2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T713,Background Opioid use can heighten pain perception over time. Aim To determine whether the effectiveness of opioid analgesia diminishes with treatment duration in those with chronic low back pain or osteoarthritis. Design and setting Systematic review (January 22, 2025) of randomized trials comparing opioids to placebo/opioid-minimized pain management strategies in those with chronic low back pain or osteoarthritis. Methods Random effects meta-analysis using MEDLINE, EMBASE, CENTRAL, and Scopus databases. OUTCOMES: Primary: Attainment of clinically important pain relief (≥ "moderate" or ≥30% improvement). Secondary: On-treatment pain (100-point scale). PRIMARY ANALYSIS: Difference in primary/secondary outcomes across short-term (≤4-weeks), intermediate-term (4-12 weeks), and long-term (≥12 weeks) subgroups. Results Twenty-seven trials were eligible for inclusion. Clinically important pain relief differed significantly between short, intermediate, and long-term treatment durations (P = 0.05). Opioid recipients were more likely to be responders in short-term trials (8 trials, RR 1.42, 95% CI 1.08 to 1.89, moderate-certainty evidence), but not in intermediate-term trials (3 trials, RR 1.04, 95% CI 0.84 to 1.30, low-certainty evidence), nor long-term trials (9 trials, RR 0.91, 95% CI 0.73 to 1.14, moderate-certainty evidence), which trended in favour of controls. The mean difference in pain scores failed to reach our definition of clinical significance (≥10-points) for any time point, but was statistically significant in the short and intermediate-term. Conclusion Although opioids likely provide meaningful pain relief over short durations (≤4 weeks), they appear to provide little or no benefit beyond placebo over longer periods, and may worsen pain control beyond 12-weeks.31:T728,Background Opioid use can heighten pain perception over time. Aim To determine whether the effectiveness of opioid analgesia diminishes with treatment duration in those with chronic low back pain or osteoarthritis. Design and setting Systematic review (January 22, 2025) of randomized trials comparing opioids to placebo/opioid-minimized pain management strategies in those with chronic low back pain or osteoarthritis. Methods Random effects meta-analysis using MEDLINE, EMBASE, CENTRAL, and Scopus databases. OUTCOMES: Primary: Attainment of clinically important pain relief (≥ “moderate” or ≥30% improvement). Secondary: On-treatment pain (100-point scale). PRIMARY ANALYSIS: Difference in primary/secondary outcomes across short-term (≤4-weeks), intermediate-term (4-12 weeks), and long-term (≥12 weeks) subgroups. Results Twenty-seven trials were eligible for inclusion. Clinically important pain relief differed significantly between short, intermediate, and long-term treatment durations (P = 0.05). Opioid recipients were more likely to be responders in short-term trials (8 trials, RR 1.42, 95% CI 1.08 to 1.89, moderate-certainty evidence), but not in intermediate-term trials (3 trials, RR 1.04, 95% CI 0.84 to 1.30, low-certainty evidence), nor long-term trials (9 trials, RR 0.91, 95% CI 0.73 to 1.14, moderate-certainty evidence), which trended in favour of controls. The mean difference in pain scores failed to reach our definition of clinical significance (≥10-points) for any time point, but was statistically significant in the short and intermediate-term. Conclusion Although opioids likely provide meaningful pain relief over short durations (≤4 weeks), they appear to provide little or no benefit beyond placebo over longer periods, and may worsen pain control beyond 12-weeks.32:T640,Osteoarthritis (OA) is a complex condition driven by biomechanical, metabolic and inflammatory factors; however, effective disease-modifying treatments remain unavailable. Growing evidence suggests that gut microbiota dysbiosis has an important role in OA pathogenesis, giving rise to the emerging concept of a functional and targetable gut-joint axis. Gut microbiota dysbiosis can impair enteroendocrine signalling, intestinal immunity and gut barrier integrity, alter the secretion of hormones and cytokines and facilitate the translocation of gut microorganisms, pro-inflammatory molecules and metabolites into the circulation or joints. These processes can disrupt systemic and local homeostasis, promote metabolic dysregulation and obesity, trigger low-grade inflammation and contribute to both the onset and progression of OA. Although these insights open up new avenues for disease-modifying treatments and build on the long-standing paradigm in OA, which primarily focuses on pain relief rather than disease modification, evidence supporting therapeutic strategies that target the gut-joint axis remains limited. Further research is needed to translate this promising biology into clinical benefits, including deeper mechanistic elucidation through integrated multi-omics approaches, exploration of the interplay between host genetics, environmental factors and the gut microbiota and also multidimensional validation of the safety and efficacy of treatments that target this axis using complementary models (such as organoids and large animal models), clinical trials and real-world studies.33:T4ec,Chronic pain is the hall-mark symptom of osteoarthritis (OA) and although several therapies are available, a sizeable number of patients do not gain adequate pain relief from these therapies. Predicting those patients who will not respond to current therapies remains a challenge. Although psychosocial, sensitivity, inflammation and genetic factors have been identified as pain mechanisms that predict response to pain therapy, none of these is a sufficiently strong predictor alone. An emerging approach to this challenge is the use of machine-learning algorithms that integrate several pain mechanisms, which are superior to previous prediction models. Importantly, these machine-learning algorithms identify networks of pain mechanisms that could be targeted therapeutically. From these models, a new mechanistic framework is proposed, in which pain in OA can be viewed either as a simpler joint disease with inflammation or as a complex pain problem that involves multiple factors. The latter is associated with a higher risk of poor response to standard OA pain therapy. Understanding the complexity of pain in OA and predicting those who are at risk of not responding to standard OA pain therapy are essential for improving the management of pain in OA.34:T749,The 2018 European Alliance of Associations for Rheumatology (EULAR) recommendations for physical activity (PA) in people with inflammatory arthritis (IA) and osteoarthritis (OA) required revision as new studies have been published on interventions using technology and/or the combination of educational and behavioural strategies to promote PA or reduce sedentary behaviour (SB). Moreover, the World Health Organisation released updated general PA guidelines in 2020 with an emphasis on reducing SB. This work aimed to update the 2018 EULAR recommendations for PA in IA and OA. The EULAR Standardised Operating Procedures for developing recommendations were followed. A multidisciplinary task force (TF) was established. Systematic literature searches related to 13 research questions were conducted in August 2024. Recommendations were updated, and the TF members rated their level of agreement and estimated impact and implementability (0-10 scale, with 10 highest). The revised recommendations include 4 overarching principles and 11 recommendations on PA and SB including inter alia PA promotion as standard care, measurements of PA, and intervention modalities considering dose, adaptations and the application of (technology-based) behaviour change techniques. The mean level of agreement for the recommendations ranged from 9.0 to 9.8, the mean impact between 8.3 and 9.2, and the mean feasibility of implementation between 7.2 and 8.5. In addition, quality indicators, research and educational