tbuckley/cabot-search huggingface dataset:
Reintroduction of immune-checkpoint inhibitors after immune-related meningitis: a case series of melanoma patients
Authors: Stefania Cuzzubbo, Pauline Tetu, Sarah Guegan, Renata Ursu, Catherine Belin, Lila Sirven Villaros, Julie Mazoyer, Coralie Lheure, Celeste Lebbe, Barouyr Baroudjian, Antoine F Carpentier
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immune-checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen-4 and programmed cell death ligand-1) are associated with several immune-related neurological disorders. Cases of meningitis related to ICIs are poorly described in literature and probably underestimated. Several guidelines are available for the acute management of these adverse events, but the safety of resuming ICIs in these patients remains unclear. We conducted a retrospective case series of immune-related meningitis associated with ICIs that occurred between October 1 2015 and October 31 2019 in two centers: Saint-Louis and Cochin hospitals, Paris, France. Diagnosis was defined by a (1) high count of lymphocytes (&gt;8 cells/mm3) and/or high level of proteins (&gt;0.45 g/L) without bacteria/virus or tumor cells detection, in cerebrospinal fluid and (2) normal brain and spine imaging. Patients were followed-up for at least 6 months from the meningitis onset. Seven cases of immune-related meningitis are here reported. Median delay of meningitis occurrence after ICIs onset was 9 days. Steroid treatment was introduced in four patients at a dose of 1 mg/kg (prednisone), allowing a complete recovery within 2 weeks. The other three patients spontaneously improved within 3 weeks. Given the favorable outcome, ICIs were reintroduced in all patients. The rechallenge was well tolerated and no patients experienced meningitis recurrence. In conclusion, in our series, the clinical course was favorable and steroids were not always required. Resuming ICIs in these patients appeared safe and can thus be considered in case of isolated meningitis. However, a careful analysis of the risk/benefit ratio should be done on a case-by-case basis.
Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy‐dependent modification of the keratinocyte immunophenotype*
Authors: K. Clayton, A. Vallejo, S. Sirvent, J. Davies, G. Porter, I.C. Reading, F. Lim, M.R. Ardern‐Jones, M.E. Polak
Journal: British Journal of Dermatology (2020)

Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of T helper (Th)1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced our understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict the importance of a specific pathway in AD or cellular responses to different inflammatory stimuli. To understand changes in keratinocyte transcriptomic programmes in human cutaneous disease during development of inflammation and in response to treatment. We performed in silico deconvolution of the whole‐skin transcriptome. Using co‐expression clustering and machine‐learning tools, we resolved the gene expression of bulk skin (seven datasets, n = 406 samples), firstly, into keratinocyte phenotypes identified by unsupervised clustering and, secondly, into 19 cutaneous cell signatures of purified populations from publicly available datasets. We identify three unique transcriptomic programmes in keratinocytes – KC1, KC2 and KC17 – characteristic of immune signalling from disease‐associated Th cells. We cross‐validate those signatures across different skin inflammatory conditions and disease stages and demonstrate that the keratinocyte response during treatment is therapy dependent. Broad‐spectrum treatment with ciclosporin ameliorated the KC17 response in AD lesions to a nonlesional immunophenotype, without altering KC2. Conversely, the specific anti‐Th2 therapy, dupilumab, reversed the KC2 immunophenotype. Our analysis of transcriptomic signatures in cutaneous disease biopsies reveals the effect of keratinocyte programming in skin inflammation and suggests that the perturbation of a single axis of immune signal alone may be insufficient to resolve keratinocyte immunophenotype abnormalities.
Rituximab Activates NOTCH1 Signaling in CLL Cells and Induces Changes in the Cytokine Repertoire Favoring a Tumor-Protective Microenvironment
Authors: Jennifer Edelmann, Karlheinz Holzmann, Doriana DiBella, Emma Vilventhraraja, Stephen A Beers, Mark Cragg, Andrejs Braun, John G. Gribben
Journal: Blood (2017)
Health‐related quality of life in patients who had partaken in milk oral immunotherapy and comparison to the general population
Authors: Tiina Kaisa Kauppila, Anna S. Pelkonen, Risto P. Roine, Marita Paassilta, Kaarina Kukkonen, Harri Sintonen, Mika Mäkelä
Journal: Allergy (2020)

