tbuckley/cabot-search huggingface dataset:
POS0635 COMPARING THE ULTRASONOGRAPHIC EVALUATION IN PATIENTS WITH JAPANESE RHEUMATOID ARTHRITIS BETWEEN BARICITINIB AND TNF ANTAGONIST THERAPY
Authors: Y. Kanayama, A. Nagata, M. Shimotake, F. Miyachi, K. Fujita, M. Koyama, S. Uno
Journal: Annals of the Rheumatic Diseases (2021)

Background: Baricitinib (BAR) and TNF antagonist are the important therapeutic agent for the treatment of rheumatoid arthritis.However there is still few studies of improvement of ultrasonographic findings in RA treated comparison with BAR and TNF. Objectives: To evaluate the clinical efficacy of BAR and TNF therapy patients with rheumatoid arthritis (RA) using ultrasonography (US). Methods: Participants comprised 16 and 45 Japanese RA patients who had recently received BAR and TNF. All patients with a diagnosis of RA according to the 2010 ACR/EULAR criteria. Patients underwent clinical and laboratory assessments every 4 weeks from baseline to 24 weeks, and US assessments at baseline, 4, 12 and 24 weeks. Gray scale (GS) and power doppler (PD) signals were scored using a semi-quantitative scale from 0 to 3 at 26 (0-78) synovial sites (22 joints) in the following joints: bilateral first to fifth metacarpopharangeal (MCP) joints (dorsal recess); first interphalangeal (IP) and second to fifth proximal interphalangeal (PIP) (dorsal recess) joints; and the wrists (dorsal radial, median and ulnar). We evaluated the improvement of GS and PD score from baseline to week 24. Results: In the patients receiving BAR (n=16) and TNF (n=45), the mean age was 55.9 vs 54.6 years old (p=0.682), disease duration was 10.2 vs 6.1 years (p=0.094), the rate of MTX use was 75% vs 89% (p=346), the mean MTX dose was 9.3 vs 10.2 mg/w (p=0.443), the rate of ACPA positive was 94% vs 82% (p=0.476), DAS28-ESR was 4.25 vs 4.61 (p=0.289), CDAI was 15.8 vs 18.5 (p=0.210), GS score was 21.6 vs 16.3 (p=0.436) and PD score was 15.0 vs 9.5 (p=0.260). The degree of improvement respective changes in GS and PD score after 4, 12 and 24 weeks were as follows: GS: -7.2 vs -3.7 (p=0.268) and PD: -7.6 vs -2.3 (p=0.158) after 4 weeks, GS: -10.9 vs -5.0 (p=0.161) and PD: -9.2 vs -3.8 (p=0.049) after 12 weeks, GS: -12.9 vs -6.1 (p=0.485) and PD: -11.3 vs -5.7 (p=0.062) after 24 weeks between BAR and TNF (Fig.1, 2). Next, The improvement rate of respective changes in GS and PD score after 4, 12 and 24 weeks were as follows: GS: -23.8% vs -11.6% (p=0.580) and PD: -30.3% vs -16.5% (p=0.343) after 4 weeks, GS: -39.6% vs -15.6% (p=0.129) and PD: -47.1% vs -30.8% (p=0.210) after 12 weeks, GS: -52.2% vs -22.2% (p=0.248) and PD: -77.1% vs -50.1% (p=0.048) after 24 weeks between BAR and TNF. Conclusion: The present study provides evidence supporting both the BAR and TNF therapy showed improvement effect over time, but in a comparison between BAR and TNF, the PD score of BAR showed a siginificant improvement effect compared to TNF at 12 and 24 weeks. It was suggeted that BAR may improve inflammatory synovitis earlier compared to TNF. Disclosure of Interests: None declared
Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial
Authors: Robert L Ferris, William C Spanos, Rom Leidner, Anthony Gonçalves, Uwe M Martens, Chrisann Kyi, William Sharfman, Christine H Chung, Lot A Devriese, Helene Gauthier, Simon I Chiosea, Lazar Vujanovic, Janis M Taube, Julie E Stein, Jun Li, Bin Li, Tian Chen, Adam Barrows, Suzanne L Topalian
Journal: Journal for ImmunoTherapy of Cancer (2021)

