Kiltz U, von Schlichting E, Dieris-Hirche J
… +4 more, Redeker I, Gerlach G, Kehyayan A, Baraliakos X
Joint Bone Spine
· 2026 May · PMID 41679373
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OBJECTIVES: We aim to evaluate the prevalence of suicidal ideation and to explore factors associated with suicidal ideation in patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). METHODS: Patients w...OBJECTIVES: We aim to evaluate the prevalence of suicidal ideation and to explore factors associated with suicidal ideation in patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). METHODS: Patients with iRMD with suicidal ideation were identified in an observational cohort as cases through the PHQ-9 and were age, gender and disease-matched (1:3) with iRMD patients without suicidal ideations as controls. Patients and disease characteristics as well as risk factors for possibly committing suicide were evaluated in all patients. A standardized clinical interview was conducted by a psychosomatic expert in cases. Factors associated with suicidal ideation were investigated using logistic regression analysis. RESULTS: In total, 95 patients out of 2,960 (3.2%) iRMD patients presented with suicidal ideation. Fifty cases and 150 controls agreed to participate. In cases, patient reported outcome and disease severity was substantially higher compared to controls. Cases were less satisfied with their lives and less optimistic compared to controls. Cases experienced a history of abuse and reported feelings of help- and hopelessness more often compared to controls. Additionally, cases had more often psychiatric disorders than controls. The most frequent psychiatric disorders in cases were affective disorders (80%), somatic stress disorders (64%) and trauma-related disorders (36%). Short disease duration, the presence of a somatoform syndrome, higher impulsivity, and a neurotic personality were associated with suicidal ideation. CONCLUSION: A substantial number of patients reported suicidal ideation. Cases were identified by factors associated with suicide in the general population whereas disease-specific factors did not differentiate between cases and controls. Short disease duration, the presence of a somatoform syndrome, higher impulsivity, and neuroticism were associated with suicidal ideation. Larger-scaled studies would be instrumental in unraveling factors of suicidal ideation.
Rosillon D, de Hooge M, Van Den Berghe T
… +2 more, Varkas G, Gvozdenović E
Joint Bone Spine
· 2026 May · PMID 41621467
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BACKGROUND: Advances in Artificial Intelligence (AI) have opened new opportunities for improving detection, as well as the accuracy and efficiency of imaging interpretation in axial spondyloarthritis (axSpA). The aim of...BACKGROUND: Advances in Artificial Intelligence (AI) have opened new opportunities for improving detection, as well as the accuracy and efficiency of imaging interpretation in axial spondyloarthritis (axSpA). The aim of this study is to summarize the performance of AI techniques versus human reader in interpreting imaging modalities (magnetic resonance imaging [MRI], computed tomography [CT] and conventional radiography [CR]) in axSpA. METHODS: In line with the PRISMA guidelines, a systematic literature review was conducted across PubMed and Scopus for studies published between 1st January 2010 and 7th June 2025. Individual performance metrics were extracted and analyzed using a meta-analysis approach. For the meta-analyses, the overall estimate was computed using the DerSimonian-Laird random effect model on both subject and image levels. Heterogeneity was assessed using Higgings I. RESULTS: A total of 1033 references were identified, 46 full texts were reviewed, and 33 studies were included. All studies were published between 2020 and 2025, with 58% in 2024/2025. Sixty-seven % of the studies originated from Asia. Most of the studies included MRI (64%) and applied Deep-learning techniques (85%). Overall performance estimates (95% CI) at subject level were: sensitivity 87% (85; 90%), specificity 80% (75; 85%), accuracy 84% (81; 87%) and receiver operating characteristic area-under-the curve 0.88 (0.86; 0.90). On image level the results were similar. CONCLUSION: The number of studies assessing AI performance in axSpA using imaging modalities has increased tremendously in the past years. Although AI showed good performance, human expert remains essential to reach diagnostic accuracy while maintaining clinical safety.
