tbuckley/cabot-search huggingface dataset:
Abstract 20890: Transcutaneous Spinal Cord Stimulation Suppresses Catecholamine-Induced Ventricular Tachycardia via Left Stellate Ganglion Modulation
Authors: Lilei Yu, Bing Huang, Xiaoya Zhou, Hong Jiang
Journal: Circulation (2016)

Introduction: Previous studies indicated spinal cord stimulation could reduce ventricular tachyarrhythmias. Hypothesis: We examined whether Transcutanenous spinal cord stimulation (TSCS) can preven...
Recent Developments in the Management of Advanced Prostate Cancer
Authors: Sandy Srinivas
Journal: Journal of the National Comprehensive Cancer Network (2020)

Numerous new options are available for the treatment of prostate cancer when it progresses beyond localized disease. Older drugs, first developed for treatment of metastatic castration-resistant prostate cancer (CRPC), are being used to treat nonmetastatic disease based on results of large randomized controlled trials. Sequencing of available treatment options is challenging for CRPC, but there is some guidance from trial data. Cross-resistance among newer hormonal drugs is a concern, and therefore switching to another class of drug is preferred. Emerging treatments on the horizon, such as PARP inhibitors in patients with BRCA2 mutations and lutetium-177 in those with prostate-specific membrane antigen (PSMA)–positive disease, may look promising to improve outcomes among those with advanced prostate cancer.
Alternative mechanisms that mediate graft-versus-host disease in allogeneic hematopoietic cell transplants
Authors: James W. Young
Journal: Journal of Clinical Investigation (2020)

Allogeneic hematopoietic cell transplantation (alloHCT) benefits increasing numbers of patients with otherwise lethal diseases. Graft-versus-host disease (GVHD), however, remains one of the most potentially life-threatening complications due to its own comorbidities and the side effects of its treatment. In this issue of the JCI, two groups have turned dogma on its head by providing evidence for alternative mechanisms of acute GVHD (aGVHD) in humans. The principle of donor T cell reactivity elicited by host antigen-presenting cells (APCs) expressing MHC-encoded major HLA disparities or expressing minor histocompatibility antigen (miHA) differences presented by identical HLA molecules remains intact. These reports, however, demonstrate that GVHD can additionally result from peripheral host T cells resident in skin and gut being stimulated against donor APCs in the form of monocyte-derived macrophages. Moreover, these donor monocyte-derived macrophages can themselves mediate cytopathic effects against resident host T cells in skin explants and against a keratinocyte-derived cell line.
Endoscopic sleeve gastroplasty, laparoscopic sleeve gastrectomy, and laparoscopic greater curve plication: do they differ at 2 years?
Authors: Gontrand Lopez-Nava, Ravishankar Asokkumar, Inmaculada Bautista-Castaño, Janese Laster, Anuradha Negi, Stephanie Fook-Chong, Javier Nebreda Duran, Eduard Espinett Coll, Jordi Pujol Gebelli, Amador Garcia Ruiz de Gordejuela
Journal: Endoscopy (2020)

