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OBJECTIVE:: Antiphospholipid syndrome (APS) and autoimmune rheumatic diseases (ARDs) are known to increase the risk for cardiovascular events (CVEs) in the general population., However, research in pregnancy is limited. We compared the occurrence of acute CVEs in pregnant women with and without ARDs or primary APS using a Californian population-based cohort. STUDY DESIGN:: This was a retrospective cohort study of pregnant individuals who delivered singleton infants in California between 2005 and 2020. Birth certificates were linked by the Study of Outcomes of Mothers and Infants to maternal records. The study was approved by institutional review boards of the State of California and the University of California San Diego. Pregnancies with ARDs were identified by ≥1 International Classification of Diseases (ICD) code for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthritis, Sjogren’s syndrome, and other ARDs (systemic sclerosis, inflammatory myositis, and vasculitides) in maternal hospital discharge, emergency, or ambulatory surgery records. Lupus nephritis (LN) was defined as SLE plus glomerulonephritis, renal failure, nephritic or nephrotic syndrome, or proteinuria. Primary APS included women with APS without concurrent ARDs. Women without ARDs or APS comprised the reference group. Acute CVEs during pregnancy and up to 6 weeks postpartum were identified by ICD codes and compared between groups. CVEs were classified as myocardial infarction, cardiovascular accident, heart failure and peripartum cardiomyopathy, inflammatory heart diseases, cardiac dysrhythmias, and venous thromboembolism (VTE). Covariates identified and adjusted for include age, race and ethnicity, insurance, education, prepregnancy body mass index, preexisting hypertension, diabetes, hyperlipidemia, depression, and substance use disorders. A log linear regression with a Poisson distribution was used to estimate the adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the associations of ARDs and APS with CVEs. Analyses were performed using Statistical Analysis Software (SAS), version 9.4 (SAS Institute, Cary, NC). Causal mediation analyses were performed for potential mediators, such as gestational diabetes, gestational hypertension, and preeclampsia. RESULTS:: Overall, 19,340 women had ARDs, 7758 had primary APS, and 7,004,334 had neither condition. The ARD and APS groups had more traditional cardiovascular risk factors. Acute CVEs were observed in 2.0% of ARD cases (388/19,340), 7.0% of primary APS cases (540/7,758), and 0.4% of reference group cases (24,402/7,004,334). The aRR for CVEs in the ARD and APS groups in comparison with the reference group was 4.1-fold (95% CI, 3.7–4.5) and 14.7-fold (95% CI, 13.5–16.0), respectively (Table). Of the 388 CVEs that occurred in women with ARDs, 164 (42%) were VTEs, 96 (25%) were heart failure or peripartum cardiomyopathy, and 92 (24%) were cardiac dysrhythmias. In primary APS cases, 453 of 540 (83%) CVEs were VTE. Acute CVEs occurred in 3.1% (159/8,422) of patients with overall SLE, in 10.7% (55/513) of patients with SLE with APS, and in 8.5% (77/903) of patients with SLE with LN (Table). The aRR for CVEs was 6-fold higher among those with SLE (95% CI, 5.3–6.8) and was notably increased with concurrent APS or LN, with aRRs of 18.1 (95% CI, 13.9–23.6) and 12.7 (95% CI, 10.1–15.9), respectively (Figure). The risks for both VTE and non-VTE CVEs was increased among pregnancies affected by ARD and APS (Figure). Five of 6 in-hospital deaths in ARD pregnancies (5/388 or 1.3%) occurred among women with acute CVEs (Table). The risks for CVEs were higher during all perinatal periods. In mediation analyses, 11.2% of the excess risk for CVE in ARD pregnancies was mediated by preeclampsia, whereas

Objectives: This study aimed to clarify the issues related to pregnancy in patients with inflammatory rheumatic diseases (RDs) and to provide useful information for developing medical services from patients' perspectives. Methods: A survey involving approximately 5000 members of the Patients Association for Collagen Vascular Diseases Japan was conducted using a questionnaire that was sent and returned by mail. The questionnaire items included age at the time of the survey, types of RDs, association of RDs with pregnancy/childbirth outcomes, and pregnancy-related supports and hindrances. Results: We received 491 completed questionnaires. The most common RD was systemic lupus erythematosus (n = 309). Approximately 60% of participants had a history of childbirth. Approximately 60% of participants had previously experienced pregnancy-related challenges due to RDs. These included concerns about the influence of drugs on babies, genetic transmission, and active disease. Patients with active disease at the time of conception were more likely to experience disease exacerbation during pregnancy, but this did not correlate with whether the pregnancy was planned. Conclusion: This study revealed that many patients with RDs experienced pregnancy-related challenges and needed appropriate support based on appropriate information. The findings here should help rheumatologists, healthcare providers, and public agencies provide counselling and information. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the performance of radionuclide-labeled fibroblast activation protein inhibitors (Al18F-NOTA-FAPI-04) PET/CT in patients with autoimmune rheumatic diseases (ARDs) and compare it with fluorine-18 (18F) labeled fluorodeoxyglucose (FDG) imaging. Methods: Fifty-eight participants with ARDs were prospectively enrolled from April 2022 to February 2024 and underwent dual-tracer PET/CT imaging. For both 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT, imaging findings were interpreted and compared. The clinical significance was compared between18F-FDG PET/CT and Al18F-NOTA-FAPI-04 PET/CT imaging. Results: 18F-FDG imaging was positive in 53 out of 58 cases (91.4%) while Al18F-NOTA-FAPI-04 imaging was positive in 55 out of 58 cases (94.8%). Overall positive rate of Al18F-NOTA-FAPI-04 imaging was as high as 18F-FDG imaging (P = 0.625). 18F-FDG imaging detected more lesions in lymph node, spleen, and bone marrow. Al18F-NOTA-FAPI-04 imaging detected more lesions in the lung, muscle, and tendon/ligament. There was no statistical difference of composing ratio of grades of clinical significance between two imaging modalities (χ2 = 2.875, P = 0.238). The superior rate of Al18F-NOTA-FAPI-04 PET/CT imaging was higher than 18F-FDG imaging (P = 0.020). In subgroup of adult-onset Still's disease, 18F-FDG imaging showed better performance than Al18F-NOTA-FAPI-04 imaging. In most of the other subgroup of ARDs, Al18F-NOTA-FAPI-04 PET/CT imaging overperformed 18F-FDG imaging. Conclusion: Both 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT imaging have excellent sensitivity in ARDs. The detection capabilities of two tracers varied according to the involving organs of ARDs. In most of ARDs except adult-onset Still's disease, Al18F-NOTA-FAPI-04 PET/CT imaging overperformed 18F-FDG imaging. Key Points • 18F-FDG and Al18F-NOTA-FAPI-04 PET/CT imaging have excellent sensitivity in diagnosing of ARDs. • 18F-FDG PET/CT imaging detected more lesions in lymph node, spleen, and bone marrow. • 18F-NOTA-FAPI-04 PET/CT imaging detected more lesions in the lung, muscle, and tendon/ligament. • 18F-NOTA-FAPI-04 PET/CT imaging overperformed18F-FDG in most subgroups of ARDs. [ABSTRACT FROM AUTHOR]

