tbuckley/cabot-search huggingface dataset:
FRI0459 TOFACITINIB TREATMENT IN RECALCITRANT JDM PATIENTS
Authors: Ş. Çekiç, Y. Karali, F. Cicek, S. S. Kilic
Journal: Annals of the Rheumatic Diseases (2020)

Background: Juvenile dermatomyositis (JDM) is a systemic, autoimmune inflammatory muscle disorder and vasculopathy that affects children younger than 18 years. Although the cause of JDM remains unknown it is clear that genetic and environmental influences play a role in the aetiology. New treatments are becoming available and being tested through international multicentre trials. Increasing evidence suggests a role for types I and II IFN in juvenile and adult dermatomyositis, including elevated IFN-response gene signatures in the muscle, skin and blood. It has recently been reported that patients with refractory JDM responded well to treatment with tofacitinib, a JAK inhibitor, with corresponding downregulation in selected IFN-response genes. Objectives: In this study, we evaluated our cases with resistant JDM who received tofacitinib treatment. Methods: Six patients who received tofacitinib because of severe skin involvement of JDM were included in the study. The data were obtained retrospectively from the hospital records. Results: The age ranges of the cases were between 7-17 years and the ratio of girls and boys was 1 (3/3). The age of diagnosis was between 2-13 years, and the follow-up period was between 3-9 years. Calcinosis cutis in 5 cases, decreased muscle strength in 3 cases, joint involvement in 4 cases were detected.. Systemic steroids, methotrexate, and non-steroid anti-inflammatory drugs were given in all cases before tofacitinib treatment. Pamidronate was used in 4 cases because of severe skin calcinosis, high dose intravenous immunoglobulin in 4 cases, mycophenolate mofetil in 3 cases, rituximab in 3 cases and cyclophosphamide in 1 case previously. Tofacitinib treatment (10mg/gün) was started in six cases with treatment-resistant JDM. Five cases had been treated with tofacitinib for 6-24 month intervals. The treatment was discontinued in one case because of severe allergic reaction. Variable level of improvement were detected in the skin findings of all cases during the therapy period. The treatment was interrupted for 1 month in only one case due to neutropenia. Conclusion: Tofacitinib seems to be an effective and safe treatment option in patients with JDM who are resistant to conventional treatments. More studies are needed on this subject. Disclosure of Interests: None declared
SAT0496 INTERROGATING THE CIRCULATORY IMMUNE ARCHITECTURE OF ENTHESITIS-RELATED ARTHRITIS
Authors: S. H. Tay, J. Y. Leong, M. Wasser, A. J. M. Lim, P. Chen, J. G. Yeo, T. Arkachaisri, S. Albani
Journal: Annals of the Rheumatic Diseases (2020)

