Screening for rheumatoid arthritis-associated interstitial lung disease-a Delphi-based consensus statement.

OBJECTIVE: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major driver of premature mortality in patients with rheumatoid arthritis (RA). Detection of RA-ILD is crucial but requires awareness among the treating physicians. To date, however, there is no international recommendation concerning screening for ILD in RA patients. METHODS: After a systematic literature review, the modified Delphi technique in combination with the nominal group technique was used to provide a Delphi consensus statement elaborated by an expert panel of pneumonologists, rheumatologists, and a radiologist. Based on the available evidence, several clusters of questions were defined and discussed until consent was reached. RESULTS: A screening algorithm for ILD in patients with RA based on clinical signs, respiratory symptoms, and risk factors has been developed. Further, the recommendations address diagnostic tools for RA-ILD and the follow-up of RA patients qualifying for ILD screening.

COVID-19 and its continuing burden after 12†months: a longitudinal observational prospective multicentre trial.

Background: Recovery trajectories from coronavirus disease 2019 (COVID-19) call for longitudinal investigation. We aimed to characterise the kinetics and status of clinical, cardiopulmonary and mental health recovery up to 1 year following COVID-19. Methods: Clinical evaluation, lung function testing (LFT), chest computed tomography (CT) and transthoracic echocardiography were conducted at 2, 3, 6 and 12 months after disease onset. Submaximal exercise capacity, mental health status and quality of life were assessed at 12 months. Recovery kinetics and patterns were investigated by mixed-effect logistic modelling, correlation and clustering analyses. Risk of persistent symptoms and cardiopulmonary abnormalities at the 1-year follow-up were modelled by logistic regression. Findings: Out of 145 CovILD study participants, 108 (74.5%) completed the 1-year follow-up (median age 56.5 years; 59.3% male; 24% intensive care unit patients). Comorbidities were present in 75% (n=81). Key outcome measures plateaued after 180 days. At 12 months, persistent symptoms were found in 65% of participants; 33% suffered from LFT impairment; 51% showed CT abnormalities; and 63% had low-grade diastolic dysfunction. Main risk factors for cardiopulmonary impairment included pro-inflammatory and immunological biomarkers at early visits. In addition, we deciphered three recovery clusters separating almost complete recovery from patients with post-acute inflammatory profile and an enrichment in cardiopulmonary residuals from a female-dominated post-COVID-19 syndrome with reduced mental health status. Conclusion: 1 year after COVID-19, the burden of persistent symptoms, impaired lung function, radiological abnormalities remains high in our study population. Yet, three recovery trajectories are emerging, ranging from almost complete recovery to post-COVID-19 syndrome with impaired mental health.

Persistent somatic symptoms are key to individual illness perception at one year after COVID-19 in a cross-sectional analysis of a prospective cohort study.

OBJECTIVE: Subjective illness perception (IP) can differ from physician's clinical assessment results. Herein, we explored patient's IP during coronavirus disease 2019 (COVID-19) recovery. METHODS: Participants of the prospective observation CovILD study (ClinicalTrials.gov: NCT04416100) with persistent somatic symptoms or cardiopulmonary findings one year after COVID-19 were analyzed (n = 74). Explanatory variables included demographic and comorbidity, COVID-19 course and one-year follow-up data of persistent somatic symptoms, physical performance, lung function testing, chest computed tomography and trans-thoracic echocardiography. Factors affecting IP (Brief Illness Perception Questionnaire) one year after COVID-19 were identified by regularized modeling and unsupervised clustering. RESULTS: In modeling, 33% of overall IP variance (R2) was attributed to fatigue intensity, reduced physical performance and persistent somatic symptom count. Overall IP was largely independent of lung and heart findings revealed by imaging and function testing. In clustering, persistent somatic symptom count (Kruskal-Wallis test: η2 = 0.31, p < .001), fatigue (η2 = 0.34, p < .001), diminished physical performance (χ2 test, Cramer V effect size statistic: V = 0.51, p < .001), dyspnea (V = 0.37, p = .006), hair loss (V = 0.57, p < .001) and sleep problems (V = 0.36, p = .008) were strongly associated with the concern, emotional representation, complaints, disease timeline and consequences IP dimensions. CONCLUSION: Persistent somatic symptoms rather than abnormalities in cardiopulmonary testing influence IP one year after COVID-19. Modifying IP represents a promising innovative approach to treatment of post-COVID-19 condition. Besides COVID-19 severity, individual IP should guide rehabilitation and psychological therapy decisions.

High expression of mTOR signaling in granulomatous lesions is not predictive for the clinical course of sarcoidosis.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease with a variable clinical presentation and disease course. There is still no reliable biomarker available, which assists in the diagnosis or prediction of the clinical course. According to a murine model, the expression level of the metabolic checkpoint kinase mechanistic target of Rapamycin complex 1 (mTORC1) in granulomas of sarcoidosis patients may be used as a clinical biomarker. MATERIAL AND METHODS: This is a retrospective analysis of 58 patients with histologically confirmed sarcoidosis. Immunohistochemical staining of granulomas from tissue samples was evaluated for the expression of activated mTORC1 signaling, including phosphorylated mTOR, its downstream effectors S6K1, 4EBP1 and the proliferation marker Ki-67. Patients were categorized according to different clinical phenotypes, serum biomarkers, and immunomodulatory therapy. RESULTS: All patients showed activated mTORC1 signaling in granulomas, which correlated with its downstream effectors S6K1 and 4EBP1 but was not related to Ki-67 expression. The mTORC1 activity revealed an association neither to disease severity nor the necessity of treatment; however, p-mTOR inversely correlated with cumulative corticosteroid dosage. CONCLUSION: Our data confirm activation of the mTORC1 pathway in sarcoidosis, supporting the hypothesis that mTOR is a significant driver in granuloma formation. However, we could not find a relationship between the degree of mTOR activation and disease severity or the need for therapy.

Methotrexate therapy impacts on red cell distribution width and its predictive value for cardiovascular events in patients with rheumatoid arthritis.

BACKGROUND: Methotrexate (MTX) is well known to affect folic acid metabolism, so MTX treatment can result in alterations of mean corpuscular volume (MCV), which may impact on red cell distribution width (RDW), as MCV levels feed into RDW calculation. We thus questioned whether RDW levels and subsequently its diagnostic utility in RA subjects, as reported before, are influenced by ongoing MTX therapy.We assessed the impact of disease modifying drug (DMARD) treatment, especially MTX, on RDW and evaluated their influence on the predictive value of RDW for cardiovascular (CV) events in patients with rheumatoid arthritis (RA). As far as we know, this is the first study evaluating the influence of MTX on RDW. METHODS: Medical treatment, disease activity, laboratory parameters and history of CV events were retrospectively analysed in 385 RA patients at disease onset and at last follow up at our clinic. Additionally, in patients with CV event, data were recorded at last follow up prior the CV event. RESULTS: Disease parameters and laboratory findings associated with a serious vascular event were older age (p < 0,001), longer disease duration (p = 0,002) and a higher RDW at diagnosis (p = 0,025). No differences in RDW levels became evident with any other treatment regimen beside MTX. MTX treated patients had significantly higher RDW compared to subjects without this drug (p < 0,001). In RA patients without MTX treatment, we found RDW level significantly different between those with versus without a CV event, whereas this difference disappeared in subjects receiving MTX. CONCLUSION: MTX impacts on RDW and might therefor reduce its prognostic value for CV events in patients taking MTX, whereas an increased RDW at diagnosis remains an early risk predictor for myocardial infarction and stroke in RA patients.