tbuckley/cabot-search huggingface dataset:
AB1036 CLINICAL MANIFESTATIONS, CLINICAL COURSE, AND OUTCOMES OF IMMUNOGLOBULIN G4 RELATED DISEASE
Authors: W. Katchamart, K. Phaopraphat, P. Ngamjanyaporn, P. Narongroeknawin, N. Kasitanon
Journal: Annals of the Rheumatic Diseases (2020)

Background: Immunoglobulin G4 related disease (IgG4-RD) is an uncommon chronic systemic autoimmune disease, pathologically characterized by lymphoplasma cell, IgG4 plasma cell or storiform fibrosis infiltration with elevated serum IgG4 level. IgG4-RD is a new disease and not widely recognized. Objectives: The aim of this study was to describe clinical manifestations and outcomes of IgG4-RD in Thai patients Methods: This multicenter retrospective cohort study included patients who aged ≥ 18 years and were diagnosed with IgG4-RD according to 2011 comprehensive or consensus diagnostic criteria, between 2000 and 2019 in four academic centers in Thailand. Baseline characteristic, laboratory and pathologic findings, treatments, and outcomes were systematically reviewed. Results: Of the 110 patients included, 71% were male with mean age (SD) of 59.6 (13.3) years and median disease duration (IQR) of 28.8 (14.6-53.5) months. Single organ involvement was observed in 60 patients (54.5%). The most common presenting organ involvement was the orbit (29%), followed by the salivary glands (19%), lacrimal glands (18%), bile duct (16%), and pancreas (11%). The most frequently affected organs were the orbits (34%), followed by the salivary glands (26%), lacrimal glands (20%), bile duct (19%), and lymph nodes (19%). Ninety-six percent (96%) had IgG4 level of more than 135 mg/dl at presentation. Most patients (92%) were treated with corticosteroid (CS) alone or in combination with immunosuppressive agents. Azathioprine (47%) and methotrexate (11%) were the most commonly used immunosuppressive agents. Additionally, 20% required surgery, and 6.4% underwent stent insertion. One-fourth (26%) were in remission with successfully CS tapering, while 37%, and 29% had complete, and partial response. Nevertheless, 22% relapse with median time to relapse (IQR) of 22.2 (12.8-41.1) months. Relapse was common in patients with orbital (p = 0.001) and lung (p= 0.007) involvement, and patients with longer disease duration (median 44.1 and 23.1 months, P=0.001), while serum IgG4 level was insignificantly higher in relapse group (median 1,085 vs. 850 mg/dL, p=0.28). Conclusion: IgG4-RD is a chronic systemic autoimmune disease with diverse manifestations, response to treatment, and outcomes. Most patients responded well to CS and immunosuppressive agents with notable relapse rate, while minority required surgery or mechanical intervention. References: [1]Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH. Clinical phenotypes of IgG4-related Disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78(3):406-12. [2]Martinez-Valle F, Fernandez-Codina A, Pinal-Fernandez I, Orozco-Galvez O, Vilardell-Tarres M. IgG4- related disease: Evidence from six recent cohorts. Autoimmun Rev. 2017;16(2):168-72 Acknowledgments: None Disclosure of Interests: None declared
Detection of Diabetes Status and Type in Youth Using Electronic Health Records: The SEARCH for Diabetes in Youth Study
Authors: Brian J. Wells, Kristin M. Lenoir, Lynne E. Wagenknecht, Elizabeth J. Mayer-Davis, Jean M. Lawrence, Dana Dabelea, Catherine Pihoker, Sharon Saydah, Ramon Casanova, Christine Turley, Angela D. Liese, Debra Standiford, Michael G. Kahn, Richard Hamman, Jasmin Divers
Journal: Diabetes Care (2020)