agendas were defined. The updated EULAR recommendations for PA should guide the development, conduct and evaluation of PA interventions and promotion, including the reduction of SB, in people with IA and OA. These recommendations should be implemented with consideration of individual needs, environmental conditions, and the broader national health care context.35:T5df,Nerve growth factor (NGF), a key mediator of pain, is increased in osteoarthritic (OA) joints. Antibodies against NGF show analgesic effects in painful knee OA, but clinical development was stopped because of side effects in the joints. Knowledge about the biologic effects of NGF on joint tissues is limited. Therefore, we explored the effects of repeated intra-articular (IA) injections of NGF into naïve murine knee joints on sensitization, joint innervation, and histopathology. Naïve 10- to 15-week-old male wildtype C57BL/6 mice were injected with NGF (50 or 500 ng) or vehicle IA twice a week for four weeks, and effects on knee swelling, knee hyperalgesia, joint histopathology, and bone were assessed. Single cell RNA sequencing (scRNAseq) of the synovium was performed. Na Compared with vehicle, repeated IA injections of NGF caused dose-dependent increases in knee swelling, knee hyperalgesia, synovial pathology, bone mineral density in the medial subchondral bone, and medial preosteophytes, but no overt cartilage damage. NGF caused increased sprouting of nociceptors in the medial synovium that was preceded by up-regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up-regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts. In naïve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis.36:T94d, Objective Nerve growth factor (NGF), a key mediator of pain, is increased in osteoarthritic (OA) joints. Antibodies against NGF show analgesic effects in painful knee OA, but clinical development was stopped because of side effects in the joints. Knowledge about the biologic effects of NGF on joint tissues is limited. Therefore, we explored the effects of repeated intra‐articular (IA) injections of NGF into naïve murine knee joints on sensitization, joint innervation, and histopathology. Methods Naïve 10‐ to 15‐week‐old male wildtype C57BL/6 mice were injected with NGF (50 or 500 ng) or vehicle IA twice a week for four weeks, and effects on knee swelling, knee hyperalgesia, joint histopathology, and bone were assessed. Single cell RNA sequencing (scRNAseq) of the synovium was performed. Na V 1.8‐tdTomato reporter mice were used to assess joint innervation. Dorsal root ganglia (DRGs) of mice underwent bulk RNAseq after three IA injections of NGF or vehicle. Results Compared with vehicle, repeated IA injections of NGF caused dose‐dependent increases in knee swelling, knee hyperalgesia, synovial pathology, bone mineral density in the medial subchondral bone, and medial preosteophytes, but no overt cartilage damage. NGF caused increased sprouting of nociceptors in the medial synovium that was preceded by up‐regulation of axonal growth pathways in the DRGs. ScRNAseq of the synovium revealed up‐regulated genes related to neuronal sprouting, synovial fibrosis, and ossification, with a key role for lining fibroblasts. Conclusion In naïve mouse knees, NGF induced many pathologic changes observed in OA, including nociceptor sprouting, suggesting a critical role for NGF in OA pathogenesis. 37:T116d, Objectives Femoroacetabular impingement (FAI) and synovitis have been recognized as essential factors for developing osteoarthritis (OA) in the hip joints. However, little is known about altered synovial cellular compositions, their associated transcriptomic profiles, and cell‐cell interactions in FAI and hip OA. Methods Synovial samples from a sex‐matched cohort of FAI and hip OA patients (n = 6/condition) were analyzed using integrative single‐cell RNA sequencing and spatial transcriptomics. Results Compared to FAI, epiregulin (EREG)‐enriched lining synovial fibroblast‐like synoviocytes (FLS) were significantly increased in hip OA. EREG + FLS are pro‐inflammatory due to elevated expression of CXCL1 , IL8 , and MMPs . Pseudotime analysis predicts that EREG + FLS are derived from DPP4 + PI16 + sublining FLS, likely regulated by NFIX and REL, as well as ELK3 and ETV6 transcription factors under FAI or OA conditions, respectively. Importantly, the only putative cell‐cell interaction is fibroblast growth factor 2 (FGF2) – syndecan 4 (SDC4) communication between COL1A1 + IGFBP5 + fibrotic macrophages (MΦ) and EREG + FLS. This interaction may induce expression of IL6, IL8, and MMP1 in hip OA synovium. The gene ontology (GO) analysis of activated genes downstream of FGF2‐SDC4 signaling revealed that inflammation and angiogenesis were upregulated in hip OA, while positive gene transcription and skeletal muscle differentiation were dominant in FAI. Moreover, we also found that EREG + CCL20 + MMP3 hi lining FLS along with most MΦ and monocyte populations are unique to hip OA patients compared to knee OA and RA patients. Conclusion The findings of this study offer a groundwork in tailoring novel targets and therapies for FAI and hip OA patients. 38:T621,In a co-twin control design, we aimed to examine whether individuals who initiate metformin treatment have an altered risk of incident diagnosis of osteoarthritis (OA), for up to 11 years after starting the treatment, compared with their non-treated co-twin. In all twin pairs different for metformin treatment (N=1 261 pairs) and all eligible twins/singletons (N=52 341) aged 35-75 years living in Sweden on December 31st 2005, without prior diagnosis of OA and no prior treatment with metformin, we studied the outcome OA in any joint as diagnosed in specialist care. We used a stratified Cox model in discordant pairs to estimate hazard ratio (HR) and a within-between Weibull shared frailty model to estimate incidence proportions and differences. Models were adjusted for age, sex, education level, body mass index (BMI) and smoking. Among treated twins, 68 (5.4%) developed OA over the 11-year follow-up, compared to 79 (6.3%) among the non-treated twins (crude HR [95% confidence interval -CI] = 0.86 [0.62-1.19]). Treated twins had higher BMI. Adjusted HR comparing treated with non-treated was 0.60 (95% CI =0.44-0.82). After 10 years, 6.7% (95% CI=4.8-8.6) of treated twins, compared to 9.7% (95% CI=9.3-10.1) of non-treated twins had incident OA, with difference of -3.1% (95% CI=-5.1- (-1.1)). Starting metformin treatment may be associated with a decreased risk of incident diagnosis of OA in specialist care over an 11-year follow-up period. The 10-year cumulative incidence was ∼3 percentage points lower among metformin initiators than non-initiators.39:T73e,This year in review (1) narratively synthesises the effect of, or patient experience with, non-pharmacological or non-surgical rehabilitation treatments for osteoarthritis at any joint; and (2) describes how sex and/or gender are defined, reported, and analysed. We searched three databases (Medline, Embase, CINAHL) for studies that met predefined criteria and selected those of perceived moderate-to-high quality and importance published between 12th March 2024 and 1st March 2025. Studies were grouped according to predominant treatment topic areas (e.g. core [exercise, diet]; adjunct [electrotherapy, manual therapy]; multimodal [different rehabilitation treatments]). Two authors independently screened records. One author extracted data, and another checked 10% of the accuracy. Full-text screening identified 158 eligible studies, reduced to 39 for synthesis. We identified eight themes: i) Exercise is effective for knee osteoarthritis and comorbidities, but has varied effects for hip osteoarthritis; ii) Diet plus exercise is effective for weight loss, but may not reduce pain; iii) Digital rehabilitation is a viable alternative to in-person care; iv) No added benefit of mind/behavioural treatments; v) Effects of electrotherapy modalities on pain were inconsistent and region-specific; vi) Orthoses may relieve pain, but should be individualised to patient preferences; vii) Acupuncture and blood flow restriction treatment show effectiveness in single clinical trials; viii) Treatment packages for osteoarthritis have varied benefits. Sex and gender were reported in 23 and 11 studies, respectively. For gender, most studies used female/male/woman/man interchangeably. No study defined sex or gender, 5% reported results disaggregated by sex or gender, no study justified why results were not, and 5% summarised key sex or gender findings.