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Objective To develop a machine learning-based prediction model for identifying hyperuricemic participants at risk of developing gout. Methods A retrospective nationwide Israeli cohort study used the Clalit Health Insurance database of 473 124 individuals to identify adults 18 years or older with at least two serum urate measurements exceeding 6.8 mg/dl between January 2007 and December 2022. Patients with a prior gout diagnosis or on gout medications were excluded. Patients' demographic characteristics, community and hospital diagnoses, routine medication prescriptions and laboratory results were used to train a risk prediction model. A machine learning model, XGBoost, was developed to predict the risk of gout. Feature selection methods were used to identify relevant variables. The model's performance was evaluated using the receiver operating characteristic area under the curve (ROC AUC) and precision-recall AUC. The primary outcome was the diagnosis of gout among hyperuricemic patients. Results Among the 301 385 participants with hyperuricemia included in the analysis, 15 055 (5%) were diagnosed with gout. The XGBoost model had a ROC-AUC of 0.781 (95% CI 0.78–0.784) and precision-recall AUC of 0.208 (95% CI 0.195–0.22). The most significant variables associated with gout diagnosis were serum uric acid levels, age, hyperlipidemia, non-steroidal anti-inflammatory drugs and diuretic purchases. A compact model using only these five variables yielded a ROC-AUC of 0.714 (95% CI 0.706–0.723) and a negative predictive value (NPV) of 95%. Conclusions The findings of this cohort study suggest that a machine learning-based prediction model had relatively good performance and high NPV for identifying hyperuricemic participants at risk of developing gout. [ABSTRACT FROM AUTHOR]

Objectives To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations for gout flares. Methods We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment and re-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation. Results One hundred and nineteen and 108 patients, respectively, were hospitalized for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n  = 94 and n  = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio [aOR] 11.5; 95% CI 4.36, 30.5; P  < 0.001). After implementation, more patients achieved a serum urate ≤360 μmol/l within 6 months of discharge (10.6% pre-implementation vs 26.8% post-implementation; aOR 3.04; 95% CI 1.36, 6.78; P  = 0.007). The proportion of patients re-hospitalized for flares was 14.9% pre-implementation vs 9.3% post-implementation (aOR 0.53; 95% CI 0.22, 1.32; P  = 0.18). Conclusion Over 90% of patients were initiated on ULT after implementing a strategy to optimize hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalizations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalized gout patients to achieve urate targets, closer primary–secondary care integration is still needed. [ABSTRACT FROM AUTHOR]

Objective Illness perceptions are views and beliefs formed in response to a health threat, and they may influence self-management behaviours and chronic disease outcomes. Despite effective medication, sub-optimal outcomes in gout are common. This study aimed to quantitatively investigate illness perceptions in gout to examine how illness perceptions relate to health outcomes. Methods Data were obtained from a randomized controlled trial in which people with gout (n  = 493) completed surveys measuring illness perceptions [Brief Illness Perception Questionnaire (B-IPQ)], gout flares, medication adherence, health-related quality of life, health-care utilization, and productivity, alongside serum urate blood tests at baseline, and at 6- and 12-month follow-ups. Multivariable linear regression identified patient factors independently associated with each B-IPQ item score. Logistic and linear regression, adjusted for age and sex, determined whether baseline B-IPQ items could predict current and future health outcomes. Results Younger individuals and those with severe gout were more likely to experience pessimistic illness perceptions at baseline. Optimistic illness perceptions were associated with lower odds of having had at least one flare in the preceding 6 months. Every 1-point increase in B-IPQ treatment control, indicating an increasingly optimistic view that gout is treatable, decreased the odds of a recent flare prior to baseline by 33% [odds ratio (OR): 0.67; 95% CI: 0.53, 0.85; P  < 0.001] and prior to the 12-month follow-up by 15% (OR: 0.85; 95% CI: 0.76,0.96; P  = 0.01). Pessimistic illness perceptions also predicted poorer medication adherence, health-related quality of life, and productivity, but not serum urate levels. Conclusion Modifying pessimistic illness perceptions, including, but not limited to, patient education, may promote prudent self-management behaviours and better outcomes in gout. Trial registration Australian New Zealand Clinical Trials Registry; https://www.anzctr.org.au/ , ACTRN12616000455460. [ABSTRACT FROM AUTHOR]

