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Objectives: To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant.Methods: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant.Results: Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men.Conclusion: Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD. [ABSTRACT FROM AUTHOR]

Background: We aimed to update the 2018 systematic literature review on the efficacy and safety of treatments for hand osteoarthritis (OA), which was based on 126 studies., Methods: We performed a systematic literature search on randomised controlled trials from June 2017 up to 31 December 2023. Risk of bias was assessed using the RoB2 tool. Meta-analyses of previous and new studies regarding the efficacy for pain, function, grip strength and OMERACT/OARSI responders were performed. Certainty of evidence was judged using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool., Results: Sixty-five new studies were included. For non-pharmacological interventions, there was low-certainty evidence for a small long-term effect of hand exercises and a moderate long-term effect of thumb orthoses for pain, and moderate-certainty evidence that assistive devices had a moderate long-term effect on function. Concerning pharmacological interventions, there was low-certainty evidence for a moderate short-term effect of oral non-steroidal anti-inflammatory drugs (NSAIDs) on pain, high- and moderate-certainty evidence for a small short-term effect of topical NSAIDs and oral glucocorticoids on function, respectively, and low-certainty evidence that oral glucocorticoids had a small short-term effect on function. Further, there was low-certainty evidence that methotrexate had a small long-term effect on pain. The heterogeneity of studies did not allow for any meta-analyses on surgery., Conclusion: The results largely support current treatment recommendations. However, there is a lack of interventions that efficiently improve grip strength, and the evidence for most current treatments is still limited. To better understand action mechanism of different treatments, future trials should include hand OA subtyping and be powered for subgroup analyses., Competing Interests: Competing interests: This study had no competing financial interests. Interests disclosed in the international Committee of Medical Journal Editors (ICMJE) conflict of interest forms are as follows: IKH has received consulting fees from Novartis and GSK and is a member of the OARSI executive committee. MK has received grants from IMI APPROACH and the Dutch Arthritis Society, royalties/licences from Wolters Kluwer and Springer Verlag, and consulting fees from AbbVie, Pfizer, Kiniksa Flexion, Galapagos, CHDR, Novartis and UCB, and she is a member of the OARSI board, the EULAR council and President of the Dutch Society for Rheumatology., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: Older individuals are at risk of malnutrition resulting from chronic diseases-related body and muscle mass reduction. In turn, nutritional deficiencies may enhance catabolic processes, leading to accelerated aging and comorbidity, thus creating a vicious cycle. Our study aimed to assess the prevalence of malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria and to determine the health correlates of malnutrition in a representative sample of community-dwelling older adults., Methods: We used the GLIM criteria to diagnose malnutrition in 5,614 participants of the PolSenior2 study. The PolSenior2 study was a population-based survey designed to assess the medical, psychological, social, and economic characteristics of community-dwelling older adults., Results: Malnutrition was diagnosed in 13.4% of the participants using the GLIM criteria. Results of multiple logistic regression showed that the risk of depression [OR 4.18, p<0.001], peptic ulcer disease [OR 2.73, p<0.001], past stroke [OR 1.71, p<0.001], cognitive impairment [OR 1.34, p = 0.015], and chronic pain [OR 1.23, p = 0.046] were independent correlates of malnutrition., Conclusion: Due to the high risk of malnutrition, special attention should be paid to individuals in late old age. Suspected malnutrition should also be considered in people at risk of depression, with peptic ulcer disease, past stroke, and cognitive impairment. Chronic pain should also prompt the diagnosis for malnutrition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Kaluźniak-Szymanowska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease., Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e. baseline) was used. Interstitial lung disease-free survival was assessed for up to 5 years of follow-up with a Cox proportional hazards model stratified on nailfold capillaroscopy pattern at baseline. The association of annual transition in nailfold capillaroscopy pattern on the risk to develop interstitial lung disease was assessed with a mixed logistic regression analysis., Results: Out of 771 eligible patients, 283 (37%) had an early pattern, 377 (49%) had an active pattern, and 111 (14%) had a late pattern. The Cox proportional hazard model including the identified confounders did not show an association between severity of nailfold capillaroscopy pattern at baseline and increased risk for interstitial lung disease during 5-year follow-up (hazard ratio (95 confidence interval; p value): 1.09 (0.86-1.39; 0.47)). The mixed logistic regression analysis