Improved vascular health linked to increased physical activity levels and reduced sedentary behavior in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by deteriorated vascular health and increased cardiovascular risk. Physical activity (PA) is recommended for cardiovascular management in RA, but evidence on the associations between objectively-measured PA and vascular health markers in RA is limited. In this cross-sectional study, eighty-two post-menopausal women with RA (62±7 years) undertook ultrasound assessments of vascular function and structure, including brachial and superficial femoral artery (BA and SFA) flow-mediated dilation; baseline and post-hyperemia peak diameters; and carotid intima-media thickness. Participants also performed a 7-day accelerometer-based assessment of PA and sedentary behavior (SB). Fitted regression models controlled for age, body mass index and disease activity were conducted to examine associations between vascular and PA outcomes. Regression analyses revealed that prolonged SB (bouts>60min) and total sedentary time were inversely associated with both baseline and peak BA diameters, with each additional hour of SB resulting in decreases of 0.08-0.1mm in these diameters (p≤0.01). Total sedentary time also showed similar negative associations with peak SFA diameters (ß=-0.14[-0.24-0.05], p<0.01). Conversely, light-intensity PA and stepping time were positively associated with both baseline and peak BA diameters, with each additional hour increasing these diameters by 0.10-0.24mm (p≤0.02). Finally, standing time was positively associated with SFA peak diameter (ß=0.11[0.01-0.20], p=0.02). No associations were found between moderate-to-vigorous PA and vascular outcomes. In conclusion, in patients with RA, SB was negatively, while light PA was positively, associated with BA and SFA diameters. These findings suggest that reducing SB and increasing PA, even at light intensities, may improve vascular health in RA.

Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study.

OBJECTIVES: Rheumatic diseases may impair reproductive success and pregnancy outcomes, but systematic evaluations across diseases are lacking. We conducted a nationwide cohort study to examine the impact of rheumatic diseases on reproductive health measures, comparing the impacts with those of other immune-mediated diseases (IMDs). METHODS: Out of all of the 5 339 804 Finnish citizens, individuals born 1964-1984 and diagnosed with any of the 19 IMDs before age 30 (women) or 35 (men) were matched with 20 controls by birth year, sex, and education. We used data from nationwide health registers to study the impact of IMDs on reproductive health measures, such as reproductive success and, for women, ever having experienced adverse maternal and perinatal outcomes. RESULTS: Several of the rheumatic diseases, particularly SLE, JIA, and seropositive RA, were associated with higher rates of childlessness and fewer children. The risks for pre-eclampsia, newborns being small for gestational age, preterm delivery, non-elective Caesarean sections, and need of neonatal intensive care were increased in many IMDs. Particularly, SLE, SS, type 1 diabetes, and Addison's disease showed >2-fold risks for some of these outcomes. In most rheumatic diseases, moderate (1.1-1.5-fold) risk increases were observed for diverse adverse pregnancy outcomes, with similar effects in IBD, celiac disease, asthma, ITP, and psoriasis. CONCLUSION: Rheumatic diseases have a broad impact on reproductive health, with effects comparable with that of several other IMDs. Of the rheumatic diseases, SLE and SS conferred the largest risk increases on perinatal adverse event outcomes.

Rhekiss-The German Register for Child Wish and Pregnancies in Inflammatory Rheumatic Diseases.

In pharmacoepidemiology, robust data are needed to judge the impact of drug treatment on pregnancy, pregnancy outcomes and breast-fed infants. As pregnant and breastfeeding women are usually excluded from randomised clinical trials, observational studies are required. One of those data sources are pregnancy registers specifically developed to focus on certain diseases or disease groups. The German Rhekiss register investigates pregnancies in women with chronic inflammatory rheumatic diseases (IRD). Rhekiss is a nationwide, multicentre, longitudinal study, in which women aged 18 years or older with an underlying IRD can be enrolled by a rheumatologist either when planning a pregnancy or in the first half of pregnancy. Data are collected prospectively at regular follow-up visits. Rheumatologists and patients provide information in a web-based system before conception (if enrolment was at the time of pregnancy planning), during and after pregnancy. A smartphone app is available for patients. Maternal and clinical information, general laboratory markers, treatment with antirheumatic and other drugs, adverse events, items related to course and outcome of pregnancy and the health of the child are uniformly assessed for all diseases. Individual information on the IRD includes classification criteria, diagnosis-specific laboratory parameters, clinical parameters and validated instruments to measure disease activity or damage. Furthermore, patient-reported outcome measures are captured. A total of 2013 individual patients have been enrolled in the register, and data on 1801 completed pregnancies are available. In summary, Rhekiss is a comprehensive and complex register that can answer various research questions about pregnancy in women with chronic IRDs.