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HP0024 Applicability of an educational-behavioural joint protection programme in practice
Authors: A Hammond, P Jeffreson, N Stacey
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Previous clinical trials proved an educational-behavioural joint protection (EB-JP) programme is more effective than “standard” teaching in increasing people with rheumatoid arthritis’ (RA) use of joint protection (JP). <h3>Objective</h3> This study aimed to investigate if rheumatology occupational therapists (OT), following a 2 day training course, can in clinical practice similarly enable people with RA to increase use of JP. <h3>Methods</h3> The study was conducted with 3 trained OTs at 3 hospitals using a randomised, crossover design. Demographic, Patient Knowledge Questionnaire (PKQ), hand and functional status measures were recorded at baseline, 3 and 6 months. The main outcome was the Joint Protection Behaviour Assessment (JPBA): a valid, reliable observational assessment of JP hand actions in kitchen activities. <h3>Results</h3> 30 people with RA participated: 27 women and 3 men, average age 52.3 years (SD 12.1) with average disease duration of 6.76 years (SD 7.02). There was no significant difference in JPBA scores at baseline between the two groups: E1 (education first) = 17% (SD 15%) and E2 (education delayed) = 20% (SD 7.4%) (p = 0.16). At 3 months E1 JPBA scores significantly increased to 41% (SD 15.9%) and E2 did not change: 25% (SD 20%) (p = 0.003). Both groups increased use of JP overall at 6 months (p &lt; 0.01). There was a significant increase in PKQ scores (p &lt; 0.00). No change in hand and functional status occurred, apart from increased grip strength (p &lt; 0.01), but the follow-up period was probably too short to identify improvements. Most participants considered the programme relevant to their needs and found the emphasis on practical training very helpful. <h3>Conclusion</h3> A 2 day training course, plus detailed programme manual, enables rheumatology OTs to deliver this programme successfully in practice, suggesting this programme should now be disseminated.
Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents
Authors: Safi U. Khan, Maninder Singh, Shahul Valavoor, Muhammad U. Khan, Ahmad N. Lone, Muhammad Zia Khan, Muhammad Shahzeb Khan, Preethi Mani, Samir R. Kapadia, Erin D. Michos, Gregg W. Stone, Ankur Kalra, Deepak L. Bhatt
Journal: Circulation (2020)

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents. Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model. In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding. The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.
Abstract 12890: A Novel Calcium Parameter, Calcium Ratio, Can Predict Minimum Lumen Area in Calcified Lesions: Optical Coherence Tomographic Study
Authors: Yutaka Matsuhiro, Masami Nishino, Kyosuke Yanagawa, Hitoshi Nakamura, Koji Yasumoto, Akihiro Tanaka, Yasuharu Matsunaga, Naotaka Okamoto, Masamichi Yano, Masaki Yamato, Yasuyuki Egami, Ryu Shutta, Jun Tanouti
Journal: Circulation (2019)

Background: Several reports have revealed that minimum lumen area (MLA) is associated with target lesion failure even with newer-generation drug-eluting stents, and calcified lesions usually induce...
Impaired Succinate Response to a Mixed Meal in Obesity and Type 2 Diabetes Is Normalized After Metabolic Surgery
Authors: Brenno Astiarraga, Laia Martínez, Victoria Ceperuelo-Mallafré, Gemma Llauradó, Margarida Terrón-Puig, M. Mar Rodríguez, Anna Casajoana, Silvia Pellitero, Ana Megía, Núria Vilarrasa, Joan Vendrell, Sonia Fernández-Veledo
Journal: Diabetes Care (2020)

OBJECTIVE To explore the meal response of circulating succinate in patients with obesity and type 2 diabetes undergoing bariatric surgery and to examine the role of gastrointestinal glucose sensing in succinate dynamics in healthy subjects. RESEARCH DESIGN AND METHODS Cohort I comprised 45 patients with morbid obesity and type 2 diabetes (BMI 39.4 ± 1.9 kg/m2) undergoing metabolic surgery. Cohort II was a confirmatory cohort of 13 patients (BMI 39.3 ± 1.4 kg/m2) undergoing gastric bypass surgery. Cohort III comprised 15 healthy subjects (BMI 26.4 ± 0.5 kg/m2). Cohorts I and II completed a 2-h mixed-meal tolerance test (MTT) before the intervention and at 1 year of follow-up, and cohort II also completed a 3-h lipid test (LT). Cohort III underwent a 3-h oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI) study. RESULTS In cohort I, succinate response to MTT at follow-up was greater than before the intervention (P &amp;lt; 0.0001). This response was confirmed in cohort II with a greater increase after 1 year of surgery (P = 0.009). By contrast, LT did not elicit a succinate response. Changes in succinate response were associated with changes in the area under the curve of glucose (r = 0.417, P &amp;lt; 0.0001) and insulin (r = 0.204, P = 0.002). In cohort III, glycemia, per se, stimulated a plasma succinate response (P = 0.0004), but its response was greater in the OGTT (P = 0.02; OGTT versus IIGI). CONCLUSIONS The meal-related response of circulating succinate in patients with obesity and type 2 diabetes is recovered after metabolic surgery.
New data on an old weapon: is argon plasma coagulation adequate treatment for dysplastic Barrett’s esophagus?
Authors: Nicholas J. Shaheen
Journal: Endoscopy (2020)

