tbuckley/cabot-search huggingface dataset:
THU0202 Pattern of radiographic damage of the hand joints in rheumatoid arthritis: a study of 193 patients
Authors: LS Ines, P Reis, MJ Santos, M Alexandre, C Silva, A Branha, A Figueiredo, D Nour, JA Da Silva, A Malcata, A Porto
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hands are some of the most frequently involved areas in rheumatoid arthritis (RA). However, observational data suggest that differences may exist between different fingers. <h3>Objectives</h3> To evaluate the pattern of radiographic damage of the wrists and small joints of the hands in RA patients. <h3>Methods</h3> Cross-sectional study of 193 RA patients, fulfilling the 1987 ACR criteria (female = 168 [87%], male = 25 [13%]; mean age = 57.0 ± 11.7 years; mean disease duration = 13.4 ± 8.1 years; RF positive = 72%). They attended consecutively our hospital-based outpatient rheumatology clinic. Radiographs of the hands were obtained from all patients. Wrists, MCP, PIP and distal interphalangeal joints (DIP) were scored using Larsen's method. All radiographs were evaluated by a single reader in a blinded fashion. The intrarreader concordance rate was &gt;0.82 for all joints. <h3>Results</h3> Mean Larsen scores were 2.25 ± 1.54 for wrists, 1.70 ± 1.49 for MCPs, 1.29 ± 1.19 for PIPs and 0.84 ± 0.74 for DIPs. There were erosive changes in 62.7% of the wrists, 39.0% of the MCPs, 27.4% of the first finger interphalangeals, 20.8% of the PIPs and 10.3% of the DIPs. Mean scores for each joint area and for each finger are presented in the Table 1 below. <h3>Conclusion</h3> Mean radiographic damage increases from DIPs to proximal joints up to the wrist. There are also differences of the damage of each joint area between fingers. Functional and mechanical factors may contribute to these differences.
AB0099 METHOTREXATE REDUCES THE INVASIVE ACTIVITIES OF PRIMARY RA SYNOVIAL FIBROBLASTS
Authors: C. R. Ng, K. Sheridan, S. Cowley, E. Dorris, D. Veale, U. Fearon, A. G. Wilson
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid Arthritis synovial fibroblasts (RASFs) are key player in tissue destruction via the production of a wide range of chemical reactions in the joint with high growth rate and resistance to mortality [1]. Methotrexate (MTX) is a dihydrofolate reductase inhibitor that attenuates inflammation within joints resulting in reduced cartilage and bone damage and is the anchor therapy for RA. Its mechanisms of action are thought to differ from its anti-proliferative effects and are known to include increased adenosine release (2), but may also involve alterations in intracellular methyl donor status resulting in alteration in DNA methylation and gene expression. Objectives: To investigate the effects of MTX on RASFs auto-aggressive activities, including invasion, migration, proliferation and apoptosis. Methods: RASF were derived from knee biopsies of RA patients taken at arthroscopy (n=9). Matrigel chambers were used to measure invasive activities. The cells were incubated with DMSO (control), 1μM or 10μM MTX for 96 hours. Wound healing (scratch assays) were used to measure migration. Proliferation and apoptosis was determined using BrdU and caspase-3/7 assays respectively. Significance was determined via repeated measures ANOVA using SPSS software. Results: Incubation with MTX resulted in significantly reduced invasive activity compared with DMSO control; 1μM (35%, p=0.006) and 10μM (58%, p=0.002) in paired samples. However MTX did not have significant effects on RASF migration, apoptosis or proliferation at either concentration. Conclusion: Our data reveals that MTX reduces the invasive potential of RASFs in vitro, this effect may contribute to the clinical efficacy of this agent. Further investigation will involve epigenome-wide methylation to determine if the DNA methylome of RASFs is altered by MTX. References: [1]Huber LC, et al. (2006) Rheumatol. 45(6):669-675. [2]Chan ES &amp; Cronstein BN (2010) Nat Rev Rheumatol 6(3):175-178. Acknowledgments: This abstract arose from work funded by the National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin Disclosure of Interests: None declared
Abstract IA19: Genomic analysis of osteosarcoma: Insights into tumor evolution and therapy response
Authors: E. Alejandro Sweet-Cordero
Journal: Cancer Research (2020)