Artificial intelligence-based quantification of pulmonary HRCT (AIqpHRCT) for the evaluation of interstitial lung disease in patients with inflammatory rheumatic diseases.

High-resolution computed tomography (HRCT) is important for diagnosing interstitial lung disease (ILD) in inflammatory rheumatic disease (IRD) patients. However, visual ILD assessment via HRCT often has high inter-reader variability. Artificial intelligence (AI)-based techniques for quantitative image analysis promise more accurate diagnostic and prognostic information. This study evaluated the reliability of artificial intelligence-based quantification of pulmonary HRCT (AIqpHRCT) in IRD-ILD patients and verified IRD-ILD quantification using AIqpHRCT in the clinical setting. Reproducibility of AIqpHRCT was verified for each typical HRCT pattern (ground-glass opacity [GGO], non-specific interstitial pneumonia [NSIP], usual interstitial pneumonia [UIP], granuloma). Additional, 50 HRCT datasets from 50 IRD-ILD patients using AIqpHRCT were analysed and correlated with clinical data and pulmonary lung function parameters. AIqpHRCT presented 100% agreement (coefficient of variation = 0.00%, intraclass correlation coefficient = 1.000) regarding the detection of the different HRCT pattern. Furthermore, AIqpHRCT data showed an increase of ILD from 10.7 ± 28.3% (median = 1.3%) in GGO to 18.9 ± 12.4% (median = 18.0%) in UIP pattern. The extent of fibrosis negatively correlated with FVC (ρ=-0.501), TLC (ρ=-0.622), and DLCO (ρ=-0.693) (p < 0.001). GGO measured by AIqpHRCT also significant negatively correlated with DLCO (ρ=-0.699), TLC (ρ=-0.580) and FVC (ρ=-0.423). For the first time, the study demonstrates that AIpqHRCT provides a highly reliable method for quantifying lung parenchymal changes in HRCT images of IRD-ILD patients. Further, the AIqpHRCT method revealed significant correlations between the extent of ILD and lung function parameters. This highlights the potential of AIpqHRCT in enhancing the accuracy of ILD diagnosis and prognosis in clinical settings, ultimately improving patient management and outcomes.

[Update on the DVO Guideline 2023 "Prophylaxis, diagnosis and treatment of osteoporosis in postmenopausal women and in men aged over 50"-What's new for rheumatology?] / Update DVO-Leitlinie 2023 "Prophylaxe, Diagnostik und Therapie der Osteoporose bei postmenopausalen Frauen und bei Männern ab dem 50. Lebensjahr" ­ Was ist neu für die Rheumatologie?

In October 2023, the organization of the German-speaking scientific osteological societies (DVO) published the revised guideline on the "Prophylaxis, diagnosis and treatment of osteoporosis in postmenopausal women and in men aged over 50." This review article reflects the new features of the guideline and their relevance in the care of patients with inflammatory rheumatic diseases.A key innovation is the change from the 10-year fracture risk to the 3­year fracture risk. Basic diagnostics are currently performed without a defined fracture threshold. Treatment thresholds for specific osteological therapy constitute another key innovation, defined as 3% to < 5%, 5% to < 10%, and from 10% for vertebral body and femoral neck fractures. If the 3­year fracture risk is > 10%, osteoanabolic therapy should primarily be carried out and antiresorptive therapy is initiated following osteoanabolic therapy. In addition, patients with osteoporosis and prolonged glucocorticoid therapy should primarily be treated osteoanabolically with teriparatide. In summary, the changes to the DVO guideline reflect the latest scientific study findings in osteology and lead to detailed differential therapy for osteoporosis.