revealed an increased annual risk for incident interstitial lung disease with increasing severity of capillaroscopic pattern (odds ratio (95% confidence interval); p value 3.76 (1.99-7.11; <0.01))., Conclusion: Our study shows that worsening of nailfold capillaroscopy has a strong association with an increased annual risk to develop interstitial lung disease. Of note, a worse scleroderma pattern at nailfold capillaroscopy is not associated with the long-term risk to develop interstitial lung disease., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.V.: none declared. J.K.B.: received consulting fees from Abbvie, Janssen and Boehringer Ingelheim, and received research grants from Roche, Galapagos Janssen, NVLE and ReumaNederland; all payments were made to her institution. J.H.: speakers bureau and consulting fees from ABBVIE,Astra-Zeneca, Boehringer Ingelheim, BMS, GSK, Janssen Pharmaceutical, Novartis, Roche, Pfizer and UCB. L.C.: none for this manuscript. L.D.: none for this manuscript. G.R.: none declared. Y.A.: received consulting fees from Boehringer Ingelheim, Janssen Pharmaceutical Companies, Astra-Zeneca, Topadur, Abbvie, Galderma, Medsenic, Prometheus regarding the management of systemic sclerosis. R.F.: none declared. J.J.A-S.: none for this manuscript. B.M.: grants from Novartis, consulting fees from Novartis, Boehringer Ingelheim, Jannsen-Cilag, GSK; speaker fees from Boehringer Ingelheim, GSK, Novartis, Otsuka, MSD; congress support from Medtalk, Pfizer, Roche, Actelion, Mepha, and MSD; and patent mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143). G.C.: none for this manuscript. J.S.: received research grants from Boehringer Ingelheim and ReumaNederland; all payments were made to her institution. T.M.: none for this manuscript. M.E.T.: received consultancy and speaker fees from Boehringer Ingelheim, Pfizer, Galapagos, MSD and Lilly. C.H.M.E.: none declared. M.C.V.: received research grants from Boehringer Ingelheim, Ferrer and Galapagos; received consulting fees from Boehringer Ingelheim and Janssen Pharmaceutical Companies of Johnson & Johnson; received speaker fees from Boehringer Ingelheim, GSK, Janssen Pharmaceutical Companies of Johnson & Johnson, MSD, and Novartis; and is treasurer of EUSTAR and steering committee member of the ERN ReCONNET., (© The Author(s) 2025.)

Growing evidence suggests that serotonin is an important mediator in the cross-talk between immune and bone cells, playing a role in the pathogenesis of various types of inflammatory arthritis (IA). However, the relationship between circulating serotonin and different outcomes in three most prevalent IA - rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), remains limited and requires further investigation. This study was performed to evaluate variations in serotonin serum levels among RA, PsA, and axSpA and to explore the utility of this biochemical marker in the assessment of disease activity and health status measurements provided by the Multi-Dimensional Health Assessment Questionnaire (MDHAQ). This was a cross-sectional study using data from the PolNorRHEUMA registry. Demographic and clinical data, as well as blood samples, were collected during routine visits to the rheumatology outpatient clinic. We included 60 patients (20 with RA, 20 with PsA, and 20 with axSpA) and 45 healthy controls, with a mean age of 49 years and 56.2% female. A reliable liquid chromatography-tandem mass spectrometry (LC-MS) method was used for the quantitative determination of serotonin in blood serum. Analysis of serotonin levels, based on 105 observations and adjusted for age, SSRI/SNRI intake and physical activity, revealed a significant elevation in the patient groups compared with the controls (p < 0.001): 134.00 ng/mL in healthy controls vs. 176.00 ng/mL in RA, 183 ng/mL in PsA, and 184.00 ng/mL in axSpA, with no statistically significant differences between the respective forms of IA. We found no significant correlation between the serotonin concentration and disease activity composite scores. A sample of 51 patients revealed a significant positive correlation between the serotonin concentration and global MDHAQ scores (β = 0.01, p = 0.009), indicating that an increase in serotonin levels is associated with worsening patient-reported health status. The serotonin serum concentration was higher in patients with RA, PsA, and axSpA than in controls, indicating its potential as a biomarker of inflammation and worse health status. The LC-MS method was successfully applied for the analysis of serum., Competing Interests: Declarations. Disclosures: None. Conflict of interest: The authors declare no conflict of interest regarding the preparation and publication of this manuscript., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography., Methods: Six GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2. Ultrasonography was conducted on temporal arteries (common superficial, frontal and parietal branches) and axillary arteries bilaterally to calculate the OGUS, the Southend score and the Halo count. Inter-reader and intra-reader reliability were assessed by intraclass correlation coefficient (ICC)., Results: Mean age of GCA patients was 78±5.1 years, 2 (33.3%) were women, and all were in clinical remission. Expert inter-reader ICC of the OGUS was 0.60 in both rounds, 0.40 in round 1 and 0.51 in round 2 for the Southend score and 0.45 and 0.52, respectively, for the