Purpose: To identify the prevalence and risk factors of coronavirus disease 2019 (COVID-19) reinfection in patients with rheumatoid arthritis (RA). Materials and Methods: This study retrospectively analyzed patients with RA with a documented COVID-19 infection between January 2021 and December 2022 at a tertiary hospital in Seoul, South Korea. Reinfection was defined as a subsequent positive test result for severe acute respiratory syndrome coronavirus 2 at least 3 months after the initial infection. Cox proportional hazards models with backward elimination were employed to assess the association between potential risk factors and risk of reinfection. Results: Of 351 included patients with RA {female, 81.5%; median age, 58.0 years [interquartile range (IQR), 48.0–66.0]}, 252 (71.8%) were treated with methotrexate and 12 (3.4%) received leflunomide during the initial infection. Over a median follow-up of 1.5 (IQR, 1.1–1.6) years, 43 (12.3%) patients experienced reinfection, equating to an incidence rate of 8.97 per 100 patient-years. The median time interval between infections was 0.8 (IQR, 0.6–1.2) years. Among the risk factors, leflunomide use showed a significant association with reinfection (hazard ratio, 2.968; 95% confidence interval, 1.057–8.335; p=0.039). However, no significant changes occurred in disease activity following reinfection [disease activity score using 28 joints: baseline median, 2.3 (IQR, 1.9– 2.8); post-reinfection median, 2.3 (IQR, 1.8–2.6), p for change=0.895]. Conclusion: In this retrospective cohort study of patients with RA with COVID-19 infection, approximately 12% of patients experienced reinfection without significant change in disease activity. Leflunomide use was associated with a higher risk of reinfection. [ABSTRACT FROM AUTHOR]

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Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial tissue transformation and fibroblast-like synoviocyte (FLS) proliferation. Galectin-3 is gaining attention as a diagnostic and prognostic biomarker for RA diagnosis. Elevated levels of Galectin-3 cause RAFLSs to stimulate and generate proinflammatory agents, contributing to cartilage degradation and osteoclast formation. This systematic review and meta-analysis aimed to evaluate published evidence and support future investigation of Galectin-3 as an early biomarker for RA. A systematic search was performed through four databases, including PubMed, the Web of Science, Scopus, and Embase, to find the studies examining Galectin-3 in individuals with RA compared to healthy controls. The risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Random-effects meta-analysis comparing serum/plasma Galectin-3 levels between individuals with RA and healthy control groups was performed to determine the standardized mean differences (SMD) along with 95% confidence intervals. Following the initial search, studies went through screening. 12 studies, involving 773 patients with RA and 411 healthy controls, were included. Meta-analysis of the included studies revealed that individuals with RA had significantly higher levels of circulatory Galectin-3 compared to healthy control groups (SMD 0.957, 95% CI 0.393 to 1.520). Univariable meta-regression showed no significant association between age, publication year, sample size, or the male percentage with effect size. According to the results, Galectin-3 might be useful as a biomarker for RA. To support these findings, further investigations of Galectin-3 as a possible early biomarker of RA is necessary. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, vascular damage, and immune dysregulation. Fractalkine or chemokine (C‐X3‐C motif) ligand 1 (CX3CL1), a chemokine and adhesion molecule, along with its receptor CX3CR1, have been implicated in the inflammatory processes of SSc. CX3CL1 functions as both a chemoattractant and an adhesion molecule, guiding immune cell trafficking. This systematic review examines the role of CX3CL1 and its receptor CX3CR1 in the pathogenesis of SSc, with a focus on pulmonary and vascular complications. Methods: A systematic literature search was conducted across databases including PubMed, Scopus, and Web of Science from inception to November 2020. The search focused on studies investigating the CX3CL1/CX3CR1 axis in the context of SSc. Results: The review identified elevated CX3CL1 expression in SSc patients, particularly in the skin and lungs, where CX3CR1 is expressed on infiltrating immune cells. Higher levels of CX3CL1 were correlated with the severity of interstitial lung disease in SSc patients, indicating a potential predictive marker for disease progression. CX3CR1‐positive monocytes and NK cells were recruited to inflamed tissues, contributing to fibrosis and tissue damage. Animal studies showed that inhibition of the CX3CL1/CX3CR1 axis reduced fibrosis and improved vascular function. Conclusion: The CX3CL1/CX3CR1 axis plays a key role in immune cell recruitment and fibrosis in SSc. Elevated CX3CL1 levels are associated with lung and vascular complications, making it a potential biomarker for disease progression and a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease. [ABSTRACT FROM AUTHOR]

Background: Among the Pentraxins, the long Pentraxin‐3 (PTX‐3) is associated with several processes, particularly in the earliest phases of the innate humoral response. Increased blood PTX‐3 concentrations have been observed in a wide range of conditions, from infectious to cardiovascular disorders. Since its increase is more rapid than C‐reactive protein (CRP), PTX‐3 can be useful to detect and monitor early inflammation. To dissect its pathophysiological role in rheumatic diseases (RD), we conducted a systematic review and meta‐analysis comparing blood PTX‐3 concentrations in RD patients and healthy individuals and investigating possible associations with clinical, demographic, and study characteristics. Methods: We performed a search of published evidence until April 2024 in PubMed, Web of Science and Scopus, which led to the selection of 60 relevant manuscripts from a total of 1072 records. Results: Our synthesis revealed a statistically significant difference in PTX‐3 concentrations between RD patients and controls (standard mean difference, SMD = 1.02, 95% CI 0.77–1.26, p <.001), that correlated with CRP concentrations. The effect size was associated with geographical region of study conduction, RD type, with a reduction of the observed heterogeneity in patients with low LDL‐cholesterol and triglycerides concentrations. Conclusions: Our study has shown a significant increase in blood PTX‐3 concentrations in RD patients, which was associated with specific patient characteristics. Nevertheless, additional studies are needed to better define the utility of measuring PTX‐3 in the early phase of RD. Our study was conducted in compliance with the PRISMA 2020 statement (study protocol available at PROSPERO CRD42024516600). [ABSTRACT FROM AUTHOR]