Pecher AC, Koetter I, Peis K
… +7 more, Klein R, Lengerke C, Vogel W, Krumm P, Schmalzing M, Wirths S, Henes J
Joint Bone Spine
· 2026 May · PMID 41620074
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OBJECTIVES: Autologous hematopoietic stem cell transplantation (aHSCT) for systemic sclerosis (SSc) is an effective treatment strategy but carries a high treatment-related mortality (TRM). Consequently, patients with sev...OBJECTIVES: Autologous hematopoietic stem cell transplantation (aHSCT) for systemic sclerosis (SSc) is an effective treatment strategy but carries a high treatment-related mortality (TRM). Consequently, patients with severe organ dysfunction have been excluded from previous randomized trials such as ASTIS. This study aimed to evaluate the feasibility and non-inferiority of a disease-manifestation - adapted chemotherapy protocol designed to mitigate toxicity to also treat patients who would have been ASTIS-ineligible. METHODS: In this prospective, open-label, monocentric, phase II non-inferiority trial at the University Hospital Tübingen, Germany, patients with progressive SSc (disease duration≤6 years) were stratified by lung and cardiac involvement. Mobilization included 1500mg/m cyclophosphamide (CYC) for patients with inflammatory interstitial lung disease (iILD) versus 1000mg/m otherwise, both reduced compared to the ASTIS protocol. Conditioning comprised rabbit anti-thymocyte globulin (4×10mg/kg); patients without cardiac involvement additionally received CYC 4×50mg/kg. In those with cardiac involvement, CYC was reduced by 50% and thiotepa (2×5mg/kg) was added. RESULTS: Between 09/2012 and 07/2022, 35 patients were treated (no iILD/cardiac involvement: n=14; iILD only: n=3; cardiac only: n=12; both: n=6). Three-year overall survival (OS) was 77%, meeting non-inferiority compared to EBMT registry data (80%). TRM within 100 days was 11% (n=4) in the whole group. CONCLUSIONS: This adapted regimen showed comparable 3y-OS in patients with advanced organ involvement who would have been excluded from prior trials. While feasibility is demonstrated, aHSCT in this high-risk population remains associated with substantial risk, and efficacy cannot be definitively established. Further studies are warranted.
Catinon M, Lifermann F, Geistel F
… +6 more, El Jammal T, Massardier V, Ter-Ovanessian B, Trunfio-Sfarghiu AM, Vincent M, Sève P
Joint Bone Spine
· 2026 May · PMID 41620073
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INTRODUCTION: Sarcoidosis is the most frequent cause of systemic non-caseating granulomatosis in rheumatology. However, prosthesis-related granulomatous reactions induced by metallic particles can mimic sarcoidosis and s...INTRODUCTION: Sarcoidosis is the most frequent cause of systemic non-caseating granulomatosis in rheumatology. However, prosthesis-related granulomatous reactions induced by metallic particles can mimic sarcoidosis and should be considered in the differential diagnosis. CASE REPORT: We report a 50-year-old woman with a right hip arthroplasty who developed acute bilateral granulomatous panuveitis. Laboratory tests excluded infection but showed systemic inflammation with elevated angiotensin-converting enzyme. PET scan revealed intense periprosthetic hypermetabolism and iliac lymphadenopathy. Lymph node biopsy demonstrated non-caseating epithelioid granulomas with multinucleated giant cells. Scanning electron microscopy with energy-dispersive X-ray spectrometry identified numerous metallic particles, mainly titanium and titanium-vanadium alloy, within granulomatous tissue. Blood titanium concentration was markedly elevated (138μg/L; normal<12). Explant analysis revealed a large wear trace at the femoral stem neck, explaining particle release. Prosthesis removal led to clinical improvement, with only mild recurrent uveitis controlled by topical corticosteroids. At one year, the patient remained clinically stable with partial remission on PET scan. CONCLUSION: Prosthesis-related granulomatosis can mimic sarcoidosis. In patients with unexplained systemic granulomatous disease and arthroplasty history, particle analysis combined with implant expertise provides decisive diagnostic information.