Endoscopic eradication therapy in Barrett’s esophagus (BE) has come full circle. Early proof of principle studies utilized heater probes and multipolar electrocoagulation demonstrated that destruction of the epithelium, combined with rigorous acid suppression, resulted in the repopulation of the treated area with squamous epithelium that appeared histologically indistinguishable from native squamous epithelium [1]. While this phenomenon was widely recognized, endoscopic treatment of BE in this manner was tedious, especially for long Barrett’s segments, and was largely confined to tertiary care centers with a special interest in the disease. The development of photodynamic therapy did little to increase the popularity of endoscopic therapy for BE, as special lasers were required and expensive photosensitizing agents had to be administered in order to achieve results, which were often underwhelming [2].
American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 2
Authors: Ted R. Mikuls, Sindhu R. Johnson, Liana Fraenkel, Reuben J. Arasaratnam, Lindsey R. Baden, Bonnie L. Bermas, Winn Chatham, Stanley Cohen, Karen Costenbader, Ellen M. Gravallese, Andre C. Kalil, Michael E. Weinblatt, Kevin Winthrop, Amy S. Mudano, Amy Turner, Kenneth G. Saag
Journal: Arthritis & Rheumatology (2020)

To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID-19) pandemic.A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included asynchronous anonymous voting by e-mail and webinars with the entire panel. Task force members voted on agreement with draft statements using a 1-9-point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7-9, 4-6, and 1-3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus.To date, the task force has approved 80 guidance statements: 36 with moderate and 44 with high consensus. These were combined, resulting in 27 final guidance statements.These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated.
NHLBI at 50: Reflections on a Half-Century of Research on the Heart, Lungs, and Blood
Authors: C. Marwick
Journal: JAMA (1998)

JUST OVER 50 years ago, on June 16, 1948, President Harry S Truman signed into law the legislation that created the National Heart Institute. Renamed the National Heart and Lung Institute in 1969, it became the National Heart, Lung, and Blood Institute (NHLBI) in 1976.
Rational use of tocilizumab in COVID-19
Authors: Siddharth Jain, Shefali Khanna Sharma
Journal: Annals of the Rheumatic Diseases (2020)

With 12 million cases and half a million deaths (as of 10 July 2020), the corona virus disease (COVID-19) has paralysed healthcare systems the world over. The observations by Potere et al 1 and mechanistic insights by Capecchi et al 2 merit a discussion of important considerations that should be borne in mind before using tocilizumab in severe COVID-19. The available evidence concerning its use, although promising, is preliminary and probably underpowered to detect important safety/efficacy signals.3 4

Patients with COVID-19 are not free from the risk of a bacterial infection, which could be secondary (nosocomial) or co-primary (community acquired). Concomitant bacterial infections have been reported in 10%–20% of COVID-19 cases and ~50% of COVID-19-related deaths, consistent with, and reminiscent of bacterial infections being the the most common cause of mortality in previous influenza pandemics.5 6 This risk is higher in old age, presence of comorbidities and those requiring invasive mechanical ventilation (all probable candidates for use of tocilizumab). A hesitancy towards the use of CT and fiberoptic bronchoscopy at …
Micrornas in Bone Marrow Mesenchymal Stromal Cells Are Differentially Expressed According to Response in Multiple Myeloma
Authors: Carlos Fernandez de Larrea, Tania Diaz, Alfons Navarro, Ester Lozano, Mari-Pau Mena, Ignacio Isola, Mª Teresa Cibeira, Laura Rosinol, Joan Bladé
Journal: Blood (2017)
Complement activation on endothelium initiates antibody-mediated acute lung injury
Authors: Simon J. Cleary, Nicholas Kwaan, Jennifer J. Tian, Daniel R. Calabrese, Beñat Mallavia, Mélia Magnen, John R. Greenland, Anatoly Urisman, Jonathan P. Singer, Steven R. Hays, Jasleen Kukreja, Ariel M. Hay, Heather L. Howie, Pearl Toy, Clifford A. Lowell, Craig N. Morrell, James C. Zimring, Mark R. Looney
Journal: Journal of Clinical Investigation (2020)