Halo count. Median ICCs for intra-reader reliability were 0.86, 0.73 and 0.65 for the OGUS, Southend score and Halo count, respectively.For non-experts, inter-reader ICCs in round 1 were 0.20 for the OGUS, 0.20 for a normalised Southend score (=score divided by available segments) and 0.35 for a normalised Halo count. After training, inter-reader reliability ICCs improved to 0.52, 0.29 and 0.54, respectively., Conclusion: Inter-reader reliability was fair to moderate, and intra-reader reliability was good for OGUS, Southend score and Halo count among experts. Inter-reader reliability of non-experts in vascular ultrasonography improved after the training., Competing Interests: Competing interests: CDu has received consultancy or speaker fees and travel expenses from AbbVie, AOP Orphan, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sandoz, UCB, Vifor and research support from Eli Lilly, Pfizer, UCB, all unrelated to this manuscript. EDM: research funding/consulting and conferences fees from AbbVie, Novartis, Roche, Pfizer, Janssen, Lilly, MSD, BMS, UC Pharma, Grünenthal and Sanofi. CPo: research grants and/or consultancy fees from AbbVie, CSL Vifor, Roche, Pfizer, Novartis, GlaxoSmithKline and AstraZeneca, all unrelated to this manuscript. CDe consulting/speaker’s fees from AbbVie, Eli Lilly, Janssen, Sparrow, Novartis, Pfizer, Roche, Galapagos and Sanofi; grant support from AbbVie and Novartis., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures. We confirm the presence of a fibroblast cell state and identify a pericyte/mural cell state with potential immunological functions. The identification of cellular properties associated with these structures and the molecular and functional interactions identified by this analysis may provide key therapeutic cues for tertiary lymphoid structures associated conditions in autoimmunity and cancer., Competing Interests: Competing interests: F.B. is an employee of Candel Therapeutics. C.D.B is the founder of Mestag Therapeutics. B.A.F. has undertaken consultancy for: Novartis, BMS, Servier, Galapagos, Roche, UCB, Sanofi, Janssen, A.Z., Otsuka, Amgen, Kiniksa and received research funding from Janssen, Servier, Galapagos, and Celgene. A.F. has consulted for Janssen and Sonoma, and has received research funding from: BMS, Roche, UCB, Nascient, Mestag, GSK, and Janssen. S.J.B. has undertaken consultancy for: Abbvie, Amgen, Argenx, Aurinia, Bain, BMS, EcoR1, Iqvia, J&J/Janssen, Kiniksa & Novartis. K.G.L. and A.P.F. are employees of F. Hoffmann-La Roche Ltd. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory tissue disease. In view of the explosive growth in research on SLE, bibliometrics was performed to evaluate the 100 top-cited papers in this realm. We performed the search with terms "systemic lupus erythematosus" the Web of Science Core Collection database on May 3, 2023. Relevant literatures were screened. Data were extracted and analyzed by SPSS. The citations of 100 top-cited SLE studies spanned from 472 to 13,557. Most studies (60 out of 100) were conducted in the United States. Total citation times were positively associated with ACY, which was negatively correlated with the length of time since publication. Approximately half of the studies focused on the underlying mechanisms of SLE. New biologic therapies garnered attention and development. Our findings provide valuable insights into the developments in crucial areas of SLE and shed contributions to future studies.

Background: Juvenile systemic lupus erythematosus (SLE) is a severe, life-threatening disease. However, the role of rituximab in managing juvenile SLE remains undefined, although early biological intervention may improve disease outcomes., Aim: To assess the differences in the outcomes of different types of rituximab administration (early and late)., Methods: In this retrospective cohort study, the information of 36 children with SLE with early (less than 6 months from onset) rituximab administration (ERA), and late (more than 1 year) rituximab administration (LRA) was analyzed. We compared initial disease characteristics at onset, at baseline (start of rituximab), and at the end of the study (EOS) at 12 months, as well as outcomes and treatment characteristics., Results: The main differences at baseline were a higher daily median dose of corticosteroids, increased MAS frequency, and a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the ERA group. No differences in the main SLE outcomes between groups at the EOS were observed. The part of lupus nephritis patients who achieved remission changed from 44% to 31% in ERA and 32% to 11% in the LRA group. Patients with ERA had a shorter time to achieve low daily corticosteroid dose (≤ 0.2 mg/kg) at 1.2 (0.9; 1.4) years compared to 2.8 (2.3; 4.0) years ( P = 0.000001) and higher probability to achieve this low dose [hazard ratio (HR) = 57.8 (95% confidence interval (CI): 7.2-463.2), P = 0.00001 and remission (SLEDAI = 0); HR = 37.6 (95%CI: 4.45-333.3), P = 0.00001]. No differences in adverse events, including severe adverse events, were observed., Conclusion: ERA demonstrated a better steroid-sparing effect and a possibility of earlier remission or low disease activity, except for lupus nephritis. Further investigations are required., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: Competing interests: The author declares consulting agreements with AstraZeneca and Aisa Pharma.