Endoscopic sleeve gastroplasty (ESG) is an effective treatment option for obesity. However, data comparing its efficacy to bariatric surgery are scarce. We aimed to compare the effectiveness and safety of ESG with laparoscopic sleeve gastrectomy (LSG) and laparoscopic greater curve plication (LGCP) at 2 years. METHODS : We reviewed 353 patient records and identified 296 patients who underwent ESG (n = 199), LSG (n = 61), and LGCP (n = 36) at four centers in Spain between 2014 and 2016. We compared their total body weight loss (%TBWL) and safety over 2 years. A linear mixed model (LMM) was used to analyze repeated measures of weight loss outcomes at 6, 12, 18, and 24 months to compare the three procedures. RESULTS : Among the 296 patients, 210 (ESG 135, LSG 43, LGCP 32) completed 1 year of follow-up and 102 (ESG 46, LSG 34, LGCP 22) reached 2 years. Their mean (standard deviation [SD]) body mass index (BMI) was 39.6 (4.8) kg/m2. There were no differences in age, sex, or BMI between the groups. In LMM analysis, adjusting for age, sex, and initial BMI, we found ESG had a significantly lower TBWL, %TBWL, and BMI decline compared with LSG and LGCP at all time points (P = 0.001). The adjusted mean %TBWL at 2 years for ESG, LSG, and LGCP were 18.5 %, 28.3 %, and 26.9 %, respectively. However, ESG, when compared with LSG and LGCP, had a shorter inpatient stay (1 vs. 3 vs. 3 days; P < 0.001) and lower complication rate (0.5 % vs. 4.9 % vs. 8.3 %; P = 0.006). CONCLUSION : All three procedures induced significant weight loss in obese patients. Although the weight loss was lower with ESG compared with other techniques, it displayed a better safety profile and shorter hospital stay.
IL-6–based mortality risk model for hospitalized patients with COVID-19
Authors: Rocio Laguna-Goya, Alberto Utrero-Rico, Paloma Talayero, Maria Lasa-Lazaro, Angel Ramirez-Fernandez, Laura Naranjo, Alejandro Segura-Tudela, Oscar Cabrera-Marante, Edgar Rodriguez de Frias, Rocio Garcia-Garcia, Mario Fernández-Ruiz, Jose Maria Aguado, Joaquin Martinez-Lopez, Elena Ana Lopez, Mercedes Catalan, Antonio Serrano, Estela Paz-Artal
Journal: Journal of Allergy and Clinical Immunology (2020)
Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002–2017: Population-based cohort study and decision analytic model
Authors: Martin C. Gulliford, Judith Charlton, Joanne R. Winter, Xiaohui Sun, Emma Rezel-Potts, Catey Bunce, Robin Fox, Paul Little, Alastair D. Hay, Michael V. Moore, Mark Ashworth
Journal: PLoS Medicine (2020)

Background Efforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed. Methods and findings We conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57–82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0–4 years old, the NNT was 29,773 (95% UI 18,458–71,091) in boys and 27,014 (16,739–65,709) in girls; over 85 years old, NNT was 262 (236–293) in men and 385 (352–421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55–64 years, the NNT was 247 (156–459) in men and 343 (234–556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65–74 years, the NNT following RTI was 1,257 (1,112–1,434) in men and 2,278 (1,966–2,686) in women; the NNT following skin infection was 503 (398–646) in men and 784 (602–1,051) in women; following UTI, the NNT was 121 (102–145) in men and 284 (241–342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period. Conclusions These stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs.
Improved cardiovascular risk prediction in patients with end-stage renal disease on hemodialysis using machine learning modeling and circulating microribonucleic acids
Authors: David de Gonzalo-Calvo, Pablo Martínez-Camblor, Christian Bär, Kevin Duarte, Nicolas Girerd, Bengt Fellström, Roland E. Schmieder, Alan G. Jardine, Ziad A. Massy, Hallvard Holdaas, Patrick Rossignol, Faiez Zannad, Thomas Thum
Journal: Theranostics (2020)

Rationale: To test whether novel biomarkers, such as microribonucleic acids (miRNAs), and nonstandard predictive models, such as decision tree learning, provide useful information for medical decision-making in patients on hemodialysis (HD). Methods: Samples from patients with end-stage renal disease receiving HD included in the AURORA trial were investigated (n=810). The study included two independent phases: phase I (matched cases and controls, n=410) and phase II (unmatched cases and controls, n=400). The composite endpoint was cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. miRNA quantification was performed using miRNA sequencing and RT-qPCR. The CART algorithm was used to construct regression tree models. A bagging-based procedure was used for validation. Results: In phase I, miRNA sequencing in a subset of samples (n=20) revealed miR-632 as a candidate (fold change=2.9). miR-632 was associated with the endpoint, even after adjusting for confounding factors (HR from 1.43 to 1.53). These findings were not reproduced in phase II. Regression tree models identified eight patient subgroups with specific risk patterns. miR-186-5p and miR-632 entered the tree by redefining two risk groups: patients older than 64 years and with hsCRP<0.827 mg/L and diabetic patients younger than 64 years. miRNAs improved the discrimination accuracy at the beginning of the follow-up (24 months) compared to the models without miRNAs (integrated AUC [iAUC]=0.71). Conclusions: The circulating miRNA profile complements conventional risk factors to identify specific cardiovascular risk patterns among patients receiving maintenance HD.
Polymorphic mobile element insertions contribute to gene expression and alternative splicing in human tissues
Authors: Xiaolong Cao, Yeting Zhang, Lindsay M. Payer, Hannah Lords, Jared P. Steranka, Kathleen H. Burns, Jinchuan Xing
Journal: Genome biology (2020)