Abstract While significant progress has been made in most other cancers to advance targeted therapy, there has been essentially no change in our approach to treatment of osteosarcoma in over 30 years. Osteosarcomas exhibit an extremely complex genome characterized by multiple copy number changes and structural alterations. Using patient-derived xenografts and primary tumors, we are employing whole-genome sequencing (WGS) and RNAseq to characterize the evolution of this disease with a goal of understanding how evolutionary constraints can identify targetable vulnerabilities. We have identified a number of potential subtypes of osteosarcoma based on copy number alterations and defined how these copy number alterations can be exploited for therapeutic benefit using a large and clinically annotated patient-derived xenograft (PDX) collection. A key current effort is to identify novel genome-informed combination therapies for this disease. To facilitate this work, we have developed a panel of cell lines derived from PDX models, which have also be characterized with regards to their genomic characteristics. We have used these cell lines to screen for response to a wide variety of drugs with the goal of matching response to specific genomic characteristics. Lastly, we are using PDX models to study the process of metastatic progression and have identified a possible role for the enzyme ENPP1 in osteosarcoma metastasis. Citation Format: E. Alejandro Sweet-Cordero. Genomic analysis of osteosarcoma: Insights into tumor evolution and therapy response [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA19.
STING differentially regulates experimental GVHD mediated by CD8 versus CD4 T cell subsets
Authors: Cameron S. Bader, Henry Barreras, Casey O. Lightbourn, Sabrina N. Copsel, Dietlinde Wolf, Jingjing Meng, Jeonghyun Ahn, Krishna V. Komanduri, Bruce R. Blazar, Lei Jin, Glen N. Barber, Sabita Roy, Robert B. Levy
Journal: Science Translational Medicine (2020)

STING differentially regulates experimental graft-versus-host disease mediated by distinct T cell subsets.
Hepatitis C-related cirrhosis will be a marginal cause of hospital admissions by 2025
Authors: Sergio Rodríguez-Tajes, Anna Pocurull, Joaquín Castillo, Gherzon Casanova, Laia Vega, Sabela Lens, Zoe Mariño, María-Carlota Londoño, Alejandro Forner, Ferran Torres, Xavier Forns
Journal: Journal of Hepatology (2020)
Image-based consensus molecular subtype (imCMS) classification of colorectal cancer using deep learning
Authors: Korsuk Sirinukunwattana, Enric Domingo, Susan D Richman, Keara L Redmond, Andrew Blake, Clare Verrill, Simon J Leedham, Aikaterini Chatzipli, Claire Hardy, Celina M Whalley, Chieh-hsi Wu, Andrew D Beggs, Ultan McDermott, Philip D Dunne, Angela Meade, Steven M Walker, Graeme I Murray, Leslie Samuel, Matthew Seymour, Ian Tomlinson, Phil Quirke, Timothy Maughan, Jens Rittscher, Viktor H Koelzer
Journal: Gut (2020)

Objective Complex phenotypes captured on histological slides represent the biological processes at play in individual cancers, but the link to underlying molecular classification has not been clarified or systematised. In colorectal cancer (CRC), histological grading is a poor predictor of disease progression, and consensus molecular subtypes (CMSs) cannot be distinguished without gene expression profiling. We hypothesise that image analysis is a cost-effective tool to associate complex features of tissue organisation with molecular and outcome data and to resolve unclassifiable or heterogeneous cases. In this study, we present an image-based approach to predict CRC CMS from standard H&amp;E sections using deep learning. Design Training and evaluation of a neural network were performed using a total of n=1206 tissue sections with comprehensive multi-omic data from three independent datasets (training on FOCUS trial, n=278 patients; test on rectal cancer biopsies, GRAMPIAN cohort, n=144 patients; and The Cancer Genome Atlas (TCGA), n=430 patients). Ground truth CMS calls were ascertained by matching random forest and single sample predictions from CMS classifier. Results Image-based CMS (imCMS) accurately classified slides in unseen datasets from TCGA (n=431 slides, AUC)=0.84) and rectal cancer biopsies (n=265 slides, AUC=0.85). imCMS spatially resolved intratumoural heterogeneity and provided secondary calls correlating with bioinformatic prediction from molecular data. imCMS classified samples previously unclassifiable by RNA expression profiling, reproduced the expected correlations with genomic and epigenetic alterations and showed similar prognostic associations as transcriptomic CMS. Conclusion This study shows that a prediction of RNA expression classifiers can be made from H&amp;E images, opening the door to simple, cheap and reliable biological stratification within routine workflows.
Temporal trends and mortality of post-ERCP pancreatitis in the United States: a nationwide analysis
Authors: Hemant Raj Mutneja, Ishaan Vohra, Andrew Go, Abhishek Bhurwal, Vatsala Katiyar, Emmanuel Palomera Tejeda, Kapil Thapa Chhetri, Muhammad Arslan Baig, Shilpa Arora, Bashar Attar
Journal: Endoscopy (2020)