[What is the potential of ChatGPT for qualified patient information? : Attempt of a structured analysis on the basis of a survey regarding complementary and alternative medicine (CAM) in rheumatology]. / Welches Potential hat ChatGPT 3.5 für eine qualifizierte Patienteninformation? : Versuch einer systematischen Analyse anhand einer Befragung zu komplementärmedizinischen Verfahren in der Rheumatologie.

INTRODUCTION: The chatbot ChatGPT represents a milestone in the interaction between humans and large databases that are accessible via the internet. It facilitates the answering of complex questions by enabling a communication in everyday language. Therefore, it is a potential source of information for those who are affected by rheumatic diseases. The aim of our investigation was to find out whether ChatGPT (version 3.5) is capable of giving qualified answers regarding the application of specific methods of complementary and alternative medicine (CAM) in three rheumatic diseases: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (GPA). In addition, it was investigated how the answers of the chatbot were influenced by the wording of the question. METHODS: The questioning of ChatGPT was performed in three parts. Part A consisted of an open question regarding the best way of treatment of the respective disease. In part B, the questions were directed towards possible indications for the application of CAM in general in one of the three disorders. In part C, the chatbot was asked for specific recommendations regarding one of three CAM methods: homeopathy, ayurvedic medicine and herbal medicine. Questions in parts B and C were expressed in two modifications: firstly, it was asked whether the specific CAM was applicable at all in certain rheumatic diseases. The second question asked which procedure of the respective CAM method worked best in the specific disease. The validity of the answers was checked by using the ChatGPT reliability score, a Likert scale ranging from 1 (lowest validity) to 7 (highest validity). RESULTS: The answers to the open questions of part A had the highest validity. In parts B and C, ChatGPT suggested a variety of CAM applications that lacked scientific evidence. The validity of the answers depended on the wording of the questions. If the question suggested the inclination to apply a certain CAM, the answers often lacked the information of missing evidence and were graded with lower score values. CONCLUSION: The answers of ChatGPT (version 3.5) regarding the applicability of CAM in selected rheumatic diseases are not convincingly based on scientific evidence. In addition, the wording of the questions affects the validity of the information. Currently, an uncritical application of ChatGPT as an instrument for patient information cannot be recommended.

[Corona vaccination under immunosuppression]. / Coronaimpfung unter Immunsuppression.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to play a major role as a severe and potentially fatal airway infection, especially in vulnerable patient groups. In view of the thin data situation on the influence of treatment and response to vaccination, at the beginning of the corona pandemic it was a major challenge to predict the tolerability and effectiveness in patients with inflammatory rheumatic diseases under immunomodulation or immunosuppression. In the meantime, numerous studies have addressed the questions of response and tolerability, at least for the COVID-19 vaccination. Even in the first months of the vaccination campaign, a small study on a single center cohort could show that apart from patients with B­cell depletion, all included patients showed a seroconversion after the first two vaccinations. This resulted in neither an increased occurrence of exacerbations of the underlying disease nor new autoimmune phenomena. Various studies have since then confirmed these data.

[Physical therapy in rheumatology : What, when and how can it be prescribed?] / Physikalische Therapie in der Rheumatologie : Was, wann und wie kann man es verschreiben?

Treatment of a rheumatic diseases without physical and occupational therapy is almost incomplete because it cannot be replaced by anything else; however, slightly less than half of all insured persons with inflammatory rheumatic diseases only receive an outpatient prescription and this proportion has hardly changed in the last 15 years. This is even more surprising as those affected persons often have limitations in functional health due to multimorbidity, which are very accessible by physical measures. The article is intended to serve as a basis for a recourse-proof prescription in order to make even greater use of the corresponding possibilities of an outpatient physical prescription in the future.

[Patient-oriented optimization of the quality of care in a specialized outpatient clinic in a tertiary rheumatology center : A qualitative study]. / Patientenorientierte Optimierung der Versorgungsqualität in der ambulanten spezialfachärztlichen Versorgung (ASV) in einem tertiären rheumatologischen Zentrum : Eine qualitative Studie.