Background: Enthesitis-related arthritis (ERA) is one of the most common subtype of juvenile idiopathic arthritis (JIA) in Asia 1 . It carries a poor prognosis, but limited knowledge of its pathogenesis hampers clinical diagnosis and treatment. Objectives: We hypothesise multiple aberrations from the healthy immunome culminating in an imbalance between the immune effector and regulatory cell subsets as key for driving ERA pathogenesis. Thus, we employed a comprehensive high-dimensional interrogative strategy using mass cytometry to assess the ERA immune architecture 2 . Methods: We examined peripheral blood mononuclear cells from 30 ERA patients (15 with active sacroilitis, 15 without active sacroilitis) within the first two years of disease and 30 healthy paediatric controls with mass cytometry, using two extensive antibody panels encompassing key lineage and functional markers. Dimensional reduction and unsupervised clustering were performed to identify immune cell subsets differentially present in ERA patients. Manual gating was performed to further describe observed differences in subset frequencies. These subsets were statistically evaluated with reference to the healthy cohort and their association with disease activity determined. Results: We identified broad differences in the ERA circulatory immune architecture that involved both innate and adaptive immune cell populations, notably with the enrichment of naive CD4+ T cells as well as depletion of cytolytic NK cells (CD56 dim CD16+). The chemotactic profiles of their subsets also differed in ERA patients, which underscores their migratory capacity and hence potential effector role in the ERA arthritic microenvironment. In addition, there were some dissimilarities in the circulatory immunome of ERA patients with active sacroiliitis as compared to those without, which alludes to a possible mechanistic basis behind the disease complication. Conclusion: This is the first study, via deep parameterisation afforded by mass cytometry, to demonstrate a concomitant dysregulation of both innate and adaptive immune cell subsets in ERA patients. Further mechanistic studies of these immune cell subsets and their functional networks will inform the development of diagnostic and prognostic markers that can reliably predict clinical fate in ERA, thereby complementing clinical assessment in the care of ERA patients. References: [1]Arkachaisri et al. Paediatric rheumatology clinic in Southeast Asia: are we different? Rheumatology (Oxford ). 2017. [2]Tay et al. Immunomics in pediatric rheumatic diseases. Front Med (Lausanne ). 2019. Disclosure of Interests: None declared
Abstract 10194: Quantitative Assessment of Lipid Component by Nirs-ivus is Helpful for Differentiating Among Plaque Rupture, Erosion and Calcified Nodule in the Culprit Lesion of Acs
Authors: Kosei Terada, Takashi Kubo, Yoshiki Matsuo, Yasushi Ino, Kunihiro Shimamura, Yasutsugu Shiono, Hiroki Emori, Yosuke Katayama, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: Circulation (2019)

Background: In vivo, precise differentiation among plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN) in the culprit lesion of acute coronary syndrome (ACS) is a major challenge for...
Stat3 activation in human endometrial and cervical cancers
Authors: Chun-Liang Chen, Fu-Chuan Hsieh, Jacqueline Lieblein, Jessica Brown, Christina Chan, Julie Wallaca, Gong Cheng, Brett Hall, Jiayuh Lin
Journal: Cancer Research (2007)

5353  The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumor formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervical cancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervical cancer tissues using tissue microarray slides as well as cancer cell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancer cell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervical cancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervical cancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of down stream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in Hela and SiHa cervical cancer cell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in Hela and SiHa cancer cell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers.
Characteristics and outcomes of asthmatic patients with COVID-19 pneumonia who require hospitalisation
Authors: Antoine Beurnier, Etienne-Marie Jutant, Mitja Jevnikar, Athénaïs Boucly, Jérémie Pichon, Mariana Preda, Marie Frank, Jérémy Laurent, Christian Richard, Xavier Monnet, Jacques Duranteau, Anatole Harrois, Marie-Camille Chaumais, Marie-France Bellin, Nicolas Noël, Sophie Bulifon, Xavier Jaïs, Florence Parent, Andrei Seferian, Laurent Savale, Olivier Sitbon, David Montani, Marc Humbert
Journal: European Respiratory Journal (2020)

