INTRODUCTION / OBJECTIVES: The association between gout and fractures remains controversial due to the competing effects of uric acid's antioxidant properties and gout-induced chronic inflammation. Our study aimed to evaluate the risk of fractures in newly diagnosed gout patients and to analyze the impact of Allopurinol medication adherence on this risk. METHODS: This nationwide cohort study utilized the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database (2002-2019). We identified 4,107 patients newly diagnosed with gout who remained on continuous allopurinol therapy during the 24-month medication assessment period and matched them 1:3 with 12,321 non-gout controls using propensity score matching. Allopurinol adherence was assessed via the Medication Possession Ratio (MPR) over a 24-month period and categorized into three groups: MPR < 0.3, 0.3 ≤ MPR < 0.8, and MPR ≥ 0.8. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for fractures (vertebral, hip, and distal radius). RESULTS: Gout patients demonstrated a significantly higher risk of overall fractures compared to the non-gout group (aHR 5.52; 95% CI 4.19-7.26). A significant inverse linear relationship was observed between allopurinol adherence and fracture risk (P for trend < .001). The risk was highest in the low-adherence group (MPR < 0.3; aHR 5.91; 95% CI 4.40-7.93) and relatively lower in the high-adherence group (MPR ≥ 0.8; aHR 4.77; 95% CI 2.94-7.72). Consistent trends were observed for vertebral (aHR 5.68) and hip (aHR 4.22) fractures. These associations remained consistent across all subgroups, including age, sex, and comorbidities. CONCLUSION: Newly diagnosed gout is associated with a substantially increased risk of fractures. Higher adherence to Allopurinol therapy is correlated with a significant reduction in this risk, suggesting that
OBJECTIVES: We examined whether annual gout flare frequency, as a marker of cumulative inflammatory burden, predicts long-term major adverse cardiovascular events (MACE). METHODS: Using the TriNetX Global Collaborative Network, we identified adults with a first EHR-recorded treated gout flare in 2017. Using a 12-month landmark exposure window, patients were classified as low (≤3), moderate (4-6), or high (≥7) flares/year. Modified MACE (myocardial infarction, stroke, heart failure) was followed from the landmark. Groups were compared using 1:1 propensity score matching. A sensitivity analysis applied a stricter flare definition (gout diagnosis with colchicine, corticosteroid, or intra-articular injection within 0-3 days; NSAIDs excluded). RESULTS: Among 44,705 patients, matching produced balanced cohorts (high vs low, 13,179 pairs; moderate vs low, 9,700 pairs). A graded dose-response was observed: at 7 years, MACE risk was higher in the high (RR 1.45; 95% CI 1.37-1.53) and moderate (RR 1.24; 1.15-1.33) groups versus low. Heart failure risk was elevated in both groups (HR 1.27 [high]; 1.17 [moderate]); stroke and myocardial infarction were elevated only in the high group (7-year HR 1.28 each), with stroke significant from 3 years. Findings were consistent under the stricter sensitivity definition (7-year MACE HR 1.19 [high] and 1.12 [moderate]; Supplementary Figure S1). CONCLUSION: Annual gout flare frequency is a graded marker of sustained cardiovascular risk. Heart failure risk rises with both moderate and high burden, whereas atherothrombotic events emerge predominantly with high flare frequency, suggesting they require greater cumulative inflammatory exposure.
OBJECTIVE: Prescribing advice recommends higher doses of allopurinol in tophaceous gout "to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels". The aim of this study was to determine whether outcomes differ between individuals with and without tophi over one year of allopurinol prescribed according to a serum urate target. METHODS: Individual level participant data from two randomised trials of gout were analysed (n=383). Both trials used allopurinol with the treat-to-target strategy and a serum urate target of <0.36mmol/L. The primary outcome was the percentage of participants with serum urate <0.36mmol/L at month 12 in those with and without tophi. Secondary outcomes included absence of gout flares. The percentages with serum urate <0.36mmol/L and the absence of gout flares were compared between those with and without tophi at baseline using the Cochran- Mantel Haenszel test, controlling for study. RESULTS: Most participants were male, of European ethnicity, and had longstanding gout. Tophi were present in 31% of participants. There was no statistically significant difference in the percentage of participants with serum urate <0.36mmol/L at 12 months between those with and without tophi (70.3 vs 73.6, p=0.76)) nor in the percentage without gout flares in the month prior to month 12 between those with and without tophi (71.4% vs 79.7%; p=0.21). CONCLUSION: Despite the higher monosodium urate crystal burden in those with tophi, key gout outcomes including urate-lowering efficacy and absence of gout flares are not different to those without tophi when prescribing allopurinol.
A newsletter apresenta os destaques do EULAR 2026, focando em novas evidências para o tratamento da Artrite Reumatoide e Espondiloartrite Axial. São discutidos estudos inovadores sobre o uso de tocilizumabe na depressão inflamatória, o efeito da tirzepatida no ácido úrico e a eficácia do upadacitinibe após falha terapêutica. O conteúdo também aborda o papel da IA no suporte a pacientes com esclerose sistêmica e um caso clínico de Doença de Vogt-Koyanagi-Harada.
Background This proof-of-concept study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABP-671, a novel URAT1 inhibitor, in healthy participants and in patients with hyperuricemia and gout. Methods This single-center, randomized, double-blind, placebo-controlled phase I/IIa clinical trial consisted of two parts: a single ascending dose study (SAD) in healthy participants (0.5, 1, 3, and 6 mg, with two participants receiving placebo and six participants receiving ABP-671 tablets per dose cohort), and a multiple ascending dose (MAD) study in patients with hyperuricemia and gout (1, 2, 4, 6 and 12 mg daily, with two patients receiving placebo and seven patients receiving ABP-671 tablets per cohort). Results Thirty-two and 45 Chinese participants were enrolled in the SAD and MAD studies, respectively. In the SAD and MAD studies, eight (25.0%) and 24 (53.3%) participants reported treatment-emergent adverse events (TEAEs), respectively; there were no serious AEs (SAEs), and no grade ≥ 3 TEAEs. In the MAD study, the maximum mean serum urate decrease from baseline in patients with gout was 17.7% (placebo), 56.4% (1 mg QD), 58.1% (2 mg QD), 69.4% (4 mg QD), 77.0% (6 mg QD), and 79.2% (12 mg QD), respectively. The maximum mean serum urate decrease from baseline in serum urate in patients with hyperuricemia was 19.9% (placebo), 50.1% (1 mg QD), 64.1% (2 mg QD), 73.2% (4 mg QD), 81.2% (6 mg QD), and 82.1% (12 mg QD), respectively. Conclusions ABP-671 had an acceptable safety profile in Chinese healthy participants and patients with hyperuricemia and gout. ABP-671 reduced serum urate levels in a dose-dependent manner. Trial registration https://chinadrugtrials.org.cn (No. CTR20211668).
A newsletter apresenta os principais destaques do congresso EULAR 2026, abordando desde a eficácia da manutenção do alopurinol na gota até novos alvos terapêuticos para a Síndrome de Sjögren. Além das atualizações clínicas, explora como fatores psicossociais e a satisfação conjugal influenciam diretamente o prognóstico e a saúde mental de pacientes com doenças reumáticas crônicas.