Objective SpA and PsA represent two frequent inflammatory rheumatic disorders characterized by an increased burden on quality of life due to the association of several comorbidities, especially cardiovascular disease (CVD). The estimated prevalence of CVD ranges from 12 to 19% and differs between the two diseases, however, the incidence of CVD is not completely known. We aimed to systematically review the literature and perform a meta-analysis of controlled observational studies to assess the incidence rate of CVD over time in SpA and PsA. Methods We performed a systematic literature review (SLR) of longitudinal studies with a study period of at least 5 years, including SpA/PsA patients and general population. The main outcome was the occurrence of CVD, including ischaemic heart disease, stroke and death from CV causes. We then performed a random-effects model for meta-analysis. Results The SLR included 34 articles, mainly focused on the association between SpA/PsA and CVD. Twenty-four articles were then selected for the meta-analysis. The overall incidence of CVD was increased in PsA [hazard ratio (HR) 1.28 (95% CI 1.15, 1.43)] and in SpA [HR 1.45 (95% CI 1.22, 1.72)] compared with the general population, with consistency across the different types of CVDs. Interestingly the incidence tended to decrease over time in PsA but not in SpA. Conclusion The SLR and meta-analysis confirmed the increased incidence of CVD in both SpA and PsA patients compared with the general population, although the increase seems to be less prominent in PsA than in SpA. Future studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objective We investigated the baseline DMARD use and post-acute sequelae of COVID-19 (PASC) risk among patients with systemic autoimmune rheumatic diseases (SARDs). Methods Patients with SARDs and confirmed COVID-19 infection at Mass General Brigham completed a survey ≥28 days after a positive PCR/antigen test to prospectively investigate their COVID-19 courses. We investigated DMARD use at COVID-19 onset and PASC risk. PASC was defined as any COVID-19 symptom that persisted for ≥28 days. We used logistic regression to estimate the odds ratios (OR) for PASC by DMARD class. We also used restricted mean survival time to determine the difference in symptom-free days by DMARD class in the 28-day period after infection. Results We analysed 510 patients with SARDs and COVID-19 from 11 March 2021 to 17 June 2023; 202 (40%) developed PASC. CD20 inhibitor (CD20i) users had significantly higher odds of developing PASC vs conventional synthetic DMARD (csDMARD) users [adjusted OR (aOR) 2.69 (95% CI 1.23, 5.88)]. IL-12/23, IL-17A or IL-23 inhibitor (IL-12/23i, IL-17Ai, IL-23i) users also had significantly higher odds of PASC [aOR 3.03 (95% CI 1.08, 8.49)]. CD20i users had significantly fewer symptom-free days vs csDMARD users [aOR −4.12 (95% CI −7.29, −0.94)]. Conclusion CD20i users had significantly higher odds of PASC and fewer symptom-free days over the 28 days following COVID-19 diagnosis compared with csDMARD users. Further research is needed to investigate whether PASC risk in CD20i users may be due to prolonged infection or other immune mechanisms. The association of IL-12/23i, IL-17Ai and IL-23i with PASC calls for additional study. [ABSTRACT FROM AUTHOR]

L'évolution des prescriptions en rhumatologie reflète un domaine médical en constante mutation, où les avancées scientifiques et les progrès technologiques redéfinissent les pratiques cliniques. Les médicaments anti-inflammatoires (AINS ou corticoïdes), autrefois largement prescrits pour soulager la douleur et l'inflammation, sont maintenant utilisés avec prudence en raison de leurs effets secondaires. L'arrivée des thérapies ciblées a offert des perspectives d'épargne médicamenteuse, mais a également soulevé des points de vigilance spécifique concernant leur tolérance. Les études pharmaco-épidémiologiques bien conçues peuvent fournir des données précieuses sur l'utilisation des médicaments dans des conditions réelles, éclairant ainsi les décisions de prescription, les politiques de remboursement et les choix thérapeutiques. The trend in rheumatology prescriptions reflects an ever-changing medical field, where scientific advances and technological progress are reshaping clinical practices. Anti-inflammatory drugs (NSAIDs or corticoids), once widely prescribed to relieve pain and inflammation, are now used with caution due to their side effects. The development of targeted therapies has opened up the prospect of drug savings, but has also raised specific points of concern regarding their safety. Well-designed pharmaco-epidemiological studies can provide valuable data on drug use in real-life conditions, informing prescribing decisions, reimbursement policies and treatment alternatives. [ABSTRACT FROM AUTHOR]

As the role of neurologists in managing patients with rheumatic diseases expands, collaboration between rheumatologists and neurologists becomes increasingly vital. This literature review provides an overview of the central nervous system (CNS) manifestations of major autoimmune rheumatic disorders, which may include parenchymal brain and meningeal disease (stroke, meningoencephalitis, meningitis), myelopathies, psychosis, chorea, seizure disorders, and various forms of cephalea. Novel findings linking specific autoimmune markers to CNS damage reveal a direct, previously underestimated link between systemic inflammation and neural injury. Besides, with the increasing use of biological therapies, it is crucial to recognize when neurological manifestations are related to adverse events of therapy, as this may significantly influence treatment decisions. Neurologists play a key role in this assessment, working closely with rheumatologists. Overall, addressing CNS involvement in rheumatic diseases is important for improving patient outcomes and advancing medical knowledge in this complex field. A thorough understanding of the neurologic aspects of rheumatic diseases is essential for optimal patient care, necessitating a multidisciplinary approach to management. [ABSTRACT FROM AUTHOR]

This study analyzed the status of medical information acquisition through social media (SM) and its impact on healthcare utilization among patients with rheumatic diseases (RDs) who visited the rheumatology department of a tertiary hospital. We consecutively evaluated 102 patients with RDs in this single-center cross-sectional survey. Using a face-to-face survey, patients were asked about the sources they used to acquire medical information, factors influencing their visits to tertiary hospitals, and the potential impact of acquiring medical information on RDs through SM. SM refers to YouTube, Facebook, Instagram, Kakao Channel, Naver Band, and X. The mean age was 42.3 years and 39% were female. The most common disease was ankylosing spondylitis (45.1%), followed by rheumatoid arthritis (20.6%). The most frequent method for acquiring medical information regarding RDs, except for rheumatologists, was internet portal sites (47.8%), followed by SM (40.2%). The most important factor influencing the decision to visit a tertiary hospital was medical doctors (51%); only 1% of the patients responded that SM was the most crucial factor in determining their visit. Most patients (77.5%) responded that acquiring medical information through SM would help them manage their diseases. Our data revealed that a substantial proportion of patients with RDs obtained medical information through SM. However, the impact of SM on visiting a tertiary hospital was minimal, suggesting that SM has become a mainstream source of medical information, yet the reliability of SM remains relatively low. Rheumatology societies should establish SM platforms capable of providing high-quality medical information. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria. Methods: We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk. Results: Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence. Conclusions: Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain. Protocol registration: PROSPERO identifier is CRD42022370846. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims Methods Results Conclusions Hydroxychloroquine (HCQ) is recommended for the long‐term treatment of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Given the complex process of HCQ metabolism and individual physiological differences, the metabolic profile of HCQ after long‐term administration is unknown. This study aimed to establish a population pharmacokinetic model for long‐term HCQ treatment in patients with rheumatic diseases and to identify the factors influencing HCQ metabolism.This study included 274 HCQ whole‐blood trough concentration data points from 203 patients with rheumatic diseases, all of whom had taken HCQ for more than 6 months, with a median duration of 36 months. A nonlinear mixed‐effects model was derived to establish a population pharmacokinetic model, and potential influencing factors were investigated. Different covariates were used to simulate the optimal dose.The final model describing the HCQ blood concentration–time profile was a compartmental model with first‐order absorption. The estimated values for apparent clearance and volume of distribution were 16.4 L/h and 1220 L, respectively. The clearance of HCQ gradually increased with increasing dosing regimens and weight gain. Monte Carlo simulations were used to determine the optimal dosage regimens for patients with different body weights and drug durations. The simulation results revealed that an initial dose of 5 mg/kg was appropriate.We developed a population pharmacokinetic model for long‐term HCQ therapy in patients with rheumatic diseases. HCQ clearance from whole blood increased progressively with increasing duration of drug administration. [ABSTRACT FROM AUTHOR]

