tbuckley/cabot-search huggingface dataset:
Covid-19: increasing demand for dialysis sparks fears of supply shortage
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The BMJ More than a quarter of patients with covid-19 on ventilators also need renal support in the form of dialysis, raising concerns that there could be significant supply problems as countries attempt to stock up on the required fluid and plastic consumables.Nephrology consultant Graham Lipkin told The BMJ, "This is an under-recognised challenge.While the original focus has been on whether we have enough ventilators and intensive care beds, it has become apparent that there is a high incidence of acute kidney injury (AKI) requiring some form of renal replacement therapy (RRT) through dialysis.With the volume of people coming into intensive care, there are increasing challenges to capacity across the system."Lipkin, who is president of the Renal Association, has been working with NHS England to develop new clinical guidelines for the prevention and optimal management of AKI in hospital.The guidance aims to reduce the incidence of AKI and therefore the demand for dialysis.According to the latest Intensive Care National Audit and Research Centre report on covid-19, 28.8% of patients in critical care receiving advanced respiratory support required renal support.
Effect of a Mammography Screening Decision Aid for Women 75 Years and Older
Authors: Mara A. Schonberg, Christine E. Kistler, Adlin Pinheiro, Alicia R. Jacobson, Gianna M. Aliberti, Maria Karamourtopoulos, Michelle Hayes, Bridget A. Neville, Carmen L. Lewis, Christina C. Wee, Angela Fagerlin, Larissa Nekhlyudov, Edward R. Marcantonio, Mary Beth Hamel, Roger B. Davis
Journal: JAMA Internal Medicine (2020)

Guidelines recommend that women 75 years and older be informed of the benefits and harms of mammography before screening.To test the effects of receipt of a paper-based mammography screening decision aid (DA) for women 75 years and older on their screening decisions.A cluster randomized clinical trial with clinician as the unit of randomization. All analyses were completed on an intent-to-treat basis. The setting was 11 primary care practices in Massachusetts or North Carolina. Of 1247 eligible women reached, 546 aged 75 to 89 years without breast cancer or dementia who had a mammogram within 24 months but not within 6 months and saw 1 of 137 clinicians (herein referred to as PCPs) from November 3, 2014, to January 26, 2017, participated. A research assistant (RA) administered a previsit questionnaire on each participant's health, breast cancer risk factors, sociodemographic characteristics, and screening intentions. After the visit, the RA administered a postvisit questionnaire on screening intentions and knowledge.Receipt of the DA (DA arm) or a home safety (HS) pamphlet (control arm) before a PCP visit.Participants were followed up for 18 months for receipt of mammography screening (primary outcome). To examine the effects of the DA, marginal logistic regression models were fit using generalized estimating equations to allow for clustering by PCP. Adjusted probabilities and risk differences were estimated to account for clustering by PCP.Of 546 women in the study, 283 (51.8%) received the DA. Patients in each arm were well matched; their mean (SD) age was 79.8 (3.7) years, 428 (78.4%) were non-Hispanic white, 321 (of 543 [59.1%]) had completed college, and 192 (35.2%) had less than a 10-year life expectancy. After 18 months, 9.1% (95% CI, 1.2%-16.9%) fewer women in the DA arm than in the control arm had undergone mammography screening (51.3% vs 60.4%; adjusted risk ratio, 0.84; 95% CI, 0.75-0.95; P = .006). Women in the DA arm were more likely than those in the control arm to rate their screening intentions lower from previsit to postvisit (69 of 283 [adjusted %, 24.5%] vs 47 of 263 [adjusted %, 15.3%]), to be more knowledgeable about the benefits and harms of screening (86 [adjusted %, 25.5%] vs 32 [adjusted %, 11.7%]), and to have a documented discussion about mammography with their PCP (146 [adjusted %, 47.4%] vs 111 [adjusted %, 38.9%]). Almost all women in the DA arm (94.9%) would recommend the DA.Providing women 75 years and older with a mammography screening DA before a PCP visit helps them make more informed screening decisions and leads to fewer women choosing to be screened, suggesting that the DA may help reduce overscreening.ClinicalTrials.gov Identifier: NCT02198690.
Potential lethal outbreak of coronavirus disease (COVID-19) among the elderly in retirement homes and long-term facilities, France, March 2020
Authors: Jean-François Etard, Philippe Vanhems, Laëtitia Atlani-Duault, René Ecochard
Journal: Eurosurveillance (2020)