B cells with low or absent expression of CD21 (CD21 lo B cells) gained attention due to their expansion in the peripheral blood of patients with immune-mediated, rheumatic diseases. This is not only observed in typical autoimmune diseases like systemic lupus erythematosus and Sjögren's disease (SjD) but also in radiographic axial spondyloarthritis (r-axSpA), which is considered an autoinflammatory disease. To gain more insight into the origins of the heterogeneous CD21 lo B-cell population, and its relation to the plasmablast (PB) compartment, we profiled the B-cell-receptor (BCR) repertoire in CD27 - and CD27 + fractions of CD21 lo B cells and early PBs using next-generation sequencing. Populations were sorted from peripheral blood of healthy individuals, SjD patients, and r-axSpA patients (n = 10 for each group). In healthy individuals and both patient groups, our findings indicate that CD27 - CD21 lo B cells, which exhibit few mutations in their BCR, may develop into CD27 + CD21 lo B cells and PBs, both marked by considerably more mutations. Given the known expansion of circulating CD27 - CD21 lo B cells in SjD and r-axSpA patients and clonal relationships with both CD27 + CD21 lo B cells and early PBs, these cells might actively contribute to (pathological) immune responses in rheumatic diseases with autoimmune and/or autoinflammatory characteristics., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Background and objectives : Systemic sclerosis (SSc) causes myocardial and microvascular impairment, with subclinical dysfunction and eventually permanent cardio-vascular damage. The long-term influence of SSc therapies on subclinical cardiovascular dysfunction is insufficiently investigated. We aimed to assess 2D and 4D cardiac ultrasound parameters of heart function in patients with different forms of SSc versus controls and to determine the evolution of cardiac function and arterial stiffness parameters under therapy. Materials and methods : A total of 60 subjects with SSc were studied at baseline; 30 SSc patients were compared to 30 matched controls. A total of 52 SSc subjects were reassessed after 1 year and 30 after 2 years of treatment. Cardiac function was evaluated through 2D standard echocardiography, tissue Doppler, speckle tracking and 4D auto LV quantification echo. Arterial stiffness was determined via the cardio-ankle vascular index and ankle brachial index. Results : At baseline, the standard echo parameters were normal. The 4D and myocardial work parameters, although in normal limits, were significantly altered in the SSc group vs. controls (4D ejection fraction 54.5 ± 8.5% in SSc vs. 63.8 ± 3.1% in controls; 4D longitudinal strain -14.2 ± 2.4% in SSc vs. -22.0 ± 2.7% in controls; global constructive work 2124.2 ± 449.5 mmHg% in SSc vs. 3102.8 ± 337.5 mmHg% in controls, for all p ≤ 0.02). Both at 1 year and 2 years of treatment, all echo and arterial stiffness parameters were similar to baseline, with no correlation to treatment type. Conclusions : SSc determines subclinical systolic dysfunction. Non-invasive assessment methods do not detect a functional cardiovascular decline in patients on classical therapy. Complex cardiac follow-up should be implemented in cases at risk for complications.

Background: The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma., Methods: Search was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science. We included case series, retrospective/prospective observational studies and interventional clinical trials. Individual-level data was analyzed using KM curves and Cox regression for overall survival (OS) and progression free survival (PFS). Time to SSIA was treated as a time-varying exposure using landmark analysis (landmark timepoint=3 months after irAE) to account for immortal time bias. For group-level data, meta-analysis compared the use of SSIA to No SSIA for irAEs., Results: Of twenty-two publications with individual-level data, 147 patients with any cancer (57 CS, 90 CS-SSIA) and 65 with melanoma (18 CS, 47 CS-SSIA) underwent landmark analysis. Twenty-two publications underwent group-level evaluation and four were included in the meta-analysis. CS-SSIA versus CS showed higher risk of all-cause mortality and progression (HR 2.75, 95%CI: 1.44-5.27, p<0.01 and HR 1.75, 95%CI: 1.07-2.85, p=0.03, respectively). Melanoma showed worse OS and PFS for CS-SSIA versus CS (HR 5.68, 95%CI: 1.31-24.67, p=0.02 and HR 2.68, 95%CI: 1.12-6.40, p=0.03, respectively). In the meta-analysis of group-level data (n=2558), we found worse OS and PFS for CS-SSIA versus No SSIA (HR 1.58, 95%CI: 1.25; 2.01, p<0.01 and 1.70, 95%CI: 1.25-2.33, p<0.01). Tumor necrosis factor-alpha inhibitors (TNFi) were the most common SSIA. In the melanoma cohort, TNFi had worse OS and PFS versus CS (HR 6.46, 95%CI: 1.43-29.19, p = 0.02 and HR 7.49, 95%CI: 2.29-24.48, p<0.01, respectively). TNFi versus Other SSIAs showed a trend toward worse OS and worse PFS (HR 6.96, 95%CI: 0.90-53.65, p=0.06 and HR 21.5, 95%CI: 2.63-175.8, p<0.01, respectively). Meta-analysis showed a concern for TNFi compared to Other SSIA (HR 1.56, 95%CI: 1.17-2.09, p<0.01 respectively)., Conclusions: While our results raise concern about the effects of CS-SSIA and TNFi for irAE therapy on tumor outcomes, prospective randomized controlled trials are needed to definitively assess the effect of SSIAs on tumor outcomes., Competing Interests: JR was on the advisory board for Deciphera for vimseltinib. TK receives research support from Sanofi and has served as a medical consultant for Genentech and Sonoma Biotherapeutics. PR reports advisory board participation for AbbVie and Unbranded speaking bureau for Amgen and has a patent pending for use of interleukin 6 axis inhibitors for viral infection associated pneumonitis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Strouse, Chan, Baccile, He, Louden, Giurcanu, Singh, Rieth, Abdel-Wahab, Katsumoto, Singh, Rouhani and Reid.)

