tbuckley/cabot-search huggingface dataset:
AB0196 SURVIVAL ANALYSIS OF TIME TO FIRST ADVERSE DRUG REACTION AND DRUG SURVIVAL IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH ADALIMUMAB AND ETANERCEPT
Authors: M. Nguyen, K. Velthuis, J. Scholl, J. Jansen, L. Kosse, P. Ten Klooster, N. Jessurun, H. Vonkeman
Journal: Annals of the Rheumatic Diseases (2021)

Background: Treatment of rheumatoid arthritis (RA) with biologic disease-modifying antirheumatic drugs (bDMARDs) has been common practice in the last two decades. However, differences in patients experiencing adverse drug reactions (ADRs) between individual bDMARDs, such as adalimumab (ADA) and etanercept (ETN), during first time treatment has not been studied yet in real-world settings. Objectives: To compare proportions of RA patients experiencing ADRs as well as survival to first ADR and drug survival during treatment with ADA and ETN. Methods: Retrospective single centre cohort study including adult patients with RA, treated with either ADA or ETN between 1 January 2003 and 30 April 2020. The proportions of patients experiencing an ADR were compared by assessing the percentage of patients, treated with either ADA or ETN, experiencing at least one ADR during their first time treatment. Survival to first ADR and drug survival were assessed by calculating time between start of treatment and first ADR and start of treatment and discontinuation of treatment respectively. Stop and restart of treatment within 90 days was considered as continuous use. Differences in proportions were statistically tested using Fisher’s Exact Test. Differences in drug survival between ADA and ETN were tested by Kaplan-Meier analysis and Log Rank tests. Results: A total of 422 patients were included in this study (ADA 259, ETN 163). For 93 patients (21.2%) an ADR was registered during first time treatment. The proportion of patients experiencing at least one ADR during their first time treatment was 22.7% for ADA and 20.2% for ETN ( p =0.628). Survival time to first ADR did not differ significantly between ADA and ETN (median survival ADA 10.34 years (95% CI [7.62-13.06], median survival ETN not reached, p =0.109, figure 1A). Median drug survival was 1.75 years for ADA (95 CI [1.38-2.11]) and 2.68 years for ETN (95% CI [1.73-3.64]). Drug survival differed significantly ( p &lt;0.001, figure 1B). Figure 1. Kaplan-Meier survival curves for adalimumab and etanercept with (a) survival to first ADR and (b) drug survival. Conclusion: Neither the proportion of patients experiencing ADRs nor survival to first ADR during first time treatment with ADA and ETN differed significantly. Drug survival of first time drug treatment of ADA was significantly lower compared to drug survival of first time drug treatment of ETN. Disclosure of Interests: My Nguyen: None declared, Kimberly Velthuis: None declared, Joep Scholl: None declared, Jurriaan Jansen: None declared, Leanne Kosse: None declared, Peter ten Klooster: None declared, Naomi Jessurun: None declared, Harald Vonkeman Consultant of: BMS, Celgene, Celltrion, Galapagos, Gilead, Janssen-Cilag, Lilly, Novartis, Pfizer, Sanofi-Genzyme, Grant/research support from: Abbvie
AB0666 PROGNOSTIC VALUE OF SERUM KREBS VON DEN LUNGEN-6 GLYCOPROTEIN CIRCULATING LEVELS IN COVID-19 PNEUMONIA: A PROSPECTIVE COHORT STUDY
Authors: D. Lobo Prat, I. Castellví, D. Castillo, S. Orozco, A. Mariscal, L. Martínez-Martínez, A. M. Millán Arciniegas, P. Moya, A. Laiz, C. Díaz-Torné, B. Magallares, S. P. Fernandez-Sanchez, S. Jeria Navarro, L. Sainz Comas, H. Codes, J. Casademont, P. Domingo, H. Corominas
Journal: Annals of the Rheumatic Diseases (2021)

Background: Currently, there are no biomarkers to predict respiratory worsening in patients with Coronavirus infectious disease, 2019 (COVID- 19) pneumonia. Objectives: We aimed to determine the prognostic value of Krebs von de Lungen-6 circulating serum levels (sKL-6) predicting COVID- 19 evolving trends. Methods: We prospectively analyzed the clinical and laboratory characteristics of 375 COVID- 19 patients with mild lung disease on admission. sKL-6 was obtained in all patients at baseline and compared among patients with respiratory worsening. Results: 45.1% of patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were higher in patients who had respiratory worsening (median [IQR] 303 [209-449] vs. 285.5 [15.8-5724], P=0.068). The best sKL-6 cut-off point was 408 U/mL (area under the curve 0.55; 33% sensitivity, 79% specificity). Independent predictors of respiratory worsening were