OBJECTIVE Diabetes surveillance often requires manual medical chart reviews to confirm status and type. This project aimed to create an electronic health record (EHR)-based procedure for improving surveillance efficiency through automation of case identification. RESEARCH DESIGN AND METHODS Youth (&amp;lt;20 years old) with potential evidence of diabetes (N = 8,682) were identified from EHRs at three children’s hospitals participating in the SEARCH for Diabetes in Youth Study. True diabetes status/type was determined by manual chart reviews. Multinomial regression was compared with an ICD-10 rule-based algorithm in the ability to correctly identify diabetes status and type. Subsequently, the investigators evaluated a scenario of combining the rule-based algorithm with targeted chart reviews where the algorithm performed poorly. RESULTS The sample included 5,308 true cases (89.2% type 1 diabetes). The rule-based algorithm outperformed regression for overall accuracy (0.955 vs. 0.936). Type 1 diabetes was classified well by both methods: sensitivity (Se) (&amp;gt;0.95), specificity (Sp) (&amp;gt;0.96), and positive predictive value (PPV) (&amp;gt;0.97). In contrast, the PPVs for type 2 diabetes were 0.642 and 0.778 for the rule-based algorithm and the multinomial regression, respectively. Combination of the rule-based method with chart reviews (n = 695, 7.9%) of persons predicted to have non–type 1 diabetes resulted in perfect PPV for the cases reviewed while increasing overall accuracy (0.983). The Se, Sp, and PPV for type 2 diabetes using the combined method were ≥0.91. CONCLUSIONS An ICD-10 algorithm combined with targeted chart reviews accurately identified diabetes status/type and could be an attractive option for diabetes surveillance in youth.
Association Between Fasting Glucose Variability in Young Adulthood and the Progression of Coronary Artery Calcification in Middle Age
Authors: Weijing Feng, Zhibin Li, Wenjie Guo, Xianglin Fan, Feiran Zhou, Kun Zhang, Caiwen Ou, Feifei Huang, Minsheng Chen
Journal: Diabetes Care (2020)

OBJECTIVE To investigate whether intraindividual variability of fasting glucose (FG) in young adulthood is associated with coronary artery calcification (CAC) progression in middle age. RESEARCH DESIGN AND METHODS We included 2,256 CARDIA (Coronary Artery Risk Development Study in Young Adults) participants with CAC assessment by computed tomography scanner at baseline (2000–2001) and 10 years later (2010–2011). CAC progression was assessed for each individual as the difference of logarithmic CAC scores at follow-up and baseline (log[CAC (follow-up) + 1] − log[CAC (baseline) + 1]). FG variability was defined by the coefficient of variation about the mean FG (FG-CV), the SD of FG (FG-SD), and the average real variability of FG (FG-ARV) during the 10-year follow-up. We investigated the association between FG variability and CAC progression with adjustment for demographics, clinical risk factors, mean FG level, change in FG level, diabetes incidence, and medication use. RESULTS After multivariable adjustment, 1-SD increment in FG-CV was associated with worse progression of CAC as demonstrated as percent change in CAC, with incident CAC 5.9% (95% CI 1.0, 10.7) and any CAC progression 6.7% (95% CI 2.3, 11.1) during 10 years. Similar findings were also observed in FG-SD and FG-ARV. CONCLUSIONS Higher FG variability during young adulthood was associated with greater CAC progression in middle age, suggesting its value in predicting risk for subclinical coronary artery diseases.
Sputum macrophage diversity and activation in asthma: Role of severity and inflammatory phenotype
Authors: Angelica Tiotiu, Nazanin Zounemat Kermani, Yusef Badi, Stelios Pavlidis, Philip M. Hansbro, Yi‐Ke Guo, Kian Fan Chung, Ian M. Adcock
Journal: Allergy (2020)

Abstract Background Macrophages control innate and acquired immunity, but their role in severe asthma remains ill‐defined. We investigated gene signatures of macrophage subtypes in the sputum of 104 asthmatics and 16 healthy volunteers from the U‐BIOPRED cohort. Methods Forty‐nine gene signatures (modules) for differentially stimulated macrophages, one to assess lung tissue‐resident cells (TR‐Mφ) and two for their polarization (classically and alternatively activated macrophages: M1 and M2, respectively) were studied using gene set variation analysis. We calculated enrichment scores (ES) across severity and previously identified asthma transcriptome‐associated clusters (TACs). Results Macrophage numbers were significantly decreased in severe asthma compared to mild‐moderate asthma and healthy volunteers. The ES for most modules were also significantly reduced in severe asthma except for 3 associated with inflammatory responses driven by TNF and Toll‐like receptors via NF‐κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL‐2 biosynthesis (all P &lt; .01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll‐like and TNF receptor activation and arachidonic acid metabolism ( P &lt; .001) and in TAC2 for the inflammasome and interferon signalling pathways ( P &lt; .001). Data were validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR‐Mφ were enriched in TAC3 and associated with mitochondrial function. Conclusions Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterized by distinct inflammatory pathways.
Randomized Controlled Trial of Advance Notification Phone Calls vs Text Messages Prior to Mailed Fecal Test Outreach
Authors: Gloria D. Coronado, Denis B. Nyongesa, Amanda F. Petrik, Jamie H. Thompson, Anne L. Escaron, Brittany Younger, Shelby Harbison, Michael C. Leo
Journal: Clinical Gastroenterology and Hepatology (2020)