Background Longitudinal serum uric acid (SUA) transition patterns and their clinical, genetic, and dietary determinants remain poorly characterized. This prospective cohort study — a secondary analysis of the Korea Genome and Epidemiology Study Health Examinee (KoGES-HEXA) cohort — aimed to characterize SUA transition patterns, identify their determinants, and examine their associations with incident hyperuricemia and gout. Methods Genomic DNA was extracted from peripheral blood leukocytes and genotyped by the KoGES infrastructure; 58,701 participants with successfully genotyped data meeting KoGES quality control criteria were initially available. After applying study-specific exclusion criteria, 54,000 participants were included in the final analysis, yielding four SUA transition groups across two examination visits: Normal SUA (81.5%), Newly Developed Hyperuricemia (NDH; 12.4%), Recovered Hyperuricemia (RH; 5.6%), and Persistently Elevated Hyperuricemia (PH; 0.6%). Cox proportional hazards models evaluated incident hyperuricemia (n = 50,676) as the primary outcome and incident gout (n = 45,333) as the secondary outcome. Genetic risk scores (GRS) were constructed from genome-wide association analysis, and machine learning models identified key predictors of incident hyperuricemia. Results Lower eGFR and higher fatty liver index showed the strongest associations with adverse SUA transition groups (OR: 4.60–7.55). A 4-SNP GRS linked to urate transporter genes was strongly associated with hyperuricemia risk (OR: 3.64, 95% CI: 3.17–4.18), with nominally significant gene-lifestyle interactions for smoking, alcohol, and plant-based diet. Plant-based diet adherence was associated with reduced incident hyperuricemia risk (HR: 0.902) and attenuated genetic susceptibility across risk strata. Baseline hyperuricemia showed the strongest association with incident gout (HR: 9.34, 95% CI: 5.74–14.2). Machine learning models achieved good discrimination (AUROC: 0.862–0.885), with eGFR, GRS, sex, and BMI as top predictors. Conclusion Longitudinal SUA transition patterns were strongly associated with incident hyperuricemia and
A newsletter analisa a busca por biomarcadores para a nefrite lúpica, destacando que, apesar de candidatos promissores como a IL-16 e o CD163 urinários, a biópsia renal ainda é o padrão-ouro indispensável. O conteúdo também aborda benefícios da combinação leflunomida e hidroxicloroquina no tratamento de Sjögren e a confiabilidade do PHQ-8 no rastreio de depressão em pacientes com dor crônica, sem viés de sobreposição somática.
Objective Hyperuricemia (HUA) is a prevalent metabolic disorder linked to substantial morbidity. Oxidative stress is a key pathogenic mechanism, yet the cumulative effect of dietary and lifestyle pro- and anti-oxidants remains unclear. The Oxidative Balance Score (OBS) offers a comprehensive metric of oxidative potential. This study aimed to investigate the association between OBS and HUA in a large, nationally representative US adult population. Methods This cross-sectional study included 29,876 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. The OBS was constructed from 16 dietary and 4 lifestyle components. HUA was defined as serum uric acid ≥ 7.0 mg/dL for men and ≥ 6.0 mg/dL for women. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between OBS quartiles and HUA. Restricted cubic splines (RCS) were employed to model non-linear relationships. Subgroup analyses were conducted by gender, age, and estimated glomerular filtration rate (eGFR). Results The overall prevalence of HUA was 20.2%. A significant inverse association was observed between OBS and HUA. After adjusting for multiple confounders, participants in the highest OBS quartile (Q4, most anti-oxidant profile) had a 42% lower odds of HUA compared to those in the lowest quartile (Q1) (OR: 0.58, 95% CI: 0.51–0.66, P-trend < 0.001). This association was more pronounced for lifestyle OBS (OR for Q4 vs. Q1: 0.35, 95% CI: 0.29–0.42) than for dietary OBS (OR for Q4 vs. Q1: 0.70, 95% CI: 0.61–0.81). RCS analysis revealed a significant nonlinear relationship (P-nonlinearity < 0.001), with the protective effect of OBS plateauing at higher scores. The inverse association was consistent across gender and age subgroups but appeared stronger in individuals with normal
A newsletter destaca o estudo RESET-RA, que apresenta a estimulação do nervo vago como uma alternativa promissora para pacientes com Artrite Reumatoide de difícil tratamento. São detalhadas as atualizações das diretrizes EULAR 2025, que reforçam o uso precoce de anti-TNF na Síndrome de Behçet e simplificam o manejo da Artrite Reumatoide após falha ao metotrexato. O conteúdo ainda aborda um caso clínico de tuberculose óssea e revisões rápidas sobre fibromialgia e gota.
Background Global gout burden is rising, yet temporal shifts in age at onset remain insufficiently characterized. Understanding secular changes in incident age distribution is essential for anticipating healthcare demands in aging populations. Methods We conducted a secondary analysis of the Global Burden of Disease Study 2023 data to evaluate global incident gout trends from 1990 to 2023. Mean age at onset, proportion of young-onset cases (< 40 years), and sex-stratified patterns were analyzed using log-linear regression. Forecasting through 2040 was performed using time-series modeling. Results Global incident gout cases increased by 158.2% between 1990 and 2023. Mean age at onset rose from 58.4 to 61.9 years, corresponding to an annual percent increase of approximately 0.18%. The proportion of young-onset cases declined from 15.8% to 9.8%. Males consistently exhibited earlier onset than females, with a stable ~ 4-year sex gap across the study period. Age-specific redistribution demonstrated progressive concentration of incident cases among individuals aged ≥ 60 years. Forecast modeling projects continued elevation in mean onset age to approximately 63.4 years by 2040. Conclusions The global expansion of gout burden is accompanied by aging of incident cohorts rather than earlier disease manifestation. These findings highlight the growing impact of demographic aging on gout epidemiology and underscore the need for age-adapted prevention and management strategies. Key Points • Global incident gout cases more than doubled between 1990 and 2023, demonstrating sustained expansion of disease burden worldwide. • Mean age at onset increased steadily over three decades, indicating progressive aging of incident gout cohorts. • The proportion of young-onset gout (40 years) declined substantially, reflecting redistribution of incidence toward older populations. • Forecast modeling projects continued elevation in age at onset through 2040, highlighting the growing influence
ABSTRACT Background and Aim The relationship of gout with the risk of dementia has been a subject of importance in current studies. There is no comprehensive meta‐analysis regarding their association. Hence, our team performed a systematic review and meta‐analysis to examine the relationship of gout with the risk of dementia. Methods We searched PubMed, EMBASE, Scopus, and Web of Science beginning at database commencement till 1 December 2022. For systematic review and meta‐analysis, 2 independent reviewers comprised observational researches that assessed the relationship of gout with risk of dementia. This research pursued the Preferred Reporting Items for Systematic reviews and Meta‐Analyses summarizing guidelines to extract and synthesize data. Our team applied the random‐effects model to determine pooled risk ratios (RRs) with 95% confidence intervals (CIs). Results Our study covered 5 observational studies. The pooled RR for the risk of overall dementia was 0.80 (95% CI: 0.58–1.10) with no evidence of publication bias. Moreover, the pooled RR demonstrated lesser risk of Alzheimer's disease (AD) at 0.70 (95% CI: 0.62–0.78) and vascular dementia at 0.68 (95% CI: 0.48–0.95) among patients with gout. An inverse association was observed in Asian people, but there was no relationship of gout with dementia among Western people. Conclusion In this meta‐analysis of observational studies, gout was not significantly associated with overall dementia risk, although inverse associations were observed for AD and vascular dementia. These findings suggest potential heterogeneity by dementia subtype and population but should be interpreted cautiously given the observational design. Well‐designed prospective studies and randomized trials are needed to clarify causality and underlying mechanisms. Protocol Registration International Platform of Registered Systematic Review and Meta‐analysis Protocols INPLASY2025110018; https://doi.org/10.37766/inplasy2025.11.0018 .