Abstract Background Mobile elements are a major source of structural variants in the human genome, and some mobile elements can regulate gene expression and transcript splicing. However, the impact of polymorphic mobile element insertions (pMEIs) on gene expression and splicing in diverse human tissues has not been thoroughly studied. The multi-tissue gene expression and whole genome sequencing data generated by the Genotype-Tissue Expression (GTEx) project provide a great opportunity to systematically evaluate the role of pMEIs in regulating gene expression in human tissues. Results Using the GTEx whole genome sequencing data, we identify 20,545 high-quality pMEIs from 639 individuals. Coupling pMEI genotypes with gene expression profiles, we identify pMEI-associated expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) in 48 tissues. Using joint analyses of pMEIs and other genomic variants, pMEIs are predicted to be the potential causal variant for 3522 eQTLs and 3717 sQTLs. The pMEI-associated eQTLs and sQTLs show a high level of tissue specificity, and these pMEIs are enriched in the proximity of affected genes and in regulatory elements. Using reporter assays, we confirm that several pMEIs associated with eQTLs and sQTLs can alter gene expression levels and isoform proportions, respectively. Conclusion Overall, our study shows that pMEIs are associated with thousands of gene expression and splicing variations, indicating that pMEIs could have a significant role in regulating tissue-specific gene expression and transcript splicing. Detailed mechanisms for the role of pMEIs in gene regulation in different tissues will be an important direction for future studies.
Rapid Decay of Anti–SARS-CoV-2 Antibodies in Persons with Mild Covid-19
Authors: F Javier Ibarrondo, Jennifer A Fulcher, David Goodman-Meza, Julie Elliott, Christian Hofmann, Mary A Hausner, Kathie G Ferbas, Nicole H Tobin, Grace M Aldrovandi, Otto O Yang
Journal: New England Journal of Medicine (2020)

Covid-19 Antibodies after Mild Infection Among 34 volunteers who had recovered from mild Covid-19 illness, antiviral antibodies to the receptor-binding domain of the viral spike protein declined wi...
Outcomes in Older Adults (age ≥ 70) with Acute Myeloid Leukemia Based on Choice of Frontline Treatment for Proliferative or Non-Proliferative Phenotype
Authors: Chetasi Talati, Andrew Kuykendall, Najla Al Ali, Jongphil Kim, Marina Sehovic, Kenneth S. Zuckerman, David A Sallman, Alan F List, Eric Padron, Rami S. Komrokji, Benjamin Djulbegovic, Martine Extermann, Kendra Sweet, Jeffrey E. Lancet
Journal: Blood (2017)
Disrupting the platelet internal membrane via PI3KC2α inhibition impairs thrombosis independently of canonical platelet activation
Authors: Maria V. Selvadurai, Mitchell J. Moon, Simon J. Mountford, Xiao Ma, Zhaohua Zheng, Ian G. Jennings, Natasha M. Setiabakti, Rizani P. Iman, Rose J. Brazilek, Nurul Aisha Z. Abidin, Gaëtan Chicanne, Sonia Severin, Alyce J. Nicholls, Connie H.Y. Wong, Jean-Yves Rinckel, Anita Eckly, Christian Gachet, Warwick S. Nesbitt, Philip E. Thompson, Justin R. Hamilton
Journal: Science Translational Medicine (2020)