Mailing fecal immunochemical test (FITs) to individuals who are due for screening (mailed FIT outreach) increases colorectal cancer (CRC) screening. Little is known about how phone-based advance notifications (primers) affect the effectiveness of mailed FIT outreach programs.We performed a prospective study of patients at a large urban health center, 50-75 years old and due for screening, with no record of a prior FIT. Participants were randomly assigned to groups that received a live phone call primer (n = 1203) or a text message primer (n = 1622), from June through December 2018. The participants were then mailed a FIT kit, followed by 2 automated calls, and live reminder calls delivered by the care team. The main outcome was completion of FIT within 3 months of assignment to the live phone call or text message group.Participants had a FIT completion rate of 16.8%, a mean age of 58 years, and 80% were Latino. In adjusted intention to treat analyses (n = 2825), FIT completion rates were higher in the patients assigned to receive a live phone call vs text message primer (percentage point difference, 3.3%; 95% CI, 0.4%-6.2%). Between-group differences increased to 7.3% points (95% CI, 3.6%-11.0%) in the per-protocol analysis of 2144 participants reached by the text message (1320/1622, 81%), live call (438/1203, 36%), or voice message (386/1203, 32%). This rate increased to 14.9% points (95% CI; 9.6%-20.1%) in the per-protocol analysis of 1758 participants reached by the text message or reached by the live call.In a randomized trial, advance notification live phone calls outperformed text messages in prompting health center patients who had not previously completed a FIT to complete a mailed FIT. Clinicaltrials.gov no: NCT03167125.
Weighing the Benefits and Risks of Proliferating Observational Treatment Assessments
Authors: Robert M. Califf, Adrian F. Hernandez, Martin Landray
Journal: JAMA (2020)

This Viewpoint discusses the role of observational study designs and data in the rapid stand-up of an evidence base for managing the COVID-19 pandemic, proposing ways to position observational research as a foundation for rapid follow-on randomized evaluation without premature overinterpretation of its findings
Anti-PEG antibodies: Properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals
Authors: Gergely Tibor Kozma, Taro Shimizu, Tatsuhiro Ishida, Janos Szebeni
Journal: Advanced Drug Delivery Reviews (2020)