Objective This study aimed to investigate alterations in the spatial distribution of urate crystals in the osteoarthritic synovium of patients with different levels of serum uric acid (SUA). Additionally, we examined the association between SUA levels and the severity of synovitis and pain in anteromedial osteoarthritis (AMOA) of the knee. Methods Patients who underwent knee arthroplasty due to AMOA were prospectively enrolled. Blood, synovial fluid, and synovium samples were collected and UA levels were quantified. The degree of synovitis was evaluated histologically, and the levels of inflammatory cytokines in the synovial fluid were measured. The spatial distribution of urate crystals in the synovium was determined using Gomori methenamine silver staining, and the pain subscale of the Western Ontario McMaster Universities Osteoarthritis Index was used to evaluate knee pain. The relationships among SUA, degree of synovitis, and knee pain were assessed using Spearman rank correlation and multivariable analyses. Results The pattern of urate crystal deposition in the osteoarthritic synovium was significantly altered in populations with different SUA levels. The capillary wall, sublining layer, and lining cells were sequentially affected. SUA level was the only risk factor for high‐grade synovitis and severe pain in the multivariate analysis. SUA level was also positively correlated with UA level in the synovial fluid and synovium, Krenn histologic score of the synovium, knee pain, and inflammatory cytokine level in the synovial fluid. Conclusion Spatial urate crystal distribution in the synovium was altered when SUA levels were elevated. Elevated SUA levels were also associated with aggravated synovitis and pain.
Objective To evaluate the relation of colchicine use to the risk of total joint arthroplasty (TJA) in individuals with gout, the most common form of arthritis for which colchicine is prescribed. Methods This new‐user design, time‐stratified, population‐based cohort study used a UK primary care database (2000–2021). We identified participants with gout who were newly prescribed colchicine after their gout diagnosis. Each colchicine initiator was propensity score matched with a noninitiator using one‐year cohort accrual blocks. The effect of colchicine on the risk of TJA was assessed using Cox proportional hazard regression. Analyses were repeated and limited to participants with both gout and knee/hip osteoarthritis (OA). Results We identified 31,478 colchicine initiators who were propensity score matched to an equal number of noninitiators (mean age 60 years, mean body mass index 30), with a median follow‐up time of 4.5 years. Colchicine initiators had a 12% lower risk of TJA than noninitiators (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.81–0.96), which remained similar after additional adjustment for confounders (HR 0.89, 95% CI 0.82–0.97). Colchicine initiators with gout had a 23% lower risk of TJA among those with knee/hip OA (HR 0.77, 95% CI 0.64–0.92) compared with noninitiators (HR 0.77, 95% CI 0.64–0.92). Conclusion In this large population‐based cohort of people with gout, colchicine initiation was associated with a modestly lower risk of TJA. Colchicine may offer a long‐term benefit in reducing the risk of joint arthroplasty in individuals with gout and knee or hip OA.
A newsletter destaca que a normalização da IgG total no primeiro ano de tratamento é um preditor de recaída superior à IgG4 na Doença Relacionada à IgG4. Discute também que pacientes com vasculite anti-MPO apresentam maior risco cardiovascular e menor tempo para eventos adversos do que os anti-PR3. Por fim, aborda como a fragilidade impacta a tolerância aos corticoides na polimialgia reumática e o papel dos iSGLT2 na redução da necessidade de alopurinol.
Chronic inflammation underlies a broad range of human diseases, including autoimmune disorders, neurodegeneration, and metabolic syndromes. While acute inflammation is essential for pathogen clearance and tissue repair, persistent activation leads to tissue damage and disease progression. Two key innate immune pathways, the complement system and inflammasomes, are crucial mediators of inflammation and are increasingly recognized as interdependent effectors that sustain chronic inflammatory states. This review examines the mechanistic crosstalk between complement activation and inflammasome signaling, with an emphasis on the NLRP3 inflammasome. We first outline how complement pathways drive inflammation through cell recruitment, cytokine induction, and failure of regulatory checkpoints. Next, we review the triggers, regulation, and persistence of inflammasome activation, highlighting the central role of NLRP3 and its engagement by diverse danger signals in chronic disease. In the main section, we detail multiple mechanistic intersections between the two systems, including shared activation triggers such as reactive oxygen species and mitochondrial damage, direct priming and activation of inflammasomes by complement components (e.g., C3a, C5a, MAC), and feedback loops driven by inflammasome-derived cytokines (IL-1β, IL-18) that enhance complement activity and immune cell recruitment. We further illustrate these interactions across disease contexts, including gout, atherosclerosis, rheumatoid arthritis, systemic lupus erythematosus, and Alzheimer's disease. In each case, complement and inflammasomes form a self-amplifying loop that exacerbates inflammation and tissue damage. We also examine the dual role of C1q as both an enhancer and suppressor of inflammasome activation, depending on the cellular and molecular environment. Finally, we discuss therapeutic strategies targeting these pathways. Complement inhibitors (e.g., eculizumab, avacopan), inflammasome inhibitors (e.g., MCC950), and IL-1β blockers (anakinra) show clinical promise, and dual-targeting approaches may offer synergistic benefit. Understanding the interplay between complement and inflammasomes provides
Hyperuricemia is a metabolic disorder linked to gout, kidney disease, and cardiovascular complications. Understanding its prevalence and risk factors across demographic groups is crucial for effective prevention and management. To evaluate the prevalence of hyperuricemia among U.S. adults by sex, age, and racial/ethnic groups, and identify common and sex-specific risk factors. Data from 34,144 U.S. adults aged ≥20 years, obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2018, were analyzed. Hyperuricemia was defined as serum uric acid levels >7.0 mg/dL in males and >6.0 mg/dL in females. Prevalence estimates were calculated, and multivariate logistic regression models identified risk factors, adjusting for confounders such as body mass index (BMI), alcohol consumption, hypertension, renal function, and other variables. A sensitivity analysis excluding participants with a history of gout was conducted to evaluate the robustness of identified associations. The overall prevalence of hyperuricemia was significantly higher in males (21.1%) compared to females (17.1%, P < 0.001). Females surpassed males in both prevalence and absolute numbers after age 50-59; by age ≥ 80, the number of female cases was more than twice that of males. Non-Hispanic Black adults had the highest prevalence (23.9% in males, 23.4% in females). Key risk factors for both sexes included obesity (OR = 3.91 in males; OR = 4.76 in females), hypertension (OR = 1.65 in males; OR = 2.09 in females), and impaired renal function (eGFR < 30 mL/min/1.73 m²: OR = 3.72 in males; OR = 15.37 in females). Alcohol consumption was positively associated with hyperuricemia in males (OR = 1.25), but not significantly so in females. Diabetes showed opposite associations: protective in males (OR = 0.72) but a risk factor in females (OR = 1.22). Medication use exhibited expected directional
Gout is a crystal-associated autoinflammatory disease triggered by monosodium urate (MSU) crystals, clinically characterized by recurrent transitions between acute inflammatory flares dominated by innate immunity and a state of "trained immunity" during the remission phase. However, previous studies have mostly focused on single time points or local lesions. Such approaches fail to systematically explain the recurrent nature of acute gout flares and the mechanisms underlying multi-system involvement. By integrating evidence from single-cell and spatial transcriptomics as well as mechanistic investigations, this review systematically summarizes the immunopathological features of gout within a spatiotemporal immune framework. At the temporal level, acute gout flares are driven by innate immune activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3)-interleukin-1β (IL-1β) inflammatory cascade. The inflammation then undergoes self-limited resolution mediated by regulatory T cells (Tregs), M2-polarized macrophages, aggregated neutrophil extracellular traps (aggNETs), and pro-resolving lipid mediators. persistent low-grade activation of monocytes/macrophages can still be observed, sustaining a state of "trained immunity." At the spatial level, integrated evidence indicates an immune gradient across the joint, bone, and circulation, ranging from focal hyper-inflammation to systemic low-grade activation. Based on these findings, we propose a time-window stratified intervention strategy centered on the NLRP3-IL-1β axis, and identify inflammatory markers in the joints, subchondral bone, and peripheral blood as the basis for spatially targeted stratification. These insights provide novel perspectives for shifting gout management from the control of individual flares to recurrence risk management and personalized therapy.