Motivated by the potential devastating effect of a COVID-19 outbreak in retirement homes and long-term facilities for dependent elderly, we present the impact of worst-case scenarios in French institutions using a specific age structure and case-age fatality ratios. The death toll could equal the yearly death toll caused by seasonal influenza in those older than 65 years or could largely exceed that, depending on the final attack rate and proportion of infected institutions.
Varicella-like exanthem as a specific COVID-19–associated skin manifestation: Multicenter case series of 22 patients
Authors: Angelo Valerio Marzano, Giovanni Genovese, Gabriella Fabbrocini, Paolo Pigatto, Giuseppe Monfrecola, Bianca Maria Piraccini, Stefano Veraldi, Pietro Rubegni, Marco Cusini, Valentina Caputo, Franco Rongioletti, Emilio Berti, Piergiacomo Calzavara-Pinton
Journal: Journal of the American Academy of Dermatology (2020)
Mutations in the Phosphoinositide 3-Kinase Pathway (PI3K) Are Associated with Poor Overall Survival (OS) in Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP
Authors: Joo Y. Song, Anamarija M. Perry, Alex F. Herrera, Pam Skrabek, Michel Nasr, Rebecca Ottesen, Janet Nikowitz, Victoria Bedell, Joyce Murata-Collins, Yuan Yuan Chen, Yuping Li, Carlos Gomez Luna, Christine McCarthy, Raju Pillai, Jinhui Wang, Xiwei Wu, Jasmine M. Zain, Auayporn P. Nademanee, Joyce Niland, Qiang Gong, Wing C Chan, Dennis D. Weisenburger
Journal: Blood (2017)
{D}ynamic {C}hromatin {T}argeting of {B}{R}{D}4 {S}timulates {C}ardiac {F}ibroblast {A}ctivation
Authors: M. S. Stratton, R. A. Bagchi, M. B. Felisbino, R. A. Hirsch, H. E. Smith, A. S. Riching, B. Y. Enyart, K. A. Koch, M. A. Cavasin, M. Alexanian, K. Song, J. Qi, M. E. Lemieux, D. Srivastava, M. P. Y. Lam, S. M. Haldar, C. Y. Lin, T. A. McKinsey
Journal: Circulation Research (2019)
Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi
Authors: Austin A. Robinson, Cory R. Trankle, Grayson Eubanks, Christopher Schumann, Paul Thompson, Ryan L. Wallace, Shouri Gottiparthi, Benjamin Ruth, Christopher M. Kramer, Michael Salerno, Kenneth C. Bilchick, Cody Deen, Michael C. Kontos, John Dent
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Left ventricular (LV) thrombi can arise in patients with ischemic and nonischemic cardiomyopathies. Anticoagulation is thought to reduce the risk of stroke or systemic embolism (SSE), but there are no high-quality data on the effectiveness of direct oral anticoagulants (DOACs) for this indication. <h3>Objective</h3> To compare the outcomes associated with DOAC use and warfarin use for the treatment of LV thrombi. <h3>Design, Setting, and Participants</h3> A cohort study was performed at 3 tertiary care academic medical centers among 514 eligible patients with echocardiographically diagnosed LV thrombi between October 1, 2013, and March 31, 2019. Follow-up was performed through the end of the study period. <h3>Exposures</h3> Type and duration of anticoagulant use. <h3>Main Outcomes and Measures</h3> Clinically apparent SSE. <h3>Results</h3> A total of 514 patients (379 men; mean [SD] age, 58.4 [14.8] years) with LV thrombi were identified, including 300 who received warfarin and 185 who received a DOAC (64 patients switched treatment between these groups). The median follow-up across the patient cohort was 351 days (interquartile range, 51-866 days). On unadjusted analysis, DOAC treatment vs warfarin use (hazard ratio [HR], 2.71; 95% CI, 1.31-5.57;<i>P</i> = .01) and prior SSE (HR, 2.13; 95% CI, 1.22-3.72;<i>P</i> = .01) were associated with SSE. On multivariable analysis, anticoagulation with DOAC vs warfarin (HR, 2.64; 95% CI, 1.28-5.43;<i>P</i> = .01) and prior SSE (HR, 2.07; 95% CI, 1.17-3.66;<i>P</i> = .01) remained significantly associated with SSE. <h3>Conclusions and Relevance</h3> In this multicenter cohort study of anticoagulation strategies for LV thrombi, DOAC treatment was associated with a higher risk of SSE compared with warfarin use, even after adjustment for other factors. These results challenge the assumption of DOAC equivalence with warfarin for LV thrombi and highlight the need for prospective randomized clinical trials to determine the most effective treatment strategies for LV thrombi.
Intergenerational Effects of Maternal Holocaust Exposure on <i>FKBP5</i> Methylation
Authors: Linda M. Bierer, Heather N. Bader, Nikolaos P. Daskalakis, Amy Lehrner, Nadine Provençal, Tobias Wiechmann, Torsten Klengel, Iouri Makotkine, Elisabeth B. Binder, Rachel Yehuda
Journal: American Journal of Psychiatry (2020)