BACKGROUND: The adaptation of structures and processes in treatment procedures can contribute to increasing patient satisfaction and is the focus of patient-oriented quality assurance. OBJECTIVE: To identify patient satisfaction as well as needs, expectations and preferences with respect to care and, based on this, to formulate recommendations for action to optimize the quality of care at a large tertiary rheumatology center. MATERIAL AND METHODS: As part of a qualitative research approach, semi-structured patient interviews and a focus group interview consisting of physicians in rheumatology training in outpatient specialist care were conducted. The quality dimensions of Donabedian were recorded. The data material was evaluated and analyzed using the content-structuring qualitative content analysis according to Kuckartz with the MAXQDA evaluation software. RESULTS: Using 12 patient interviews and a focus group of 3 future rheumatologists, recommendations for action to optimize the quality of care were derived on the basis of the structural, process and outcome quality. There was a need for optimization in the areas of personnel management, internal practice processes, practice equipment and treatment processes in the outpatient clinic. CONCLUSION: The results from the patient interviews and the focus group revealed the aspects in need of optimization. The methodology and results of this study can serve as a reference point for analyses of other rheumatology clinics in order to improve the quality of care within the framework of patient-oriented quality management and continuous further development.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Varicella zoster virus reactivation following COVID-19 vaccination in patients with autoimmune inflammatory rheumatic diseases: A cross-sectional Chinese study of 318 cases.

Recently, varicella-zoster virus (VZV) reactivation has been observed after the administration of coronavirus disease 2019 (COVID-19) vaccines. Autoimmune inflammatory rheumatic diseases (AIIRDs) patients are at a higher risk for VZV reactivation for immunocompromised status. The study aimed to investigate the adverse events (AEs), especially VZV reactivation, following vaccination against  severe acute respiratory syndrome coronavirus-2 in a Chinese cohort of AIIRD patients. A cross-sectional survey using an online questionnaire was conducted among AIIRD patients and healthy controls (HCs). Multivariate logistic regression was used to identify potential factors associated with VZV reactivation. 318 AIIRD patients and 318 age and sex-matched HCs who got COVID-19 inactivated vaccines were recruited. The main AIIRDs are rheumatoid arthritis (31.8%) and systemic lupus erythematous (23.9%). Most of patients (85.5%) had stable disease and 13.2% of them had aggravation after vaccination. Compared to HCs, patients had higher rates of rash (p = 0.001), arthralgia (p < 0.001) and insomnia (p = 0.007). In addition, there were 6 (1.9%) AIIRD patients and 5 (1.6%) HCs reported VZV reactivation after the COVID-19 vaccination (p = 0.761). Multivariate logistic regression analysis illustrated that diabetes mellitus (odd ratio [OR], 20.69; 95% confidence interval [CI], 1.08-396.79; p = 0.044), chronic hepatitis B virus infection (OR, 24.34; 95% CI, 1.27-466.74; p = 0.034), and mycophenolate mofetil (OR, 40.61; 95% CI, 3.33-496.15; p = 0.004) independently identified patients with VZV reactivation. Our findings showed that the inactivated COVID-19 vaccination was safe for AIIRD patients though some patients could suffer from VZV reactivation.

Cost-effectiveness of cognitive behavioural and personalized exercise interventions for reducing fatigue in inflammatory rheumatic diseases.

OBJECTIVES: To estimate the cost-effectiveness of a cognitive behavioural approach (CBA) or a personalized exercise programme (PEP), alongside usual care (UC), in patients with inflammatory rheumatic diseases who report chronic, moderate to severe fatigue. METHODS: A within-trial cost-utility analysis was conducted using individual patient data collected within a multicentre, three-arm randomized controlled trial over a 56-week period. The primary economic analysis was conducted from the UK National Health Service (NHS) perspective. Uncertainty was explored using cost-effectiveness acceptability curves and sensitivity analysis. RESULTS: Complete-case analysis showed that, compared with UC, both PEP and CBA were more expensive [adjusted mean cost difference: PEP £569 (95% CI: £464, £665); CBA £845 (95% CI: £717, £993)] and, in the case of PEP, significantly more effective [adjusted mean quality-adjusted life year (QALY) difference: PEP 0.043 (95% CI: 0.019, 0.068); CBA 0.001 (95% CI: -0.022, 0.022)]. These led to an incremental cost-effectiveness ratio (ICER) of £13 159 for PEP vs UC, and £793 777 for CBA vs UC. Non-parametric bootstrapping showed that, at a threshold value of £20 000 per QALY gained, PEP had a probability of 88% of being cost-effective. In multiple imputation analysis, PEP was associated with significant incremental costs of £428 (95% CI: £324, £511) and a non-significant QALY gain of 0.016 (95% CI: -0.003, 0.035), leading to an ICER of £26 822 vs UC. The estimates from sensitivity analyses were consistent with these results. CONCLUSION: The addition of a PEP alongside UC is likely to provide a cost-effective use of health care resources.