Nephrolithiasis is commonly observed in patients with gout; however, the role of asymptomatic hyperuricemia in stone formation remains unclear. This study evaluated the association between serum uric acid levels and nephrolithiasis in a large health screening population. We conducted a cross-sectional analysis of 31,198 Korean adults who underwent health checkups between 2010 and 2020. Clinical parameters included anthropometric measures, blood pressure, serum uric acid, renal and hepatic function markers, lipid profiles, glycemic indices, inflammatory biomarkers, serum calcium, and vitamin D3 levels. Nephrolithiasis was defined as the presence of at least one renal stone ≥5 mm detected by ultrasonography and/or kidney-ureter-bladder radiography. Hierarchical logistic regression models (unadjusted, age- and BMI-adjusted, and fully adjusted) were used to assess associations separately in men and women. Median serum uric acid concentrations were 6.0 mg/dL in men and 4.4 mg/dL in women. In men, higher serum uric acid levels were associated with nephrolithiasis across hierarchical models. In fully adjusted analyses, serum uric acid remained significantly associated with stone prevalence, and men in the highest uric acid quartile (≥6.9 mg/dL) had higher odds compared with those in the lowest quartile (adjusted OR: 3.546; 95% CI: 1.240-10.144). No statistically significant association was observed in women. Higher serum uric acid levels were associated with nephrolithiasis in men but not in women in this cross-sectional analysis. These findings contribute to the epidemiologic understanding of sex-specific differences in stone risk; prospective studies are needed to clarify causality and potential clinical implications.
Gout is a prevalent inflammatory arthropathy driven by monosodium urate crystal deposition, yet the causal relationships between circulating biomarkers and disease susceptibility remain incompletely characterized. Establishing robust causal associations and mapping them to specific effector genes and tissues is essential for identifying mechanistically informed therapeutic targets. We conducted a comprehensive multi-omics Mendelian randomization study integrating a meta-analysis of three large-scale gout genome-wide association studies (N = 1,538,494) with genome-wide data for 233 metabolites, 179 lipid species, and 926 plasma proteins. Findings were replicated in an independent cohort (N = 327,457). Summary-data-based Mendelian randomization and Bayesian colocalization (HyPrColoc) were applied to map causal biomarkers to tissue-specific effector genes using expression quantitative trait loci data from kidney, liver, and whole blood. Candidate genes were experimentally validated in monosodium urate-stimulated THP-1 macrophages. We identified 32 metabolites, one lipid species (TAG 54:3), and two protective plasma proteins (ISLR2, ITIH3) with replicated causal associations with gout. Triglyceride-rich very-low-density lipoprotein particles and circulating isoleucine emerged as prominent risk factors. Multi-tissue transcriptomic mapping prioritized PRELID1 (kidney), NIPAL1 (liver), LMAN2 (whole blood), and CAD as high-confidence effector genes with strong colocalization evidence (posterior probability >0.70). Functional validation confirmed concordant transcriptional and translational dysregulation of these genes following inflammatory stimulation. This integrative analysis establishes a causal framework linking specific lipoprotein subfractions, amino acid metabolism, and novel effector genes to gout pathogenesis, elucidating the systemic metabolic architecture of the disease and identifying potential therapeutic candidates warranting further preclinical investigation before clinical translation.
Objective This study investigated that serum metabolomics, prior to ULT initiation, could serve as a biomarker for responsiveness to colchicine prophylaxis in patients with gout commencing treat‐to‐target ULT. Methods We studied a multicenter prospective cohort (n=409) initiating treat‐to‐target ULT plus colchicine prophylaxis. Untargeted metabolomics were measured at enrollment. We defined putative colchicine‐response or colchicine non‐response as no‐flare, or > 1 flare, respectively, during 6 months after first colchicine dose. Cox regression and machine learning models defined the metabolomic signatures associated with reported flare activity on colchicine prophylaxis in the cohort. Results In our cohort, 36.9% participants experienced at least one flare. Many inflammation‐related metabolites were differentially abundant in the recurrent flare group and correlated with recurrent flare risk. A significant association was found between a four‐metabolite risk score and gout flare activity (adjusted hazard ratio 3.21, 95% CI 2.24‐4.59), independent of the adjusted clinical factors. The machine learning model, which incorporated the top‐ranked metabolites selected by MUVR along with traditional clinical factors, reached an area under the receiver operating characteristic of 0.771 (95% CI 0.713‐0.828) and 0.724 (95% CI 0.611‐0.837) for predicting flare risk in the discovery and validation cohort, respectively. Conclusions Metabolomic profile‐defined inflammation status was associated with gout flare outcomes in ULT initiators receiving colchicine prophylaxis. Identification of these novel metabolomic predictive signatures prior to ULT could potentially help optimize clinical decision‐making for flare prophylaxis colchicine dosing and duration in the first 6 months after initiation of treat‐to‐target ULT in gout. image
People with gout and combined-type hyperuricemia, defined as renal urate overload and renal urate under-excretion, have diminished responsiveness to urate-lowering therapy. Emerging observational data suggest that urine alkalization might improve responsiveness to febuxostat. Hence, this prospective study evaluated the urate-lowering efficacy of citrate mixture added to febuxostat in people with gout and combined-type hyperuricemia. Patients with combined-type hyperuricemia and low urine pH (< 6.2) were prospectively enrolled from a gout clinic. All were treated with febuxostat (initially 20 mg daily, escalated to 40 mg daily if serum urate (SU) ≥360µmol/L). Citrate mixture (3.5 g twice daily, open label) was added according to shared decision of both physician and patient (alkalization vs. non-alkalization). Participants were followed for 12 weeks, with primary endpoint being achievement of SU < 360 µmol/L at final assessment. We enrolled 234 eligible patients, with 194 completing 12 weeks follow-up (98 non-alkalization and 96 with alkalization). At week 12, more patients in the alkalization group achieved SU < 360µmol/L (57.3% vs. 39.8%, P < 0.05), with significantly increased renal urate excretion, and lower febuxostat doses (mean ± S.D, 31.9 ± 9.9 vs. 34.7 ± 8.9 mg, P < 0.05). Additionally, metabolic measures including the triglyceride concentration and triglyceride-glucose index were lower, and high-density lipoprotein cholesterol concentration as well as insulin sensitivity were higher in the alkalization group. The incidence of adverse events was similar between groups. Adjunctive urine alkalization with febuxostat demonstrated a superior urate-lowering response and improved metabolic abnormalities in male with gout and combined-type hyperuricemia. ChiCTR, http://www.chictr.org.cn, ChiCTR2100043573.
