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Background: Early diagnosis and treatment of inflammatory rheumatic diseases can prevent consequential damage such as permanently limited mobility and joint or organ damage. Simultaneously, there is an increasing deficit in medical care owing to the lack of rheumatological capacity. Rural regions are particularly affected. Objectives: The available unconfirmed diagnoses of the study Rheuma-VOR were analysed regarding another definitive inflammatory rheumatic disease. Materials and methods: The returned questionnaires of the rheumatologists participating in Rheuma-VOR were screened for definitive inflammatory rheumatic diseases other than the required diagnosis of rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. Results: Of 910 unconfirmed diagnoses, in 245 patients another definitive diagnosis could be confirmed. A total of 29.8% of the diagnoses corresponded to degenerative joint changes or chronic pain syndrome, whereas 26.1% involved different forms of inflammatory arthritis. The majority of diagnoses (40.5%) were collagenosis or vasculitis, Discussion: The available data show that a rheumatological presentation was indicated for the majority of patients. Owing to the increasing deficits in medical care a prior selection of the patients is crucial to make optimal use of restricted rheumatological capacities., Hintergrund: Eine frühe Diagnose und Behandlung entzündlich-rheumatischer Erkrankungen kann Folgeschäden wie dauerhafte Einschränkungen der Mobilität und Gelenk- oder Organschäden verhindern. Gleichzeitig besteht ein größer werdendes Versorgungsdefizit aufgrund fehlender rheumatologischer Kapazitäten. Betroffen sind besonders die ländlichen Regionen. Ziel der Arbeit: Die vorliegenden nicht bestätigten Diagnosen der Studie Rheuma-VOR wurden hinsichtlich des Vorliegens einer anderen definitiven entzündlich-rheumatischen Erkrankung analysiert. Material und Methoden: Die eingegangenen Fragebögen der an der Rheuma-VOR-Studie teilnehmenden Rheumatolog:innen wurden nach Vermerken anderer entzündlich-rheumatischer Erkrankungen als der geforderten Diagnose einer rheumatoiden Arthritis, Psoriasis-Arthritis oder Spondyloarthritis gescreent. Ergebnisse: Von 910 „nicht bestätigten“ Diagnosen waren bei 245 Patient:innen andere gestellte Diagnosen auszuwerten. Insgesamt 29,8 % der Diagnosen entsprechen degenerativen Gelenkveränderungen oder chronischen Schmerzsyndromen, bei 26,1 % lagen verschiedene Formen entzündlicher Arthritiden vor. Der Großteil der Diagnosen (40,5 %) entfiel auf Kollagenosen und Vaskulitiden, wobei die Polymyalgia rheumatica mit 20 % am häufigsten diagnostiziert wurde (49 Patient:innen). Diskussion: Die vorliegenden Daten zeigen, dass bei einem Großteil der Patient:innen die rheumatologische Vorstellung indiziert war. Aufgrund der ambulanten Versorgungsdefizite ist eine vorherige Selektion des Patientenguts essenziell, um die eingeschränkten Kapazitäten bestmöglich zu nutzen.

Contains fulltext : 252186.pdf (Publisher’s version ) (Open Access), BACKGROUND AND AIMS: Detection of autoantibodies is a mainstay of diagnosing autoimmune hepatitis (AIH). However, conventional autoantibodies for the workup of AIH lack either sensitivity or specificity, leading to substantial diagnostic uncertainty. We aimed to identify more accurate serological markers of AIH with a protein macroarray. APPROACH AND RESULTS: During the search for more-precise autoantibodies to distinguish AIH from non-AIH liver diseases (non-AIH-LD), IgG antibodies with binding capacities to many human and foreign proteins were identified with a protein macroarray and confirmed with solid-phase ELISAs in AIH patients. Subsequently, polyreactive IgG (pIgG) was exemplarily quantified by reactivity against human huntingtin-interacting protein 1-related protein in bovine serum albumin blocked ELISA (HIP1R/BSA). The diagnostic fidelity of HIP1R/BSA binding pIgG to diagnose AIH was assessed in a retrospective training, a retrospective multicenter validation, and a prospective validation cohort in cryoconserved samples from 1,568 adults from 10 centers from eight countries. Reactivity against HIP1R/BSA had a 25% and 14% higher specificity to diagnose AIH than conventional antinuclear and antismooth muscle antibodies, a significantly higher sensitivity than liver kidney microsomal antibodies and antisoluble liver antigen/liver pancreas antigen, and a 12%-20% higher accuracy than conventional autoantibodies. Importantly, HIP1R/BSA reactivity was present in up to 88% of patients with seronegative AIH and in up to 71% of AIH patients with normal IgG levels. Under therapy, pIgG returns to background levels of non-AIH-LD. CONCLUSIONS: pIgG could be used as a promising marker to improve the diagnostic workup of liver diseases with a higher specificity for AIH compared to conventional autoantibodies and a utility in autoantibody-negative AIH. Likewise, pIgG could be a major source of assay interference in untreated AIH.

The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy. CIR analyses treated relapses and AML deaths as events, deaths from other causes as competing risks, and survivors in remission were censored. CIR was improved on the midostaurin arm (HR = 0.71 (95% CI, 0.54-0.93); p = 0.01), both overall and within European LeukemiaNet 2017 risk classification subsets when post-transplant events were considered in the analysis as events. However, when transplantation was considered as a competing risk, there was overall no significant difference between the risks of relapse on the two randomized arms. Patients still in remission after consolidation with high-dose cytarabine entered the maintenance phase, continuing with either midostaurin or placebo. Analyses were inconclusive in quantifying the impact of the maintenance phase on the overall outcome. In summary, midostaurin reduces the CIR.

There is currently no approved treatment for primary Sjögren’s syndrome, a disease thatprimarily affects adult women. The difficulty in developing effective therapies is -in part-because of the heterogeneity in the clinical manifestation and pathophysiology of the disease.Finding common molecular signatures among patient subgroups could improve our under-standing of disease etiology, and facilitate the development of targeted therapeutics. Here,we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syn-drome patients based on the multi-omic profiling of whole blood samples from a Europeancohort of over 300 patients, and a similar number of age and gender-matched healthyvolunteers. Using transcriptomic, genomic, epigenetic, cytokine expression andflow cyto-metry data, combined with clinical parameters, we identify four groups of patients withdistinct patterns of immune dysregulation. The biomarkers we identify can be used bymachine learning classifiers to sort future patients into subgroups, allowing the re-evaluationof response to treatments in clinical trials.