sKL-6 serum levels, age &gt;51 years, time hospitalized, and dyspnea on admission. Patients with baseline sKL-6 ≥ 408 U/mL had a 39% higher risk of developing respiratory aggravation seven days after admission. In patients with serial determinations, sKL-6 was also higher in those who subsequently worsened (median [IQR] 330 [219-460] vs 290.5 [193-396]; p&lt;0.02). Conclusion: sKL-6 has a low sensibility to predict respiratory worsening in patients with mild COVID-19 pneumonia. Baseline sKL-6 ≥ 408 U/mL is associated to a higher risk of respiratory worsening. sKL-6 levels are not useful as a screening tool to stratify patients on admission but further research is needed to investigate if serial determinations of sKL-6 may be of prognostic use. References: [1]Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. 5. [2]Tian W, Jiang W, Yao J, Nicholson CJ, Li RH, Sigurslid HH, et al. Predictors of mortality in hospitalized COVID-19 patients: A systematic review and meta-analysis. J Med Virol. 2020. [3]Wang D, Li R, Wang J, Jiang Q, Gao C, Yang J, et al. Correlation analysis between disease severity and clinical and biochemical characteristics of 143 cases of COVID-19 in Wuhan, China: a descriptive study. BMC Infect Dis. 2020;20(1):519. Disclosure of Interests: None declared.
Edward Jenner and the Discovery of Smallpox Vaccination.
Journal: JAMA (1930)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Despite Big Buildup, Few Benefit From Medicare’s Advance Care Planning Coverage
Authors: Mary Chris Jaklevic
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Visceral Obesity Promotes Lung Cancer Progression—Toward Resolution of the Obesity Paradox in Lung Cancer
Authors: Joseph Barbi, Santosh K. Patnaik, Sarabjot Pabla, Robert Zollo, Randall J. Smith, Stephanie N. Sass, Aravind Srinivasan, Cara Petrucci, Robert Seager, Jeffrey Conroy, Eric Kannisto, Xialong Wang, Shrunjal Shah, Rohit Gosain, Kris Attwood, Charles Roche, Sai Yendamuri
Journal: Journal of Thoracic Oncology (2021)
Integrated Single-Cell Atlas of Endothelial Cells of the Human Lung
Authors: Jonas C. Schupp, Taylor S. Adams, Carlos Cosme, Micha Sam Brickman Raredon, Yifan Yuan, Norihito Omote, Sergio Poli, Maurizio Chioccioli, Kadi-Ann Rose, Edward P. Manning, Maor Sauler, Giuseppe DeIuliis, Farida Ahangari, Nir Neumark, Arun C. Habermann, Austin J. Gutierrez, Linh T. Bui, Robert Lafyatis, Richard W. Pierce, Kerstin B. Meyer, Martijn C. Nawijn, Sarah A. Teichmann, Nicholas E. Banovich, Jonathan A. Kropski, Laura E. Niklason, Dana Pe’er, Xiting Yan, Robert J. Homer, Ivan O. Rosas, Naftali Kaminski
Journal: Circulation (2021)

Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium.We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species analysis or disease relevance, we applied the same methods to scRNAseq data obtained from mouse lungs or from human lungs with pulmonary hypertension.Six lung scRNAseq datasets were reanalyzed and annotated to identify >15 000 vascular EC cells from 73 individuals. Differential expression analysis of EC revealed signatures corresponding to endothelial lineage, including panendothelial, panvascular, and subpopulation-specific marker gene sets. Beyond the broad cellular categories of lymphatic, capillary, arterial, and venous ECs, we found previously indistinguishable subpopulations; among venous EC, we identified 2 previously indistinguishable populations: pulmonary-venous ECs (COL15A1neg) localized to the lung parenchyma and systemic-venous ECs (COL15A1pos) localized to the airways and the visceral pleura; among capillary ECs, we confirmed their subclassification into recently discovered aerocytes characterized by EDNRB, SOSTDC1, and TBX2 and general capillary EC. We confirmed that all 6 endothelial cell types, including the systemic-venous ECs and aerocytes, are present in mice and identified endothelial marker genes conserved in humans and mice. Ligand-receptor connectome analysis revealed important homeostatic crosstalk of EC with other lung resident cell types. scRNAseq of commercially available primary lung ECs demonstrated a loss of their native lung phenotype in culture. scRNAseq revealed that endothelial diversity is maintained in pulmonary hypertension. Our article is accompanied by an online data mining tool (www.LungEndothelialCellAtlas.com).Our integrated analysis provides a comprehensive and well-crafted reference atlas of ECs in the normal lung and confirms and describes in detail previously unrecognized endothelial populations across a large number of humans and mice.