Head and neck squamous cell carcinomas (HNSCCs) are common malignancies caused by carcinogens, including tobacco and alcohol, or infection with human papillomavirus (HPV). Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) pathway are effective against unresectable recurrent/metastatic HNSCC. Here, we explored the safety and efficacy of anti-PD-1 therapy in at-risk resectable HPV-positive and HPV-negative HNSCC in the neoadjuvant setting.The phase I/II CheckMate 358 trial in virus-associated cancers assessed neoadjuvant nivolumab in patients with previously untreated, resectable HPV-positive or HPV-negative HNSCC. Patients received nivolumab 240 mg intravenously on days 1 and 15, with surgery planned by day 29. Safety/tolerability (primary endpoint) was assessed by monitoring adverse events (AEs) and surgical delays. Radiographic response was measured before surgery using RECIST v1.1, adapted for a single post-nivolumab evaluation. Pathologic specimens were examined for treatment response using immune-based criteria.From November 2015 to December 2017, 52 patients with AJCC (seventh edition) stage III-IV resectable HNSCC received neoadjuvant nivolumab (26 HPV-positive, 26 HPV-negative). Any-grade treatment-related AEs (TRAEs) occurred in 19 patients (73.1%) and 14 patients (53.8%) in the HPV-positive and HPV-negative cohorts, respectively; grade 3-4 TRAEs occurred in five (19.2%) and three patients (11.5%), respectively. No patient had a protocol-defined TRAE-related surgical delay (>4 weeks). Thirty-eight patients were reported as undergoing complete surgical resection, 10 had a planned post-nivolumab biopsy instead of definitive surgery due to a protocol misinterpretation, and four did not undergo surgery or biopsy, including two with tumor progression. Radiographic response rates in 49 evaluable patients were 12.0% and 8.3% in the HPV-positive and HPV-negative cohorts, respectively. There were no complete pathologic responses by site or central review in operated patients. Among 17 centrally evaluable HPV-positive tumors, one (5.9%) achieved major pathological response and three (17.6%) achieved partial pathologic response (pPR); among 17 centrally evaluable HPV-negative tumors, one (5.9%) achieved pPR.Neoadjuvant nivolumab was generally safe and induced pathologic regressions in HPV-positive (23.5%) and HPV-negative (5.9%) tumors. Combinatorial neoadjuvant treatment regimens, and continued postoperative therapy for high-risk tumors, are warranted in future trials to enhance the efficacy of this approach.ClinicalTrials.gov NCT02488759; https://clinicaltrials.gov/ct2/show/NCT02488759.
Improving the Assessment of COVID-19–Associated Posttraumatic Stress Disorder
Authors: Brian P. Marx, Paula P. Schnurr, Matthew J. Friedman
Journal: JAMA Psychiatry (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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 Psychiatry journal
Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy
Authors: Felix Wiedmann, Christoph Beyersdorf, Xiao Bo Zhou, Manuel Kraft, Amelie Paasche, Natasa Jávorszky, Susanne Rinné, Henry Sutanto, Antonius Büscher, Kathrin I Foerster, Antje Blank, Ibrahim El-Battrawy, Xin Li, Siegfried Lang, Ursula Tochtermann, Jamila Kremer, Rawa Arif, Matthias Karck, Niels Decher, Gunther van Loon, Ibrahim Akin, Martin Borggrefe, Stefan Kallenberger, Jordi Heijman, Walter E Haefeli, Hugo A Katus, Constanze Schmidt
Journal: Cardiovascular Research (2021)

Abstract Aims TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF. Methods and results Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram. Conclusion Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.
Choose wisely: imaging for diagnosis of axial spondyloarthritis
Authors: Torsten Diekhoff, Iris Eshed, Felix Radny, Katharina Ziegeler, Fabian Proft, Juliane Greese, Dominik Deppe, Robert Biesen, Kay Geert Hermann, Denis Poddubnyy
Journal: Annals of the Rheumatic Diseases (2021)