Arterial thrombosis causes heart attacks and most strokes and is the most common cause of death in the world. Platelets are the cells that form arterial thrombi, and antiplatelet drugs are the mainstay of heart attack and stroke prevention. Yet, current drugs have limited efficacy, preventing fewer than 25% of lethal cardiovascular events without clinically relevant effects on bleeding. The key limitation on the ability of all current drugs to impair thrombosis without causing bleeding is that they block global platelet activation, thereby indiscriminately preventing platelet function in hemostasis and thrombosis. Here, we identify an approach with the potential to overcome this limitation by preventing platelet function independently of canonical platelet activation and in a manner that appears specifically relevant in the setting of thrombosis. Genetic or pharmacological targeting of the class II phosphoinositide 3-kinase (PI3KC2α) dilates the internal membrane reserve of platelets but does not affect activation-dependent platelet function in standard tests. Despite this, inhibition of PI3KC2α is potently antithrombotic in human blood ex vivo and mice in vivo and does not affect hemostasis. Mechanistic studies reveal this antithrombotic effect to be the result of impaired platelet adhesion driven by pronounced hemodynamic shear stress gradients. These findings demonstrate an important role for PI3KC2α in regulating platelet structure and function via a membrane-dependent mechanism and suggest that drugs targeting the platelet internal membrane may be a suitable approach for antithrombotic therapies with an improved therapeutic window.
Reconceptualizing Triage to Incorporate Principles of Risk and Uncertainty: An Example from Deep Brain Stimulation Patients with Treatment-Resistant Disorders
Authors: Lavina Kalwani, Kristin Kostick, Eric A. Storch, Gabriel Lázaro-Muñoz
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force
Fear of Coronavirus Disease 2019—An Emerging Cardiac Risk
Authors: Benjamin S. Wessler, David M. Kent, Marvin A. Konstam
Journal: JAMA Cardiology (2020)