Objectives: To evaluate the combination of novel colour Doppler ultrasound (CDUS), greyscale ultrasound (GSUS), and oscillometric indices of macroangiopathy in patients with idiopathic inflammatory myopathies (IIM). Second, to explore the associations between these imaging markers and both patient-related and disease-related characteristics, as well as traditional cardiovascular (CV) risk factors., Methods: We conducted CDUS to evaluate arterial compliance markers, specifically the resistance (RI) and pulsatility (PI) indices, both in the common (CCA) and internal carotid arteries (ICA) of patients with IIM and healthy controls. Additionally, we performed GSUS examinations to measure carotid intima-media thickness (cIMT), identify plaques, and quantify cumulative carotid calcification surface. Oscillometric assessments determined aortic stiffness using carotid-femoral pulse wave velocity (cfPWV)., Results: We recruited 82 IIM patients and 88 healthy controls. Patients showed significantly higher cIMT (padj=0.014), CCA-RI (padj=0.005), CCA-PI (padj=0.002), ICA-RI (padj=0.003), and ICA-PI (padj=0.024), compared with controls. RI and PI of CCA and ICA were higher in patients with lower lung function vital capacity, respectively (all; p< 0.05). cfPWV correlated positively with traditional CV-risk factors including age (rho = 0.546, p< 0.001), mean arterial pressure (rho = 0.331, p= 0.003), diabetes (p= 0.007), and hyperlipidemia (p= 0.032), and associated negatively with lung CO-diffusion (rho=-0.329, p= 0.031)., Conclusion: In one of the largest CV surrogate marker studies in IIM, patients exhibited increased carotid pulsatility, resistance, and atherosclerosis compared with controls. Lower lung function parameters predicted aortic stiffness and Doppler indices, suggesting a possible link between lung involvement and increased CV risk. Angiopathy markers may reveal significant vascular abnormalities in IIM patients, enhancing CV screening and risk classification., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background : Kidney cancer accounts for approximately 2% of all diagnosed cancers and fatalities worldwide, and a notable increase in its incidence has been observed in recent years. Previous studies have identified various risk factors for renal cell carcinoma (RCC), including age, gender, smoking, hypertension, overweight, and obesity. However, limited information is available regarding the correlation between RCC risk factors and tumor lateralization. Objectives : To investigate the relationship between body mass index (BMI) and the lateralization of kidney tumors in patients undergoing surgery for renal cell carcinoma. Moreover, we aim to evaluate the impact of lateralization of malignant kidney tumors on overall survival (OS) and cancer-specific survival (CSS). Materials and Methods : This single-center study included 287 patients who underwent surgical treatment for kidney tumors between January 2016 and December 2019. The patients were allocated into the following groups based on their BMI: normal (18.5-24.99 kg/m 2 ), overweight (25-29.99 kg/m 2 ), or obese (≥30 kg/m 2 ). The study collected demographic and histopathological data, as well as patient history, including risk factors such as smoking and hypertension. Results : Right-sided kidney tumors occurred more frequently (55.05%, n = 158) than left-sided ones (44.95%, n = 129). A statistically significant relationship ( p = 0.04731) was observed between BMI and the frequency of right-sided kidney tumors in the overweight group (70 vs. 43 cases). There was no correlation between BMI and the occurrence of kidney tumors in the normal BMI and obesity groups. Furthermore, the analysis revealed no association between the lateralization of kidney tumors, smoking, and hypertension. The 5-year survival rate was 62%, with a mean follow-up duration of 104 months (approximately 8.5 years). No statistically significant difference was observed between the right- and left-sided cancer groups, with survival rates of 58% and 66%, respectively ( p = 0.652). Conclusions : This study highlighted that right-sided kidney tumors occurred significantly more frequently in overweight individuals in our cohort of patients. No association was observed between lateralization of kidney cancer and overall survival (OS) or cancer-specific survival (CSS).