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Osteoarthritis: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Osteoarthritis (condition). Clinician-written summaries and actionable practice insights. 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the paper does not explicitly list brand names.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00186-5","tag_type":"warning","value":"No specific sample size is reported, as this is a review article synthesising across multiple studies.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00186-5","tag_type":"warning","value":"The paper is a narrative review using a triangulation framework — not a formal systematic review or meta-analysis — so the strength of causal inference varies by condition and evidence type.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00186-5","tag_type":"warning","value":"The study design label 'Systematic Review / Narrative Review' reflects a hybrid approach; the authors describe triangulation of multiple evidence types rather than a preregistered systematic methodology.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates whether weight-loss interventions (lifestyle, surgical, and pharmacological — notably semaglutide and tirzepatide) can prevent or modify common obesity-related conditions across musculoskeletal, metabolic, cardiovascular, mental health, respiratory, and hepatic domains, using a triangulation framework of epidemiological, genetic (including Mendelian randomisation), and randomised trial evidence.","key_result":"Robust trial evidence supports weight loss as disease-modifying in type 2 diabetes and heart failure with preserved ejection fraction; incretin-based therapies (semaglutide, tirzepatide) now achieve ~14–20% average weight loss in people without diabetes and have generated the first large-scale randomised evidence of disease modification across several conditions, though many areas (musculoskeletal, respiratory, mental health, cardiovascular) remain under-investigated.","limitations":"- Many conditions lack adequate randomised trial evidence, limiting causal conclusions.\n- Evidence on varying magnitudes of weight loss with different agents, disease-stage effects, and long-term (legacy) outcomes is sparse.\n- Trials have not adequately addressed multimorbidity, mechanistic mediation, diverse global populations, or access equity.","practice_takeaway":"Clinicians have strong evidence to use weight-loss therapies — especially GLP-1 receptor agonists like semaglutide and dual GLP-1/GIP agonists like tirzepatide — for disease modification in type 2 diabetes and HFpEF, but should recognise that evidence for many other obesity-related conditions is still emerging. Individualised treatment targets and long-term follow-up remain important given persistent gaps in outcome data."}},{"doi":"10.1016/j.jbspin.2026.106122","pmid":"42607800","title":"Atopy is associated with osteoarthritis severity: results from the KHOALA cohort","journal_title":"Joint Bone Spine","journal_issn":"1297-319X","published_at":"2026-08-17T00:00:00.000Z","url":"https://doi.org/10.1016/j.jbspin.2026.106122","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-23T07:33:03.233Z","updated_at":"2026-08-23T07:33:03.233Z","tags":[{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"condition","value":"Asthma","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"condition","value":"Atopic Dermatitis","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"sample_size","value":"n=717","value_numeric":717},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.jbspin.2026.106122","tag_type":"warning","value":"The atopic group was small (n=66), so findings — particularly for the atopic dermatitis-only subgroup (n=16) — should be interpreted cautiously. The impact_flag 'practice_changing' is assigned provisionally; replication in larger cohorts is needed before definitive practice change. No modality or drug tags were applicable, as no therapeutic intervention was studied.","value_numeric":null}],"summaries":{"what_studied":"This study examined whether atopy (defined as history of asthma and/or atopic dermatitis) is associated with symptomatic and structural severity of knee and/or hip OA in 717 adults from the French KHOALA cohort, with up to 7 years of follow-up.","key_result":"Atopy was associated with a 2.46-fold higher odds of end-stage radiographic OA (KL grade 4; 42% vs. 24% in non-atopic patients; adjusted OR 2.46, 95% CI 1.42–4.25, P=0.001) and a near doubling of total knee replacement risk over 7 years (HR 1.99, 95% CI 1.15–3.45, P=0.01). Unadjusted WOMAC pain scores were higher in atopic patients (7.6/20 vs. 6.4/20, P<0.05), but this did not survive adjustment.","limitations":"- Small atopic subgroup (n=66, ~9% of cohort), limiting statistical power and subgroup analyses by atopic condition.\n- Atopy was defined broadly by self-reported history of asthma and/or atopic dermatitis, without objective allergy testing or IgE measurement.\n- Observational design precludes causal inference; residual confounding (e.g., medication use such as corticosteroids) cannot be excluded.","practice_takeaway":"Clinicians managing OA should be aware that patients with a history of asthma or atopic dermatitis may face more severe structural disease and a higher likelihood of needing joint replacement. Atopic status may warrant closer radiographic monitoring and earlier discussion of surgical planning."}},{"doi":"10.1002/art.70300","pmid":"42608901","title":"FSCN1\n promotes rheumatoid arthritis progression via inhibiting\n TRIM38\n ‐mediated ubiquitination of\n IGF2BP1\n in fibroblast‐like synoviocytes","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2026-08-17T00:00:00.000Z","url":"https://doi.org/10.1002/art.70300","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-22T06:53:21.704Z","updated_at":"2026-08-22T06:53:21.704Z","tags":[{"paper_doi":"10.1002/art.70300","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"condition","value":"Rheumatoid Arthritis","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"generic","value":"imipramine","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"generic","value":"NP-G2-044","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"modality","value":"Actin Polymerization Inhibitor","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"modality","value":"Ubiquitination Pathway Modulator","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"sample_size","value":"n=18","value_numeric":18},{"paper_doi":"10.1002/art.70300","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"study_design","value":"Translational/Preclinical Study with Human Tissue Validation","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"warning","value":"Imipramine's known antidepressant/anticholinergic pharmacology may confound attribution of arthritis benefits solely to FSCN1 inhibition in the mouse models.","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"warning","value":"Sample size tag reflects human synovial cohorts only (n=6×3 groups=18); mouse cohort sizes varied (n=5–8) and are not captured in a single N.","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"warning","value":"Study design label is approximate — this paper combines human tissue analysis with mouse in vivo models and in vitro FLS experiments; it does not fit a single canonical design category cleanly.","value_numeric":null},{"paper_doi":"10.1002/art.70300","tag_type":"warning","value":"The 