Abstract Background Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common and most serious complication of ERCP. Our aim was to estimate the nationwide incidence, temporal trends, and mortality of PEP in the United States and to establish risk factors associated with PEP development. Methods This was a retrospective cohort study analyzing Nationwide Inpatient Sample data from 2011 to 2017 using International Classification of Diseases codes. The primary outcomes were trends in PEP incidence and predictors of PEP development. Secondary outcomes were in-hospital mortality, length of hospital stay, and admission to the intensive care unit. Results Of 1 222 467 adult patients who underwent inpatient ERCP during the study period, 55 225 (4.5 %) developed PEP. The hospital admission rate of PEP increased by 15.3 %, from 7735 in 2011 to 8920 in 2017 (odds ratio [OR] 1.23, 95 % confidence interval [CI] 1.04 – 1.46; P = 0.02). The overall rate of mortality increased from 2.8 % of PEP cases in 2011 to 4.4 % in 2017 (OR 1.62, 95 %CI 1.10 – 2.38; P = 0.01). Multiple patient-related (alcohol use, cocaine use, obesity, chronic kidney disease, heart failure), procedure-related (therapeutic ERCP, sphincterotomy, pancreatic duct stent placement, sphincter of Oddi dysfunction), and hospital-related (teaching hospitals, hospitals located in the West and Midwest) factors that impact the occurrence of PEP were identified. Conclusions Our study showed rising hospital admission and mortality rates associated with PEP in the United States. This calls for a greater recognition of this life-threatening complication and amelioration of its risk factors, whenever possible.
Selectivity of Janus Kinase Inhibitors in Rheumatoid Arthritis and Other Immune-Mediated Inflammatory Diseases: Is Expectation the Root of All Headache?
Authors: Masayoshi Harigai, Suguru Honda
Journal: Drugs (2020)