[Mechanisms of immunological tolerance and their dysregulation in rheumatic diseases]. / Mechanismen immunologischer Toleranz und ihrer Dysregulation bei rheumatischen Erkrankungen.

The major tasks of the immune system are protection against infectious agents, maintaining homeostasis by recognizing and neutralizing noxious substances from the environment, and monitoring pathological, e.g. neoplastic tissue changes. It accomplishes these tasks through complex interactions of cellular and humoral components of the innate and adaptive immune system. This review article focuses on a central problem of self versus non-self discrimination in the development of B and T lymphocytes as carriers of adaptive immunity. During maturation of the lymphocytes in the bone marrow, large repertoires of lymphocyte receptors are randomly generated by somatic recombination, which as a whole have the capability of recognizing any foreign antigen. In order to reduce the implicit risk of autoaggressive immunity that might arise from evolutionary conserved structural motifs in self and foreign antigens, the adaptive immune system must provide redundant mechanisms (clonal deletion, anergy, quiescence and suppression) to eliminate or inactivate lymphocytes expressing highly avid receptors for autoantigens. Thus, the provision of costimulatory signals resulting in a reduced activation threshold of potentially autoreactive anergic T cells through infection, molecular mimicry, disrupted apoptosis regulation, altered "self" by post-translational modification, genetic changes in transcription factors with critical importance for thymic tolerance induction or signaling components of apoptosis can lead to a disruption of self-tolerance and the induction of pathogenic autoimmunity.

[How many patients with inflammatory rheumatic diseases have the technical prerequisites for video consultations and are also willing to use this to carry out visits by medical specialist visits?] / Wie viele Patienten mit entzündlich rheumatischen Erkrankungen haben die technischen Voraussetzungen für Videosprechstunden und sind bereit, fachärztliche Visiten so durchzuführen?

BACKGROUND: The currently disseminating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and limited capacities in outpatient rheumatological care, pose questions about possible alternatives to clinical visits, also in view of the digital revolution. It is unclear whether and to what extent patients with inflammatory rheumatic diseases are willing and in a position to deal with the new media, such as video consultation. METHODS: In the middle of the pandemic in May 2020 outpatients were surveyed using a standardized questionnaire in order to document their possibilities and willingness to participate in a video consultation. The treating physicians were asked whether carrying out a video consultation was considered to be a possible and meaningful option. RESULTS: Overall, 232 patients with inflammatory rheumatic diseases were surveyed (64.7% female, average age 54.0 ± 15.2 years), seropositive (n = 58) and seronegative (n = 51) rheumatoid arthritis (RA), spondyloarthritis (SpA, n = 77) including axial SpA (axSpA) and psoriatic arthropathy (PsA) as well as collagenosis and vasculitis (CoV, n = 46). The mean duration of disease was 5.5 ± 8.2 years, whereby in 75 patients (32.3%) it was the first diagnosis. The mean disease activity (0-10, subjective patient self-estimation) was 4.7 ± 2.5. Overall, 176 patients were basically aware of the possibility to carry out video consultations (75.9%) and 166 considered that they were technically capable to participate (71.6%) but only 131 were principally willing to participate (56.5%). Logistic regression analyses showed that the willingness to participate in video consultations decreased with increasing age (ß = 0.28, p = 0.01). According to the medical estimation video consultations were thought to be principally possible for 161 patients for technical reasons (69.4%) and for 127 for medical reasons (54.7%); however, a video consultation within the framework of treatment was only considered to be meaningful by the physician for 76 patients (32.8%). CONCLUSION: Not all patients can or want to participate in video consultations and the willingness declines with increasing age. The estimation of the meaningfulness of video consultations by physicians was also limited to approximately one third of the patients surveyed. This must be taken into consideration for the future planning of video consultations.

Prevalence and risk factors of monoclonal gammopathy in patients with autoimmune inflammatory rheumatic disease: A systematic review and meta-analysis.