Objectives In 2015, the 20-item Tophus Impact Questionnaire (TIQ-20) was developed as a tophus-specific patient-reported outcome measure. The aim of this study was to determine whether TIQ-20 scores change during urate-lowering therapy. Methods We analysed data from a 2-year clinical trial of allopurinol dose escalation using a treat-to-target serum urate approach. For participants with tophaceous gout, the longest diameter of up to three index tophi was measured, using Vernier calipers, and the TIQ-20 was recorded at study visits. Participants at the one site were invited to participate in a dual-energy CT (DECT) substudy. Participants were included in this analysis if they had tophaceous gout and TIQ-20 scores available at baseline, Year 1 and Year 2 (n  = 58, 39 with DECT data). Data were analysed using a mixed-model approach to repeated measures. Results Improvements were observed in all tophus measures over the 2-year period. The mean (s. d.) TIQ-20 scores reduced over 2 years from 3.59 (1.77) to 2.46 (1.73), P  < 0.0001, and the mean (95% CI) TIQ-20 change over the 2 years was –1.13 (–1.54, –0.71). The effect size (Cohen's d) for the change in the sum of the index tophi diameter over 2 years was 0.68, for the DECT urate volume was 0.50, and for the TIQ-20 was 0.71. Conclusion For people with tophaceous gout treated with allopurinol using a treat-to-target serum urate approach, improvements in TIQ-20 occurred, as did improvements in physical and imaging tophus measures. These findings demonstrate that the TIQ-20 is a responsive patient-reported instrument of tophus impact. [ABSTRACT FROM AUTHOR]

Objectives Frequent gout attacks in the initial introduction of urate-lowering therapy (ULT) are significant causes of poor drug adherence and ULT discontinuation. Initial low-dose urate-lowering drugs may be effective in reducing gout flares, however robust evidence is sparse. The aim of this study was therefore to assess the association of initial dose urate-lowering drugs with gout flares in adult males with gout during the initial introduction of ULT. Methods This cohort study obtained data on consecutive gout patients from a single-centre gout cohort study from August 2017 to October 2020. A standard questionnaire was applied to collect demographic and clinical information, and biochemical parameters were tested on the same day. The primary endpoint was to estimate the association of initial dose febuxostat with gout flares, using Cox hazard models with inverse probability of treatment weighting (IPTW). Results A total of 582 gout patients were included in this study. During the 6-week follow-up, 71 (12.2%) patients suffered gout flares. In the main analysis using Cox hazard models with IPTW, compared with colchicine prophylaxis, initial low-dose febuxostat alone had no statistical significance with the increased risk of gout flares [hazard ratio (HR) 1.26; 95% CI 0.58, 2.72], while initial high-dose febuxostat was associated with an increased risk of gout flares (HR 3.08; 95% CI 1.34, 7.07). Conclusions This observational study demonstrated that initial low-dose febuxostat was equally effective in preventing gout flares as colchicine prophylaxis, while initial high-dose febuxostat alone was associated with an increased risk of gout flares. [ABSTRACT FROM AUTHOR]

Colchicine has an important role in managing various conditions, including gout, familial Mediterranean fever, amyloidosis, Behçet's syndrome, recurrent pericarditis and calcium pyrophosphate deposition disease. The adverse effect profile of colchicine is well understood. However, due to its narrow therapeutic index, colchicine has been associated with overdose and fatalities. When ingested in toxic amounts, the mainstay of management is supportive care. Strategies to minimize the risk of colchicine poisoning can focus on three broad causes: unauthorized access, intentional overdose and inappropriate dosing. Culturally safe and appropriate education about storage and appropriate use of colchicine is essential to minimize the risk of overdose. [ABSTRACT FROM AUTHOR]

Objectives Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase. Methods COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety. Results During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P  = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (−73.79% and −47.96%, P  = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only. Conclusions SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase. Clinical trial registration NCT03905512. [ABSTRACT FROM AUTHOR]

The article discusses a study which evaluated adherence to allopurinol using urinary oxypurinol in a cohort of patients with gout and primary hyperuricemia. Topics discussed include data used in the study, most reasonable explanation for undetectable urine oxypurinol level, and demographics and biochemical analyses.