Janus kinase (JAK) is a signal transducer and activator of a protein transcription system that transduces signals from cell surface cytokine and growth factor receptors to the nucleus. Recently developed JAK inhibitors (JAKinibs) inhibit JAKs non-selectively or selectively and down-regulate the effects of corresponding ligands (i.e. cytokines and growth factors). JAKinibs are efficacious against rheumatoid arthritis and other immune-mediated inflammatory diseases and are being increasingly prescribed clinically. Regarding safety, JAKinib use is associated with common or unique changes in laboratory parameters; however, incidence rates of serious adverse drug reactions (ADRs) associated with these changes are low. Opportunistic and other infections, including tuberculosis, are the most critical ADRs of treatment with JAKinibs, and screening and monitoring of patients should be carefully performed. Incidence rates of herpes zoster (HZ) in patients receiving JAKinibs are high in Japan and Korea, and modestly high in other countries. Filgotinib may not be associated with an elevated risk for HZ, but long-term safety data are lacking. Data from clinical development programmes and post-marketing surveillance have indicated no increased risk for malignancy or serious cardiac events; however, long-term observational studies are necessary. Despite the non-elevated risk of gastrointestinal perforations, patients with older age and/or a history of diverticulitis or receiving non-steroidal anti-inflammatory drugs should be carefully evaluated to determine the risk-benefit balance. The incidence rates of venous thromboembolism with all approved doses are similar to that expected in the population, although there are discrepancies in the placebo-controlled portion of the baricitinib clinical development programmes. Regulatory agencies in the USA and Europe suggested a higher risk for thrombotic events in patients receiving JAKinibs. Pharmacokinetic studies demonstrated that dose adjustment should be considered for JAKinib use in patients with moderate-to-severe renal or hepatic dysfunction, depending on the metabolism of each drug. Long-term observational studies enrolling patients with diverse clinical backgrounds are required to strike a risk-benefit balance in clinical settings.
Coronary Artery Calcification and Complications in Patients With COVID-19
Authors: Jean Guillaume Dillinger, Fatima Azzahra Benmessaoud, Théo Pezel, Sebastian Voicu, Georgios Sideris, Naima Chergui, Lounis Hamzi, Anthony Chauvin, Pierre Leroy, Jean François Gautier, Damien Sène, Patrick Henry
Journal: JACC. Cardiovascular imaging (2020)
CFTR is a negative regulator of γδ T cell IFN-γ production and antitumor immunity
Authors: Yuanyuan Duan, Guangqiang Li, Miaomiao Xu, Xiaofei Qi, Mingxia Deng, Xuejia Lin, Zhiwei Lei, Yi Hu, Zhenghu Jia, Quanli Yang, Guangchao Cao, Zonghua Liu, Qiong Wen, Zhenhua Li, Jie Tang, Wei Kevin Zhang, Pingbo Huang, Limin Zheng, Richard A. Flavell, Jianlei Hao, Zhinan Yin
Journal: Cellular and Molecular Immunology (2020)
Complete Metabolic Response Assessed by FDG PET/CT to FOLFOXIRI-Bevacizumab in First-Line Treatment of BRAFV600E Mutated Metastatic Colorectal Cancer
Authors: Karim Amrane, Romain le Pennec, Ulrike Schick, Jean-Philippe Metges, Ronan Abgral
Journal: Clinical Nuclear Medicine (2020)

Abstract Triplet chemotherapy (FOLFOXIRI) + bevacizumab regimen is indicated as first-line treatment of BRAF V600E -mutated metastatic colorectal cancer (mCRC). Nevertheless, its proven therapeutic efficacy in clinical trials was solely based on partial morphologic responses assessed by CT. To date, only 1 case of complete response assessed by FDG PET/CT was reported in literature in BRAF V600E -mutated mCRC, but treated with doublet chemotherapy (FOLFIRI) + cetuximab regimen. We report a complete metabolic response assessed by FDG PET/CT, maintained over time (13 months) in a 60-year-old woman with BRAF V600E -mutated mCRC treated by FOLFOXIRI-bevacizumab. This also confirms that FDG PET/CT is emerging as a useful approach for therapeutic assessment of targeted drugs in mCRC.
Successful re-intervention through stent mesh after novel antireflux covered metal biliary stent placement
Authors: Koichiro Mandai, Shiho Nakamura, Koji Uno, Kenjiro Yasuda
Journal: Endoscopy (2020)