Objective: There is growing evidence that exposure to trauma prior to conception can affect offspring. The authors have reported that adult offspring of Holocaust survivors showed lower methylation of FK506 binding protein 5 (FKBP5) intron 7, site 6 compared with Jewish comparison volunteers. The present study sought to replicate this finding in a larger sample and to examine parental and offspring correlates of observed effects. Methods: Cytosine methylation was measured in blood using pyrosequencing. The independent replication sample consisted of 125 Holocaust offspring and 31 control subjects. Additional analyses, performed in a larger sample of 147 offspring and 40 control subjects that included the 31 previously studied participants, examined associations of parental trauma–related variables (i.e., sex of the exposed parent, parental posttraumatic stress disorder, age at Holocaust exposure) and offspring characteristics (i.e., childhood trauma exposure, lifetime psychiatric diagnoses, psychotropic medication use, FKBP5 rs1360780 genotype, FKBP5 gene expression, and neuroendocrine measures) with offspring FKBP5 methylation. Results: FKBP5 site 6 methylation was significantly lower in Holocaust offspring than in control subjects, an effect associated with maternal Holocaust exposure in childhood and with lower offspring self-reported anxiety symptoms. FKBP5 gene expression was elevated in Holocaust offspring. FKBP5 methylation was associated with indices of glucocorticoid sensitivity but not with basal FKBP5 gene expression. Conclusions: This study replicates and extends the previously observed decrement in FKBP5 intron 7, site 6 methylation in Holocaust offspring. The predominance of this effect in offspring of mothers exposed during childhood implicates maternal developmental programming as a putative mechanism.
Pulmonary rehabilitation
Authors: M K Sridhar
Journal: BMJ (1997)

Chronic lung diseases cause considerable disability. In Britain, one in 10 men and one in 20 women aged over 65 suffer from chronic obstructive pulmonary disease alone, and chronic lung disease is estimated to be responsible for over 25 million lost working days each year.1 For the vast majority of these patients–including those with smoking induced bronchitis, emphysema, and chronic severe asthma–there is no prospect of a cure. It was, and in many places still is, common practice for these patients to seek medical help and undergo investigations that establish a diagnosis, only to be told that there is very little or nothing that can be done. However, increasing evidence suggests that these patients will benefit from taking part in a multi-disciplinary pulmonary rehabilitation programme.2 3