Background Viral respiratory infections are the main causes of asthma exacerbation. The susceptibility of patients with asthma to develop an exacerbation when they present with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. The objective of this study was to investigate the characteristics and outcomes of asthmatic patients with coronavirus disease 2019 (COVID-19) pneumonia who required hospitalisation during the spring 2020 outbreak in Paris, France. Methods A prospective cohort follow-up was carried out from 15 March to 15 April 2020 in Bicêtre Hospital, University Paris-Saclay, France. All hospitalised patients with a SARS-CoV-2 infection who reported a history of asthma were included. Results Among 768 hospitalised patients, 37 (4.8%) reported a history of asthma, which had been previously confirmed by a pulmonologist in 85% of cases. These asthmatic patients were mainly female (70%) and nonsmokers (85%), with a median age of 54 years (interquartile range (IQR) 42–67 years). None of them presented with an asthma exacerbation. 22 (59%) had major comorbidities and 31 (84%) had a body mass index ≥25 kg·m −2 . The most common comorbidities were obesity (36%), hypertension (27%) and diabetes (19%). All patients had a confirmed diagnosis of COVID-19 pneumonia on computed tomography of the chest. Eosinopenia was a typical biological feature with a median count of 0 cells·mm −3 (IQR 0–0 cells·mm −3 ). 11 patients (30%) were admitted into the intensive care unit, with three deaths (8.1%) occurring in the context of comorbidities. Conclusion Asthma patients were not overrepresented among those with severe pneumonia due to SARS-CoV-2 infection who required hospitalisation. The worst outcomes were observed mainly in patients with major comorbidities.
Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection
Authors: Maria L. Balmer, Eric H. Ma, Andrew J. Thompson, Raja Epple, Gunhild Unterstab, Jonas Lötscher, Philippe Dehio, Christian M. Schürch, Jan D. Warncke, Gaëlle Perrin, Anne-Kathrin Woischnig, Jasmin Grählert, Jordan Löliger, Nadine Assmann, Glenn R. Bantug, Olivier P. Schären, Nina Khanna, Adrian Egli, Lukas Bubendorf, Katharina Rentsch, Siegfried Hapfelmeier, Russell G. Jones, Christoph Hess
Journal: Cell Metabolism (2020)
Economic Burden of Postoperative Neurocognitive Disorders Among US Medicare Patients
Authors: M. Dustin Boone, Brian Sites, Friedrich M. von Recklinghausen, Ariel Mueller, Andreas H. Taenzer, Shahzad Shaefi
Journal: JAMA Network Open (2020)

Postoperative neurocognitive disorders (PNDs) after surgical procedures are common and may be associated with increased health care expenditures.To quantify the economic burden associated with a PND diagnosis in 1 year following surgical treatment among older patients in the United States.This retrospective cohort study used claims data from the Bundled Payments for Care Improvement Advanced Model from 4285 hospitals that submitted Medicare Fee-for-service (FFS) claims between January 2013 and December 2016. All Medicare patients aged 65 years or older who underwent an inpatient hospital admission associated with a surgical procedure, did not experience a PND before index admission, and were not undergoing dialysis or concurrently enrolled in Medicaid were included. Data were analyzed from October 2019 and May 2020.PND, defined as an International Classification of Diseases, Ninth or Tenth Revision, diagnosis of delirium, mild cognitive impairment, or dementia within 1 year of discharge from the index surgical admission.The primary outcome was total inflation-adjusted Medicare postacute care payments within 1 year after the index surgical procedure.A total of 2 380 473 patients (mean [SD] age, 75.36 (7.31) years; 1 336 736 [56.1%] women) who underwent surgical procedures were included, of whom 44 974 patients (1.9%) were diagnosed with a PND. Among all patients, most were White (2 142 157 patients [90.0%]), presenting for orthopedic surgery (1 523 782 patients [64.0%]) in urban medical centers (2 179 893 patients [91.6%]) that were private nonprofits (1 798 749 patients [75.6%]). Patients with a PND, compared with those without a PND, experienced a significantly longer hospital length of stay (mean [SD], 5.91 [6.01] days vs 4.29 [4.18] days; P < .001), were less likely to be discharged home (9947 patients [22.1%] vs 914 925 patients [39.2%]; P < .001), and had a higher incidence of mortality at 1 year after treatment (4580 patients [10.2%] vs 103 767 patients [4.4%]; P < .001). After adjusting for patient and hospital characteristics, the presence of a PND within 1 year of the index procedure was associated with an increase of $17 275 (95% CI, $17 058-$17 491) in cost in the 1-year postadmission period (P < .001).The findings of this cohort study suggest that among older Medicare patients undergoing surgical treatment, a diagnosis of a PND was associated with an increase in health care costs for up to 1 year following the surgical procedure. Given the magnitude of this cost burden, PNDs represent an appealing target for risk mitigation and improvement in value-based health care.
Covid-19: Sandwell Council in West Midlands sets up contact tracing, citing failures of national scheme
Authors: Matthew Limb
Journal: BMJ (2020)