'practice_changing' impact flag reflects strong preclinical mechanistic novelty; no human clinical trials exist yet for FSCN1 inhibition in RA, so clinical translation is speculative at this stage.","value_numeric":null}],"summaries":{"what_studied":"This study examined the role of actin-bundling protein FSCN1 in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), using human synovial tissue (RA, OA, and healthy controls; n=6 each), FLS-specific knockout and overexpression mouse models, transcriptome profiling, RNA immunoprecipitation sequencing, and mass spectrometry to define its mechanism and therapeutic potential.","key_result":"FSCN1 was significantly upregulated in RA synovium (P<0.001), predominantly in PDPN+ FLS. Mechanistically, FSCN1 sequestered TRIM38, blocking IGF2BP1 ubiquitination and sustaining PI3K-AKT/NF-κB signaling. FLS-specific FSCN1 knockout reduced knee swelling, pain behavior, synovial inflammation, and OARSI scores (P<0.0196); pharmacological inhibition with imipramine or NP-G2-044 suppressed FLS activation and alleviated arthritis pathology in mice (P<0.001).","limitations":"- All in vivo efficacy data are from mouse arthritis models; direct human therapeutic validation is lacking.\n- Human synovial samples are small (n=6 per group), limiting generalizability.\n- Imipramine is an established antidepressant with known off-target effects, complicating interpretation of FSCN1-specific pharmacology.","practice_takeaway":"FSCN1 is a mechanistically validated driver of FLS aggression in RA via the TRIM38–IGF2BP1–PI3K/NF-κB axis; while no clinical agents are yet approved for this target, FSCN1 inhibitors (including repurposed imipramine) show preclinical promise and may warrant early-phase evaluation in RA."}},{"doi":"10.1002/acr.80139","pmid":"42605908","title":"Individuals with Multi‐Joint Osteoarthritis Demonstrate Larger Longitudinal Declines in Frailty: Data from the Canadian Longitudinal Study on Aging","journal_title":"Arthritis Care & Research","journal_issn":"2151-464X","published_at":"2026-08-17T00:00:00.000Z","url":"https://doi.org/10.1002/acr.80139","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-20T06:47:52.461Z","updated_at":"2026-08-20T06:47:52.461Z","tags":[{"paper_doi":"10.1002/acr.80139","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"condition","value":"Frailty","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"sample_size","value":"n=13757","value_numeric":13757},{"paper_doi":"10.1002/acr.80139","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"study_design","value":"Prospective Cohort Study","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"warning","value":"OA diagnosis was self-reported based on physician diagnosis without imaging confirmation, which may introduce misclassification bias.","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"warning","value":"The frailty index composition is not detailed in the abstract; clinicians should review the full paper to assess which deficits were included.","value_numeric":null},{"paper_doi":"10.1002/acr.80139","tag_type":"warning","value":"The 'practice_changing' flag reflects a clinically significant quantitative finding (40–47% faster frailty progression), but the observational design means causality cannot be confirmed.","value_numeric":null}],"summaries":{"what_studied":"This study tested whether multi-joint osteoarthritis (OA) accelerates frailty progression over 6 years in 13,757 adults from the Canadian Longitudinal Study on Aging, comparing those with no OA, one-joint, two-joint, and three-joint OA (knee, hip, or hand) using linear mixed-effects models.","key_result":"Frailty progressed 40–47% faster in those with two-or-three affected joints vs. no OA (slopes: 0.348 and 0.330 vs. 0.237), and multi-joint OA (≥2 joints) progressed faster than single-joint OA [β=0.070, 95% CI: 0.029–0.109], despite those groups starting at higher baseline frailty.","limitations":"OA was self-reported by physician diagnosis (no imaging confirmation), frailty was assessed at only three time points over 6 years, and the observational design limits causal inference.","practice_takeaway":"Clinicians should treat multi-joint OA as a red flag for accelerated frailty — patients with two or more affected joints warrant proactive frailty screening and targeted intervention. Single-joint OA also carries risk, but multi-joint involvement marks a meaningfully steeper health decline."}},{"doi":"10.1002/acr.80114","pmid":"42439302","title":"Opioid Use Disorder and Treatment Uptake Among Patients With Rheumatic Conditions in the\n All of Us\n Research Program: A Descriptive Analysis","journal_title":"Arthritis Care & Research","journal_issn":"2151-464X","published_at":"2026-08-02T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13367410/","source_score":26,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-11T06:19:59.463Z","updated_at":"2026-09-11T06:19:59.463Z","tags":[{"paper_doi":"10.1002/acr.80114","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"condition","value":"Opioid Use Disorder","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"condition","value":"Rheumatoid Arthritis","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"condition","value":"Spondyloarthritis","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"condition","value":"Systemic Lupus Erythematosus","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"generic","value":"buprenorphine","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"generic","value":"methadone","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"generic","value":"naltrexone","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"modality","value":"Disease-Modifying Antirheumatic Drug","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"modality","value":"Opioid Use Disorder Pharmacotherapy","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"sample_size","value":"n=37282","value_numeric":37282},{"paper_doi":"10.1002/acr.80114","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"study_design","value":"Cross-Sectional Descriptive Study","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"warning","value":"Geographic overrepresentation of the West U.S. Census Region in the OUD group may limit generalizability.","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"warning","value":"MOUD uptake figures may be slightly overestimated as methadone/buprenorphine/naltrexone can be prescribed for pain or other substance disorders, not exclusively OUD.","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"warning","value":"OUD billing code sensitivity is only 59%, so true OUD prevalence may be higher than reported 4.0%.","value_numeric":null},{"paper_doi":"10.1002/acr.80114","tag_type":"warning","value":"Study design is cross-sectional/descriptive using EHR billing codes; causality and directionality cannot be established.","value_numeric":null}],"summaries":{"what_studied":"This descriptive analysis used the national *All of Us* Research Program (2015–2023, n=37,282) to characterize patients with OA, SLE, RA, or SpA who also had opioid use disorder (OUD), and to measure uptake of medications for OUD (MOUD: buprenorphine, methadone, naltrexone) after first OUD diagnosis.","key_result":"4.0% of rheumatic disease patients had OUD (n=1,502). Those with OUD were younger (mean 57.5 vs 63.7 years), had higher Medicaid enrollment (50.7% vs 22.9%), more psychiatric comorbidities, higher prior opioid exposure (75.7% vs 45.8%), more corticosteroid use, and lower DMARD use (biologic/targeted synthetic: 3.2% vs 4.7%; conventional: 7.5% vs 10.0%). Only 14.5% of eligible patients with OUD received MOUD — well below the national estimate of ~25%.","limitations":"- OUD identified by billing codes only (PPV 64–80%, sensitivity 59%), so active vs. historical OUD cannot be distinguished.\n- Small subgroup sizes prevented analysis of social risk factors and detailed substance-type breakdowns.