Summary Systemic sclerosis (SSc) is a severe autoimmune disease characterized by vasculopathy, fibrosis, and dysregulated immunity, with hallmark autoantibodies targeting nuclear antigens such as centromere protein (ACA) and topoisomerase I (ATA). These autoantibodies are highly prevalent and disease‐specific, rarely coexisting, thus serving as crucial biomarkers for SSc diagnosis. Despite their diagnostic value, their roles in SSc pathogenesis remain unclear. This review summarizes current literature on ACA and ATA in SSc, comparing them to autoantibodies in other rheumatic diseases to elucidate their potential pathogenic roles. Similarities are drawn with anti‐citrullinated protein antibodies (ACPA) in rheumatoid arthritis, particularly regarding disease specificity and minimal pathogenic impact of antigen binding. In addition, differences between ANA and ACPA in therapeutic responses and Fab glycosylation patterns are reviewed. While ACA and ATA are valuable for disease stratification and monitoring activity, understanding their origins and the associated B cell responses is critical for advancing therapeutic strategies for SSc. [ABSTRACT FROM AUTHOR]

Objective: Transitional care is essential to maintain the continuity of care in younger patients with rheumatic diseases. In this study, we aimed to assess the transition readiness of rheumatology patients who had already transferred from pediatric to adult care using a questionnaire. Materials and Methods: We included young adult rheumatology patients who had already transferred to adult rheumatology care. The Transition Readiness Assessment Questionnaire (TRAQ) was used in the adult rheumatology clinic to assess the patients’ readiness; a retrospective chart review was conducted to include diagnosis, age at diagnosis, age at transfer, and current age. Results: Three hundred and ten patients (184 female and 126 male) participated in this study. The mean age at diagnosis, the mean age at transfer, and the mean age at the time of the study were 10.7 ± 4.29, 21.1 ± 1.69, and 24.0 ± 2.26 years, respectively. Most of the patients had familial Mediterranean fever, followed by arthritis, connective tissue disorders, and other diseases. Tracking health issues was the lowest-scored domain. Females scored significantly higher than males in the tracking health issue domain (P = .006) and managing health issue domain (P = .028) but not in the overall TRAQ score (P = .053). Patients in different diagnosis and transfer age groups scored similarly across the domains. Conclusion: In this study, females performed better than males in 2 domains of the TRAQ questionnaire. Diagnoses or transfer age groups were not associated with TRAQ outcomes. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the awareness, experiences, and beliefs of individuals with osteoarthritis (OA) regarding their healthcare management, along with assessing their overall satisfaction levels. Methods: A cross‐sectional online survey was conducted in Italy, Sweden, and Russia, rigorously developed based on OA international guidelines in collaboration with healthcare professionals and individuals with OA. Participants over 40 years of age with self‐reported hip and/or knee OA were eligible. The analytical framework included descriptive analysis (assessment of awareness levels for 'recommended', 'optional', and 'not recommended' treatments), analysis of suggested treatments and taken treatments, exploration of beliefs, barriers and satisfaction analysis (0–100 scale). Results: A total of 401 participants (mean age: 59.7, 78.3% female, 28% Italian, 49% Swedish, 23% Russian) contributed to the study. In Sweden, 57%–72% accurately identified recommended treatments, while in Russia, the range was 34%–91%, and in Italy, it was 35%–73%. The predominant suggested and taken treatments were oral anti‐inflammatory drugs in Italy (87/81%) and Russia (97/97%) and specific exercise in Sweden (84/79%). Notably, only Sweden reached a consensus on the effectiveness of exercise for everyone, while Russia and Italy insisted on radiographic findings as a prerequisite for exercise. Mean satisfaction levels were 59.7 (Italy), 47.4 (Sweden), and 35.2 (Russia). Conclusions: This study uncovered variations in awareness, treatment preferences, and beliefs among the three countries, underscoring the necessity for tailored education on OA management that accounts for regional differences across Europe. [ABSTRACT FROM AUTHOR]

Objective This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other ANA-associated rheumatic diseases (AARDs) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns. Methods : This retrospective observational study included patients with AARDs such as SLE, SSc, SS, MCTD and PM/DM who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA) and titres. Logistic regression analysis of Cytoplasmic and ncANA patterns was performed to differentiate ASS from other AARDs. Result : The 981 diagnosed cases of AARDs consisted of SS (n  = 451), SSc (n  = 264), SLE (n  = 201), PM/DM (n  = 104), MCTD (n  = 52) and ASS, including PM/DM (n  = 64). Of these, 155 patients had ≥2 overlapping diseases; however, there was no overlap between AARDs and ASS. ASS is more likely to occur when the cytoplasmic titre is positive and the ncANA <320. Receiver operating characteristic analysis of the Cytoplasmic and ncANA range revealed an area under the receiver operating characteristic curve of 0.885 (95% CI: 0.844–0.927). Conclusion : It is important to detect cytoplasmic patterns as an ANA screening test for ASS diagnosis, even if the titre is low. Additionally, combining the cytoplasmic and ncANA patterns yields more accurate ASS screening results. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the number one cause of death worldwide. Women are at increased risk of death from CVD, but the mechanisms for how and why this occurs remain elusive. One subset of women who are exceptionally vulnerable to CVD are those with rheumatic diseases (RDs). Indeed, women account for 80% of all RDs, disorders that encompass a broad range of autoimmune and autoinflammatory diseases that lead to chronic inflammation and pathology. The clear association of increased CVD risk in women with RD is thought to be mediated by a number of factors, including RD pathology itself, pharmacological induction of CVD, and/or as yet unidentified mechanisms. As such, elucidation of the causes and treatments of these pathologies has given rise to a new subspecialty of cardiology: cardio-rheumatology. Here, we review and discuss the CVD risks in patients with RDs, the associated sex disparities in RD and CVD care, as well as the current therapeutic and interventional options available to specifically help women with RDs. We hope this discussion will provide guidance and support to patients, as well as to cardio-rheumatologists, as these groups are the most uniquely positioned to radically improve CVD care in these individuals. Moreover, we are hopeful this discussion may lead to better, more efficacious approaches to treating these disorders in women in the near future. [ABSTRACT FROM AUTHOR]

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls. [ABSTRACT FROM AUTHOR]