A novel antireflux covered metal stent (Kawasumi Duckbill Biliary Stent; Kawasumi Laboratories, Inc., Tokyo, Japan) has recently become available for malignant biliary obstruction in Japan. This is a laser-cut covered self-expandable metal stent (SEMS) with a duckbill-shaped antireflux valve attached to the duodenal end ([Fig. 1]). The valve is closed except when bile is flowing out; it can therefore prevent reﬂux of duodenal contents into the bile duct. However, this design makes re-intervention via the duodenal end of the stent challenging. Here, we describe a successful re-intervention through the stent mesh after this novel SEMS was in place.
SAT0199 Aortic aortic root function in patients with rheumatoid arthritis: evaluation by s with rheumatoid arthritis: evaluation by
Authors: D Evcik, M Alpaslan, E Onrat
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Aortic Root Function in Patients with Rheumatoid Arthritis: Evaluation by M-Mode Echocardiography. <h3>Objectives</h3> To evaluate aortic root function in patients with rheumatoid arthritis. <h3>Methods</h3> 29 patients with rheumatoid arthritis (RA) (mean age 51 years) and 29 healthy subjects (mean age 49 years) participated in the study. In addition to the standard echocardiographic examination, aortic root function was evaluated in these groups by transthoracic M-mode echocardiography. RA was diagnosed according to the ARA criteria of 1987. Blood pressure with end-systolic (AoS) and end-diastolic (AoD) M-mode measurements of ascending aorta were used to calculate the indices of aortic root function: beta index (Peterson’s elastic modulus), cross-sectional aortic compliance, aortic stiffness index and aortic root distensibility. The mean values of the two groups were compared by covariance analysis, taking age as the covariant. A p value &lt;0.05 was assumed to be significant. <h3>Results</h3> AoS and AoD were significantly higher in patients with RA than the control group (p &lt; 0.05). Aortic stiffness and beta indexes were significantly higher in RA group when compared with the controls. <h3>Conclusion</h3> When compared with the controls AoS, AoD, beta index and aortic stiffness index are significantly higher in patients with RA. This may affect cardiac function in patients with RA at long term. <h3>References</h3> Leibowitz WB. The heart in rheumatoid arthritis (rheumatoid disease). A clinical and pathological study of 62 cases. Ann Intern Med. 1963;58:102–23 Gravallese E, Corson J, Coblyn JS, <i>et al</i>. Rheumatoid arthritis: a rarely recognized but clinically significant entity. Medicine 1989;68:95–106 Urschel CW, Covell JW, Sonnenblick EH, Ross J, Braunwald E. Effects of decreased aortic compliance on performance of the left ventricle. Am J Physiol. 1968;214:298–304 Kelly RP, Tunin R, Kass DA. Effect of reduced aortic compliance on cardiac efficiency and contractile function of <i>in situ</i> canine left ventricle. Circ Res. 1992;71:490–502
Immobilization after injury alters extracellular matrix and stem cell fate
Authors: Amanda K. Huber, Nicole Patel, Chase A. Pagani, Simone Marini, Karthik R. Padmanabhan, Daniel L. Matera, Mohamed Said, Charles Hwang, Ginny Ching-Yun Hsu, Andrea A. Poli, Amy L. Strong, Noelle D. Visser, Joseph A. Greenstein, Reagan Nelson, Shuli Li, Michael T. Longaker, Yi Tang, Stephen J. Weiss, Brendon M. Baker, Aaron W. James, Benjamin Levi
Journal: Journal of Clinical Investigation (2020)

Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO.
Shropshire trust is under threat of special administration as CQC reports “escalating concerns”
Authors: Clare Dyer
Journal: BMJ (2020)

A hospital trust embroiled in a police investigation of its maternity services is facing the rare threat of being put into special administration unless it improves patient care throughout its departments.

A Care Quality Commission (CQC) inspection of medical wards at Shrewsbury and Telford Hospital NHS Trust in early June found “ongoing and escalating concerns” about patient safety and poor care becoming “normalised.”

The inspection report is not yet published, but the findings were outlined in a letter to NHS England from Ted Baker, the CQC’s chief inspector of hospitals. The letter, leaked to the Independent newspaper,1 requested an …
Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review
Authors: A. Cortegiani, M. Ippolito, M. Greco, V. Granone, A. Protti, C. Gregoretti, A. Giarratano, S. Einav, M. Cecconi
Journal: Pulmonology (2020)

Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight.
Assessment of Pediatrician Awareness and Implementation of the Addendum Guidelines for the Prevention of Peanut Allergy in the United States
Authors: Ruchi S. Gupta, Lucy A. Bilaver, Jacqueline L. Johnson, Jack W. Hu, Jialing Jiang, Alexandria Bozen, Jennifer Martin, Jamie Reese, Susan F. Cooper, Matthew M. Davis, Alkis Togias, Samuel J. Arbes
Journal: JAMA Network Open (2020)

The 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States recommend that pediatricians assess infant peanut allergy risk and introduce peanut in the diet at age 4 to 6 months. Early introduction has the potential to prevent peanut allergy development.