Single-cell transcriptome analysis identifies skin-specific T-cell responses in systemic sclerosis
Authors: Alyxzandria M Gaydosik, Tracy Tabib, Robyn Domsic, Dinesh Khanna, Robert Lafyatis, Patrizia Fuschiotti
Journal: Annals of the Rheumatic Diseases (2021)

Although T cells have been implicated in the pathogenesis of systemic sclerosis (SSc), a comprehensive study of T-cell-mediated immune responses in the affected skin of patients with progressive SSc is lacking. Droplet-based single-cell transcriptome analysis of SSc skin biopsies opens avenues for dissecting patient-specific T-cell heterogeneity, providing a basis for identifying novel gene expression related to functional pathways associated with severity of SSc skin disease.Single-cell RNA sequencing was performed by droplet-based sequencing (10x Genomics), focusing on 3729 CD3+ lymphocytes (867 cells from normal and 2862 cells from SSc skin samples) from skin biopsies of 27 patients with active SSc and 10 healthy donors. Confocal immunofluorescence microscopy of progressive SSc skin samples validated transcriptional results and visualised spatial localisations of T-cell subsets.We identified several subsets of recirculating and tissue-resident T cells in healthy and SSc skin that were associated with distinct signalling pathways. While most clusters shared a common gene expression signature between patients and controls, we identified a unique cluster of recirculating CXCL13+ T cells in SSc skin which expressed a T helper follicular-like gene expression signature and that appears to be poised to promote B-cell responses within the inflamed skin of patients.Current available therapies to reverse or even slow progression of SSc lead to broad killing of immune cells and consequent toxicities, including death. Identifying the precise immune mechanism(s) driving SSc pathogenesis could lead to innovative therapies that selectively target the aberrant immune response, resulting in better efficacy and less toxicity.
A Role for SMARCB1 in Synovial Sarcomagenesis Reveals That SS18–SSX Induces Canonical BAF Destruction
Authors: Jinxiu Li, Timothy S. Mulvihill, Li Li, Jared J. Barrott, Mary L. Nelson, Lena Wagner, Ian C. Lock, Amir Pozner, Sydney Lynn Lambert, Benjamin B. Ozenberger, Michael B. Ward, Allie H. Grossmann, Ting Liu, Ana Banito, Bradley R. Cairns, Kevin B. Jones
Journal: Cancer Discovery (2021)

Reduced protein levels of SMARCB1 (also known as BAF47, INI1, SNF5) have long been observed in synovial sarcoma. Here, we show that combined Smarcb1 genetic loss with SS18-SSX expression in mice synergized to produce aggressive tumors with histomorphology, transcriptomes, and genome-wide BAF-family complex distributions distinct from SS18-SSX alone, indicating a defining role for SMARCB1 in synovial sarcoma. Smarcb1 silencing alone in mesenchyme modeled epithelioid sarcomagenesis. In mouse and human synovial sarcoma cells, SMARCB1 was identified within PBAF and canonical BAF (CBAF) complexes, coincorporated with SS18-SSX in the latter. Recombinant expression of CBAF components in human cells reconstituted CBAF subcomplexes that contained equal levels of SMARCB1 regardless of SS18 or SS18-SSX inclusion. In vivo, SS18-SSX expression led to whole-complex CBAF degradation, rendering increases in the relative prevalence of other BAF-family subtypes, PBAF and GBAF complexes, over time. Thus, SS18-SSX alters BAF subtypes levels/balance and genome distribution, driving synovial sarcomagenesis. SIGNIFICANCE: The protein level of BAF component SMARCB1 is reduced in synovial sarcoma but plays a defining role, incorporating into PBAF and SS18-SSX-containing canonical BAF complexes. Reduced levels of SMARCB1 derive from whole-complex degradation of canonical BAF driven by SS18-SSX, with relative increases in the abundance of other BAF-family subtypes.See related commentary by Maxwell and Hargreaves, p. 2375.This article is highlighted in the In This Issue feature, p. 2355.