OBJECTIVES: To investigate the mechanism by which fibroblast-derived extracellular vesicles (EVs) carrying miR-25-3p alleviate knee osteoarthritis (KOA) with proof-of-concept (POC) in a murine KOA model through targeting...OBJECTIVES: To investigate the mechanism by which fibroblast-derived extracellular vesicles (EVs) carrying miR-25-3p alleviate knee osteoarthritis (KOA) with proof-of-concept (POC) in a murine KOA model through targeting TAF15 to inhibit NF-κB signaling pathway activation. METHODS: miR-25-3p mimic/inhibitor-transfected murine fibroblast EVs were co-cultured with ATDC5 chondrocytes. Chondrocyte proliferation, migration, and apoptosis were assessed via CCK-8, Transwell, and TUNEL assays. Inflammatory cytokines (TNF-α, IL-1β, IL-6) were measured by ELISA and qPCR. miR-25-3p/TAF15 binding was verified via dual-luciferase assay, with TAF15 expression and NF-κB subunit (p65/IκBα) interactions analyzed by Western blot and co-immunoprecipitation (Co-IP). In vivo, monosodium iodoacetate (MIA)-induced KOA mice received intra-articular miR-25-3p-loaded EVs, with therapeutic effects evaluated by ELISA, H&E staining, and immunohistochemistry. RESULTS: Fibroblast-derived EVs carrying miR-25-3p promoted chondrocyte proliferation and migration, inhibited apoptosis, and reduced inflammatory cytokine secretion in vitro. Mechanistically, miR-25-3p directly targeted TAF15, downregulating its expression and disrupting interactions between TAF15 and p65/IκBα, thereby suppressing NF-κB nuclear translocation and transcriptional activity. In the KOA mouse model, intra-articular administration of miR-25-3p-loaded EVs alleviated cartilage degradation, synovial inflammation, and pain sensitivity, thus confirming the POC of this EV-based strategy in murine KOA accompanied by decreased NF-κB-mediated pro-inflammatory gene expression. CONCLUSION: Fibroblast-derived EVs delivering miR-25-3p mitigate KOA progression in a murine model by targeting TAF15 to inhibit NF-κB signaling as verified by POC in a murine KOA model, highlighting a novel EV-based therapeutic strategy for experimental KOA.
OBJECTIVES: Despite the importance of activity for rehabilitating patients with rheumatic and musculoskeletal diseases (RMDs), the activity levels remain suboptimal in many patients. This is partly due to kinesiophobia a...OBJECTIVES: Despite the importance of activity for rehabilitating patients with rheumatic and musculoskeletal diseases (RMDs), the activity levels remain suboptimal in many patients. This is partly due to kinesiophobia and avoidance behaviors triggered by concerns about pain or joint damage. This systematic review aimed to synthesize the available evidence to identify factors associated with kinesiophobia in patients with RMDs. METHODS: We searched 11 databases (PubMed, Web of Science, CINAHL, Cochrane Library, EMBASE, PsycINFO, Scopus, China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP, SinoMed) from the time of database inception to October 11, 2025. Eligible studies were English/Chinese articles reporting factors associated with kinesiophobia in patients with RMDs. Letters, editorials, conference abstracts/presentations, and duplicate records were excluded. Study selection, quality assessment, and data extraction were independently conducted by two reviewers. The biopsychosocial model guided factor classification. RESULTS: A total of 17 studies (7,356 participants) were included, comprising one longitudinal study and 16 cross-sectional studies. Sixteen studies were rated as high quality. Guided by the biopsychosocial model, poor physical function, negative psychological states, low self-efficacy, and inadequate social support were identified as main correlates of kinesiophobia in patients with RMDs. CONCLUSION: Kinesiophobia is prevalent in patients with RMDs, with its correlates aligning with the biopsychosocial model. Targeted multidimensional interventions (optimizing physical function, psychological regulation, and social support) may mitigate kinesiophobia and improve rehabilitation outcomes.