A newsletter detalha as atualizações do ACR 2025, evidenciando que a resistência insulínica é o fator causal da hiperuricemia na gota e reforçando a segurança de diversos imunobiológicos durante a gestação e lactação. Além disso, aborda a eficácia de imunossupressores em manifestações não-critério da síndrome antifosfolípide e novas perspectivas sobre o metabolismo do ferro nas espondiloartrites.
A newsletter destaca as principais atualizações do ACR 2025, focando na emergência dos T Cell Engagers (TCEs) como uma terapia celular mais acessível para o tratamento de doenças autoimunes graves. O conteúdo também revisa a falta de evidências robustas para terapias alternativas na osteoartrite de joelho e compila novos guidelines para o manejo de lúpus, gota e artrite idiopática juvenil.
A newsletter destaca o papel da inteligência artificial na redução da variabilidade diagnóstica da Síndrome de Sjögren e a caracterização de um subgrupo de progressão rápida na DISH associado a riscos metabólicos. Além disso, reforça que fatores metabólicos, e não o metotrexato, são os principais vilões da fibrose hepática na artrite psoriásica, e explora novas tecnologias para predição de flares e tratamentos intra-articulares.
A newsletter explora o papel emergente dos agonistas de GLP-1 na reumatologia, evidenciando melhorias em marcadores inflamatórios e desfechos clínicos, apesar da necessidade de estudos com maior robustez metodológica. Destaca-se também o uso da ultrassonografia para diferenciar fenótipos inflamatórios de quadros de sensibilização central na Artrite Psoriásica difícil de tratar, além de evidências que favorecem o uso de prednisona em relação à colchicina na artrite por pirofosfato de cálcio.
Transcutaneous auricular vagus nerve stimulation (taVNS) has recently emerged as a focal noninvasive neuromodulatory approach in anti-inflammatory therapeutics. The vagus nerve functions as a critical neuroimmune interface, tonically suppressing proinflammatory cytokine release via the cholinergic anti-inflammatory pathway (CAP). This mechanism provides substantial therapeutic potential across a spectrum of inflammatory disorders, including postoperative systemic inflammation. Clinical trials have demonstrated the anti-inflammatory efficacy of taVNS, supporting its expanded use in rheumatoid arthritis, systemic lupus erythematosus, gout, inflammatory bowel disease (IBD), and other immune-mediated disorders. Investigations into postoperative inflammation and metabolic syndrome are now emerging. In this review, we synthesize the anatomical substrate, mechanistic framework, and disease-specific applications of taVNS, with a particular emphasis on how stimulation parameters influence therapeutic outcomes. Finally, we outline current challenges and propose future directions to advance research and clinical translation.
Bidirectional two-sample Mendelian randomization (MR) was used to evaluate the potential causal effects of birth weight and uric acid levels (the exposures) and the development of gout (the outcome). Genetic instruments derived from aggregated genome-wide association study data of European ancestry were used to investigate the associations between birth weight (261,932 samples, 9,851,867 single-nucleotide polymorphisms [SNPs]), uric acid levels (110,347 samples, 4,865,122 SNPs), and gout (337,159 samples, including 4807 cases and 332,352 controls, 10,894,596 SNPs). The inverse variance weighting method was used for primary causal estimates, and a series of sensitivity analyses were performed to assess the robustness of the results. The study found that birth weight was negatively associated with uric acid levels (odds ratio [OR] = 0.849; 95% confidence interval [CI]: 0.786-0.917; P < .001) and correspondingly had a negative impact on gout risk (OR = 0.997; 95% CI: 0.994-0.9997; P = .032). In reverse MR analyses, genetic liability for gout was strongly associated with lower birth weight (OR = 0.380; 95% CI: 0.222-0.650; P < .001). This indicates that individuals with a higher genetic predisposition to gout have 62% lower odds of having a higher birth weight. However, the reverse MR analysis of birth weight and uric acid levels was influenced by horizontal pleiotropy and could not provide additional scientific insights. Genetically predicted higher birth weight demonstrated a protective causal effect on serum urate levels. Specifically, each 1-standard deviation increase in birth weight was associated with a 15.1% reduction in the odds of hyperuricemia (OR = 0.849; 95% CI: 0.786-0.917; P < .001). This causal estimate was robust across sensitivity analyses, including the weighted median and MR-Egger methods, with no evidence of directional pleiotropy (Egger intercept P > .05). Leave-one-out analysis confirmed that the results were not driven by any single influential genetic variant.