The aim of the study was to elucidate predictors associated with the initial choice of vascular access (VA) type. The secondary aim was to determine the initial VA's median utilization time and the factors governing it. This prospective cohort study included 387 hemodialysis (HD) patients admitted to the Clinic for Hemodialysis, Clinical Center University of Sarajevo, in consecutive order between January 2006 and December 2016. We selected the primary predictors for the initial VA type using a random forest algorithm. We further quantified factors governing the initial choice of VA: temporary catheters (TC), compared to arteriovenous fistula (AVF), using multivariate logistic regression. Finally, we used log-rank and Cox regression models to estimate the median time on each initial VA and find predictors governing it. Of the 387 patients, 265 (68,5%) used TC at dialysis initiation and 122 (31,5 %) AVF. Predictors of the TC's vs. AVF's initial use were older age (OR=1.02, CI=1.0, 1.03, p=0.03) and primary cause of CKD, particularly diabetes, compared to all other causes of kidney disease (CKD). Median time on initial AVF was 57.0 months (95%CI =36.9, 64.1), and on initial TC 4.99 months (95%CI =2.69, 8.48). Younger age (HR=.98,95%CI=.97, .99, p=.01), male sex (HR=1.51, 95%CI=1.05, 2.19, p=.03), and hypertension (HR=1.63, 95%CI=1.13,2.36, p=.01) predicted median time on initial TC, while older age (HR for patients>70years = 1.86, 95%CI=1.09, 3.17, p=.02), and diabetes (HR=1.97, 95%CI=1.19, 3.24, p=.01), predicted median time on initial AVF. These results point to late VA referrals and delays in transitioning to permanent VA., Competing Interests: Conflicts of interest The authors certify no conflict of interest with any financial organization regarding the material discussed in the manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Secondary lymphoid organs such as lymph nodes (LNs) are the home of peripheral tolerance mechanisms which control autoreactive T cells and prevent immune responses to self-antigen. In systemic autoimmunity, there is a clear failure of these peripheral tolerance mechanisms that leads to chronic inflammation and tissue destruction, highlighting the role for LNs as possible gatekeepers of autoimmunity. In recent years there has been a shift in research focus towards tissue sites in autoimmune diseases ranging from type 1 diabetes to rheumatoid arthritis in an effort to better characterise pathogenesis and guide diagnostic and therapeutic decisions. Although this has yielded great insight, it fails to tackle the initial break in tolerance that initiates disease progression which is most likely originating in peripheral LNs. In the majority of autoimmune diseases a preclinical phase is recognised. This is characterised by the presence of autoantibodies, which is indicative of a break in immune tolerance, and the absence of clinically apparent inflammation or tissue destruction. This review explores how our current knowledge of LNs in the preclinical and established phases of autoimmune diseases provides insight into possibly shared pathological mechanisms that drive disease progression and highlight the gaps in our knowledge that may help uncover new therapeutic avenues for intervention and prevention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To assess the need to treat forefoot lesions in rheumatoid arthritis (RA) patients who are unaware of their foot problems., Methods: From April to September 2022, 116 RA patients at our clinic were administered the Self-Administered Foot Evaluation Questionnaire (SAFE-Q), a self-assessment questionnaire on foot-related issues, and underwent forefoot radiography. We also assessed the occurrence of falls one year later. Among the 88 patients who were unaware of foot problems, we analysed the frequency and type of forefoot deformities and conducted a multivariate analysis to identify factors predicting falls during the 12-month follow-up., Results: Of the unaware patients, 64 (72.7%) had forefoot deformities and 17 (19.3%) experienced falls within the first year. The fall group had a history of falls and lower SAFE-Q scores but did not significantly differ from others in terms of forefoot deformities. Multivariate analysis identified a history of falls and lower SAFE-Q scores as predictive factors for future falls., Conclusions: Decreased foot-related quality of life is a risk factor for falls, even in patients who are unaware of their foot problems. Physicians should regularly assess foot-related quality of life using tools such as SAFE-Q to help prevent falls in RA patients., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: This study aims to estimate the vaccination rate against herpes zoster (HZ) among public Primary Health Care (PHC) visitors eligible for vaccination based on the National guidelines. It also aims to explore the determinants associated with vaccination utilizing the health beliefs model (HBM)., Materials and Methods: A cross-sectional study was conducted between October and December 2022. The study took place in two public PHC units in the Heraklion prefecture, Crete, Greece. Eligible participants were visitors of the selected health units aged 60-75 years. The questionnaire elicited information on participants' demographic data, health habits, and chronic illnesses. The HBM tool adapted for HZ vaccination was also used., Results: Four hundred primary care attendees participated in the study. Most participants were women (58.5%), with a mean age of 68.1 (±4.9) years. Fifteen percent of participants reported a history HZ illness, while 147 (36.8%) reported being vaccinated against HZ. Older age and respiratory illnesses were associated with higher rates of vaccination. Perceived threat (OR: 1.057; 95% CI 1.022-1.093; p=0.001), perceived vaccination benefits (OR: 1.327; 95% CI 1.179-1.492; p<0.0001), and motivation for action (OR: 2.601; 95% CI 2.122-3.187; p<0.0001) increased the odds of receiving HZ vaccination. Conversely, perceived barriers such as safety concerns were found to decrease the odds of HZ vaccination (OR: 0.845; 95% CI 0.803-0.889; p<0.0001)., Conclusions: This study identified specific determinants positively associated with HZ vaccination, highlighting the need to enhance the education of healthcare professionals in personalized patient counseling., (Copyright © 2024 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Single cell RNA sequencing has provided unprecedented insights into the molecular cues and cellular heterogeneity underlying human disease. However, the high costs and complexity of single cell methods remain a major obstacle for generating large-scale human cohorts. Here, we compare current state-of-the-art single cell multiplexing technologies, and provide a widely applicable demultiplexing method, SoupLadle, that enables simple, yet robust high-throughput multiplexing leveraging genetic variability of patients., Competing Interests: Competing interests: R.K. is a founder, shareholder and board member of Sequantrix GmbH, a member of the scientific advisory board of Hybridize Therapeutics, and has received honoraria for advisory boards and talks from Bayer, Chugai, Pfizer, Roche, Genentech, Lilly, and GSK and has received research funding from Travere Therapeutics, Galapagos, Novo Nordisk and Ask Bio. S.H. reports funding from Novo Nordisk and Ask Bio. K.H. and S.H. are co-founders of Sequantrix GmbH. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Objective: High disease activity status (HDAS) in patients with systemic lupus erythematosus (SLE) is associated with adverse long-term outcomes. We examined the frequency of lupus low disease activity state (LLDAS) and remission (REM) attainment in HDAS patients and whether their attainment was associated with improved patient outcomes., Methods: Demographic, clinical and outcomes data, collected prospectively from a multinational cohort between 2013 and 2020, were analysed. Disease activity was assessed using SLEDAI-2K. HDAS was defined as SLEDAI-2K ≥ 10. Patients' first visit with SLEDAI-2K ≥ 10 was assigned as baseline. Survival analyses were performed to examine the associations between cumulative and sustained LLDAS and REM attainment in HDAS patients and subsequent organ damage accrual and flare., Results: 1,029 HDAS patients with a median study duration of 2.7 years [IQR: 1.0, 4.8] were studied. LLDAS and REM were attained at least once by 71% (LLDAS-ever, n = 726) and 41% (REM-ever, n = 418) of patients. Approximately one-fifth of patients attained ≥50% cumulative time in LLDAS or REM. 37% (n = 385) of patients attained ≥3months of sustained LLDAS, with progressively lower proportions of patients attaining longer periods of sustained LLDAS. Lower proportions of patients attained sustained REM. Attainment of cumulative and sustained LLDAS or REM provided significant protection against damage accrual and flare in HDAS patients. Sustained periods of LLDAS and REM were difficult to achieve and therefore a more stringent target, but provided the most protection against damage accrual or flare., Conclusion: LLDAS and REM were achievable targets in HDAS patients, and provided significant protection against adverse outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Spondyloarthritides (SpAs) are a group of common rheumatic diseases that often cause limited mobility and lower back pain. Physiotherapy is an integral part of treatment, but access to physiotherapy limits treatment success. Digital health applications (DHAs) enable home-based physiotherapy and could significantly improve access for SpAs patients. The aim is to investigate the clinical effects of the DHA ViViRA compared with those of standard physiotherapy., Methods: SpAs patients with chronic back pain were enrolled in a randomized controlled trial. The intervention group received ViViRA DHA, whereas the control group received standard physiotherapy. Pain (verbal rating scale, PAIN-Detect), quality of life (SF-36) and mobility (BASMI) were assessed at baseline and after 12 weeks as the primary outcomes., Results: Data from 59 participants (71.2% female, mean age 45.2 years) were analyzed. The intervention group showed a significant improvement in mobility (average BASMI score: baseline: 1.1 [range 0.7-1.5]; follow-up: 1.0 [range 0.5-1.4]; p = 0.05), whereas the control group showed a significant decrease in mobility (baseline: 1.5 [range 1.1-1.9]; follow-up: 1.8 [range 1.4-2.2]; p = 0.00). The intervention group demonstrated lower pain intensity (VRS pain level at week 3.5 ± 2.8) than did the control group (VRS pain level at week 4.5 ± 2) after 12 weeks., Conclusion: Our results highlight the efficacy of DHAs such as ViViRA in the treatment of lower back pain in SpAs patients. Compared with the current gold standard, physiotherapy, DHA use results in superior outcomes. However, further larger studies are needed to confirm these promising results., Trial Registration: The study is registered in the German clinical trial registry (DRKS) under the following ID: DRKS00031254., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the medical faculty ethics committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany (22-425-Bm) and registered in the German Clinical Trials Register (DRKS-ID DRKS00031254). Participation in the study was voluntary. All patients gave their written informed consent before study inclusion. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: In systemic sclerosis (SSc) patients, fatigue is the highest ranked symptom affecting quality of life (QoL), followed by Raynaud phenomenon (RP). We report results from a pilot study (NCT04854850) of the Apollo wearable device in SSc patients., Methods: Twenty-five adult participants with SSc, moderate fatigue and RP were enrolled. Participants completed a 4-week intervention, during which they wore the Apollo device daily for a minimum of 15 minutes. The primary outcome was change on the PROMIS-Fatigue 13a (PROMIS-Fatigue) scale at 4 weeks. (ClinicalTrials.gov Identifier: NCT04854850) RESULTS: After 4 weeks of using the Apollo wearable, participants reported less fatigue on the PROMIS-Fatigue (p <0.001) scale. The average daily number of RP attacks declined (p < 0.01), as did the Raynaud condition score (p<0.001) after 4 weeks of use. Average device usage (2.87 hours per day) far exceeded the requested time, and no adverse events occurred. The PROMIS-29 sub scores assessment demonstrated quality of life (QoL) improvement in physical function (p <0.01), sleep disturbance (p = 0.001), and ability to participate in social roles and activities (p < 0.001). Significant improvements were also noted for depression (p < 0.01) and disability (p < 0.05) measures., Conclusion: Use of the Apollo wearable for four weeks was associated with improvement in fatigue and RP symptom in SSc patients, with improved QoL measures and lower depression scores. Future studies should further test the efficacy of the Apollo wearable in these domains and SSc patient QoL.

