-apalutamide exposure and common treatment-emergent adverse events including fatigue, fall, skin rash, weight loss, and arthralgia. Results: A total of 21% of patients in the apalutamide arm experienced dose reductions diminishing the average daily dose to 209 mg instead of 240 mg. Within the relatively narrow exposure range, no statistically significant relationship was found between MFS and apalutamide and N-desmethyl-apalutamide exposure. Within apalutamide-treated subjects, skin rash and weight loss had a statistically significant association with higher apalutamide exposure. Conclusions: The use of apalutamide at the recommended dose of 240 mg once daily provided a similar delay in metastases across the SPARTAN patient population, regardless of exposure. The exploratory exposure–safety analysis supports dose reductions in patients experiencing adverse events.
A Grading System for Invasive Pulmonary Adenocarcinoma: A Proposal From the International Association for the Study of Lung Cancer Pathology Committee
Authors: Andre L. Moreira, Paolo S.S. Ocampo, Yuhe Xia, Hua Zhong, Prudence A. Russell, Yuko Minami, Wendy A. Cooper, Akihiko Yoshida, Lukas Bubendorf, Mauro Papotti, Giuseppe Pelosi, Fernando Lopez-Rios, Keiko Kunitoki, Dana Ferrari-Light, Lynette M. Sholl, Mary Beth Beasley, Alain Borczuk, Johan Botling, Elisabeth Brambilla, Gang Chen, Teh-Ying Chou, Jin-Haeng Chung, Sanja Dacic, Deepali Jain, Fred R. Hirsch, David Hwang, Sylvie Lantuejoul, Dongmei Lin, John W. Longshore, Noriko Motoi, Masayuki Noguchi, Claudia Poleri, Natasha Rekhtman, Ming-Sound Tsao, Erik Thunnissen, William D. Travis, Yasushi Yatabe, Anja C. Roden, Jillian B. Daigneault, Ignacio I. Wistuba, Keith M. Kerr, Harvey Pass, Andrew G. Nicholson, Mari Mino-Kenudson
Journal: Journal of Thoracic Oncology (2020)
IL6 Fuels Durable Memory for Th17 Cell–Mediated Responses to Tumors
Authors: Hannah M. Knochelmann, Connor J. Dwyer, Aubrey S. Smith, Jacob S. Bowers, Megan M. Wyatt, Michelle H. Nelson, Guillermo O. Rangel Rivera, Joshua D. Horton, Carsten Krieg, Kent Armeson, Gregory B. Lesinski, Mark P. Rubinstein, Zihai Li, Chrystal M. Paulos
Journal: Cancer Research (2020)

The accessibility of adoptive T-cell transfer therapies (ACT) is hindered by the cost and time required for product development. Here we describe a streamlined ACT protocol using Th17 cells expanded only 4 days ex vivo. While shortening expansion compromised cell yield, this method licensed Th17 cells to eradicate large tumors to a greater extent than cells expanded longer term. Day 4 Th17 cells engrafted, induced release of multiple cytokines including IL6, IL17, MCP-1, and GM-CSF in the tumor-bearing host, and persisted as memory cells. IL6 was a critical component for efficacy of these therapies via its promotion of long-term immunity and resistance to tumor relapse. Mechanistically, IL6 diminished engraftment of FoxP3+ donor T cells, corresponding with robust tumor infiltration by donor effector over regulatory cells for the Day 4 Th17 cell product relative to cell products expanded longer durations ex vivo. Collectively, this work describes a method to rapidly generate therapeutic T-cell products for ACT and implicates IL6 in promoting durable immunity of Th17 cells against large, established solid tumors. SIGNIFICANCE: An abbreviated, 4-day ex vivo expansion method licenses Th17 cells to confer long-lived immunity against solid malignancies via induction of systemic IL6 in the host.See related commentary by Fiering and Ho, p. 3795.
Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing
Authors: Danny Rischin, Michael R Migden, Annette M Lim, Chrysalyne D Schmults, Nikhil I Khushalani, Brett G M Hughes, Dirk Schadendorf, Lara A Dunn, Leonel Hernandez-Aya, Anne Lynn S Chang, Badri Modi, Axel Hauschild, Claas Ulrich, Thomas Eigentler, Brian Stein, Anna C Pavlick, Jessica L Geiger, Ralf Gutzmer, Murad Alam, Emmanuel Okoye, Melissa Mathias, Vladimir Jankovic, Elizabeth Stankevich, Jocelyn Booth, Siyu Li, Israel Lowy, Matthew G Fury, Alexander Guminski
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort ( NCT02383212 ) and the pivotal Phase 2 study ( NCT02760498 ). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study ( NCT02760498 ). Methods The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability. Results For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined. Per ICR, Kaplan–Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1. Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%). Conclusion In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses. Trial registration number Clinicaltrials.gov, NCT02760498 . Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498
Do Brief Preventive Interventions for Patients at Suicide Risk Work?
Authors: Nadine M. Melhem, David Brent
Journal: JAMA Psychiatry (2020)

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Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial
Authors: Jay P Mohr, Jessica R Overbey, Andreas Hartmann, Rüdiger von Kummer, Rustam Al-Shahi Salman, Helen Kim, H Bart van der Worp, Michael K Parides, Marco A Stefani, Emmanuel Houdart, Richard Libman, John Pile-Spellman, Kirsty Harkness, Charlotte Cordonnier, Ellen Moquete, Alessandra Biondi, Catharina J M Klijn, Christian Stapf, Alan J Moskowitz
Journal: The Lancet Neurology (2020)
DNA Methylation and Brain‐Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia
Authors: Andrea Polli, Manosij Ghosh, Jelena Bakusic, Kelly Ickmans, Dora Monteyne, Brigitte Velkeniers, Bram Bekaert, Lode Godderis, Jo Nijs
Journal: Arthritis & Rheumatology (2020)

Objective The epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study was undertaken to explore the role of brain‐derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM). Methods A repeated‐measures study was conducted in 54 participants (28 patients with CFS/FM and 26 matched healthy controls). Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. Serum BDNF (sBDNF) protein levels were measured using enzyme‐linked immunosorbent assay, while polymorphism and DNA methylation were measured in blood using pyrosequencing technology. To assess the temporal stability of the measures, participants underwent the same assessment twice within 4 days. Results Repeated‐measures mixed linear models were used for between‐group analysis, with mean differences and 95% confidence intervals (95% CIs) shown. Compared to controls, serum BNDF was higher in patients with CFS/FM (F = 15.703; mean difference 3.31 ng/ml [95% CI 1.65, 4.96]; P = 0.001), whereas BDNF DNA methylation in exon 9 was lower (F = 7.543; mean difference −2.16% [95% CI −3.93, −0.83]; P = 0.007). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF levels (F = 7.137, β = −0.408 [95% CI −0.711, −0.105]; P = 0.009), which in turn predicted participants’ symptoms (F = 14.410, β = 3.747 [95% CI 1.79, 5.71]; P = 0.001) and widespread hyperalgesia (F = 4.147, β = 0.04 [95% CI 0.01, 0.08]; P = 0.044). Conclusion Our findings indicate that sBDNF levels are elevated in patients with CFS/FM and that BDNF methylation in exon 9 accounts for the regulation of protein expression. Altered BDNF levels might represent a key mechanism explaining CFS/FM pathophysiology.