Gout and hyperuricemia, linked to purine metabolism abnormalities or impaired uric acid excretion, are rising with lifestyle changes. Effective self-management and health literacy are crucial for gout management. While large language models (LLMs) show promise in enhancing health management, their potential on gout patient education remains underexplored. This study aimed to evaluate the accuracy and readability of responses generated by three LLMs, including DeepSeek-V3, DeepSeek-R1, and GPT-5, to questions based on the gout and hyperuricemia guidelines published by the American College of Rheumatology (ACR). Based on the ACR gout guidelines, a set of 42 questions was curated and submitted to three LLMs. Their responses were independently rated on a 5-point Likert scale by three expert gout and hyperuricemia specialists against the guidelines. Accuracy was rated as either an average score of ≥ 4 (low threshold) or 5 (high threshold). The readability of the responses was assessed by Microsoft Word, which provided metrics including the word count, character count, Flesch Reading Ease (FRE) score, Flesch-Kincaid Grade Level (FKGL), and Automated Readability Index (ARI) were calculated. Our findings reveal that response accuracy was significantly higher for GPT-5 compared to DeepSeek-V3 (P < 0.001), with no significant difference between GPT-5 and DeepSeek-R1 (P > 0.05). In terms of readability, GPT-5 produced the most complex responses (FKGL: 12.89 ± 2.22, ARI: 14.87 ± 2.40), while DeepSeek-R1 generated the longest outputs. LLMs show potential in generating responses that are consistent with clinical guidelines for gout management. The deployment of LLMs in gout patient education and clinical decision support necessitates the simultaneous optimization of both accuracy and readability. Key Points • This study is the first to systematically evaluate the agreement with ACR gout guidelines and readability of three state-of-the-art LLMs (DeepSeek-V3, DeepSeek-R1, GPT-5) in gout
Renal impairment and gout are mutually exacerbating conditions, yet the global burden of gout attributable to kidney dysfunction remains unquantified. This study examines trends in gout-related disability associated with renal impairment to inform global health strategies. Data were extracted from the global burden of disease (GBD) 2021. The age-standardized disability-adjusted life years (DALYs) rate and estimated annual percentage change (EAPC) were analysed. A Bayesian Age-Period-Cohort (BAPC) model was implemented to project disease burden. Health inequality analyses were conducted to assess absolute and relative inequalities across socio-demographic index (SDI) regions. The global burden of gout attributable to renal impairment was estimated at 200,033 DALYs (95% Uncertainty Interval (UI): 125,245-296,812) globally. Age-standardized DALY rate increased from 1.47 (95% UI: 0.91-2.21) per 100,000 population in 1990 to 2.36 (95% UI: 1.48-3.50) in 2021 (EAPC 0.67). Significant geographical disparities were observed, with inequality analysis revealing a disproportionate concentration in high SDI regions. Male exhibited elevated age-standardized DALYs compared to females, with both genders exhibiting progressive age-dependent increases. Projection models indicated a potential decline trend in the global burden of renal impairment-associated gout. This study systematically quantifies the global burden of gout attributable to renal impairment, revealing significant disparities across regions, genders, and age. The burden was predominantly concentrated in high-SDI regions, with male sex and advanced age identified as significant individual-level risk factors. These findings highlight the importance of tailored management strategies for high-risk populations, particularly elderly individuals with renal impairment. Key Points • An increasing global burden of gout attributable to renal impairment was observed from 1990 to 2021. Substantial geographical heterogeneity was noted across countries and regions, with the burden showing a positive correlation with the Socio-demographic Index. The disparity in disease burden
To examine, in patients with gout using escalating urate-lowering therapy (ULT), the treatment duration and allopurinol dose required to attain the serum urate (SU) target (< 360 μmol/L; < 6 mg/dL). We studied patients in the NOR-Gout prospective cohort with a recent gout flare and increased SU (> 360 μmol/L). Patients escalated allopurinol dosage until reaching the SU treatment target of <360 µmol/L, switching, if needed, to febuxostat. Of 211 patients, 95.2% were male; mean ± sd age was 56.7 ± 13.7 years, disease duration 8.1 years, 16.6% had clinical tophi, and 12.8% used allopurinol at cohort entry. Mean SU (μmol/L) was reduced from 500 at baseline to 312 at 1 year and 325 at 2 years. Target SU was attained at least once during year 1 by 197 patients (93.4%). Median time to attaining the treatment target was 2 months (mean 2.9 months), and median allopurinol dose was 200 mg (mean 243 mg). Eighty per cent of patients reached the treatment target by 3 months. Patients with SU >480 μmol/L at baseline needed a median of 3 months to attain target SU versus 2 months for patients with SU <480 μmol/L (log-rank p < 0.001). A switch to febuxostat was seen in 12.4% at year 1 and 15.1% at year 2. Treat-to-target ULT using allopurinol leads to attainment of the SU target within 2-3 months at low doses for most patients. Very few patients did not achieve the treatment target at least once during year 1. ACTRN12618001372279.
Hyperuricemia has traditionally been viewed primarily as a cause of gout; however, accumulating evidence indicates that elevated serum uric acid (sUA) is also associated with increased cardiovascular and renal risk. Recent epidemiological studies suggest that adverse outcomes may occur at sUA levels well below the classic crystal-based thresholds, particularly in patients with high cardiovascular risk. This expert consensus document was developed by a multidisciplinary European panel of cardiology, internal medicine, nephrology, and hypertension specialists. The recommendations are based on a critical narrative review of the literature published, including large cohort studies, meta-analyses, randomized controlled trials, and contemporary European guidelines (ESC, ESH, KDIGO, EULAR). Particular emphasis was placed on outcome-driven serum urate thresholds and clinically applicable risk stratification. Hyperuricemia is common and increasingly prevalent, especially among individuals with hypertension, chronic kidney disease, obesity, diabetes, and established cardiovascular disease. Elevated sUA is independently associated with cardiovascular mortality, heart failure, stroke, and faster progression of chronic kidney disease. However, randomized trials have not shown clear cardiovascular or renal benefit from routine urate-lowering therapy in patients with asymptomatic hyperuricemia. Based on current evidence, this consensus proposes a risk-based, individualized approach to hyperuricemia management and presents a pragmatic six-rung therapeutic ladder integrating lifestyle measures, optimization of comorbidities, and pharmacological urate-lowering therapy when clinically indicated. Hyperuricemia should be recognized as a relevant cardiovascular and renal risk factor rather than a benign biochemical finding. Serum urate measurement can improve risk stratification in selected high-risk populations. While routine treatment of asymptomatic hyperuricemia cannot be universally recommended, targeted urate-lowering strategies may be appropriate in patients with high cardiovascular risk, symptomatic disease, or very high sUA levels. Future randomized trials are needed to define whether urate-lowering therapy can improve hard
The rising burden of endocrine and metabolic diseases demands scalable and accessible screening tools. Here we developed Reti-Pioneer, a multitask retinal imaging framework that integrates quality-aware modules with pre-trained foundation models for efficient, multidisease detection. In general, the framework was developed using 107,730 color fundus photographs from both community-based and hospital-based cohorts and achieved area under the receiver operating characteristic curve values on internal test data of 0.833 (95% confidence interval 0.810-0.856) for type 2 diabetes mellitus, 0.832 (0.799-0.866) for gout, 0.787 (0.742-0.833) for osteoporosis, 0.740 (0.726-0.755) for hypertension, 0.736 (0.721-0.751) for hyperlipidemia and 0.699 (0.667-0.730) for thyroid disease. The framework generalized well to six external cohorts from both resource-limited and high-resource settings, and showed biological interpretability via plasma proteomic correlations. In a primary care silent trial, it completed screening in 30.6 ± 6.0 s per case, notably faster than standard laboratory workflows. A subsequent clinical pilot for type 2 diabetes mellitus yielded an area under the receiver operating characteristic curve of 0.776 (0.710-0.842) and negative predictive value of 0.966 (0.946-0.983), surpassing the Finnish Diabetes Risk Score, with high acceptance from clinicians and patients. Overall, Reti-Pioneer could provide a translatable, low-cost pathway from oculomics to actionable clinical screening.
Inflammatory arthritis, especially rheumatoid arthritis (RA), imposes substantial morbidity that diminishes quality of life and escalates health care costs when left untreated. Timely diagnosis and treatment are pivotal. However, limited access to rheumatologists underscores the importance of triaging referrals based on symptom severity. We developed a protocol for using infrared thermography (IRT) to detect joint inflammation and implemented it in an academic primary care clinic as a screening tool for rheumatology referrals. We enrolled people with RA, osteoarthritis (OA), and controls to undergo joint power doppler ultrasound (PDUS) and IRT. IRT image analysis employed manual segmentation with specialized software to determine surface joint temperatures. IRT temperature cutoff points using PDUS as the gold standard for joint inflammation were established. Subsequently, we recruited people with hand or foot joint pain and fast-tracked to rheumatology those surpassing IRT cutoff points for joint inflammation. Thirty-two people with RA, 10 with OA, and 9 controls were enrolled. Most participants (86.3%) were females, and 37.3% were black. Temperature measurements showed robust interrater reliability. Cutoff points at metacarpophalangeal (MCP) (T center ≥32.93 °C, T mean ≥32.67 °C) and wrist (T center ≥33.76 °C, T mean ≥33.79 °C) joints discriminated between inflamed and noninflamed joints. Of the 20 pilot participants, N = 10 (50%) were referred to rheumatology using IRT findings, with N = 8 (80%) seen within 4 weeks. Diagnoses included osteoarthritis, gout, and calcium pyrophosphate deposition disease. IRT demonstrates potential as a reliable tool for identifying inflamed joints and offers a feasible pathway for identifying patients with joint-level thermal abnormalities who may benefit from expedited rheumatologic evaluation. Further research is needed to refine IRT-based rheumatology referral protocols and optimize their utilization.