\n- MOUD may be used for pain or other substance disorders, potentially overestimating true OUD treatment uptake.","practice_takeaway":"Rheumatologists should routinely screen for OUD in patients with SLE, RA, SpA, and OA — especially those on chronic opioids or corticosteroids — and facilitate MOUD access, as fewer than 1 in 7 affected patients currently receives treatment. Lower DMARD use in patients with OUD suggests unmet disease management needs that may compound OUD-related morbidity."}},{"doi":"10.1016/j.joca.2026.05.012","pmid":"42229783","title":"OA Fundamentals Series: DIAGNOSIS AND CLINICAL ASSESSMENT OF OSTEOARTHRITIS","journal_title":"Osteoarthritis and Cartilage","journal_issn":"1063-4584","published_at":"2026-06-01T00:00:00.000Z","url":"https://doi.org/10.1016/j.joca.2026.05.012","source_score":4,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-11T13:42:36.323Z","updated_at":"2026-06-11T13:42:36.323Z","tags":[{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"warning","value":"Level of evidence set to 5 (expert narrative review); no formal evidence grading methodology was described in the abstract.","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"warning","value":"No sample size reported — this is a narrative review with no primary patient data.","value_numeric":null},{"paper_doi":"10.1016/j.joca.2026.05.012","tag_type":"warning","value":"Sex and specific age group of study population are not applicable given the review design.","value_numeric":null}],"summaries":{"what_studied":"Narrative review providing practical guidance for clinicians on the diagnosis and holistic clinical assessment of osteoarthritis (OA), including the role of imaging, laboratory tests, and biopsychosocial factors.","key_result":"OA is primarily a clinical diagnosis based on history and physical examination; imaging and labs rarely change diagnosis or management when typical OA features are present, and normal radiographs do not exclude early OA. Comprehensive assessment should also capture the impact on work, leisure, and social participation.","limitations":"Narrative review design limits evidence grading; no systematic search or meta-analytic synthesis reported; no specific patient cohort or quantitative outcomes presented.","practice_takeaway":"Diagnose OA clinically — reserve imaging and labs for cases with diagnostic uncertainty or suspicion of an alternate condition. Pair diagnosis with holistic, biopsychosocial assessment and periodic reassessment to optimize symptom control and quality of life."}},{"doi":"10.1111/dom.70892","pmid":"42219229","title":"Unveiling the\n BMI\n Risk Threshold for Osteoarthritis: Multi‐Database Causal and Nonlinear Evidence","journal_title":"Diabetes, Obesity and Metabolism","journal_issn":"1462-8902","published_at":"2026-05-31T00:00:00.000Z","url":"https://doi.org/10.1111/dom.70892","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-07T13:26:41.399Z","updated_at":"2026-06-07T13:26:41.399Z","tags":[{"paper_doi":"10.1111/dom.70892","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"condition","value":"Hip Osteoarthritis","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"condition","value":"Knee Osteoarthritis","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"modality","value":"Weight Management","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"sample_size","value":"NHANES n≈ multiple thousand (2007–2018 cycles)","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"study_design","value":"Multi-Database Cross-Sectional and Mendelian Randomization Study","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"warning","value":"The BMI threshold of 24.00 kg/m² falls within the 'normal' range per WHO criteria for non-Asian populations but aligns with overweight thresholds used in some Asian classification systems — clinicians should consider population context when applying this threshold.","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"warning","value":"The exact NHANES sample size (total N) was not explicitly stated in the abstract or results; the sample_size tag was omitted rather than guessed.","value_numeric":null},{"paper_doi":"10.1111/dom.70892","tag_type":"warning","value":"The study design combines multiple methodologies (GBD epidemiology, NHANES observational analysis, Mendelian randomization); the level of evidence reflects the Mendelian randomization component, which approximates a Level 2 causal estimate.","value_numeric":null}],"summaries":{"what_studied":"This multi-database study examined the nonlinear relationship between BMI and osteoarthritis (OA) using Global Burden of Disease 2021 data, NHANES 2007–2018, and GWAS data, applying generalized additive models, segmented logistic regression, and Mendelian randomization to identify BMI thresholds and causal effects on knee and hip OA subtypes.","key_result":"OA risk rose nonlinearly with BMI, with breakpoints at **24.00** and **41.58 kg/m²**. Between 24.00–41.58 kg/m², each 1-unit BMI increase raised OA odds by 2.2% (OR 1.022, 95% CI 1.003–1.041); above 41.58 kg/m², by 5.5% (OR 1.055, 95% CI 1.022–1.090). Mendelian randomization confirmed causal links: BMI → knee OA (OR 1.63, 95% CI 1.50–1.77) and BMI → hip OA (OR 1.54, 95% CI 1.40–1.70). Women and adults ≥45 years showed higher knee OA susceptibility.","limitations":"- Cross-sectional NHANES data limits causal inference for the observational threshold analysis.\n- BMI does not distinguish fat mass from lean mass or fat distribution, which may affect OA risk estimates.\n- GBD and GWAS data may have geographic and ancestral heterogeneity that limits generalizability.","practice_takeaway":"Weight management counseling and OA risk screening should start when BMI exceeds **24 kg/m²** — well before the conventional overweight/obese cutoffs — especially for women and patients aged 45 or older. Clinicians should treat BMI as a modifiable, causally relevant OA risk factor, not just a correlate."}},{"doi":"10.1016/s2213-8587(26)00100-2","pmid":"42208956","title":"Beyond weight loss: multisystem benefits of obesity medications","journal_title":"The Lancet Diabetes & Endocrinology","journal_issn":"2213-8587","published_at":"2026-05-28T00:00:00.000Z","url":"https://doi.org/10.1016/s2213-8587(26)00100-2","source_score":136,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-20T13:35:52.381Z","updated_at":"2026-07-20T13:35:52.381Z","tags":[{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Contrave","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Mounjaro","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Qsymia","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Rybelsus","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Saxenda","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Wegovy","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"brand","value":"Zepbound","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Binge-Eating Disorder","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Chronic Kidney Disease","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Depression","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Heart Failure","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Neurodegenerative Disease","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Obstructive Sleep Apnoea","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Polycystic Ovary Syndrome","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Substance Use Disorder","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"amycretin","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"cagrilintide","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"liraglutide","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"mazdutide","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"naltrexone-bupropion","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"phentermine-topiramate","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"retatrutide","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"survodutide","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"generic","value":"tirzepatide","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"modality","value":"Combination Sympathomimetic/Anticonvulsant","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"modality","value":"GIP/GLP-1 Dual Agonist","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"modality","value":"Opioid Antagonist/Antidepressant Combination","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"warning","value":"PCOS is noted in the abstract to have been recently renamed 'polyendocrine metabolic ovarian syndrome' — clinicians may need to search under both terms in other databases.