Inflammatory rheumatic diseases (IRDs), encompassing a broad spectrum of chronic disorders, typically necessitate prolonged therapeutic intervention. Nevertheless, these diseases can sometimes manifest as severe emergencies requiring prompt and extensive medical intervention. Urgent intervention is essential for effectively recognizing and managing these situations, as they have the potential to be life-threatening and can result in severe morbidity and mortality. Emergencies in IRDs can occur with different frequencies and manifestations, including nervous system issues, severe infections, thrombosis-emboli, renal crises, gastrointestinal issues, and cardiovascular events. The fact that these events can occur across different IRDs underscores the necessity for heightened awareness and readiness among healthcare professionals. The pathophysiologic mechanisms that cause rheumatic emergencies are complex and involve multiple factors. These emergencies frequently arise due to the interplay between the inflammatory characteristics of rheumatic diseases and different systemic triggers. Early detection and treatment can have a substantial impact on an individual's prognosis in cases of severe and life-threatening disorders that require prompt recognition. Rapid decision-making and urgent care are required to effectively address rheumatic emergencies, as well as the implementation of a diagnostic flowchart. This article provides an overview of the emergencies linked to IRDs, classifying and assessing them individually. This article aims to enhance healthcare professionals' knowledge and awareness of critical situations by examining current recommendations and pathophysiological information. Implementing standardized diagnostic and treatment methods, providing patient education, and conducting continuing research into the underlying mechanisms are essential for enhancing the management of these critical situations and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Inflammatory rheumatic diseases (IRDs) refer to a range of persistent disorders that have a major influence on several physiological systems. Although there is much evidence connecting IRDs to sexual dysfunction and fertility problems, research specifically focusing on male infertility in relation to these diseases is sparse. This review addresses the complicated connection between IRDs and male infertility, emphasising the physiological, psychological, and pharmacological aspects that influence reproductive health outcomes in men with rheumatic conditions. We explore the effects of IRDs and their treatments on many facets of male reproductive well-being, encompassing sexual functionality, semen characteristics, and hormonal balance. Additionally, we present a comprehensive analysis of the present knowledge on the impact of several categories of anti-rheumatic drugs on male reproductive function. Although there is an increasing awareness of the need of addressing reproductive concerns in individuals IRDs, there is a noticeable lack of research especially dedicated to male infertility. Moving forward, more comprehensive research is needed to determine the prevalence, risk factors, and mechanisms driving reproductive difficulties in males with IRDs. We can better assist the reproductive health requirements of male IRD patients by expanding our understanding of male infertility in the setting of rheumatic disorders and implementing holistic methods to care. [ABSTRACT FROM AUTHOR]

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9–18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02–8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15–0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients. [ABSTRACT FROM AUTHOR]

Objective. Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. Methods. Persons aged = 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as = 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. Results. Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004). Conclusion. In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections. [ABSTRACT FROM AUTHOR]

Objective. We sought to evaluate the quality and timeliness of patient-reported outcome (PRO) measure reporting, which have not been previously studied. Methods. Clinical trials that informed new US Food and Drug Administration (FDA) approvals for the first rheumatological indication between 1995 and 2021 were identified. Data were recorded to determine whether collected PROs were published, met minimum clinically important difference (MCID) or statistical significance (P < 0.05) thresholds, and were consistent with Consolidated Standards of Reporting Trials (CONSORT)-PRO standards. Hazard ratios and Kaplan-Meier estimate were used to assess the time from FDA approval to PRO publication. Results. Thirty-one FDA approvals corresponded with 110 pivotal trials and 262 reported PROs. Of the 90 included studies, 1 (1.1%) met all 5 recommended items, 10 (11.1%) met 4 items, 17 (18.9%) met 3 items, 21 (23.3%) met 2 items, 26 (28.9%) met 1 item, and 15 (16.7%) met none of the reporting standards. Most PROs met MCID thresholds (149/262; 56.9%) and were statistically significant (223/262; 85.1%). Of our subset analysis, one-third of PROs were not published upfront (70/212; 33%) and 1 of 9 (22/212; 10.4%) remained unpublished = 4 years after initial trial reporting. Publication rates were highest for the Health Assessment Questionnaire-Disability Index (97.4%) and lowest for the 36-item Short Form Health Survey (81.8%). Less than half of these published PROs met MCID and statistical significance thresholds (94/212; 44.3%). Conclusion. One in 9 PROs remained unpublished for = 4 years after initial trial reporting, and compliance with CONSORT-PRO reporting guidelines was poor. Efforts should be made to ensure PROs are adequately reported and expeditiously published. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Nursology is the property of Ataturk University Coordinatorship of Scientific Journals and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aimed to evaluate the impact of Complementary and Alternative Medicine (CAM) use on functional status and pain relief in patients with Chronic Rheumatic Diseases (CRDs) using the Visual Analogue Pain Scale (VAS) and Health Assessment Questionnaire (HAQ). This cross-sectional multicentre study involved patients from rheumatology outpatient clinics who met the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) criteria for rheumatic disease diagnosis. The exclusion criteria included acute flares or comorbid conditions that could interfere with the outcomes. Data collection included demographic and clinical data, pharmacotherapy, CAM usage, and its impact on the VAS and HAQ scales. The study included 126 patients. A significant proportion (57%) reported CAM use, with a preference for one (67%) or multiple (33%) modalities. CAM users exhibited significantly lower VAS scores, indicating reduced pain perception, and lower HAQ scores, suggesting better functional status than non-users. Correlation analyses highlighted strong positive associations between patient age, disease duration, and CAM use preference, as well as between educational level and specific CAM therapies. CAM use among patients with CRDs is associated with significant improvements in pain perception and functional capacity, as evidenced by lower VAS and HAQ scores. These findings suggest the potential of CAM to complement conventional rheumatology treatments, highlighting its value in patient-centered care and indicating its role in improving patient outcomes. However, the study's cross-sectional design and reliance on self-reported data necessitate further research for causal inferences and robust establishment of CAM efficacy. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the presence of various serum autoantibodies and multi-system effects, predominantly affecting young female patients. The pathogenesis of SLE involves a combination of genetic factors, environmental triggers, and pathogen invasions that disrupt immune cell activation, leading to the release of autoantibodies and chronic inflammation. Mitochondria, as the primary cellular powerhouses, play a crucial role in SLE development through their control of energy generation, reactive oxygen species (ROS) production, and cellular apoptotic pathways. Dysregulation of mitochondrial structure and function can contribute to the immune dysregulation, oxidative stress, and inflammation seen in SLE. Recent research has highlighted the impact of mitochondrial dysfunction on various immune cells involved in SLE pathogenesis, such as T-lymphocytes, B-lymphocytes, neutrophils, and plasmacytoid dendritic cells. Mitochondrial dysfunction in these immune cells leads to increased ROS production, disrupted mitophagy, and alterations in energy metabolism, contributing to immune dysregulation and inflammation. Moreover, genetic variations in mitochondrial DNA (mtDNA) and abnormalities in mitochondrial dynamics have been linked to the pathogenesis of SLE, exacerbating oxidative stress and immune abnormalities. Targeting mitochondrial function has emerged as a promising therapeutic approach for SLE. Drugs such as sirolimus, N-acetylcysteine, coenzyme Q10, and metformin have shown potential in restoring mitochondrial homeostasis, reducing oxidative stress, and modulating immune responses in SLE. These agents have demonstrated efficacy in preclinical models and clinical studies by improving disease activity, reducing autoantibody titers, and ameliorating organ damage in SLE patients. In conclusion, this review underscores the critical role of mitochondria in the pathogenesis of SLE and the potential of targeting mitochondrial dysfunction as a novel therapeutic strategy for improving outcomes in SLE patients. Further investigation into the mechanisms underlying mitochondrial involvement in SLE and the development of targeted mitochondrial therapies hold promise for advancing SLE treatment and enhancing patient care. [ABSTRACT FROM AUTHOR]