OBJECTIVE: To systemically investigate the prevalence and risk factors of monoclonal gammopathy (MG) in patients with autoimmune inflammatory rheumatic disease (AIIRD). METHODS: A literature search was conducted using databases of PubMed, EMBASE, and Web of Science for relevant studies from inception to 31 July 2021. The pooled prevalence, odds ratio (OR), weighted mean difference (WMD), and 95% confidence interval (CI) were calculated with Stata 16.0 using a random or fixed effects model. RESULTS: In 17 included studies involving 6667 AIIRD patients, the pooled prevalence of MG in AIIRD patients was 7% (95%CI: 0.06-0.09). Compared to general populations, patients with Sjögren's syndrome (SS) possessed the highest risk for MG (OR 4.51; 95%CI: 3.39-5.74), followed by systemic lupus erythematosus (OR 3.99; 95%CI: 2.84-5.14), ankylosing spondylitis (OR 2.04; 95%CI: 1.11-2.97), and rheumatoid arthritis (OR 2.00; 95%CI: 1.79-2.22). Older age (WMD = 5.17 years; 95%CI: 0.68-9.66), higher erythrocyte sedimentation rate (WMD = 14.04 mm/H; 95%CI: 7.77-20.30), higher serum gammaglobulins level (WMD = 1.92 mg/dl, 95%CI: 0.51-3.32) were associated with a greater risk of MG in AIIRD patients. CONCLUSIONS: MG prevalence was higher in AIIRD patients, especially in SS patients. Older age, higher erythrocyte sedimentation rate, and hypergammaglobulins were risk factors for MG in AIIRD patients.

JAK inhibition in the treatment of inflammatory rheumatic diseases.

The most common immune-mediated inflammatory rheumatic diseases, rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis and have reached significant advances in recent years with the introduction of biological therapies against cytokines and immune cells, but also against intracellular enzymes, specifically Janus kinases (JAKs). Intracellular JAK signalling is activated by binding of various cytokines or growth factors to the respective cellular receptors, allowing the activation of STAT (Signal Transducers and Activators of Transcription) transcription factors and ultimately the transcription of genes with important roles during the innate and adaptive immune response. Four Janus kinases have been described: JAK1, JAK2, JAK3 and tyrosine kinase-2 (TYK2). Four JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) are currently approved for the treatment of rheumatoid arthritis, and some for the treatment of psoriatic arthritis and axial spondyloarthritis. JAK inhibitors have varying selectivity against individual kinases. Some JAK inhibitors are being tested in other rarer systemic connective tissue diseases. The general advantages of JAK inhibitors are oral administration, rapid onset of action, and efficacy in monotherapy. The safety profile of JAK inhibitors compared with biologic therapy appears to be comparable, with a higher incidence of herpes zoster, and an increased incidence of major cardiovascular disease, thromboembolic complications, and cancer in at-risk patients is discussed. The aim of this paper will be to summarize the latest findings on JAK inhibitors in approved indications for the most common rheumatic diseases.

[Systemic lupus erythematosus and antiphospholipid syndrome: past, present, future].

Immune-inflammatory (autoimmune and autoinflammatory) rheumatic diseases are widespread severe chronic inflammatory diseases and also "models" for studying the fundamental mechanisms of pathogenesis and approach to pharmacotherapy of other diseases associated with autoimmunity and/or autoinflammation. Uncontrolled inflammation leading to hypercoagulation forms the basis of "thromboinflammation", which is considered a universal pathogenetic mechanism of organ involvement in immune-inflammatory rheumatic diseases, as well as in COVID-19 and atherosclerotic vascular lesions (atherothrombosis). Thrombo-inflammatory mechanisms play a crucial role in systemic lupus erythematosus and antiphospholipid syndrome. Russian rheumatology, under the leadership of academician Valentina Alexandrovna Nasonova, greatly contributed to the research of these disorders. This article addresses the current view about the overlapping pathogenetic mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome, the relevance of these studies during the COVID-19 pandemic, and the prospects for antithrombotic and anti-inflammatory therapy.

Real-time vs static scoring in musculoskeletal ultrasonography in patients with inflammatory hand osteoarthritis.