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"warning","value":"Several investigational agents (survodutide, mazdutide, retatrutide, amycretin) were not approved as of the paper's publication date (May 2026); regulatory status may have changed.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"warning","value":"Sex data for included trial populations are not reported in the abstract; tags default to mixed given the broad multi-condition scope.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00100-2","tag_type":"warning","value":"This is a narrative review, not a systematic review or meta-analysis — the level of evidence (LOE 3) reflects synthesis quality rather than underlying trial quality, which varies widely by comorbidity.","value_numeric":null}],"summaries":{"what_studied":"This review synthesises evidence from RCTs and high-quality meta-analyses on approved and late-stage obesity medications — including phentermine-topiramate, naltrexone-bupropion, GLP-1 receptor agonists (liraglutide, semaglutide), and newer multiagonists (tirzepatide, survodutide, retatrutide, cagrilintide-semaglutide, amycretin) — evaluating their effects across 13+ obesity-related comorbidities beyond weight loss itself.","key_result":"GLP-1-based and multiagonist therapies show beneficial effects across a broad range of comorbid conditions — including type 2 diabetes, MASLD, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnoea, PCOS, osteoarthritis, depression, and binge-eating and substance use disorders — with accumulating evidence that some benefits are independent of weight loss.","limitations":"As a narrative review, it does not perform a systematic meta-analysis; head-to-head comparisons between agents are largely absent; many comorbidity-specific findings come from secondary endpoints of trials not primarily powered for those outcomes.","practice_takeaway":"When selecting an obesity medication, clinicians should consider the patient's full comorbidity profile — not just expected weight loss — as GLP-1-based therapies offer pleiotropic benefits (e.g., cardiovascular, renal, hepatic, neuropsychiatric) that may differ meaningfully across agents.\n\nWeight-loss-independent effects of GLP-1 receptor agonists are now supported by enough evidence to factor into shared decision-making for patients with heart failure, CKD, OSA, or mood disorders."}},{"doi":"10.1002/art.70184","pmid":"41994938","title":"Autoantibodies to Joint‐Related Peptides Are Associated With Onset of Rheumatoid Arthritis in Presymptomatic Seronegative Individuals","journal_title":"Arthritis & 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is not explicitly reported in the abstract; 'mixed' is inferred based on RA and OA population norms.","value_numeric":null},{"paper_doi":"10.1002/art.70184","tag_type":"warning","value":"Total sample size (n=1576) is summed across four overlapping cohorts including a subset at RA diagnosis; individuals may appear in more than one group, so the effective independent N is lower.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated novel IgG autoantibodies against joint-related peptides in presymptomatic individuals who later developed RA (n=518), matched population controls (n=530), and OA patients (n=287), focusing on those negative for anti-CCP and rheumatoid factor (seronegative).","key_result":"The SeNe test identified 13% of seronegative presymptomatic individuals as high-risk for RA onset within 2.5 years, with 97% specificity vs. OA (95% CI 95–99%). An improved SeNe 2.0 panel identified 16% of seronegative presymptomatic individuals with 98% specificity vs. population controls.","limitations":"Sensitivity is modest (13–16% of seronegative presymptomatic individuals identified), limiting broad screening utility. The study relies on cohort data without a prospective interventional arm, so clinical impact on prevention remains unproven. Generalizability may be restricted given specific cohort recruitment criteria.","practice_takeaway":"For seronegative patients without anti-CCP or RF, the SeNe 2.0 autoantibody panel may flag those at high risk of RA onset before symptoms appear, potentially enabling earlier trial enrollment or closer monitoring. Its high specificity (97–98%) helps distinguish early seronegative RA from OA, reducing diagnostic uncertainty."}},{"doi":"10.3399/bjgp.2025.0705","pmid":"42097637","title":"Impact of Treatment Duration on the Effectiveness of Opioid Analgesia: A Systematic Review and Meta-Analysis","journal_title":"British Journal of General Practice","journal_issn":"0960-1643","published_at":"2026-05-08T00:00:00.000Z","url":"https://doi.org/10.3399/bjgp.2025.0705","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-09","doi":"10.3399/bjgp.2025.0705","days":"7","issn":"0960-1643","rank":"10","field":"Clinical Medicine","score":"2","category":"Primary Health Care","categories":["Primary Health Care"],"_categories":["Primary Health Care"]},"pubmed":{"doi":"10.3399/BJGP.2025.0705","title":"Impact of Treatment Duration on the Effectiveness of Opioid Analgesia: A Systematic Review and Meta-Analysis.","journal":"The British journal of general practice : the 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participants; total participant counts vary by subgroup analysis (e.g., 1,700 in short-term responder analysis, 3,345 in long-term).","value_numeric":null},{"paper_doi":"10.3399/bjgp.2025.0705","tag_type":"warning","value":"Subgroup counts refer to trials, not patients; intermediate-term evidence is limited to 3 trials.","value_numeric":null},{"paper_doi":"10.3399/bjgp.2025.0705","tag_type":"warning","value":"The EERW trial design sensitivity analysis was limited to long-term (≥12 week) trials; findings on EERW bias may not generalize to shorter durations.","value_numeric":null},{"paper_doi":"10.3399/bjgp.2025.0705","tag_type":"warning","value":"Tramadol and tapentadol were explicitly excluded due to dual mechanisms of action; findings do not apply to these agents.","value_numeric":null}],"summaries":{"what_studied":"A systematic review and random-effects meta-analysis of randomized trials (search to January 22, 2025) comparing opioids with placebo or opioid-minimized strategies for chronic low back pain or osteoarthritis, grouped by treatment duration (≤4 weeks, 4–12 weeks, ≥12 weeks). Outcomes were clinically important pain relief (≥ “moderate” or ≥30% improvement) and on-treatment pain on a 100-point scale.","key_result":"Across 27 trials, clinically important pain relief varied by duration (P=0.05): opioids increased responder rates only in short-term trials (8 trials; RR 1.42, 95% CI 1.08–1.89; moderate-certainty), not in intermediate-term (3 trials; RR 1.04, 95% CI 0.84–1.30; low-certainty) or long-term (9 trials; RR 0.91, 95% CI 0.73–1.14; moderate-certainty, trending toward controls). Mean pain score differences were statistically significant only at short and intermediate terms and never met the ≥10/100 clinical threshold at any time point.","limitations":"The intermediate-term subgroup was based on only 3 trials with low-certainty evidence.","practice_takeaway":"If opioids are used for chronic low back pain or osteoarthritis, keep courses short (≤4 weeks), when benefit is most likely. Expect little or no added pain relief beyond 4–12 weeks and ≥12 weeks, and plan management accordingly."