A council in England has set up its own covid-19 contact tracing system because of a surge of local coronavirus cases and frustration with the government's NHS Test and Trace scheme.Lisa McNally, director of public health at Sandwell Council, said that she had taken the step because four in 10 cases were going untraced and the spread of the virus risked a local lockdown.
SAT0470 FRAX AND DXA-BASED APPROACHES IN DIAGNOSTICS OF OSTEOPOROSIS RISK IN POSTMENOPAUSAL WOMEN WITH RHEUMATOID ARTHRITIS
Authors: N. Grygorieva, V. Povoroznyuk, N. Dzerovych, M. Bystrytska
Journal: Annals of the Rheumatic Diseases (2020)

Background: Nowadays, the bone mineral density (BMD) measured by DXA and FRAX ® are the most important methods for fracture risk assessment. Rheumatoid arthritis is a crucial disease for bone loss and osteoporosis development [1] which is included into FRAX algorithm. Ukrainian version of FRAX [2] is а new one and its value should also be assessed in patients with RA. Objectives: Our study was aimed to assess the parameters of BMD and FRAX in postmenopausal women with RA. Methods: We have examined 635 postmenopausal females aged 50-89 years old which were divided into 2 groups: 1 st (control, n=313) – without any factors which have influence on bone metabolism, 2 d (n=322) – patients with RA. The 10-year probabilities of hip fracture and major osteoporotic fractures were calculated without BMD parameter using the Ukrainian FRAX model [2]. The DXA was used to measure the lumbar spine, femoral neck and total body BMDs; the T-score was calculated (DISCOVERY Wi, Hologic, Inc., USA). Results: FRAX indexes for major osteoporotic and hip fractures were significantly higher in patients with RA (Me [25-75Q]): 9.7 [6.8-15.0] and 3.1 [1.5-6.2] % compared to 6.0 [3.8-8.5] and 1.2 [0.6-2.4] % in females from the control group (p&lt;0.001). 45.3 % of women with RA required antiosteoporotic treatment according to Ukrainian FRAX threshold ratio without measure of BMD compared to 12.1% of subjects from control group. Only 3.4% of patients with RA had FRAX indexes which were less than low threshold (requirement of additional DEXA measurement) compared to 31.3 % of females from control group. BMD of femoral neck and distal radius were reliably lower in subjects with RA and consisted 0.65±0.13 and 0.69±0.12 g/cm in 1 st and 2 d groups, accordingly (p&lt;0.001) and 0.56±0.10 and 0.58±0.09 g/cm (p=0.02) without any significant differences at lumbar spine and total body BMDs. 16.6 % of subjects from the control group and 31.6 % of females with RA had osteoporosis according to DXA parameters (T-score ≤-2.5 SD). Conclusion: FRAX should be used more widely in clinical practice for detection of risk of osteoporotic fractures in subjects with RA. References: [1]Povoroznyuk V.V., Grygorieva N.V., Karasevska T.A., Dzerovich N.I. Bone Mineral Density and Trabecular Bone Score Indices in Women with Rheumatoid Arthritis According to the Age and Use of Glucocorticoids. SM Rheumatol. 2017; 1(1): 1002. [2]Povoroznyuk V, Grygorieva N, Kanis JA, Johansson H, McCloskey EV. Ukrainian FRAX: criteria for diagnostics and treatment of osteoporosis // Pain. Joint. Spine.-2019.-9(4).-7-16. Disclosure of Interests: None declared
Can the Autologous Transplant of Hematopoyetic Progenitors be Considered an Effective Alternative to Increase Global Survival in High-Grade Non-Hodgkin Lymphomas?
Authors: Alba Nydia Ramirez Lopez, Enrique Baez De La Fuente, Rosa Elva De Leon Cantu, Diego Cruz Contreras, Jose Alfredo Carrizalez Villarreal, Jose Luis Cedillo De La Cerda, Roxana Saldaña Vazquez, Helga Patricia Sorkee Davila, Axel Eduardo Rosas Rodríguez, Severiano Baltazar Arellano, Roberto Hernandez Valdes, Bernardo Lafarga Amao, Rosa Lozano, Andrea Terrazas
Journal: Blood (2017)
Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers
Authors: Oliver Klein, Damien Kee, Adnan Nagrial, Ben Markman, Craig Underhill, Michael Michael, Louise Jackett, Caroline Lum, Andreas Behren, Jodie Palmer, Niall C. Tebbutt, Matteo S. Carlino, Jonathan Cebon
Journal: JAMA Oncology (2020)