Objective To assess the diagnostic accuracy of radiography (X-ray, XR), CT and MRI of the sacroiliac joints for diagnosis of axial spondyloarthritis (axSpA). Methods 163 patients (89 with axSpA; 74 with degenerative conditions) underwent XR, CT and MR. Three blinded experts categorised the imaging findings into axSpA, other diseases or normal in five separate reading rounds (XR, CT, MR, XR +MR, CT +MR). The clinical diagnosis served as reference standard. Sensitivity and specificity for axSpA and inter-rater reliability were compared. Results XR showed lower sensitivity (66.3%) than MR (82.0%) and CT (76.4%) and also an inferior specificity of 67.6% vs 86.5% (MR) and 97.3% (CT). XR +MR was similar to MR alone (sensitivity 77.5 %/specificity 87.8%) while CT+MR was superior (75.3 %/97.3%). CT had the best inter-rater reliability (kappa=0.875), followed by MR (0.665) and XR (0.517). XR +MR was similar (0.662) and CT+MR (0.732) superior to MR alone. Conclusions XR had inferior diagnostic accuracy and inter-rater reliability compared with cross-sectional imaging. MR alone was similar in diagnostic performance to XR+MR. CT had the best accuracy, strengthening the importance of structural lesions for the differential diagnosis in axSpA.
Zn-Mg and Zn-Cu alloys for stenting applications: From nanoscale mechanical characterization to in vitro degradation and biocompatibility
Authors: Claudia García-Mintegui, Laura Catalina Córdoba, Judit Buxadera-Palomero, Andrea Marquina, Emilio Jiménez-Piqué, Maria-Pau Ginebra, José Luis Cortina, Marta Pegueroles
Journal: Bioactive Materials (2021)

In the recent decades, zinc (Zn) and its alloys have been drawing attention as promising candidates for bioresorbable cardiovascular stents due to its degradation rate more suitable than magnesium (Mg) and iron (Fe) alloys. However, its mechanical properties need to be improved in order to meet the criteria for vascular stents. This work investigates the mechanical properties, biodegradability and biocompatibility of Zn-Mg and Zn-Cu alloys in order to determine a proper alloy composition for optimal stent performance. Nanoindentation measurements are performed to characterize the mechanical properties at the nanoscale as a function of the Zn microstructure variations induced by alloying. The biodegradation mechanisms are discussed and correlated to microstructure, mechanical performance and bacterial/cell response. Addition of Mg or Cu alloying elements refined the microstructure of Zn and enhanced yield strength (YS) and ultimate tensile strength (UTS) proportional to the volume fraction of secondary phases. Zn-1Mg showed the higher YS and UTS and better performance in terms of degradation stability in Hanks' solution. Zn-Cu alloys presented an antibacterial effect for S. aureus controlled by diffusion mechanisms and by contact. Biocompatibility was dependent on the degradation rate and the nature of the corrosion products.
AB0239 PERSISTENCE TO BIOLOGICAL DMARDS TNF INHIBITORS VS BIOLOGICAL DMARDS NO TNF INHIBITORS AFTER FAILURE TO SYNTHETIC CONVENTIONAL DMARDS IN RA PATIENTS TREATED IN STANDARD CLINICAL PRACTICE
Authors: B. Hernández-Cruz, P. Muñoz Reinoso, I. García Hernández, G. Jurado Quijano, L. Fernández de la Fuente Bursón, I. M. Fernández-Maeztu Palacín, A. Fernández Reboul Fernández, D. Ruiz-Montesinos, J. J. Pérez Venegas
Journal: Annals of the Rheumatic Diseases (2021)