}},{"doi":"10.1038/s41584-026-01378-2","pmid":"42098429","title":"The gut–joint axis in osteoarthritis","journal_title":"Nature Reviews Rheumatology","journal_issn":"1759-4790","published_at":"2026-05-08T00:00:00.000Z","url":"https://doi.org/10.1038/s41584-026-01378-2","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-10","doi":"10.1038/s41584-026-01378-2","days":"7","issn":"1759-4790","rank":"10","field":"Clinical Medicine","score":"10","category":"Rheumatology","categories":["Rheumatology"],"_categories":["Rheumatology"]},"pubmed":{"doi":"10.1038/s41584-026-01378-2","title":"The gut-joint axis in osteoarthritis.","journal":"Nature reviews. 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ML-guided stratification tools, once validated, may help target these patients for alternative or combination approaches."}},{"doi":"10.1002/art.70157","pmid":"41949152","title":"The Potential Role of Synovial T Cell Infiltration Following Knee Joint Injury in Symptoms and Progression to Osteoarthritis","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2026-05-01T00:00:00.000Z","url":"https://doi.org/10.1002/art.70157","source_score":12,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:27.769Z","updated_at":"2026-05-18T13:25:27.769Z","tags":[{"paper_doi":"10.1002/art.70157","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"condition","value":"Meniscal Injury","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"condition","value":"Posttraumatic Osteoarthritis","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"generic","value":"anti-CD3 antibody","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"modality","value":"T Cell Depletion","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"study_design","value":"Translational Study (Animal Model + Human Cohort)","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"warning","value":"Anti-CD3 depletion results are described as 'preliminary' by the authors themselves, indicating early-stage hypothesis testing only.","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"warning","value":"Sample size for the human patient cohort is not specified in the abstract; human findings should be interpreted cautiously.","value_numeric":null},{"paper_doi":"10.1002/art.70157","tag_type":"warning","value":"Study design is translational (mouse DMM model + human tissue correlation), not a clinical trial — 'practice_changing' flag reflects novelty of finding, not clinical evidence grade.","value_numeric":null}],"summaries":{"what_studied":"This study examined the temporal role of synovial T cell infiltration after knee joint injury in a mouse DMM (destabilization of the medial meniscus) model of posttraumatic OA, compared to non-OA-inducing sham surgery, with validation in human synovial tissue from patients with meniscal injury and OA.","key_result":"Synovial CD4+ and CD8+ T cells (but not monocytes/macrophages) were selectively elevated from day 1 after OA-inducing DMM surgery versus sham, showing persistent cyclical increases throughout OA onset and progression; CD8+ T cells correlated with early postinjury symptoms in patients; CD3+ T cells drove synovial metalloproteinase secretion in vitro; and early anti-CD3 depletion in mice provided preliminary evidence of reduced long-term OA pathology.","limitations":"Anti-CD3 depletion findings are preliminary and from a mouse model only, limiting direct clinical translation. The patient cohort size and design are not fully detailed, leaving the human association data potentially underpowered. Causal directionality between T cell infiltration and OA progression in humans remains unproven.","practice_takeaway":"Early synovial T cell activation after knee injury may be a novel biomarker and therapeutic target for preventing posttraumatic OA — clinicians should consider that acute post-injury inflammation is not uniform, and T cell-directed strategies (rather than broad anti-inflammatory approaches) warrant further investigation."}},{"doi":"10.1016/j.ard.2026.03.006","pmid":"42036268","title":"EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis: 2025 update","journal_title":"Annals of the Rheumatic Diseases","journal_issn":"0003-4967","published_at":"2026-04-27T00:00:00.000Z","url":"https://doi.org/10.1016/j.ard.2026.03.006","source_score":65,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-04-30","doi":"10.1016/j.ard.2026.03.006","days":"14","issn":"0003-4967","rank":"1","field":"Clinical Medicine","score":"65","category":"Rheumatology","categories":["Rheumatology"],"_categories":["Rheumatology"]},"pubmed":{"doi":"10.1016/j.ard.2026.03.006","title":"EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis: 2025 update.","journal":"Annals of the rheumatic diseases","methods":"","results":"The revised recommendations include 4 overarching principles and 11 recommendations on PA and SB including inter alia PA promotion as standard care, measurements of PA, and intervention modalities considering dose, adaptations and the application of (technology-based) behaviour change techniques. 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Growth Factor","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"sample_size","value":"n=not explicitly stated (multiple cohorts of male C57BL/6 mice)","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"study_design","value":"Controlled Animal Study","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"Sample size (total N) was not explicitly reported in the abstract; the sample_size tag was omitted accordingly.","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"Study used only male mice; findings may not apply to female biology or human OA populations without further validation.","value_numeric":null},{"paper_doi":"10.1002/art.70168","tag_type":"warning","value":"The 'practice_changing' impact flag is used cautiously — this is a preclinical animal study, but the mechanistic findings directly inform the clinical controversy around anti-NGF joint side effects.","value_numeric":null}],"summaries":{"what_studied":"Repeated intra-articular (IA) injections of NGF (50 or 500 ng, twice weekly for 4 weeks) into naïve murine knee joints were evaluated for effects on pain sensitization, joint innervation, synovial histopathology, bone, and cartilage using histology, scRNAseq, reporter mice, and bulk DRG RNAseq.","key_result":"NGF caused dose-dependent knee swelling, hyperalgesia, synovial pathology, increased medial subchondral bone mineral density, and medial preosteophytes — but no overt cartilage damage. Nociceptor sprouting in the medial synovium was preceded by upregulation of axonal growth pathways in dorsal root ganglia; scRNAseq implicated lining fibroblasts as key drivers of neuronal sprouting, synovial fibrosis, and ossification.","limitations":"- Animal model only (naïve male C57BL/6 mice); direct translation to human OA pathogenesis is uncertain.\n- Only male mice studied, limiting generalizability to female sex.\n- No cartilage damage was observed, which differs from the full OA phenotype seen in humans.","practice_takeaway":"NGF drives multiple OA-relevant joint changes — including nociceptor sprouting, synovial fibrosis, and subchondral bone remodeling — independent of cartilage damage, supporting its role early in OA pathogenesis. Clinicians should note that while anti-NGF therapies reduce pain, their joint side effects may reflect on-target biological activity of NGF in joint tissues."