Pulmonary rehabilitation was born of the recognition that, while most chronic lung diseases are not amenable …
Early delivery and prolonged treatment with nimodipine prevents the development of spasticity after spinal cord injury in mice
Authors: Maite Marcantoni, Andrea Fuchs, Peter Löw, Dusan Bartsch, Ole Kiehn, Carmelo Bellardita
Journal: Science Translational Medicine (2020)

Prolonged treatment with nimodipine soon after spinal cord injury in mice prevents spasticity by blocking L-type calcium channels Ca V 1.3.
Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome
Authors: Rosita Rigoni, Elena Fontana, Kerry Dobbs, Veronica Marrella, Valentina Taverniti, Virginia Maina, Amanda Facoetti, Giovanna D’Amico, Waleed Al-Herz, Mario Ernesto Cruz-Munoz, Catharina Schuetz, Andrew R. Gennery, Elizabeth K. Garabedian, Silvia Giliani, Deborah Draper, Ghassan Dbaibo, Raif S. Geha, Isabelle Meyts, Thomas Tousseyn, Benedicte Neven, Despina Moshous, Alain Fischer, Ansgar Schulz, Andrea Finocchi, Douglas B. Kuhns, Danielle L. Fink, Michail S. Lionakis, Muthulekha Swamydas, Simone Guglielmetti, Julie Alejo, Ian A. Myles, Stefania Pittaluga, Luigi D. Notarangelo, Anna Villa, Barbara Cassani
Journal: Journal of Allergy and Clinical Immunology (2020)

Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS).The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified.We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2R229Q/R229Q (Rag2R229Q) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt.We show that memory/activated T cells from patients with OS and from the Rag2R229Q mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad Th1/Th2/Th17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q mice results in increased frequency of Ccr4+ splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by Th1 effector T cells.These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS.
Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer
Authors: Charles Dolladille, Stéphane Ederhy, Marion Sassier, Jennifer Cautela, Franck Thuny, Ariel Cohen, Sophie Fedrizzi, Basile Chrétien, Angélique Da-Silva, Anne-Flore Plane, Damien Legallois, Paul Milliez, Véronique Lelong-Boulouard, Joachim Alexandre
Journal: JAMA Oncology (2020)

Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE).To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences.This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included.The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge.A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs.This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.
Abcb10 Physically Interacts with Mitoferrin1 to Enhance Its Stability for Heme Synthesis in the Erythroid Mitochondria
Authors: Wen Chen, Liangtao Li, Nathaniel B. Langer, Prasad N. Paradkar, Iman J. Schultz, Brigham B. Hyde, Orian S. Shirihai, Jerry Kaplan, Barry H. Paw
Journal: Blood (2008)
Sixty seconds on . . . the RECOVERY trial
Authors: Gareth Iacobucci
Journal: BMJ (2020)

What's this?The Randomised Evaluation of covid-19 therapy (aka RECOVERY) 1 is one of the largest national covid-19 clinical trials set up in England.Led by University of Oxford and funded by the government through the National Institute for Health Research, this major hospital based study is testing the effectiveness of new or existing drugs for treating the virus.
Clinical features of covid-19
Authors: Pauline Vetter, Diem Lan Vu, Arnaud G L’Huillier, Manuel Schibler, Laurent Kaiser, Frederique Jacquerioz
Journal: BMJ (2020)

In January 2020, coronavirus SARS-CoV-2 was identified as the cause of an outbreak of severe pneumonia, now known to be a complication of the coronavirus disease 2019 (covid-19). 1 Since then, the spread of covid-19 has increased exponentially, with the World Health Organization declaring a pandemic on 11 March. 2 By 15 April, more than 1 900 000 cases and 123 000 deaths had been reported worldwide.
Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the <scp>SDF</scp>‐1/<scp>CXCR4</scp> signalling pathway
Authors: Zexu Dang, Elisa Avolio, Anita C. Thomas, Ashton Faulkner, Antonio P. Beltrami, Celeste Cervellin, Albino Carrizzo, Anna Maciag, Yue Gu, Elena Ciaglia, Nicoletta Finato, Antonio Damato, Gaia Spinetti, Aishah Alenzi, Stephen J. Paisey, Carmine Vecchione, Annibale A. Puca, Paolo Madeddu
Journal: European Journal of Heart Failure (2020)