Objective This study aimed to examine the interactions between ultraprocessed food (UPF) consumption and genetic predisposition with the risk of gout. Methods This prospective cohort study analysed 181 559 individuals from the UK Biobank study who were free of gout at baseline. UPF was defined according to the NOVA classification. Assessment of genetic predisposition for gout was developed from a genetic risk score of 33 single nucleotide polymorphisms. Cox proportional hazards were used to estimate the associations between UPF consumption, genetic predisposition and the risk of gout. Results Among the 181 559 individuals in the study, 1558 patients developed gout over 1 648 167 person-years of follow-up. In the multivariable adjustment model, compared with the lowest quartile of UPF consumption, the hazard ratio (HR) and 95% CI of the highest UPF consumption was 1.16 (1.01, 1.33) for gout risk, and there was a non-linear correlation between UPF consumption and the development of gout. In substitution analyses, replacing 20% of the weight of UPF in the daily intake with an equal amount of unprocessed or minimally processed food resulted in a 13% lower risk of gout (HR: 0.87; 95% CI: 0.79, 0.95). In the joint-effect analysis, the HR (95% CI) for gout was 1.90 (1.39, 2.60) in participants with high genetic predisposition and high UPF consumption, compared with those with low genetic predisposition and low UPF consumption. Conclusion In summary, UPF consumption was found to be associated with a higher risk of gout, particularly in those participants with genetic predisposition to gout. Our study indicated that reducing UPF consumption is crucial for gout prevention. [ABSTRACT FROM AUTHOR]

Objective Spontaneous serum uric acid (SUA) decrease has been found in many patients during acute gout attacks, but its mechanism remains unclear. Methods The spontaneous regulation of SUA during a gout attack and its possible causes were evaluated in patients with gout. The mechanism of the spontaneous SUA decrease was further studied in Caco2 cells and a monosodium urate (MSU)-induced gout model of wild-type mice and ABCG2−/− mice. The urate transport function of intestinal epithelial cells was detected by transwell culture of Caco2 cells. Expression of ATP-binding cassette super-family G member 2 (ABCG2), IL-1β and phosphoinositide 3-kinase (PI3K)/Akt was analysed using real-time PCR, western blotting, or immunofluorescence assays. Results SUA decreased during acute gout attacks in both the gout patients and MSU-induced gouty mice. Increased serum CRP and IL-1β levels were correlated with the SUA decrease. Intestinal uric acid excretion and expression of ABCG2 were upregulated in the mice during acute gout attacks. In the ABCG2−/− mice, intestinal uric acid excretion significantly decreased during gout attacks. In an in vitro study of a transwell culture, ABCG2 and its upstream PI3K/Akt pathway were significantly upregulated in intestinal epithelial cells. However, ABCG2 expression and its associated intestinal uric acid transport were inhibited when PI3K/Akt was blocked by a PI3K inhibitor, LY294002. Conclusions Increased intestinal urate excretion resulted in spontaneous SUA downregulation during acute gout attacks. Inflammation-induced PI3K/Akt activation and ABCG2 expression in epithelial cells might contribute to the upregulation of intestinal uric acid excretion. [ABSTRACT FROM AUTHOR]