Conjugation of polyethylene glycols (PEGs) to proteins or drug delivery nanosystems is a widely accepted method to increase the therapeutic index of complex nano-biopharmaceuticals. Nevertheless, these drugs and agents are often immunogenic, triggering the rise of anti-drug antibodies (ADAs). Among these ADAs, anti-PEG IgG and IgM were shown to account for efficacy loss due to accelerated blood clearance of the drug (ABC phenomenon) and hypersensitivity reactions (HSRs) entailing severe allergic symptoms with occasionally fatal anaphylaxis. In addition to recapitulating the basic information on PEG and its applications, this review expands on the physicochemical factors influencing its immunogenicity, the prevalence, features, mechanism of formation and detection of anti-PEG IgG and IgM and the mechanisms by which these antibodies (Abs) induce ABC and HSRs. In particular, we highlight the in vitro, animal and human data attesting to anti-PEG Ab-induced complement (C) activation as common underlying cause of both adverse effects. A main message is that correct measurement of anti-PEG Abs and individual proneness for C activation might predict the rise of adverse immune reactions to PEGylated drugs and thereby increase their efficacy and safety.
THU0067 Is Treat-To-Target Really Working? A Longitudinal Analysis in Biodam
Authors: S. Ramiro, R. Landewé, D. van der Heijde, O. FitzGerald, M. Østergaard, J. Homik, O. Elkayam, J.C. Thorne, M. Larche, G. Ferraccioli, M. Backhaus, G. Boire, B. Combe, T. Schaeverbeke, A. Saraux, M. Dougados, S. Adami, M. Govoni, L. Sinigaglia, A. Cantagrel, C.F. Allaart, C. Barnabe, C.O. Bingham, P.P. Tak, D. van Schaardenburg, H.B. Hammer, R. Dadashova, E. Hutchings, J. Paschke, W.P. Maksymowych
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> A Treat-to-Target approach (T2T), treating patients with RA towards a target, either remission or low disease activity (T2T-REM or T2T-LDA) is nowadays recommended. However it has never been assessed whether such a strategy in daily clinical practice really leads to more patients meeting that target. <h3>Methods</h3> BIODAM is a 2-year prospective cohort including patients in daily practice with RA from 10 countries, who were started or changed on DMARD and/or anti-TNF treatment and were followed-up every 3 months. Participating physicians were required to practice T2T per protocol. Per visit was decided whether a patient was treated according to T2T or not. T2T-REM was considered met: i) if a patient had already a disease activity score below the target (DAS28-CRP&lt;2.6); or ii) if treatment was intensified (by increasing dosage or adding drugs) upon a DAS28≥2.6. T2T-LDA was computed using the benchmark for low disease activity (LDA) (DAS28&lt;3.2) (T2T-LDA). The main outcome was the presence or absence of ACR/EULAR-boolean remission 3 months after T2T-REM or T2T-LDA. Another outcome analysed was sustained remission (present &gt;6 months). The relationship between T2T and ACR/EULAR Boolean remission 3 months later (or sustained remission) was investigated using generalized estimating equations with auto-regression. <h3>Results</h3> In total 3084 visits of 539 patients (mean (SD) age: 56 (13) years, 76% female, disease duration 6 (8) years). In 68% of the visits, T2T-REM was applied (in 79% of the visits T2T-LDA was applied). ACR/EULAR-boolean remission was reached in 15% of the visits. Appropriate application of T2T-REM led to a 50% higher likelihood of ACR/EULAR-boolean remission 3 months later than not applying T2T-REM. Both T2T-REM and T2T-LDA strategies led to lower disease activity (with an exception of DAS28 remission or DAS28-LDA). Only 9% of the treatment intensifications followed upon a DAS28 between 2.6 and 3.2, and 79% of the intensifications were applied upon a DAS&gt;3.2. Following T2T strategies led to higher achievement of sustained remission (table). <h3>Conclusions</h3> A treat-to-target approach, even with a modest benchmark (DAS28 = 3.2), works and leads to a higher achievement of (sustained) ACR/EULAR-remission. Our study illustrates the importance of acting upon the data that is routinely collected in a clinical encounter. Rheumatologists should be encouraged to follow a treat-to-target approach in order to improve the outcome of their patients. <h3>Disclosure of Interest</h3> None declared
Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study
Authors: Carolina Garcia-Vidal, Gemma Sanjuan, Estela Moreno-García, Pedro Puerta-Alcalde, Nicole Garcia-Pouton, Mariana Chumbita, Mariana Fernandez-Pittol, Cristina Pitart, Alexy Inciarte, Marta Bodro, Laura Morata, Juan Ambrosioni, Ignacio Grafia, Fernanda Meira, Irene Macaya, Celia Cardozo, Climent Casals, Adrian Tellez, Pedro Castro, Francesc Marco, Felipe García, Josep Mensa, José Antonio Martínez, Alex Soriano, Verónica Rico, Marta Hernández-Meneses, Daiana Agüero, Berta Torres, Ana González, Lorena de la Mora, Jhon Rojas, Laura Linares, Berta Fidalgo, Natalia Rodriguez, David Nicolas, Laia Albiach, José Muñoz, Alex Almuedo, Daniel Camprubí, Ma Angeles Marcos, Daniel Camprubí, Catia Cilloniz, Sara Fernández, Jose M. Nicolas, Antoni Torres
Journal: Clinical Microbiology and Infection (2020)
SARS-CoV-2 infection in immunocompromised patients: humoral versus cell-mediated immunity
Authors: Jia Wei, Jianping Zhao, Meifang Han, Fankai Meng, Jianfeng Zhou
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The coronavirus disease 2019 (COVID-19) pandemic placed unprecedented pressure on various healthcare systems, including departments that use immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy and immunosuppression therapy in organ transplantation units. The true impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on immunocompromised CAR T-cell therapy recipients and kidney transplant recipients (KTRs) has not yet been established. Case presentation In this report, we compare two patients with severe COVID-19 pneumonia in either the humoral or cell-mediated immunodeficient states. The first patient was a man in his early 30s who was diagnosed with refractory multiple myeloma. He received fully humanized, anti-B-cell maturation antigen, CAR T-cell therapy before 4 months and achieved strict complete remission. He was infected with SARS-CoV-2 starting on January 26, 2019 and gradually progressed to severe pneumonia. Throughout the clinical progression of the disease, SARS-CoV-2 could not be cleared due to his humoral immunodeficient state. During this period of his severe COVID-19 pneumonia, elevated cytotoxic T-cells were observed in this patient’s peripheral blood while elevated plasma levels of interleukin (IL)-2R, IL-6, tumor necrosis factor α, and ferritin were observed in his cytokine profiles. This patient eventually progressed into acute respiratory distress syndrome and recieved non-invasive ventilatory support. He failed to generate specific SARS-CoV-2 antibodies and died of respiratory failure on day 33 (d33). The second patient was a 52-year-old kidney transplant recipient (KTR) who took ciclosporin after renal transplantation for more than 7 years. He confirmed SARS-CoV-2 infection on January 20, 2019 and gradually progressed into severe pneumonia on d16 with a slightly elevated B-cell percentage and normal T-lymphocyte subsets. Viral clearance occurred together with the generation of specific anti-immunoglobulin G-SARS-CoV-2 antibodies after 2 weeks of treatment. He was symptom-free and discharged from the hospital on d42. Conclusion We report a CAR T-cell therapy recipient diagnosed with COVID-19 for the first time. His virus clearance failure and life-threating cytokine storm during SARS-CoV-2 infection suggested that any decision to proceed CAR T-cell therapy during COVID-19 pandemics will require extensive discussion of potential risks and benefits. Immunosuppressant treatment based on ciclosporin could be relatively safe for KTRs diagnosed with COVID-19. Trial registration number ChiCTR-OPN-1800018137.
Abstract 10: Effect of coincident infections in acute Kawasaki disease
Authors: Toshiaki Jibiki, Yuji Hashimoto, Masaki Kanazawa, Izumi Kato, Yoshinori Morita, Katsuaki Abe, Ayumi Shikino, Hideaki Fukushima, Manao Koudaira, Misato Yoshida, Emi Sugita, Fumie Ishiwada
Journal: Circulation (2015)