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Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The spectrum of pediatric rheumatological disorders is diverse and they are important differential diagnoses in a variety of clinical scenarios. Basic investigations not only provide supporting evidence for the diagnosis of a rheumatological illness but also help in exclusion of other diseases as well as for monitoring the activity of disease. Among these, complete blood count, biochemical assays including tests for inflammatory response, urine analysis, and various autoantibodies are often used. In addition, depending on the clinical features, imaging and tissue biopsies are used to confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Amaç: Masajın romatolojik hastalıklarda semptom kontrolüne yönelik etkisini değerlendirmektir. Yöntemler: Araştırmaya CINAHL, Cochrane Library, ProQuest, PubMed, Science Direct, Web of Science ve ULAKBİM veri tabanlarında İngilizce ve Türkçe anahtar kelimeler kullanılarak, 2000- 2023 tarihleri arasında ulaşılan çalışmalar dahil edildi. Araştırma PRISMA-P kontrol listesi ve Cochrane Risk of Bias temel alınarak hazırlandı. Dahil edilme kriterleri; 18 yaş ve üzeri, romatolojik hastalığa bağlı semptom bildiren katılımcıları dahil eden, randomize kontrollü çalışma tasarımında olan, İngilizce ve Türkçe dilinde yayınlanmış çalışmalardır. Bulgular: Araştırmada 3.704 çalışma incelendi ve dahil edilme kriterlerine uygun 16 randomize kontrollü çalışma saptandı. Yapılan masajın ağrı şiddeti, analjezik kullanımı, anksiyete, depresif durum, sabah tutukluğunu azalttığı, uyku kalitesi ve hareket açıklığını arttırdığı saptandı. Derlemeye dahil edilen bir araştırmada masajın uyku sorunlarını azaltmadığı, iki farklı çalışmada ise uzun vadede masajın semptom yönetiminde fayda sağlamadığı belirlendi.Sonuç: Romatolojik hastalıkların semptom kontrolünde kullanılan masaja yönelik optimal bir süre ve teknik bulunmamakla birlikte, masaj sıklıkla osteoartrit ve fibromiyaljide kullanılmaktadır. Masaj uygulaması semptom kontrolü sağlayarak hastaların fizyolojik ve psikolojik iyilik halini arttırmaktadır. Bu nedenle semptom kontrolünde hemşirelik bakım uygulamalarında masaja yer verilmesi önerilmektedir.

Abstract Although the terms “rare diseases” (RD) and “orphan diseases” (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades.

OBJECTIVE: In a large multi-racial/ethnic cohort of women, we examined racial/ethnic disparities in preterm birth (PTB) risk stratified by autoimmune rheumatic disease (ARD) type, which included systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Birth records linked to hospital discharge data of singleton births in California from 2007 to 2012 were leveraged for a retrospective cohort study including women with SLE or RA. The relative risk of PTB (< 37 versus ≥ 37 weeks gestation) was compared among different racial/ethnic groups (Asian, Hispanic, Non-Hispanic (NH) Black, and NH White) and stratified by ARD type. Results were adjusted for relevant covariates using Poisson regression. RESULTS: We identified 2874 women with SLE and 2309 women with RA. NH Black, Hispanic, and Asian women with SLE were 1.3 to 1.5 times more likely to have PTB compared to NH White women. NH Black women with RA were 2.0 to 2.4 times more likely to have PTB compared to Asian, Hispanic, or NH White women. The NH Black-NH White and NH Black-Hispanic disparity in PTB risk was significantly higher in women with RA compared to SLE or the general population. CONCLUSION: Our findings highlight the racial/ethnic disparities for risk of PTB among women with SLE or RA and highlight that several of the disparities are higher for women with RA compared to those with SLE or the general population. These data may provide important public health information for addressing racial/ethnic disparities in the risk of preterm birth, particularly among women with RA. Key Points • There is an unmet need for studies that evaluate racial/ethnic disparities in birth outcomes specifically in women with RA or SLE. • This is one of the first studies describing racial/ethnic disparities in PTB risk for women with RA, and to draw conclusions regarding Asian women in the USA with rheumatic diseases and PTB. • These data provide important public health information for addressing racial/ethnic disparities in the risk of preterm birth among women with autoimmune rheumatic diseases.

Abstract Background Patients with rheumatoid arthritis (RA) have an increased risk of developing serious infections (SIs) vs. individuals without RA; efforts to predict SIs in this patient group are ongoing. We assessed the ability of different machine learning modeling approaches to predict SIs using baseline data from the tofacitinib RA clinical trials program. Methods This analysis included data from 19 clinical trials (phase 2, n = 10; phase 3, n = 6; phase 3b/4, n = 3). Patients with RA receiving tofacitinib 5 or 10 mg twice daily (BID) were included in the analysis; patients receiving tofacitinib 11 mg once daily were considered as tofacitinib 5 mg BID. All available patient-level baseline variables were extracted. Statistical and machine learning methods (logistic regression, support vector machines with linear kernel, random forest, extreme gradient boosting trees, and boosted trees) were implemented to assess the association of baseline variables with SI (logistic regression only), and to predict SI using selected baseline variables using 5-fold cross-validation. Missing values were handled individually per prediction model. Results A total of 8404 patients with RA treated with tofacitinib were eligible for inclusion (15,310 patient-years of total follow-up) of which 473 patients reported SIs. Amongst other baseline factors, age, previous infection, and corticosteroid use were significantly associated with SI. When applying prediction modeling for SI across data from all studies, the area under the receiver operating characteristic (AUROC) curve ranged from 0.656 to 0.739. AUROC values ranged from 0.599 to 0.730 in data from phase 3 and 3b/4 studies, and from 0.563 to 0.643 in data from ORAL Surveillance only. Conclusions Baseline factors associated with SIs in the tofacitinib RA clinical trial program were similar to established SI risk factors associated with advanced treatments for RA. Furthermore, while model performance in predicting SI was similar to other published models, this did not meet the threshold for accurate prediction (AUROC > 0.85). Thus, predicting the occurrence of SIs at baseline remains challenging and may be complicated by the changing disease course of RA over time. Inclusion of other patient-associated and healthcare delivery-related factors and harmonization of the duration of studies included in the models may be required to improve prediction. Trial registration ClinicalTrials.gov: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT02831855; NCT02092467.