OBJECTIVES: Agreement between real-time and static ultrasonography has not been studied in musculoskeletal diseases. We studied this agreement in inflammatory hand OA. METHODS: Ultrasonography was performed blinded to clinical information of 30 joints of 75 patients with hand OA, treated with prednisolone in a randomized placebo-controlled double-blind trial. Images were scored real-time at acquisition and stored images were scored static (paired in known chronological order) for inflammatory features and osteophytes (score 0-3). Agreement between methods was studied at joint level with quadratic weighted kappa. At patient level intra-class correlations (ICC) of sum scores and change in sum-scores (delta baseline-week 6) were calculated. Responsiveness of scoring methods was analysed with generalized estimating equations (GEE) with treatment as independent and ultrasonography findings as dependent variable. RESULTS: Agreement at baseline was good to excellent at joint level (kappa 0.72-0.88) and moderate to excellent at patient level (ICC 0.58-0.91). Agreement for change in sum scores was poor to fair for synovial thickening and effusion (ICC 0.18 and 0.34, respectively), while excellent for Doppler signal (ICC 0.80). Real-time ultrasonography discriminated between prednisolone and placebo with a mean between-group difference of synovial thickening of -2.5 (95% CI: -4.7, -0.3). Static ultrasonography did not show a decrease in synovial thickening. CONCLUSION: While cross-sectional agreement between real-time and static ultrasonography is good, static ultrasonography measurement of synovial thickening did not show responsiveness to prednisone therapy while real-time ultrasonography did. Therefore, when ultrasonography is used in clinical trials, real-time dynamic scoring should remain the standard for now.

[Nailfold capillaroscopy-Principles and clinical application]. / Kapillarmikroskopie ­ Grundlagen und klinische Anwendung.

Nailfold capillaroscopy is a rapid and easily applicable differential diagnostic technique that allows direct visualization of the microcirculation. Abnormal findings in nailfold capillaroscopy are closely associated with connective tissue diseases, such as systemic sclerosis. The clinical manifestation of impaired microcirculation is Raynaud's phenomenon, which is a classical symptom of connective tissue diseases. Nailfold capillaroscopy is increasingly used in various fields of medicine, therefore it is important to define methods for the acquisition and analysis of the results of nailfold capillary and to have a uniform definition of abnormal capillaries. This article discusses image acquisition and analysis, various capillaroscopic techniques, normal and abnormal capillaroscopic features and their significance, scoring systems and reliability of image acquisition and interpretation.

Diabetes-Modifying Antirheumatic Drugs: The Roles of DMARDs as Glucose-Lowering Agents.

Systemic inflammation represents a shared pathophysiological mechanism which underlies the frequent clinical associations among chronic inflammatory rheumatic diseases (CIRDs), insulin resistance, type 2 diabetes (T2D), and chronic diabetes complications, including cardiovascular disease. Therefore, targeted anti-inflammatory therapies are attractive and highly desirable interventions to concomitantly reduce rheumatic disease activity and to improve glucose control in patients with CIRDs and comorbid T2D. Therapeutic approaches targeting inflammation may also play a role in the prevention of prediabetes and diabetes in patients with CIRDs, particularly in those with traditional risk factors and/or on high-dose corticosteroid therapy. Recently, several studies have shown that different disease-modifying antirheumatic drugs (DMARDs) used for the treatment of CIRDs exert antihyperglycemic properties by virtue of their anti-inflammatory, insulin-sensitizing, and/or insulinotropic effects. In this view, DMARDs are promising drug candidates that may potentially reduce rheumatic disease activity, ameliorate glucose control, and at the same time, prevent the development of diabetes-associated cardiovascular complications and metabolic dysfunctions. In light of their substantial antidiabetic actions, some DMARDs (such as hydroxychloroquine and anakinra) could be alternatively termed "diabetes-modifying antirheumatic drugs", since they may be repurposed for co-treatment of rheumatic diseases and comorbid T2D. However, there is a need for future randomized controlled trials to confirm the beneficial metabolic and cardiovascular effects as well as the safety profile of distinct DMARDs in the long term. This narrative review aims to discuss the current knowledge about the mechanisms behind the antihyperglycemic properties exerted by a variety of DMARDs (including synthetic and biologic DMARDs) and the potential use of these agents as antidiabetic medications in clinical settings.