The objective of this study was to describe the musculoskeletal ultrasound features of asymptomatic hyperuricaemia using the Outcome Measures in Rheumatology (OMERACT) gout semiquantitative scoring system and examine relationships between ultrasound lesions. Participants with serum urate ≥0.48 mmol/L, no previous gout flares, and no subcutaneous tophi (n = 269) underwent a standardised ultrasound examination of bilateral patellar tendons, knee, first and second metatarsophalangeal joints (MTPs), and Achilles tendon. Double contour, tophus, and aggregates were scored according to the OMERACT gout ultrasound semiquantitative scoring system (0-3, with score >1 indicating a definite finding), together with erosion, synovial hypertrophy, and power Doppler activity in the scanned joints. In addition to elementary lesion sum scores, the sum of the semiquantitative double contour scores and tophus scores was calculated for each participant (semiquantitative double contour-tophus [SQDT] sum score, maximum 60). There were 38.7% of participants with at least 1 definite double contour and/or tophus on ultrasound. The median (IQR) SQDT sum score was 2 (0-4). Double contour scores contributed most to the SQDT sum score, followed by first MTP tophus scores. Double contour was associated with synovial hypertrophy at the first and second MTP, and tophus was associated with erosion, synovial hypertrophy, and power Doppler activity at the first MTP. Definite ultrasound features of gout can be identified in more than one-third of people with asymptomatic hyperuricemia. However, the amount of monosodium urate crystal deposition on ultrasound, assessed using the OMERACT gout ultrasound scoring system, is low. In asymptomatic hyperuricemia without clinical evidence of gout, ultrasound features of gout are associated with subclinical joint damage and inflammation.
This study aimed to clarify the latest epidemiologic trends, economic costs, and key drivers of musculoskeletal disorders (MSDs) in high-income regions, where the disease burden has increased despite high overall healthcare spending. Utilising data from the Global Burden of Disease 2023 database, we analysed the trends in incidence, prevalence, and years lived with disability (YLDs) for MSD across 36 high-income countries from 1990 to 2023. Bayesian meta-regression models were employed to quantify the burden attributable to major risk factors. A cross-national transfer model was used to estimate the direct healthcare economic costs associated with MSD in 2023. Spearman correlation analysis was applied to explore the relationship between the Sociodemographic Index (SDI) and disease burden, and trends in disease burden were forecasted for the period 2024 to 2050. Between 1990 and 2023, the total number of incident cases, prevalent cases, and YLDs for MSD in high-income regions increased by 36.75%, 54.28%, and 49.36%, respectively. Although the age-standardised incidence rate decreased by 4.07%, the standardised prevalence and YLD rates increased by 5.04% and 3.98%, respectively, indicating a continuously growing absolute disease burden. Low back pain and osteoarthritis accounted for the largest proportion of the disease burden. For all MSD subtypes except gout, the burden was higher in females than in males. In 2023, the direct medical costs associated with MSD reached as high as $327.68 billion, with the United States accounting for >45% of this amount. Regarding risk factors, the proportion of YLDs attributable to high body mass index increased from 8.3% in 1990 to 10.7% in 2023. The contribution of occupational ergonomic factors remained stable at approximately 7.7%, whereas the smoking-related burden decreased by 30%. Correlation analysis revealed no significant association
Gout is traditionally monitored through serum urate levels (SUA). However, the inflammatory component of the disease may not fully parallel short-term urate fluctuations. We aimed to evaluate longitudinal within-patient dynamics of systemic inflammatory activation and to determine whether inflammation persists beyond clinically apparent flares and may not always reflect contemporaneous SUA. Patients with gout were assessed across three successive outpatient clinic visits. Systemic immune-inflammation index (SII), calculated from the values of the complete blood count, and SUA were measured at each visit. Gout flares, as documented in medical records, were analyzed in relation to inflammatory indices, SUA, and visit order using models adjusted for age and sex. Median SII was significantly higher in patients with gout compared with controls (544.5 vs. 383.9, p < 0.001). Non-flare visits were associated with lower SII values compared with flare visits (β = -203.7, SE = 52.6, p < 0.001), independent of age, sex, visit order, and SUA levels. Notably, visit-specific SUA was not independently associated with SII, and no interaction was observed between flare status and SUA. Elevated inflammatory activity was detectable across visits and was not fully explained by acute flare episodes. Systemic inflammatory activity in gout may persist beyond clinically apparent flares and may not always be fully captured by serum urate levels alone. These findings suggest that inflammatory activity and urate levels do not always align in routine clinical practice, highlighting the potential value of complementary inflammatory assessment.
Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)-with deletions and duplications typically associated with reduced and increased protein levels, respectively-and uncovered previously unknown protein-protein interactions (trans-pQTLs). Our PheWAS recapitulated known associations and uncovered associations in both coding and non-coding regions. Notably, we identified a rare deletion in ZNF451 associated with increased leukocyte telomere length and a non-coding deletion of a SLC2A9 enhancer associated with reduced gout risk. In addition, by combining CNVs with protein-coding single nucleotide variants and indels, we enhanced the power of our study to detect gene-disease associations. Finally, we leveraged this multiomics dataset to identify several pQTLs that constitute candidate biomarkers, including TMPRSS5 for Charcot-Marie-Tooth disease type 1A. This multiancestry whole-genome-sequence CNV PheWAS offers insights into the roles of CNVs in human health outcomes and could serve as a valuable resource for therapeutic development.
Gout is among the most prevalent arthritides worldwide and is associated with high morbidity, cardiovascular risk, and substantial healthcare burden. Despite effective urate-lowering therapies (ULT), many patients remain undertreated, particularly those with severe or complex disease. Nurse-led gout management has improved outcomes in primary care, but data in multimorbid tertiary center populations are lacking. We aimed to evaluate the effectiveness of a supervised nurse-led gout clinic in achieving and maintaining serum urate (SU) targets in a tertiary hospital cohort. In this observational study at the University Hospital (Inselspital) Bern we report on the performance during May 2023 and Jan 2026 in 69 patients with confirmed gout per a restricted panel of EULAR/ACR 2015 classification criteria. Patients were assigned to SU targets of ≤ 300 µmol/L (group 1: severe gout) or ≤ 360 µmol/L (group 2: non-severe gout). An Advanced Practice Nurse (APN) provided education, a rheumatologist provided pharmacological management per 2016 EULAR/ACR guidelines. SU levels, flare frequency, prophylaxis, and treatment adjustments were monitored, with follow-up at six and twelve months. Group 1 required higher allopurinol doses than group 2 (p ≤ 0.01). SU targets were achieved in 80% of group 1 regimens and 68% of Group 2. Flare rates and prophylaxis use were comparable. At six/twelve months follow-up, 62/67% of group 1 and 85/88% of group 2 maintained SU targets. Failures were often due to external treatment modifications. No major ULT-related adverse events were observed. Supervised nurse-led gout management effectively achieves SU targets in this difficult-to-manage cohort. Maintaining SU targets may benefit from shorter follow-up intervals and enhanced education for patients and healthcare providers.