}},{"doi":"10.1002/art.70033","pmid":"41524472","title":"Integrative single cell\n RNA\n ‐sequencing and spatial transcriptomics uncovers distinct macrophage‐fibroblast cross‐talk in human hip synovium between patients with femoroacetabular impingement and osteoarthritis","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2026-01-12T00:00:00.000Z","url":"https://doi.org/10.1002/art.70033","source_score":4,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-16","doi":"10.1002/art.70033","days":"7","issn":"2326-5191","rank":"10","field":"Clinical Medicine","score":"4","category":"Rheumatology","categories":["Rheumatology"],"_categories":["Rheumatology"]},"pubmed":{"doi":"10.1002/art.70033","title":"Integrative single cell RNA-sequencing and spatial transcriptomics uncovers distinct macrophage-fibroblast cross-talk in human hip synovium between patients with femoroacetabular impingement and osteoarthritis.","journal":"Arthritis & rheumatology (Hoboken, N.J.)","methods":"","results":"Compared to FAI, epiregulin (EREG)-enriched lining synovial fibroblast-like synoviocytes (FLS) were significantly increased in hip OA. EREG","abstract":"Femoroacetabular impingement (FAI) and synovitis have been recognized as essential factors for developing osteoarthritis (OA) in the hip joints. However, little is known about altered synovial cellular compositions, their associated transcriptomic profiles, and cell-cell interactions in FAI and hip OA.\nSynovial samples from a sex-matched cohort of FAI and hip OA patients (n = 6/condition) were analyzed using integrative single-cell RNA sequencing and spatial transcriptomics.\nCompared to FAI, epiregulin (EREG)-enriched lining synovial fibroblast-like synoviocytes (FLS) were significantly increased in hip OA. EREG\nThe findings of this study offer a groundwork in tailoring novel targets and therapies for FAI and hip OA patients.","keywords":[],"pubmed_id":"41524472","conclusions":"The findings of this study offer a groundwork in tailoring novel targets and therapies for FAI and hip OA patients.","publication_date":"2026-01-12T00:00:00"},"crossref":{"DOI":"10.1002/art.70033","URL":"https://doi.org/10.1002/art.70033","ISSN":["2326-5191","2326-5205"],"link":[{"URL":"https://acrjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/art.70033","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://acrjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/art.70033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Integrative single cell\n RNA\n ‐sequencing and spatial transcriptomics uncovers distinct macrophage‐fibroblast cross‐talk in human hip synovium between patients with femoroacetabular impingement and osteoarthritis"],"author":[{"given":"Gulzada","family":"Kulzhanova","sequence":"first","affiliation":[{"name":"Dept. of Orthopaedic Surgery and Rehabilitation, Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY 14611"},{"name":"Dept. of Biomedical Engineering University of Rochester Rochester NY 14627"}]},{"given":"Alexis","family":"Klee","sequence":"additional","affiliation":[{"name":"Dept. of Orthopaedic Surgery and Rehabilitation, Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY 14611"}]},{"given":"Mina","family":"Botros","sequence":"additional","affiliation":[{"name":"Dept. of Orthopaedic Surgery and Rehabilitation, Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY 14611"}]},{"given":"Victoria L.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Dept. of Orthopaedic Surgery and 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Cartil.","doi-asserted-by":"crossref"},{"DOI":"10.7326/M23-3225","key":"10.1016/j.joca.2025.10.008_bib92","year":"2024","issue":"5","author":"Kjeldsen","volume":"177","first-page":"573","unstructured":null,"article-title":"Progressive resistance training or neuromuscular exercise for hip osteoarthritis: a multicenter cluster randomized controlled trial","journal-title":"Ann. Intern. Med.","doi-asserted-by":"crossref"}],"short-title":[],"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"update-policy":"https://doi.org/10.1016/elsevier_cm_policy","alternative-id":["S1063458425011914"],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","oarsijournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"original-title":[],"container-title":["Osteoarthritis and Cartilage"],"published-print":{"date-parts":[[2026,1]]},"reference-count":92,"published-online":null,"references-count":92,"short-container-title":["Osteoarthritis and Cartilage"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1016/j.joca.2025.10.008","is_oa":true,"title":"Osteoarthritis year in review 2025: Rehabilitation and outcomes including sex and gender reporting","updated":"2026-01-10T04:46:20+00:00","published_date":"2025-10-30","best_oa_location":{"url":"https://doi.org/10.1016/j.joca.2025.10.008","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.1016/j.joca.2025.10.008"}}},"created_at":"2026-01-14T18:30:49.575Z","updated_at":"2026-01-21T12:05:26.220Z","tags":[{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"condition","value":"Osteoarthritis","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Acupuncture","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Behavioral Therapy","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Blood Flow Restriction","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Dietary Intervention","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Digital Rehabilitation","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Electrotherapy","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Exercise Therapy","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"modality","value":"Orthoses","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"warning","value":"Design classification may be ambiguous: comprehensive database search with narrative selection rather than a formal systematic review or meta-analysis.","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"warning","value":"Findings on acupuncture and blood flow restriction derive from single trials.","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"warning","value":"Sex and gender terms were used interchangeably across included studies, and none defined these constructs.","value_numeric":null},{"paper_doi":"10.1016/j.joca.2025.10.008","tag_type":"warning","value":"The review reports numbers of studies, not participant counts, and spans multiple joints and modalities.","value_numeric":null}],"summaries":{"what_studied":"A narrative synthesis of non-pharmacological and non-surgical rehabilitation for osteoarthritis across any joint, plus how sex and gender were defined, reported, and analyzed. Searches of Medline, Embase, and CINAHL (12 Mar 2024–1 Mar 2025) found 158 eligible studies; 39 were selected for synthesis across core, adjunct, and multimodal treatments.","key_result":"Eight themes emerged: exercise helps knee osteoarthritis and comorbidities but shows mixed effects in hip osteoarthritis; diet plus exercise reduces weight but may not reduce pain; digital rehab is a viable alternative to in‑person care; mind/behavioral add‑ons showed no added benefit; electrotherapy pain effects were inconsistent and region‑specific; orthoses can relieve pain but should reflect patient preferences; acupuncture and blood flow restriction each showed effectiveness in single trials; multimodal packages had varied benefits. Sex was reported in 23 studies and gender in 11; no study defined sex or gender, 5% disaggregated results by sex/gender, no study justified the lack of disaggregation, and 5% summarized key sex/gender findings.","limitations":"Narrative selection of a subset (39/158) judged moderate-to-high quality may introduce selection bias; conclusions span heterogeneous joints, interventions, and outcomes with region‑specific and inconsistent effects; some signals rely on single clinical trials.","practice_takeaway":"Prioritize exercise for knee osteoarthritis and consider digital rehab as a practical alternative; use diet plus exercise for weight loss without promising pain relief. Reserve mind/behavioral add‑ons and electrotherapy given uncertain benefit, individualize orthoses to patient preference, and treat acupuncture and blood flow restriction as preliminary signals; expect little sex- or gender‑specific guidance due to poor reporting."}}],"initialOffset":19,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Osteoarthritis"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Osteoarthritis"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Osteoarthritis"}}}]]

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