We are in the midst of the coronavirus disease 2019 (COVID-19) pandemic and, as many clinicians across the globe, we are seeing firsthand the pain and death caused by COVID-19.While there are more than 300 clinical trials currently under way for this illness, there are as yet no specific therapies broadly accepted to decrease mortality.In response to dire predictions and a lack of effective treatments, authorities across the world continue to recommend a series of aggressive mitigation strategies to slow the spread of COVID-19.While early fears of widespread death and overwhelmed hospitals have played an important role in sounding the alarm about this pandemic and motivated important social distancing measures, these fears are also causing substantial harm.In this Viewpoint, using cardiac disease as an example, we explore the hazards associated both with the pandemic and initial response.We argue that clinicians' ability to modulate fear-a sensitive but nonspecific response to threats-will be a major determinant of the magnitude of the pandemic's effects.
THU0085 RESOLVIN D5 MODULATES TH17/TREG CELL DIFFERENTIATION AND SUPPRESSES OSTEOCLASTOGENESIS
Authors: H. Yamada, J. Saegusa, S. Sendo, Y. Ueda, T. Okano, Y. Fujikawa, Y. Yamamoto, T. Nagamoto, Y. Ichise, I. Naka, K. Akashi, A. Onishi, M. Shinohara, A. Morinobu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Resolution phase of acute inflammation has been recognized not passive but active process during the last 2 decades. This active process is highly regulated by novel families of potent bioactive lipid mediators, which are coined as specialized proresolving mediators (SPMs) including resolvins. Little has been known, however, about how resolvins are involved in chronic inflammation, such as rheumatoid arthritis (RA). Objectives: To investigate whether lipid mediators (LM) are involved in the pathogenesis of RA. Methods: We investigated lipid mediator profiling in the paws of SKG arthritis mice by using lipid chromatography (LC) /mass spectrometry (MS) /MS-based LM metabololipidomics. CD4 + T cells from spleens of SKG mice were cultured on anti-CD3/ CD28Abs precoated plate with IL-6/TGF-β, anti-IFNγ/IL-4 and analyzed by flow cytometry. CD4 + T cells were labeled with CFSE, and cell proliferation was analyzed by flow cytometry. Mouse bone marrow cells were cultured with M-CSF and RANKL, and TRAP-positive multinucleated cells were defined as osteoclasts. Osteoclast differentiation markers were analyzed by qRT-PCR. RvD5 or normal saline was administered daily into the peritoneal cavity of arthritic SKG mice. Results: RvE3, RvD1, RvD3, RvD5 and Maresin2 were significantly elevated on the paws of arthritic SKG mice. Among the elevated SPMs, only RvD5 levels on arthritic paws were significantly correlated with arthritis disease activity (Figure 1). We demonstrated that RvD5 suppressed Th17 cell differentiation, and facilitated Treg cell differentiation in vitro . In addition, RvD5 inhibited CD4 + T cell proliferation. Furthermore, RvD5 attenuated osteoclast differentiation (Figure 2) and interfered osteoclastogenesis at the molecular level. In the in vivo experiment, incidence of arthritis tended to be lower in RvD5-treated mice than that in control group, although there was no significant difference. Conclusion: RvD5 is increased in the paws of arthritic mice, and that RvD5 suppresses Th17 cell differentiation and CD4 + T cell proliferation, facilitates Treg cell differentiation, and suppresses osteoclastogenesis. References: [1]Serhan, C. N. 2014. Pro-resolving lipid mediators are leads for resolution physiology. Nature 510: 92-101. [2]Buckley, C. D., Gilroy, D. W., Serhan, C. N. 2014. Proresolving lipid mediators and mechanisms in the resolution of acute inflammation. Immunity 40: 315-27. [3]Colas, R. A., Shinohara, M., Dalli, J., Chiang, N., Serhan, C. N. 2014. Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue. Am J Physiol Cell Physiol 307: C39-54. Acknowledgments: The authors thank Shino Natsui (Department Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine) for providing technical assistance. Disclosure of Interests: None declared
More than Warm Fuzzy Feelings: The Imperative of Institutional Morale in Hospital Pandemic Responses
Authors: Jeremy R. Garrett, Leslie Ann McNolty
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethics Lessons From Seattle's Early Experience With COVID-19Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force
Risk factors for self-harm in prison: a systematic review and meta-analysis
Authors: Louis Favril, Rongqin Yu, Keith Hawton, Seena Fazel
Journal: The Lancet Psychiatry (2020)

Self-harm is a leading cause of morbidity in prisoners. Although a wide range of risk factors for self-harm in prisoners has been identified, the strength and consistency of effect sizes is uncertain. We aimed to synthesise evidence and assess the risk factors associated with self-harm inside prison.
Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial
Authors: Hermine I Brunner, Carlos Abud-Mendoza, Diego O Viola, Inmaculada Calvo Penades, Deborah Levy, Jordi Anton, Julia E Calderon, Vyacheslav G Chasnyk, Manuel A Ferrandiz, Vladimir Keltsev, Maria E Paz Gastanaga, Michael Shishov, Alina Lucica Boteanu, Michael Henrickson, Damon Bass, Kenneth Clark, Anne Hammer, Beulah N Ji, Antonio Nino, David A Roth, Herbert Struemper, Mei-Lun Wang, Alberto Martini, Daniel Lovell, Nicolino Ruperto
Journal: Annals of the Rheumatic Diseases (2020)

Objectives This ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE). Methods Patients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and ‘30 alternative’ definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing. Results Ninety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL. Conclusion The belimumab intravenous pharmacokinetics and benefit–risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate. Trial registration number NCT01649765 .
Maryland’s Experience With the COVID-19 Surge: What Worked, What Didn’t, What Next?
Authors: H. Gwon, M. Haeri, D. E. Hoffmann, A. Khan, A. Kelmenson, J. F. Kraus, C. Onyegwara, C. Paradissis, G. Povar, J. Schwartz, F. Sheikh, A. J. Tarzian
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethics Lessons From Seattle’s Early Experience With COVID-19Positive Public Health Ethics: Toward Flourishing and Resilient Communities and IndividualsCOVID in NYC: What We Could Do Better