Lantian Xie,1,&ast; Yan Chen,1,&ast; Lifan Zhang,1– 3 Lidan Zhao,4 Tao Li,5 Xiaochun Shi,1,2 Xiaoqing Liu1– 3 1Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China; 4Department of Rheumatology and Clinical Immunology, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Email shixch7722@163.com; liuxq@pumch.cnObjective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients.Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI.Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment.Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients′ compliance with LTBI screening and TPT.Keywords: rheumatic diseases, latent tuberculosis infection, tuberculosis preventive treatment, knowledge, attitudes

Background:Ankylosing spondylitis (AS) is the prototype of spondyloarthropathies and one of the common rheumatic diseases (RDs). Various degrees of cognitive impairment have been reported with most autoimmune RDs. Objectives:To estimate the prevalence of cognitive impairment in AS patients and its relationship to disease activity and functional limitations and the effect of various sociodemographic and clinical characteristics on cognitive function in AS patients. Materials and Methods:This case–control study comprised 100 patients with AS and 100 healthy subjects who were matched for age, gender, and educational level. Private interviews were conducted with participants to complete the questionnaire and evaluate cognitive function using the 6-item Cognitive Impairment Test (6-CIT) and the Montreal Cognitive Assessment (MoCA). Results:According to MoCA, 48% of AS patients and 16% of healthy controls were cognitively impaired (P = 0.001). By 6-CIT, 6% of the AS group had cognitive impairment, whereas all 100 controls had normal cognitive function (P = 0.029). There was a significant direct correlation between 6-CIT score with marital status (P = 0.020), BMI (P = 0.021), and Bath Ankylosing Spondylitis Disease Activity Index (P = 0.008) and inverse correlation with employment (P = 0.015), education (P = 0.008), and family income (P = 0.12). There was significant direct correlation between MoCA with employment (P = 0.009), education (P = 0.005), family income (P = 0.022), and use of non-steroidal anti-inflammatory drugs (NSAIDs) (P = 0.008) and inverse correlation with marital status (P = 0.002). Conclusions:Patients with AS have a higher degree of cognitive impairment than healthy individuals. It is associated with disease activity, lower socioeconomic status, being widowed, and obesity. Use of NSAIDs is associated with lower cognitive impairment.

Abstract Background Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures. Methods The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture. Results The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516). Conclusions RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.

Intravenous immunoglobulins (IVIG) are the most commonly used immunobiological agents produced from donor blood. They were first used in the mid-twentieth century for the treatment of primary immunodeficiencies. Later, they were successfully used to treat a variety of autoimmune, inflammatory and other diseases. There are currently a growing number of basic and clinical studies looking at the mechanism of action and efficacy of different doses of IVIG. At the same time, much remains unclear, contradictory, and some data are mutually exclusive.

Abstract Introduction Glucocorticoids (GCs) play a crucial role in the treatment of many rheumatic diseases regarding their anti-inflammatory and immunosuppressive effects. Inappropriate use of GCs can exacerbate GC-related problems besides complex treatment regimens and miscellaneous well-established adverse events. Although several guidelines exist for managing these problems, there is lack of real-life studies evaluating the problems at the patient level. This study aims to identify GC-related problems among patients with rheumatic diseases and address how they have been solved. Methods This prospective follow-up study was conducted between January 2021 and June 2022 at a university rheumatology outpatient clinic and included patients using GCs. A clinical pharmacist assessed patients for possible GC-related problems at baseline, 3 months, and 6 months. Identified problems, their causes, interventions to address these problems, and their outcomes were categorized using the Pharmaceutical Care Network Europe (PCNE v9.1) classification system. The resolution of the problems was evaluated at the patient’s next follow-up visit. Results A total of 156 patients were included, and 236 GC-related problems were identified in 66% of the patients. Adverse drug events (possible) accounted for the highest proportion of GC-related problems (94.1%), and the most common causes were lack of laboratory monitoring of GC-related adverse events (41.5%) and lack of drug treatment despite existing indications (39.8%). The median cumulative prednisolone dose was higher in patients with GC-related problems (3115 vs. 5455 mg, p = 0.007). The clinical pharmacist suggested 381 interventions: 47.7% (n = 182) at the ‘prescriber level’, 31.8% (n = 121) at the ‘patient level’, and 20.5% (n = 78) at the ‘drug level’. Of those interventions, 98% were accepted, and 80.1% of the problems were solved. Conclusions This study showed that the prevalence of GC-related problems is high in patients with rheumatic diseases. Integrating clinical pharmacists into the multidisciplinary rheumatology team provides an advantage in effectively identifying and managing GC-related problems at an early stage.

The utilization of artificial intelligence (AI) in rheumatic diseases has enhanced the diagnostic accuracy of rheumatic diseases, enabled the prediction of patient outcomes, expanded treatment options, and facilitated the provision of individualized medical solutions. The research in this field has been progressively growing in recent years. Consequently, there is a need for bibliometric analysis to elucidate the current state of advancement and predominant research foci in AI applications within rheumatic diseases. Additionally, it is crucial to identify key contributors and their interrelations in this field. This study aimed to conduct a bibliometric analysis to investigate the current research hotspots and collaborative networks in the application of AI in rheumatic disease in recent years. A comprehensive search was conducted in Web of Science for articles on artificial intelligence in rheumatic diseases, published in SSCI and SCI-EXPANDED until January 1, 2024. Utilizing software tools like VOSviewers and CiteSpace, we analyzed various parameters including publication year, journal, country, institution, and authorship. This analysis extended to examining cited authors, generating reference and citation network graphs, and creating co-citation network and keyword maps. Additionally, research hotspots and trends in this domain were evaluated. As of January 1, 2024, a total of 3508 articles have been published on the application of artificial intelligence (AI) in rheumatic disease, exhibiting a steady rise in both the annual publication frequency and rate. "Scientific Reports" emerged as the leading journal in terms of relevant publications. The United States stood out as the predominant country in terms of the volume of published papers, with the University of California, San Francisco (UCSF) being the most prolific and frequently cited institution. Among authors, Young Ho Lee and Valentina Pedoia were noted for their significant contributions, with Pedoia achieving the highest average citation count per publication. Machine learning emerged as a prominent and central keyword. The trend indicates a growing interest in AI research within rheumatologic diseases, with its role expected to become increasingly pivotal in the field. This study presents a comprehensive summary of research trends and developments in the application of artificial intelligence (AI) in rheumatic diseases. It offers insights into potential collaborations and prospects for future research, clarifying the research frontiers and emerging directions in recent years. The findings of this study serve as a valuable reference for scholars studying rheumatology and immunology. [ABSTRACT FROM AUTHOR]