Background: There are no RA response predictors for our patients. The decision to initiate a first biological depends on multiple factors such as rheumatologist experience, clinical characteristics of the patient and health system. What is clear is that the best strategy is T2T. Objectives: To know the clinical characteristics and persistence of the first biological DMARD in patients receiving bDMARDS TNF inhibitors vs DMARDs aimed at other targets. Methods: A observational cohort of adult RA patients (ACR/EULAR 2010) in a rheumatology department of a third-level university hospital. All patients were treated with a first bDMARD marketed in Spain, from 2010 to December 2020 and prescribed according to product data sheet. Biological drugs were divided into TNF inhibitors drugs (adalimumab, etanercept, infliximab, golimumab, certolizumab) and Other targets (abatacept, rituximab, sarilumab, tocilizumab). Clinical data, duration of treatment and EULAR response were collected from each patient. The data were analyzed with descriptive, bivariate statistics and survival analysis adjusted for age, sex, FR, erosions and duration of the disease. Results: Data were collected from 332 patients (table 1). Patients treated with other target bDMARDs were mostly female, with higher activity, shorter disease duration, and treated without MTX.b Survival graphs showed that regardless of the target chosen as fist bDMARD, EULAR response rates and persistence to the drug were similar. Table 1. Variable TNF inhibitors n=194 Other targets n = 138 Total n =332 p n (%) n (%) n (%) 0.02 Female 142 (73) 115 (83) 257 (77) 0.2 FR + 163 (82) 121 (88) 284 (86) 0.6 ACPA + 125 (63) 84 (61) 209 (63) 0.9 Erosions 177 (89) 80 (58) 257 (77) 0.01 Concomitant MTX 153 (77) 62 (47) 215 (65) 0.003 EULAR response Good 103 (77) 67 (71) 170 (75) 0.2 Moderate 24 (18) 16 (17) 40 (17) No 7 (5) 11 (11) 18 (8) Mean ± SD Mean ± SD Mean ± SD Age (years) 55.7 ± 13.3 57.6 ± 11.9 56.5 ± 12.7 0.1 Evolution of RA (years) 9.6 ± 10.2 7.5 ± 7.5 8.7 ± 9.2 0.04 Persistence (months) 19.3 ± 20.5 16.07 ± 15.11 17.5 ± 18.5 0.04 DAS28VSG4V basal 5.02 ± 1.5 5.59 ± 1.03 5.25 ± 1.3 0.001 DAS28VSG4V final 2.68 ± 1.1 2.84 ± 1.4 2.7 ± 1.25 0,31 Conclusion: Patients receiving Anti-TNF vs bDMARD with other mechanisms of action have clinical differences. However, the response and persistence to the drug are similar, perhaps due to the implementation of the correct T2T strategy. Disclosure of Interests: None declared
OP0015 GENOMIC RISK SCORE FOR ADVANCED OSTEOARTHRITIS IN OLDER ADULTS
Authors: P. Lacaze, G. Polekhina, A. Bakshi, M. Riaz, A. Owen, A. Franks, Y. Wang, J. Abidi, J. Tiller, S. Orchard, J. Mcneil, F. Cicuttini
Journal: Annals of the Rheumatic Diseases (2021)

Background: Osteoarthritis (OA) is a major cause of disability, with treatment options mostly limited to advanced disease when joint replacement is indicated. Recent genome-wide association analysis more than doubled the number of OA-associated variants identified (1, 2), extending the feasibility of identification of high-risk individuals. Objectives: Including these variants, we calculated polygenic risk scores (PRSs) and performed validation in a well-characterised population of older individuals. Methods: We calculated PRSs for knee and hip OA respectively, using joint replacement surgeries as markers of advanced disease in 12,724 older individuals of European descent in the ASPREE trial. We considered in-trial joint replacement (hospitalizations during median 4.7 years follow-up) and pre-trial joint replacement from self-reported medical history. Multivariable models examined the effect of PRS as a continuous variable (per standard deviation [SD]) and categorical variable (low-risk [0-20%], medium-risk [21-80%], high-risk [81-100%] groups), adjusting for age, sex and BMI. Results: Mean population age at baseline was 75 years and 54.9% of participants were female. In total, 1478 (11.6%) participants had knee replacements and 1324 (10.4%) had hip replacements. Female sex, higher BMI and age were associated with higher risk of knee and hip replacements. PRSs as continuous variables per SD were associated with knee (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.04-1.17) and hip (OR 1.18, 95% CI 1.11-1.25) replacements. We found meaningfully different rates of knee or hip joint replacement occurring between low-, medium- and high-risk PRS groups. Participants in the high-risk PRS group, compared with the low, had a higher risk of knee replacements (OR=1.35, CI 1.12-1.62), and hip replacements (OR 1.66, 95% CI 1.37-2.02). We found no interaction between PRS and sex, and no collinearity between PRS and BMI, suggesting PRS is an independent risk factor for OA. Conclusion: Joint-specific genomic risk scores predict advanced OA in older adults, independent of age, sex and BMI. Stronger associations are observed for hip versus knee OA. Our study provides some of the first evidence of potential clinical utility of genomic risk prediction for OA, which may help identify individuals who would benefit most from targeted clinical management and preventive intervention. References: [1]Tachmazidou I, Hatzikotoulas K, Southam L , et al. 2019. Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet, 51, 230-236 [2]Zengini E, Hatzikotoulas K, Tachmazidou I , et al. 2018. Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis. Nat Genet, 50, 549-558 Disclosure of Interests: None declared
Immunogenicity in humans of a transdermal multipeptide melanoma vaccine administered with or without a TLR7 agonist
Authors: Max O Meneveau, Gina R Petroni, Elise P Salerno, Kevin T Lynch, Mark Smolkin, Elizabeth Woodson, Kimberly A Chianese-Bullock, Walter C Olson, Donna Deacon, James W Patterson, William W Grosh, Craig L Slingluff
Journal: Journal for ImmunoTherapy of Cancer (2021)