Background: An increased number of double-negative T (DNT) cells expressing the αβ T cell receptor (αβ + DNT cells) is one of the diagnostic criteria for autoimmune lymphoproliferative syndrome (ALPS). Moreover, these cells are expanded in a widely used murine model for lupus. However, the homeostasis of αβ + DNT cells remains inadequately investigated in rheumatic disorders, especially in pediatric patients., Methods: In this cross-sectional, prospective, and observational study, children with rheumatic disorders and healthy controls were recruited to analyze the quantity and characteristics of circulating DNT cells using flow cytometry., Results: Overall, the two study groups did not differ in their total DNT cell pool in the bloodstream. However, the number of αβ + DNT cells was significantly higher in rheumatic children than that in the controls, whereas the γδ + DNT cells remained similar. This expansion in the circulating pool of αβ + DNT cells was comparable across different rheumatic diseases, all showing significant differences from the controls in this regard. Moreover, no significant correlation was found between αβ + DNT cell numbers and disease activity., Conclusions: These preliminary results indicate that circulating αβ + DNT cells are significantly expanded in children with rheumatic disorders; however, this finding appears to be a nonspecific (disease-unrelated) marker of autoimmunity. Further and larger studies are necessary to better investigate and define the role of DNT cells in pediatric rheumatic diseases., Competing Interests: Declarations. Conflict of interest: No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The author Dimitri Poddighe is a member of the Editorial Board for the World Journal of Pediatrics. The paper was handled by other editor and has undergone rigorous peer review process. Author Dimitri Poddighe was not involved in the journal’s review of, or decisions related to this manuscript. Ethical approval: This human research was approved by both the Institutional Research Ethical Committee of Nazarbayev University (application N644/14112022, approved on 10.01.2023) and the Institutional Review Board of UMC (application n.8, approved on 14.11.2023). This study has been conducted in compliance with the principles outlined in the Declaration of Helsinki. Consent for publication: Written informed consent was acquired from the guardians of study participants., (© 2024. The Author(s).)

Double-negative (CD4-CD8-) T (DNT) cells have been implicated in autoimmune lymphoproliferative syndrome (ALPS), where their expansion inside the circulating pool of T cells represents a diagnostic criterion. Recent experimental evidence has supported the immunomodulatory roles of DNT cells, and studies in adult patients have suggested that they may be altered in some immune-mediated conditions. This study aimed to retrieve available data on circulating DNT cells in pediatric rheumatic disorders that do not arise in the context of ALPS through a systematic literature review of 3 scientific databases (PubMed, Scopus, and Web of Science). The final output of the systematic literature search consisted of 8 manuscripts, including cross-sectional (n=6) and longitudinal (n=2) studies. Overall, the pooled population of patients includes children affected with pediatric systemic lupus erythematosus (n= 104), juvenile idiopathic arthritis (n=92), Behçet's disease (n=15), mixed connective tissue disease (n=8), juvenile dermatomyositis (n=6), and Kawasaki disease/multisystem inflammatory disease in children (n=1 and n=14, respectively); moreover, one study also included 11 children with a high titer of antinuclear antibody but no diagnosis of rheumatic disease. All studies except one included a control group. The number of DNT cells were increased in most studies of children with rheumatic diseases. Even if such a limited number of studies and their great heterogeneity in several methodological aspects do not allow for reliable conclusions about the relevance of DNT cells in specific rheumatic conditions in children, this cell population deserves further investigation in this pathological setting through well-designed clinical studies.

Objectives: To explore whether the balance of CD226 and TIGIT is disturbed in CD3+CD56-TCRαβ+CD4-CD8- (DN) T cells and have a better understanding of the potential role of DN T cells in the pathogenesis of primary Sjögren's syndrome (pSS)., Methods: The percentage of DN T cells as well as the expression of CD226 and TIGIT was identified by flowmetry. After in vitro stimulation, we further detected the expression of activation and cytotoxic marker, as well as intracellular cytokines secreted by DN T cells., Results: DN T cells were found to expand in the peripheral blood of pSS patients (1.77±0.66%) and correlate with IgG (r=0.451, p<0.05), C3 (r=-0.438, p<0.05) and C4 (r=-0.470, p<0.05). Imbalanced CD226/TIGIT was observed on peripheral DN T cells of pSS patients, especially the overexpression of inhibitory immunoreceptor TIGIT. The expression ratio of TIGIT and CD226 on DN T cells was elevated in pSS patients and correlated with ESSDAI scores≥5 (r=0.743, p<0.05). Besides, these DN T cells were found to be activated and show strong cytotoxicity., Conclusions: The balance between CD226 and TIGIT on DN T cells was disturbed and correlated with the disease activity in pSS patients, which may be implicated in the pathogenesis of pSS.