Although hyperuricemia (HUA) is required for gout development, only a fraction of individuals with elevated serum urate progress to the disease. Metabolomic profiling may help uncover biological mechanisms and improve prediction of gout onset. We conducted a prospective metabolomics analysis among 32,563 HUA individuals in the UK Biobank. Baseline plasma metabolites were measured, and differences between individuals who developed gout (n = 2,856) and those who did not were identified. Cox proportional hazards models with false discovery rate correction assessed metabolite-gout associations. Significant metabolites and clinical factors were selected using LASSO-Cox and stepwise regression to construct a gout risk score (GRS). Model performance was evaluated in a test set using survival analysis and time-dependent receiver operating characteristic (ROC) curves. Sensitivity and subgroup analyses, along with validation in an independent validation set and transcriptomic profiling, tested the robustness and biological relevance of results. The final GRS incorporated six metabolites and three clinical variables. It was strongly associated with incident gout (HR = 2.94, 95% CI 2.66-3.23), and individuals in the top quartile had markedly higher risk. The model showed stable predictive ability, with time-dependent AUCs of 0.81-0.79 in the training set and 0.85-0.79 in the test set across 1-10 years. Further validation of the GRS in the independent validation set confirmed the performance. Transcriptomic analyses independently revealed enrichment of inflammatory and lipid-metabolic pathways, consistent with the metabolites included in the GRS. We developed a lipid- and inflammation-related GRS that effectively predicts gout onset among HUA individuals, offering a useful tool for early risk stratification and targeted prevention. Key Points • An NMR-based metabolomics analysis identified several lipid- and inflammation-related metabolites strongly associated with incident gout among individuals with hyperuricemia. • A
The year 2025 marked a significant evolution in the understanding and management of gout, characterised by a growing focus on personalised medicine and multidimensional pathogenetic models.This review provides a comprehensive analysis of the scientific literature published during 2025, highlighting key advancements across several fields. Specifically, we discuss emerging epidemiological trends, such as the rising incidence of early-onset gout, and the integration of artificial intelligence into diagnostic imaging. Groundbreaking genetic studies are explored, identifying early-onset disease as a potentially distinct subset, alongside new insights into the 'gut-kidney axis' and the role of the microbiome in urate homeostasis.Furthermore, this review examines updated pathogenetic mechanisms involving immunometabolic reprogramming and evaluates the latest therapeutic strategies for both gouty arthritis and asymptomatic hyperuricaemia.
To assess the longitudinal association between carotid atherosclerosis and ultrasound signs of urate crystal deposition and musculoskeletal inflammation in gout. We carried out a single-centre, observational, prospective study including consecutive patients with crystal-proven gout from a rheumatology unit. Ultrasound assessments were performed at baseline (M0) and six months (M6) and 12 months (M12) after initiating urate-lowering therapy. Six joints and four tendons were scanned to detect urate crystal deposits (double contour, aggregates, and tophi); local inflammation was identified based on the power Doppler (PD) signal. The carotid arteries were scanned for increased intima-media thickness and atheromatous plaques according to the Mannheim consensus. The association between changes in carotid arteries, deposits, and PD signal in the M0-M6 and M6-M12 periods was studied using the chi-square and Fisher exact tests. Of the 103 patients included, 91 (88.3%) and 78 (75.7%) underwent the M6 and M12 evaluations, respectively. At M0, the mean number of locations with deposits and a positive PD signal was 9.9 (SD 4.1) and 1.1 (SD 1.1). Carotid atheromatous plaque was identified in 59%. During study, near of 97% received ULT and almost half of patients used lipid-lowering drugs. At M6, no association was found between changes in carotid and musculoskeletal variables. However, at M12, plaque regression was more common in those with an absent PD signal than in those with a persistent PD signal (64.0% vs. 28.6%, p=0.017). No association was noted with changes in crystal deposits. After 12 months of urate-lowering treatment, the absence of musculoskeletal inflammation at ultrasound in gout patients was closely linked to improvements in carotid atheromatous plaques.
Uric acid (UA) acts as an antioxidant but, when elevated, contributes to gout. Higher body mass index (BMI) is consistently linked to increased UA, and dyslipidemia correlates with UA levels. However, the extent to which these lipid fractions mediate the BMI-UA relationship remains limited, especially in the context of aging populations in China. This study aims to investigate the association between BMI and UA among Chinese adults and to quantify the mediating roles of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) in this relationship using nationally representative China Health and Retirement Longitudinal Study (CHARLS) data. We analyzed cross-sectional data from 8238 participants in the 2011 wave of the CHARLS, serum lipids were measured via standard CHARLS protocols. Covariates included demographics, lifestyle, clinical history, blood pressure, fasting glucose, sleep, and physical activity. Two multivariable linear regression models estimated the BMI-UA association before and after adjusting for TG, TC, HDLC, and LDLC. A parallel mediation analysis decomposed BMI's total effect on UA into direct and indirect components via each lipid parameter, using 5000 bootstrapped samples. Multivariable linear regression showed that BMI was positively associated with UA (β = 0.12, P < .001, adjusted R2 = 0.19). After adjusting for lipid mediators, the association remained significant but attenuated (β = 0.09, P < .001, adjusted R2 = 0.23). Mediation analysis revealed that high serum TG, TC, and HDLC explain a meaningful part (28.4%) of the BMI-UA association (total indirect effect = 0.714, 95% confidence interval: 0.557-0.881), whereas LDLC shows no significant mediating role (indirect effect = -0.118, 95% confidence interval:-0.267-0.021). Serum TG, TC, and HDLC explain a meaningful part of the BMI-UA association, whereas LDLC shows no significant mediating role. These results highlight lipid metabolism as one pathway linking adiposity with
Internal medicine physicians are often the first physicians from whom patients with rheumatic conditions seek guidance, and they collaborate with rheumatologists when caring for these patients. Here, we summarize 6 studies published in the rheumatology literature in 2025 of relevance to internal medicine specialists and subspecialists who are not rheumatologists. The first study concerns the treat-to-target urate strategy for gout. The second study compared the benefits of a very-low-calorie diet and exercise compared with exercise alone in patients with hip osteoarthritis. The investigators of the third study examined the step counts of purposeful walking and incidence of symptomatic knee osteoarthritis. The fourth study explored the burden of nonarticular pain on quality of life in patients with early rheumatoid arthritis. The fifth study suggested that metformin showed promise in improving knee pain, stiffness, and function in patients with knee osteoarthritis. The last study compared nonsteroidal anti-inflammatory drugs with colchicine in preventing gout exacerbation when initiating urate-lowering therapy. These articles offer new insights for the management of rheumatic conditions that internal medicine physicians often manage.