Musculoskeletal manifestations of transthyretin amyloidosis (ATTR) are common, early in the disease course (usually years before cardiac involvement), and are potentially predictive. They include carpal tunnel syndrome (...Musculoskeletal manifestations of transthyretin amyloidosis (ATTR) are common, early in the disease course (usually years before cardiac involvement), and are potentially predictive. They include carpal tunnel syndrome (CTS), trigger finger, atraumatic tears of the brachial biceps tendon or rotator cuff, spinal stenosis, and large joint osteoarthritis. These extra-cardiac 'red flags' for ATTR amyloidosis may present individually or in clusters, particularly in older males, several years in advance of signs of ATTR cardiomyopathy (ATTR-CM), such as arrhythmia or heart failure. Deposition of ATTR in the heart leads to severe, often fatal, ATTR-CM that can now be effectively treated. Available treatments slow amyloid fiber deposition but do not allow fiber removal, making early diagnosis and early treatment crucial to improve prognosis. Orthopedists' and rheumatologists' knowledge, recognition, and participation in the diagnostic pathway of amyloidosis-related musculoskeletal conditions may help increase suspicion, facilitate early diagnosis, allowing prompt disease-modifying treatment, improving patient outcomes. If surgical intervention is required in patients with these red flags, tissue biopsy at the time of surgery may allow early diagnosis of ATTR deposition, followed by cardiologic screening and/or patient referral to amyloidosis specialty centers if amyloid deposition is evident in biopsy findings. To improve awareness among orthopedic and rheumatology specialists, this narrative review summarizes the published literature on musculoskeletal disorders associated with ATTR amyloidosis, presents relevant diagnostic pathways and indications for histologic examination to facilitate identification of at-risk patients among large numbers of patients, and suggests appropriate follow-up approaches for patients in whom amyloidosis is detected during musculoskeletal surgical procedures.
Exosomes, as nanoscale extracellular vesicles, have emerged as vital mediators of intercellular communication through the delivery of functional cargos such as proteins, lipids, DNA, and regulatory RNAs, including microR...Exosomes, as nanoscale extracellular vesicles, have emerged as vital mediators of intercellular communication through the delivery of functional cargos such as proteins, lipids, DNA, and regulatory RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and small interfering RNAs (siRNAs). Their natural biocompatibility, targeting ability, and ability to cross biological barriers make them promising therapeutic tools for osteoarthritis (OA), a degenerative joint disease characterized by cartilage degradation and chronic inflammation. In recent years, the bioengineering of exosomes has opened new avenues for enhancing their therapeutic potential in cartilage regeneration and OA treatment. This review comprehensively summarizes recent progress in exosome engineering, including the selection of parental cells, the design and targeting of exosomes, and advanced bioengineering techniques such as RNA, protein, and drug loading, as well as surface modification. We further discuss scalable approaches for exosome purification and mass production, and the incorporation of exosomes into biomaterial scaffolds or hydrogels to enable controlled release and localized delivery. In addition, we explore therapeutic strategies involving gene therapy, chemotherapy, immunotherapy, and protein therapy, highlighting the versatility of engineered exosomes in modulating inflammation, promoting chondrocyte survival, and restoring cartilage homeostasis. Emerging technologies such as synthetic exosome mimics and vexosomes are also discussed, offering insight into future directions for enhanced delivery efficiency and clinical translation. By integrating molecular biology, materials science, and therapeutic design, engineered exosomes represent a powerful platform for precision treatment of OA. This review aims to provide a theoretical foundation and practical reference for future research and clinical application in exosome-based osteoarthritis therapy.
Joint Bone Spine
· 2026 Mar · PMID 41456726
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This was a young female patient admitted to the rheumatology department with nasal and chest pain, which led to a diagnosis of polychondritis. Her medical history included myelodysplastic syndrome (MDS), which had been c...This was a young female patient admitted to the rheumatology department with nasal and chest pain, which led to a diagnosis of polychondritis. Her medical history included myelodysplastic syndrome (MDS), which had been considered stable during a hematological reassessment a few days earlier. During the evaluation, we observed immature blood cells and biological markers of macrophage activation. This acute rheumatological manifestation allowed us to diagnose rapidly progressive acute leukemia and offer her early treatment. She is currently in remission.