Antibodies targeting human leukocyte antigen (HLA)/major histocompatibility complex (MHC) proteins limit successful transplantation and transfusion, and their presence in blood products can cause lethal transfusion-related acute lung injury (TRALI). It is unclear which cell types are bound by these anti-leukocyte antibodies to initiate an immunologic cascade resulting in lung injury. We therefore conditionally removed MHC class I (MHC I) from likely cellular targets in antibody-mediated lung injury. Only the removal of endothelial MHC I reduced lung injury and mortality, related mechanistically to absent endothelial complement fixation and lung platelet retention. Restoration of endothelial MHC I rendered MHC I-deficient mice susceptible to lung injury. Neutrophil responses, including neutrophil extracellular trap (NET) release, were intact in endothelial MHC I-deficient mice, whereas complement depletion reduced both lung injury and NETs. Human pulmonary endothelial cells showed high HLA class I expression, and posttransfusion complement activation was increased in clinical TRALI. These results indicate that the critical source of antigen for anti-leukocyte antibodies is in fact the endothelium, which reframes our understanding of TRALI as a rapid-onset vasculitis. Inhibition of complement activation may have multiple beneficial effects of reducing endothelial injury, platelet retention, and NET release in conditions where antibodies trigger these pathogenic responses.
Biomaterial Based Strategies for Engineering New Lymphatic Vasculature
Authors: Kevin T. Campbell, Eduardo A. Silva
Journal: Advanced Healthcare Materials (2020)

The lymphatic system is essential for tissue regeneration and repair due to its pivotal role in resolving inflammation, immune cell surveillance, lipid transport, and maintaining tissue homeostasis. Loss of functional lymphatic vasculature is directly implicated in a variety of diseases, including lymphedema, obesity, and the progression of cardiovascular diseases. Strategies that stimulate the formation of new lymphatic vessels (lymphangiogenesis) could provide an appealing new approach to reverse the progression of these diseases. However, lymphangiogenesis is relatively understudied and stimulating therapeutic lymphangiogenesis faces challenges in precise control of lymphatic vessel formation. Biomaterial delivery systems could be used to unleash the therapeutic potential of lymphangiogenesis for a variety of tissue regenerative applications due to their ability to achieve precise spatial and temporal control of multiple therapeutics, direct tissue regeneration, and improve the survival of delivered cells. In this review, the authors begin by introducing therapeutic lymphangiogenesis as a target for tissue regeneration, then an overview of lymphatic vasculature will be presented followed by a description of the mechanisms responsible for promoting new lymphatic vessels. Importantly, this work will review and discuss current biomaterial applications for stimulating lymphangiogenesis. Finally, challenges and future directions for utilizing biomaterials for lymphangiogenic based treatments are considered.
SAT0509 MYCOPHENOLATE MOFETIL VERSUS AZATHIOPURINE FOR THE MAINTENANCE TREATMENT OF CONNECTIVE-TISSUE RELATED INTERSTITIAL LUNG DISEASE FOLLOWING CYCLOPHOSPHAMIDE TREATMENT
Authors: H. Satiş, M. Onut, R. Bilici Salman, H. Babaoglu, N. Atas, A. Avanoğlu Güler, H. Karadeniz, D. Yapar, N. Kayahan, S. Haznedaroglu, B. Goker, M. A. Ozturk, A. Tufan, H. Türktaş
Journal: Annals of the Rheumatic Diseases (2020)

Background: Cyclophosphamide (CYC) had a good response rates when used as an induction regimen for the treatment of connective tissue related interstitial lung disease (CTD-ILD). But the safety profile of CYC necessitates the usage of a second line treatment for maintenance Objectives: To compare the effect of mycophonetil (MMF) and azatiyopurin (AZA) for maintanance therapy following cyclophsphomide treatment in CTD-ILD Methods: Between 2009 and 2019 all interstitial lung disease patients admitting rheumatology or pulmonology department were retrospectively evaluated and patients treated with cyclophospamide as an induction regimen and having not progression were selected. Among those, as a second line regimen treated with MMF or AZA were included. Primary end point was treatment responses at 6th months Results: 68 patients treated with CYC for the first line treatment. 46 patients treated with either MMF (n:22) or AZA (n:24) for the maintenance. Scleroderma patients were the largest group and consituted 63% of the population. MMF group had worse FVC values and more involvement in lung paranchyme at the begining of the treatment. In univariate analysis FVC (lt) values and lung involvement (%) on HRCT at the start of the treatment, and disease subtype were associated significantly with treatment responses.After adjusted with these factors, in multivariate analysis, AZA treatment was associated with the increased risk of progression (odds ratio 5,8, 95% CI 1,061-31,09) as compared with MMF treatment Conclusion: MMF had better results compared to AZA in the treatment of CTD-ILD,after the usage of CYC treatment. References: [1]Barnes, H., et al., Cyclophosphamide for connective tissue disease-associated interstitial lung disease. Cochrane Database Syst Rev, 2018. 1 (1): p. Cd010908. Table 1. Patient and disease characteristics at the start of the treatment and treatment responses at the 6th months of the treatment: FVC forced vital capacity MMF (22) AZA (24) p Lung involvement (%) 36% 23,3% 0,022 FVC (lt) 1,96 2,55 0,021 FVC (%) 71% 81% &lt;0,001 FVC change at 6th month (lt) -,02 -0,19 0,051 FVC change at 6th month (%) -0,42 -5,81 0,068 Progression 23,8% 50% 0,118 Disclosure of Interests: None declared