Abstract Aims Homozygosity for a four‐missense single‐nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long‐living individuals. Delivery of this longevity‐associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell‐derived factor‐1 (SDF‐1). Here, we investigated if delivery of the LAV‐BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy. Methods and results Compared with age‐matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV‐BPIFB4 gene therapy using an adeno‐associated viral vector serotype 9 (AAV9) . In contrast, AAV9 wild‐type‐ BPIFB4 exerted no benefit. Interestingly, LAV‐BPIFB4 ‐treated mice showed increased SDF‐1 levels in peripheral blood and myocardium and up‐regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF‐1 up‐regulation was instrumental to LAV‐BPIFB4‐ induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF‐1 CXCR4 receptor. Conclusions In mice with type‐2 diabetes, LAV‐BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes‐induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease.
Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus Nephritis
Authors: Juan M. Mejia-Vilet, Xiaolan L. Zhang, Cristino Cruz, Mayra L. Cano-Verduzco, John P. Shapiro, Haikady N. Nagaraja, Luis E. Morales-Buenrostro, Brad H. Rovin
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Although many biomarkers have been tested in lupus nephritis, none have advanced to clinical practice. Treatment is often guided by the level of proteinuria, which lacks the necessary sensitivity to differentiate disease activity from chronic damage to the kidneys. The authors evaluated urinary CD163 as an activity biomarker of lupus nephritis in two large multiethnic populations, with longitudinal follow-up of biomarker expression and testing against clinical and histologic disease activity. They demonstrated that urinary CD163 correlated with disease severity, lupus nephritis class, and histologic activity. Furthermore, the course of urinary CD163 in response to treatment discriminated among response groups and faithfully reflected the disease’s histologic activity in repeated kidney biopsies. These findings suggest that urinary CD163 shows promise as a biomarker reflecting histologic inflammation in lupus nephritis. Background Clinical distinction between patients with lupus nephritis who have active inflammation or chronic kidney damage is challenging. Studies have shown soluble CD163, which derives from cleavage of the CD163 M2c macrophage receptor and can be quantified in urine, correlates with active lupus nephritis. Methods We measured urine CD163 at lupus nephritis flares in patients from a Mexican cohort and cross-sectional and longitudinal United States cohorts. We also performed serial urine CD163 measurements during the treatment of flares in a subset of patients from the Mexican and longitudinal United States cohorts, and assessed response to therapy at 12 months. In addition, we evaluated urinary CD163 agreement with histologic activity in 19 patients from the Mexican cohort who had repeated kidney biopsies on follow-up. Results Urinary CD163 levels were significantly higher in patients with active lupus nephritis than in patients with active extrarenal SLE, inactive SLE, and other glomerular diseases, and correlated with disease clinical severity, histologic class, and the histologic activity index. Urinary CD163 increased from 6 months preflare to flare, diminishing progressively in complete and partial responders, whereas it remained elevated in nonresponders. Urinary CD163 &lt;370 ng/mmol at 6 months predicted complete renal response at 12 months with &gt;87% sensitivity and &gt;87% specificity. Urinary CD163 &lt;370 ng/mmol or &gt;370 ng/mmol perfectly agreed ( κ =1.0) with a histologic activity index ≤1 or &gt;1 in repeated biopsies, respectively. Evaluation of urinary CD163 in patients with persistent proteinuria at 6 months improved the prediction of who would achieve complete renal response at 12 months. Conclusions Urinary CD163 reflects histologic inflammation in lupus nephritis and is a promising activity biomarker that varies over time with lupus nephritis activity and treatment.