Molto A, Arnaud L, Chartier M
… +3 more, Panes A, Lemeille P, Fautrel B
Joint Bone Spine
· 2026 May · PMID 41443535
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OBJECTIVES: The study aimed to describe nationwide treatment sequences in French patients with rheumatoid arthritis (RA) initiating a first biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD...OBJECTIVES: The study aimed to describe nationwide treatment sequences in French patients with rheumatoid arthritis (RA) initiating a first biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). METHODS: This analysis is based on the French National Health Claims Database (SNDS), covering over 67 million people. Patients with RA (ICD-10 codes M05, M060, M068 or M069) and ≥2 b/tsDMARD dispensings from January 1, 2014 to December 31, 2019 were included, and followed until December 31, 2020 or death. Differences in patients characteristics at each b/tsDMARD initiation were tested with Mann Whitney U tests and χ tests. RESULTS: Overall, 26 478 patients were identified (mean (SD) age 57.0 years (±14.4)) including 70.9% females. The most frequent first-line of b/tsDMARD were TNF inhibitors (TNFi) (62.6%), followed by abatacept (CTLA4-Ig) (12.0%), rituximab (11.0%), IL-6R inhibitors (IL-6Ri) (10.0%), and JAK inhibitors (JAKi) (3.9%). The mean (SD) follow-up duration was 3.8 years (±1.7 years,), for a total of 100 332 person-years. Throughout the study period, 12,662 patients (47.8%) maintained their first b/tsDMARD, while 7531 (28.4%) switched to a second b/tsDMARD, and 3046 (11.1%) to a third b/tsDMARD, after a mean duration of 54.1 (±34.0), 31.9 (±27.8) and 25.9 (±22.2) months, respectively. In terms of mode of action associated profiles, the main discrepancies were age, higher in CD20i and LT modulator patients, and comorbidities, more prevalent in CD20i treated patients. CONCLUSION: In this nation-wide analysis of 26 478 patients, TNFi was the most frequently dispensed first-line b/tsDMARD, with LT modulators and IL-6i preferred in second-line therapy.
OBJECTIVES: Sarcopenia is a muscle disease characterized by the progressive loss of muscle mass, strength, and function. Despite evolving definitions, validated diagnostic tools for younger individuals, especially those...OBJECTIVES: Sarcopenia is a muscle disease characterized by the progressive loss of muscle mass, strength, and function. Despite evolving definitions, validated diagnostic tools for younger individuals, especially those with cancer or chronic diseases, remain lacking. Oncological treatments can lead to severe muscle deconditioning. Many patients face limited follow-up and remain physically diminished in post-cancer period. We aimed to determine the prevalence of sarcopenia in post-cancer patients and to highlight its occurrence even in younger individuals and long after completion of oncological treatments. METHODS: We performed prospective and standardized muscle assessment through: physical activity questionnaires (International Physical Activity Questionnaire [IPAQ] and Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls [SARC-F]); functional tests (grip strength, 6-minute walk, and 30-second chair stand tests); and appendicular lean mass (ALM) index measurement by dual-energy X-ray absorptiometry (DXA; ALM/height in kg/m). RESULTS: Ninety-eight patients (68 females) were included (age (mean±SD) 53.8±11.0 years and body mass index (BMI) 27.8±6.4kg/m). Fifty-five had solid tumors (41 metastatic) with a post-treatment duration of 20.3±21.75 months. SARC-F score was 1.5±1.6. Grip strength and ALM index were 27.3±11.7kg and 6.4±1.4kg/m respectively. Considering cancer as a sarcopenia at risk status, we used European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria and identified 27 (27.6%) patients with sarcopenia. Patients with sarcopenia were younger (50.2±11.6 vs 55.2±12.0 years; P=0.07), more frequently in remission and long after treatment, and had lower BMI (23.3±3.2 vs 29.5±6.5kg/m; P<0.0001) compared to patients without sarcopenia. When using SARC-F for screening, only 5 patients were detected, underlining its poor sensitivity in this setting. CONCLUSION: Sarcopenia is highly prevalent in post-cancer patients including younger individuals and those in long-term remission. The 2019 EWGSOP2 criteria, combining ALM and functional tests, effectively identified sarcopenia but screening with SARC-F may not be suitable in the post-cancer population.