SARS-CoV-2の進化的解析:非構造蛋白質6(NSP6)の変異はウイルスオートファジーに影響を及ぼす【JST・京大機械翻訳】
Authors: Benvenuto Domenico, Angeletti Silvia, Giovanetti Marta, Bianchi Martina, Pascarella Stefano, Cauda Roberto, Ciccozzi Massimo, Cassone Antonio
Journal: Journal of Infection (2020)
BRD4 inhibition boosts the therapeutic effects of epidermal growth factor receptor-targeted chimeric antigen receptor T cells in glioblastoma
Authors: Lin Xia, Jun-yi Liu, Zao-zao Zheng, Yu-jie Chen, Jian-cheng Ding, Ya-hong Hu, Guo-sheng Hu, Ning-shao Xia, Wen Liu
Journal: Molecular Therapy (2021)

Glioblastoma (GBM) is the deadliest brain malignancy without effective treatments. Here, we reported that epidermal growth factor receptor-targeted chimeric antigen receptor T cells (EGFR CAR-T) were effective in suppressing the growth of GBM cells in vitro and xenografts derived from GBM cell lines and patients in mice. However, mice soon acquired resistance to EGFR CAR-T cell treatment, limiting its potential use in the clinic. To find ways to improve the efficacy of EGFR CAR-T cells, we performed genomics and transcriptomics analysis for GBM cells incubated with EGFR CAR-T cells and found that a large cohort of genes, including immunosuppressive genes, as well as enhancers in vicinity are activated. BRD4, an epigenetic modulator functioning on both promoters and enhancers, was required for the activation of these immunosuppressive genes. Accordingly, inhibition of BRD4 by JQ1 blocked the activation of these immunosuppressive genes. Combination therapy with EGFR CAR-T cells and JQ1 suppressed the growth and metastasis of GBM cells and prolonged survival in mice. We demonstrated that transcriptional modulation by targeting epigenetic regulators could improve the efficacy of immunotherapy including CAR-T, providing a therapeutic avenue for treating GBM in the clinic. Glioblastoma (GBM) is the deadliest brain malignancy without effective treatments. Here, we reported that epidermal growth factor receptor-targeted chimeric antigen receptor T cells (EGFR CAR-T) were effective in suppressing the growth of GBM cells in vitro and xenografts derived from GBM cell lines and patients in mice. However, mice soon acquired resistance to EGFR CAR-T cell treatment, limiting its potential use in the clinic. To find ways to improve the efficacy of EGFR CAR-T cells, we performed genomics and transcriptomics analysis for GBM cells incubated with EGFR CAR-T cells and found that a large cohort of genes, including immunosuppressive genes, as well as enhancers in vicinity are activated. BRD4, an epigenetic modulator functioning on both promoters and enhancers, was required for the activation of these immunosuppressive genes. Accordingly, inhibition of BRD4 by JQ1 blocked the activation of these immunosuppressive genes. Combination therapy with EGFR CAR-T cells and JQ1 suppressed the growth and metastasis of GBM cells and prolonged survival in mice. We demonstrated that transcriptional modulation by targeting epigenetic regulators could improve the efficacy of immunotherapy including CAR-T, providing a therapeutic avenue for treating GBM in the clinic.