Experimental cancer vaccines are traditionally administered by injection in subcutaneous tissue or muscle, commonly with adjuvants that create chronic inflammatory depots. Injection of melanoma-derived peptides induces T cell responses; however, the depots that form following injection may inhibit optimization of the immune response. In skin, epidermal Langerhans cells (LC) are a dominant source of professional antigen presenting cells. We hypothesized that: (1) applying melanoma-derived peptides topically, in proximity to LC, could be immunogenic and safe, with low vaccine-site toxicity and (2) topical toll-like receptor 7 (TLR7) agonist would increase immunogenicity of the peptide vaccine.
Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10
Authors: Claire Bouvard, Ly Tu, Martina Rossi, Agnès Desroches-Castan, Nihel Berrebeh, Elise Helfer, Caroline Roelants, Hequn Liu, Marie Ouarné, Nicolas Chaumontel, Christine Mallet, Christophe Battail, Andreas Bikfalvi, Marc Humbert, Laurent Savale, Thomas Daubon, Pascale Perret, Emmanuelle Tillet, Christophe Guignabert, Sabine Bailly
Journal: Cardiovascular Research (2021)

Abstract Aims BMP9 and BMP10 mutations were recently identified in patients with pulmonary arterial hypertension, but their specific roles in the pathogenesis of the disease are still unclear. We aimed to study the roles of BMP9 and BMP10 in cardiovascular homeostasis and pulmonary hypertension using transgenic mouse models deficient in Bmp9 and/or Bmp10. Methods and results Single- and double-knockout mice for Bmp9 (constitutive) and/or Bmp10 (tamoxifen inducible) were generated. Single-knock-out (KO) mice developed no obvious age-dependent phenotype when compared with their wild-type littermates. However, combined deficiency in Bmp9 and Bmp10 led to vascular defects resulting in a decrease in peripheral vascular resistance and blood pressure and the progressive development of high-output heart failure and pulmonary hemosiderosis. RNAseq analysis of the lungs of the double-KO mice revealed differential expression of genes involved in inflammation and vascular homeostasis. We next challenged these mice to chronic hypoxia. After 3 weeks of hypoxic exposure, Bmp10-cKO mice showed an enlarged heart. However, although genetic deletion of Bmp9 in the single- and double-KO mice attenuated the muscularization of pulmonary arterioles induced by chronic hypoxia, we observed no differences in Bmp10-cKO mice. Consistent with these results, endothelin-1 levels were significantly reduced in Bmp9 deficient mice but not Bmp10-cKO mice. Furthermore, the effects of BMP9 on vasoconstriction were inhibited by bosentan, an endothelin receptor antagonist, in a chick chorioallantoic membrane assay. Conclusions Our data show redundant roles for BMP9 and BMP10 in cardiovascular homeostasis under normoxic conditions (only combined deletion of both Bmp9 and Bmp10 was associated with severe defects) but highlight specific roles under chronic hypoxic conditions. We obtained evidence that BMP9 contributes to chronic hypoxia-induced pulmonary vascular remodelling, whereas BMP10 plays a role in hypoxia-induced cardiac remodelling in mice.
The hidden history of hypersensitivity pneumonitis
Authors: Hayley Barnes, Kirk Jones, Paul Blanc
Journal: European Respiratory Journal (2021)

Hypersensitivity pneumonitis (HP) is a relatively new construct, first reported in the early 20th century, despite major aetiological factors (farming, bird husbandry) having been part of human activities for millennia. Initial confirmed HP reports included exposure to farming and forestry (1932) and bird exposure (1965), much more recently than is often assumed. Later changes in occupational and living practices have led to HP associated with isocyanates, machine coolants, indoor mould, hot tubs and other exposures. Evolution of our pathological understanding of interstitial lung disease in general, wider computed tomography utilisation and advances in immunology and genomics have shaped our modern conceptualisation of HP. Examining historical accounts of HP and its causative factors not only considers when the first cases were recognised, but also explores why the disease emerged at specific times and places, and may provide further insights relevant to the mechanisms underlying HP and disease prevention.