Showing papers by "Jens Schmidt published in 2021"

A Systematic Review and Meta-Analysis to Inform Cancer Screening Guidelines in Idiopathic Inflammatory Myopathies

Abstract: Objectives To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. Methods A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared to the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesised via narrative review. Results Sixty nine studies were included in the meta-analysis. Dermatomyositis subtype (RR 2.21), older age (WMD 11.19), male gender (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73), and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. Polymyositis (RR 0.49) and clinically amyopathic dermatomyositis (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. Computed tomography (CT) scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. Discussion Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.

Chance or challenge, spoilt for choice? New recommendations on diagnostic and therapeutic considerations in hereditary transthyretin amyloidosis with polyneuropathy: the German/Austrian position and review of the literature

Abstract: Hereditary transthyretin amyloidosis is caused by pathogenic variants (ATTRv) in the TTR gene. Alongside cardiac dysfunction, the disease typically manifests with a severely progressive sensorimotor and autonomic polyneuropathy. Three different drugs, tafamidis, patisiran, and inotersen, are approved in several countries, including the European Union and the United States of America. By stabilizing the TTR protein or degrading its mRNA, all types of treatment aim at preventing amyloid deposition and stopping the otherwise fatal course. Therefore, it is of utmost importance to recognize both onset and progression of neuropathy as early as possible. To establish recommendations for diagnostic and therapeutic procedures in the follow-up of both pre-symptomatic mutation carriers and patients with manifest ATTRv amyloidosis with polyneuropathy, German and Austrian experts elaborated a harmonized position. This paper is further based on a systematic review of the literature. Potential challenges in the early recognition of disease onset and progression are the clinical heterogeneity and the subjectivity of sensory and autonomic symptoms. Progression cannot be defined by a single test or score alone but has to be evaluated considering various disease aspects and their dynamics over time. The first-line therapy should be chosen based on individual symptom constellations and contra-indications. If symptoms worsen, this should promptly implicate to consider optimizing treatment. Due to the rareness and variability of ATTRv amyloidosis, the clinical course is most importantly directive in doubtful cases. Therefore, a systematic follow-up at an experienced center is crucial to identify progression and reassure patients and carriers.

Antisynthetase Syndrome-Associated Interstitial Lung Disease: Monitoring of Immunosuppressive Treatment Effects by Chest Computed Tomography.

Abstract: Background: Antisynthetase syndrome (ASyS) is a rare autoimmune disease characterized by inflammatory myopathy, arthritis, fever, and interstitial lung disease (ILD). Pulmonary involvement in ASyS significantly increases morbidity and mortality and, therefore, requires prompt and effective immunosuppressive treatment. Owing to the rarity of ASyS, limited data exists on progression and prognosis of ILD under immunosuppression. Objectives: The objective of the study was to evaluate the radiological progression and outcome measures of ILD with immunosuppressive therapy in patients with ASyS. Methods: Twelve patients with ASyS-associated ILD (ASyS-ILD) were included. Demographic and clinical data, including organ involvement, pulmonary function tests (PFT), laboratory parameters, imaging studies, and treatment regimens were retrospectively analyzed from routinely collected data. The extent of ground glass opacities, fibrotic changes and honeycombing was analyzed and scored using high-resolution chest computed tomography (HRCT) scans. HRCT findings were compared between baseline and follow-up examinations. In addition, patients were stratified depending on whether they had received rituximab (RTX) or not. Results: Pulmonary function tests revealed stable lung function and follow-up HRCT scans showed an improvement of radiological alterations in the majority of ASyS patients under immunosuppressive therapy. We did not detect significant differences between the RTX- and non-RTX-treated groups, but the RTX-treated patients more frequently had myositis and relapsing disease. Conclusions: Radiographic alterations in ASyS-associated ILD respond to immunosuppressive treatment. RTX is a feasible treatment option with similar clinical and radiographic outcomes in patients with relapsing disease and clinically apparent myositis.

Inflammatory myopathies: Shedding light on promising agents and combination therapies in clinical trials.

Abstract: Introduction Due to new insights into the pathogenesis of inflammatory myopathies -in short myositis- and the urgent need for new treatment options in patients who are refractory to standard therapy, multiple novel drugs have been developed and studied in clinical trials. In light of this exciting development, a critical evaluation of the present data is necessary in order to identify the best pathway to future treatment of inflammatory myopathies. Areas covered This review focuses on the current evidence from clinical trials in myositis and encompasses dermatomyositis, polymyositis, necrotizing myopathy, antisynthetase-syndrome, overlap myositis and inclusion body myositis. The results of studies on new therapeutic agents are summarized, in particular larger cohort studies and randomized trials from recent years. When such data were not available, earlier and smaller representative studies were included instead. Expert opinion Current studies in most myositis subtypes have shown positive effects of novel biologicals such as abatacept, sifalimumab, JAK-Inhibitors as well as known agents such as rituximab, but further studies are needed to confirm these observations. In inclusion body myositis, the eagerly awaited recent therapeutic trials have missed their primary endpoints, except for the phase 2 study with rapamycin, which has demonstrated significant improvements in secondary endpoints. Future trials will also need to focus on combination therapies of multiple immunomodulatory agents.

Ursache von Muskelschwäche: Spektrum neuromuskulärer Erkrankungen und diagnostisches Vorgehen

Abstract: Das Leitsymptom der muskularen Schwache kann auf das Vorliegen einer neuromuskularen Erkrankung zuruckzufuhren sein, findet sich jedoch auch bei einer Reihe anderer Faktoren wie Elektrolytveranderungen, Vitaminmangel, Schilddrusenerkrankungen, Bewegungsmangel oder bei unerwunschten Arzneimittelnebenwirkungen. Einer grundlichen Anamnese und korperlichen Untersuchung kommt daher in der differentialdiagnostischen Abklarung eine grose Bedeutung zu. Die zeitliche Entwicklung, das Verteilungsmuster sowie Begleitsymptome erlauben oftmals bereits eine erste diagnostische Einordnung. Bei begrundetem Verdacht auf das Vorliegen einer neuromuskularen Erkrankung sollte die weiterfuhrende Diagnostik durch einen Neurologen oder ein neuromuskulares Zentrum erfolgen. Zu den wichtigsten neuromuskularen Erkrankungen mit Leitsymptom einer muskularen Schwache gehoren die neuromuskularen Ubertragungsstorungen, Neuropathien, erbliche und erworbene Myopathien sowie Motoneuronerkrankungen. Diese Ubersicht stellt die wichtigsten Ursachen fur eine muskulare Schwache zusammen und zeigt das zu empfehlende diagnostische Vorgehen auf.