We investigated prevalence of coincident infections in acute Kawasaki disease (KD) to know the possible effects of infections on diagnosis of KD, clinical course, therapy decision and coronary outcomes. Single center consecutive 344 KD patients hospitalized in our institution, between January 2009 and December 2013 were retrospectively analyzed. Patients those were positive for bacterial culture, rapid antigen tests or elevated levels of pathogen specific antibodies were counted as KD patients with infection. Pathogen unproven patients those presented with apparent respiratory or gastrointestinal symptoms regarding infections were also counted as KD patients not to underestimate number of patients with suspected infections. Overall, 125 KD patients were grouped as KD patients with infection (Group1). Group1 included 125 patients with 73 upper respiratory tract infection, 21 bronchitis, 7 pneumonia, 3 acute otitis media and 21 gastroenterocolitis, respectively. Remaining 219 KD patients were grouped as KD without infection (Group2). Appropriate antibiotic or antiviral treatments were done for each pathogen proven infection. Distribution of age and sex, day of admission, diagnosis and treatment, prevalence of initial treatment regimen and rate of additional therapy, duration of fever, laboratory findings except serum albumin value, and coronary outcomes were similar between the groups. We showed that presence of coincident infections have no effects on clinical course, treatment decision and coronary outcomes on KD.
Abstract 16044: Pterostilbene Ameliorates Lipid Peroxidation and Increases Glucose-6-Phosphate Dehydrogenase Activity in Erythrocytes Subjected to High Glucose Conditions
Authors: Mariah Richins, Jennifer Meyer
Journal: Circulation (2018)

Cardiovascular complications are a hallmark of diabetes. One factor leading to cardiovascular damage is hyperglycemia, which can promote an accumulation of reactive oxygen species, leading to a mod...