Fasting can affect the body's inflammatory response, and this has been linked to potential health benefits, including improvements for people with rheumatic diseases. In this work, we evaluated, in vitro, how changes in nutrient availability alter the inflammatory response of macrophages. Macrophage-differentiated THP1 cells were cultured, deprived of FCS or subjected to cycles of FCS deprivation and restoration to mimic intermittent fasting. Changes in the macrophage phenotype, the cells' response to inflammatory stimuli and the level of mitochondrial alteration were assessed. The results indicate that while periods of serum starvation are associated with a decrease in IL1β and TNFα expression, consistent with an anti-inflammatory response, intermittent serum starvation cycles promote a pro-inflammatory phenotype. Rapid changes in reducing capacity and mitochondrial response were also observed. Of note, while some changes, such as the production of oxygen free radicals, were reversed with refeeding, others, such as a decrease in reducing capacity, were maintained and even increased. This study shows that different fasting protocols can have diverging effects and highlights that time-limited nutrient changes can significantly affect macrophage functions in cell cultures. These findings help elucidate some of the mechanisms by which specific fasting dietary interventions could help control inflammatory diseases. [ABSTRACT FROM AUTHOR]

Introduction: Glucocorticoids (GCs) play a crucial role in the treatment of many rheumatic diseases regarding their anti-inflammatory and immunosuppressive effects. Inappropriate use of GCs can exacerbate GC-related problems besides complex treatment regimens and miscellaneous well-established adverse events. Although several guidelines exist for managing these problems, there is lack of real-life studies evaluating the problems at the patient level. This study aims to identify GC-related problems among patients with rheumatic diseases and address how they have been solved. Methods: This prospective follow-up study was conducted between January 2021 and June 2022 at a university rheumatology outpatient clinic and included patients using GCs. A clinical pharmacist assessed patients for possible GC-related problems at baseline, 3 months, and 6 months. Identified problems, their causes, interventions to address these problems, and their outcomes were categorized using the Pharmaceutical Care Network Europe (PCNE v9.1) classification system. The resolution of the problems was evaluated at the patient's next follow-up visit. Results: A total of 156 patients were included, and 236 GC-related problems were identified in 66% of the patients. Adverse drug events (possible) accounted for the highest proportion of GC-related problems (94.1%), and the most common causes were lack of laboratory monitoring of GC-related adverse events (41.5%) and lack of drug treatment despite existing indications (39.8%). The median cumulative prednisolone dose was higher in patients with GC-related problems (3115 vs. 5455 mg, p = 0.007). The clinical pharmacist suggested 381 interventions: 47.7% (n = 182) at the 'prescriber level', 31.8% (n = 121) at the 'patient level', and 20.5% (n = 78) at the 'drug level'. Of those interventions, 98% were accepted, and 80.1% of the problems were solved. Conclusions: This study showed that the prevalence of GC-related problems is high in patients with rheumatic diseases. Integrating clinical pharmacists into the multidisciplinary rheumatology team provides an advantage in effectively identifying and managing GC-related problems at an early stage. [ABSTRACT FROM AUTHOR]

Background: This study aims to determine the rate of inflammatory rheumatic diseases (IRDs) in a cohort of initial referrals and the efficacy of prioritising appointments to the early arthritis clinic (EAC) based on symptom duration. Methods: In the present study, we used algorithm-based telephone triage to assign routine care appointments according to the time between symptom onset and request for an appointment (cut-off criterion: 6 months). This retrospective, monocentric analysis evaluated the effectiveness of our triage in identifying patients with IRDs as a function of the assigned appointment category (elective, EAC, or emergency appointment). Results: A total of 1407 patients were included in the study (34.7% male; 65.3% female). Of the 1407 patients evaluated, 361 (25.7%) presented with IRD. There were significant differences in the frequency of inflammatory diagnoses between appointment categories (p < 0.001): elective 13.8%, EAC 32.9%, and emergency 45.9%. The sample without the emergency category included a total of 1222 patients. The classification into "inflammatory" or "non-inflammatory" in this subsample was as follows: Sensitivity was 37.7%, and specificity was 92.6%. The positive predictive value (PPV) was 59.8%, and the negative predictive value (NPV) was 83.6%. Overall, 80.2% of patients were correctly assigned using the appointment category and C-reactive protein (CRP). Conclusions: The algorithm-based triage system presented here, which focuses on the time between symptom onset and request for an appointment, allows for the prioritisation of appointments in favour of patients with IRDs and thus earlier initiation of therapy. [ABSTRACT FROM AUTHOR]

This paper aims to compare the cellular immune response to the SARS-CoV-2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD) and healthy controls. A prospective longitudinal study was conducted between April 2021 and December 2022 at the Tel Aviv Medical Center. Children <18 years, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 vaccine, were included. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 receptor-binding domain antibodies. Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T cells following stimulation with SARS-CoV-2 Spike peptide mix. The study included 20 pAIIRD patients and 11 controls. The mean age of participants was 12.6 ± 2.94 years, with 58.1% females. The cellular response to the BNT162b2 vaccine was statistically similar in both groups. However, the humoral response was statistically lower in pAIIRD compared with the healthy control group. There was no statistically significant correlation between the humoral response and cellular response. During the study period, 43.75% of AIIRD children and 72.7% of controls had a breakthrough COVID-19 infection (P = 0.48). Bivariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect. Compared with healthy controls, pAIIRD demonstrated similar cellular responses. Patients showed reduced humoral response compared with healthy adolescents, but similar breakthrough infection rates. These findings may support the importance of the cellular response in protecting against COVID-19 infections. Pediatric rheumatic patients may be vulnerable to COVID-19 infections due to their disease and immunosuppressive medications. Compared with healthy controls, pediatric patients with autoimmune inflammatory rheumatic diseases demonstrated similar cellular responses and COVID-19 breakthrough infection rates, but reduced humoral responses. These findings may support the importance of the cellular response in protecting against COVID-19 infections. Graphical Abstract [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) involvement in autoimmune rheumatic diseases represents a significant challenge for clinicians across all specialties. While most reviews on the subject focus on neurological manifestations within a specific rheumatic disease, few descriptions shift from neurological clinical syndromes to achieve rheumatological diagnoses. This narrative review aims to synthesize current knowledge on the diagnosis and management of CNS manifestations occurring in the most prevalent rheumatic conditions in adults. We searched the MEDLINE database using the terms "central nervous system", "rheumatic diseases", "systemic lupus erythematosus", "rheumatoid arthritis", "Sjögren syndrome", and "vasculitis". The search strategy included review articles from 2019 to 2024, published in English, Spanish, or Portuguese. We explored the pathophysiological mechanisms linking autoimmunity to CNS pathology, emphasizing the role of syndromic reasoning, autoantibody profiles, and imaging modalities as tools for diagnosis and determination of inflammatory activity. The review also discusses differential diagnoses through a stepwise approach to neurological syndromes, summarized in diagnostic flowcharts, and presents updated treatment options. Although our approach is primarily semiology-based, the complexity of the subject invites future endeavors involving new technologies, such as functional MRI, MR spectroscopy, and nuclear medicine. [ABSTRACT FROM AUTHOR]