POS1469-HPR THE ASSESSMENT OF FRACTURE RISK AND OSTEOPOROSIS RATE AMONG PATIENTS OVER 50 YEARS OLD UNDERGOING MEDICAL REHABILITATION
Authors: L. Marchenkova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Taking a course of physical rehabilitation creates the prerequisites for falls and injuries in patients at high risk of fractures. Data on fracture risk and prevalence of osteoporosis in older patients starting medical rehabilitation can change the approach of doctors to the development of rehabilitation programs and the management of such patients. Objectives: To assess the prevalence of osteoporosis, individual risk factors for osteoporosis as well as the proportion of people with high risk of osteoporotic low-energy fractures among patients over 50 years old undergoing treatment according to the “medical rehabilitation” profile. Methods: The study group comprised of 600 patients (426 women and 174 men) aged 50 to 84 years, average age 64.25 ± 10.17 years, undergoing treatment in a rehabilitation department. This was a cross-sectional study in the form of unified questionnaire, including data concerning age, weight, height, BMI, clinical and rehabilitation diagnosis, anamnesis of the main disease, anamnesis vitae, presence of osteoporosis diagnosis in the anamnesis, its treatment, osteoporosis risk factors estimation. An assessment of 10-year probability of osteoporotic fractures was carried out using Russian model of online FRAX® calculator. Results: 41.8% patients in the study sample had osteoporosis risk factors, including 31.2% of subjects had 3 risk factors or more. 38.0% patients showed a high fracture risk according to the FRAX calculator. 34.1% had a diagnosis of osteoporosis, and 45.8% already had osteoporotic fractures. Among those who did not undergo densitometry examination, 69.9% had a history of low-traumatic fractures, and only 58.5% of patients with an established diagnosis of osteoporosis and 26.8% of those at high risk of fractures received effective therapy for osteoporosis. Conclusion: Population of patients over 50 years old undergoing rehabilitation is characterized by high frequency of osteoporosis and probability of fractures, and insufficient quality of osteoporosis verification and anti-osteoporotic therapy administration at the same time. Disclosure of Interests: None declared
Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage
Authors: Anna Barkaway, Loïc Rolas, Régis Joulia, Jennifer Bodkin, Tchern Lenn, Charlotte Owen-Woods, Natalia Reglero-Real, Monja Stein, Laura Vázquez-Martínez, Tamara Girbl, Robin N. Poston, Matthew Golding, Rebecca S. Saleeb, Aude Thiriot, Ulrich H. von Andrian, Johan Duchene, Mathieu-Benoit Voisin, Cleo L. Bishop, David Voehringer, Axel Roers, Antal Rot, Tim Lämmermann, Sussan Nourshargh
Journal: Immunity (2021)

Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, we found that in aged mice, neutrophils adhered to vascular endothelium in inflamed tissues but exhibited a high frequency of reverse transendothelial migration (rTEM). This retrograde breaching of the endothelium by neutrophils was governed by enhanced production of the chemokine CXCL1 from mast cells that localized at endothelial cell (EC) junctions. Increased EC expression of the atypical chemokine receptor 1 (ACKR1) supported this pro-inflammatory milieu in aged venules. Accumulation of CXCL1 caused desensitization of the chemokine receptor CXCR2 on neutrophils and loss of neutrophil directional motility within EC junctions. Fluorescent tracking revealed that in aged mice, neutrophils undergoing rTEM re-entered the circulation and disseminated to the lungs where they caused vascular leakage. Thus, neutrophils stemming from a local inflammatory site contribute to remote organ damage, with implication to the dysregulated systemic inflammation associated with aging.
Seroprevalence of SARS-CoV-2 antibodies in a national hospital and affiliated facility after the second epidemic wave of Japan
Authors: Shohei Yamamoto, Akihito Tanaka, Yusuke Oshiro, Masamichi Ishii, Hironori Ishiwari, Maki Konishi, Kouki Matsuda, Mitsuru Ozeki, Kengo Miyo, Kenji Maeda, Tetsuya Mizoue, Wataru Sugiura, Hiroaki Mitsuya, Haruhito Sugiyama, Norio Ohmagari
Journal: Journal of Infection (2021)

Healthcare workers (HCWs) are at high risk for coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1,2 However, relative to the general population, there was no increase in the infection risk among HCWs in hospitals with adequate control measures against the infection.3 Studies on the source of infection among HCWs showed a stronger association with community factors than occupational factors,4–6 suggesting the importance of infection prevention outside the hospital.