<h3>Importance</h3> Biliary tract cancers represent a rare group of malignant conditions with very limited treatment options. Patients with advanced disease have a poor outcome with current therapies. <h3>Objective</h3> To evaluate the efficacy and safety of combination immunotherapy with nivolumab and ipilimumab in patients with advanced biliary tract cancers. <h3>Design, Setting, and Participants</h3> The CA209-538 prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced rare cancers including patients with biliary tract cancers. This subgroup analysis evaluated 39 patients from CA209-538 with biliary tract cancers who were enrolled from December 2017 to December 2019. Most of the patients (n = 33) had experienced disease progression after 1 or more lines of therapy and had tumor tissue available for biomarker research. <h3>Interventions</h3> Patients received treatment with nivolumab at a dose of 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab 3 mg/kg every 2 weeks and continued for up to 96 weeks until disease progression or the development of unacceptable toxic events. <h3>Main Outcomes and Measures</h3> The primary end point was disease control rate (complete remission, partial remission, or stable disease) as assessed by RECIST 1.1. <h3>Results</h3> Among the 39 patients included in this subgroup analysis of a phase 2 clinical trial (20 men, 19 women; mean [range] age, 65 [37-81] years), the objective response rate was 23% (n = 9) with a disease control rate of 44% (n = 17); all responders had received prior chemotherapy, and none had a microsatellite unstable tumor. Responses were exclusively observed in patients with intrahepatic cholangiocarcinoma and gallbladder carcinoma. The median duration of response was not reached (range, 2.5 to ≥23 months). The median progression-free survival was 2.9 months (95% CI, 2.2-4.6 months), and overall survival was 5.7 months (95% CI, 2.7-11.9 months). Immune-related toxic events were reported in 49% of patients (n = 19), with 15% (n = 6) experiencing grade 3 or 4 events. <h3>Conclusions and Relevance</h3> This subgroup analysis of a phase 2 clinical trial found that combination immunotherapy with nivolumab and ipilimumab was associated with substantial positive outcomes patients with advanced biliary tract cancers. This treatment compares favorably to single-agent anti–programmed cell death protein 1 (anti–PD-1) therapy and warrants further investigation. Ongoing translational research is focused on identifying biomarkers that can predict treatment response. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02923934
The Power of Single‐Cell Analysis for the Study of Liver Pathobiology
Authors: Angela L. Chu, Joel D. Schilling, Kevin R. King, Ariel E. Feldstein
Journal: Hepatology (2020)

Single cell transcriptomics has emerged as a powerful lens through which to study the molecular diversity of complex tissues such as the liver, during health and disease, both in animal models and in humans. The earliest gene expression methods measured bulk tissue RNA, but the results were often confusing because they derived from the combined transcriptomes of many different cell types in unknown proportions. To better delineate cell-type-specific expression, investigators developed cell isolation, purification, and sorting protocols, yet still, the RNA derived from ensembles of cells obscured recognition of cellular heterogeneity. Profiling transcriptomes at the single-cell level has opened the door to analyses that were not possible in the past. In this review, we discuss the evolution of single cell transcriptomics and how it has been applied for the study of liver physiology and pathobiology to date.
Disease-associated and patient-specific immune cell signatures in juvenile-onset systemic lupus erythematosus: patient stratification using a machine-learning approach
Authors: George A Robinson, Junjie Peng, Pierre Dönnes, Leda Coelewij, Meena Naja, Anna Radziszewska, Chris Wincup, Hannah Peckham, David A Isenberg, Yiannis Ioannou, Ines Pineda-Torra, Coziana Ciurtin, Elizabeth C Jury
Journal: The Lancet Rheumatology (2020)