Objectives In patients with gout there is a lack of longitudinal studies on the course of work productivity. We explored longitudinal changes in and predictors of work productivity over 2 years. Methods Patients in the NOR-Gout observational study with a recent gout flare and serum urate (sUA) >360 µmol/l attended tight-control visits during escalating urate lowering therapy according to a treat-to-target strategy. From the Work Productivity and Activity Impairment (WPAI) questionnaire, scores for work productivity and activity impairment were assessed over 2 years together with the Beliefs about Medicines Questionnaire and a variety of demographic and clinical variables. Results At baseline patients had a mean age of 56.4 years and 95% were males. WPAI scores at baseline were 5.0% work missed (absenteeism), 19.1% work impairment (presenteeism), 21.4% overall work impairment and 32.1% activity impairment. Work productivity and activity impairment improved during the first months, and remained stable at 1 and 2 years. Comorbidities were not cross-sectionally associated with WPAI scores at baseline, but predicted worse work impairment and activity impairment at year 1. The Beliefs about Medicines Questionnaire subscale with concerns about medicines at baseline independently predicted worse overall work impairment and worse activity impairment at year 1. Conclusions In patients with gout who were intensively treated to the sUA target, work productivity and activity impairment were largely unchanged and at 1 year predicted by comorbidities and patient concerns about medication. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether the lactate dehydrogenase D (LDHD) gene deficiency causes juvenile-onset gout. Methods We used whole-exome sequencing for two families and a targeted gene-sequencing panel for an isolated patient. d- lactate dosages were analysed using ELISA. Results We demonstrated linkage of juvenile-onset gout to homozygous carriage of three rare distinct LDHD variants in three different ethnicities. In a Melanesian family, the variant was (NM_153486.3: c.206C>T; rs1035398551) and, as compared with non-homozygotes, homozygotes had higher hyperuricaemia (P  = 0.02), lower fractional clearance of urate (P  = 0.002), and higher levels of d -lactate in blood (P  = 0.04) and urine (P  = 0.06). In a second, Vietnamese, family, very severe juvenile-onset gout was linked to homozygote carriage of an undescribed LDHD variant (NM_153486.3: c.1363dupG) leading to a frameshift followed by a stop codon, p.(AlaGly432fsTer58). Finally, a Moroccan man, with early-onset and high d -lactaturia, whose family was unavailable for testing, was homozygous for another rare LDHD variant [NM_153486.3: c.752C>T, p.(Thr251Met)]. Conclusion Rare, damaging LDHD variants can cause autosomal recessive early-onset gout, the diagnosis of which can be suspected by measuring high d -lactate levels in the blood and/or urine. [ABSTRACT FROM AUTHOR]

The article describes a case of a male patient with carpal tunnel syndrome due to gouty tophi. Topics mentioned include the removal of gouty deposits under the epineurium of the median nerve by surgery, the need of continuous monitoring of uric acid levels and regulation of diet, the use of dual-source computed tomography to diagnose and treat joint deformities caused by tophi, and the administration of dexamethasone to prevent neuro-edema.

Objectives We aimed to clarify the genetic overlaps underlying obesity-related traits, serum urate, and gout. Methods We conducted a comprehensive genome-wide cross-trait analysis to identify genetic correlation, pleiotropic loci, and causal relationships between obesity (the exposure variable), gout (the primary outcome) and serum urate (the secondary outcome). Summary statistics were collected from the hitherto largest genome-wide association studies conducted for BMI (N  = 806 834), waist-to-hip ratio (WHR; N  = 697 734), WHR adjusted for BMI (WHRadjBMI; N  = 694 649), serum urate (N  = 288 649), and gout (N cases = 13 179 and N controls = 750 634). Results Positive overall genetic correlations were observed for BMI (⁠ r g   = 0.27, P  = 6.62 × 10−7), WHR (⁠ r g   = 0.22, P  = 6.26 × 10−7) and WHRadjBMI (⁠ r g   = 0.07, P  = 6.08 × 10−3) with gout. Partitioning the whole genome into 1703 LD (linkage disequilibrium)-independent regions, a significant local signal at 4q22 was identified for BMI and gout. The global and local shared genetic basis was further strengthened by the multiple pleiotropic loci identified in the cross-phenotype association study, multiple shared gene–tissue pairs observed by Transcriptome-wide association studies, as well as causal relationships demonstrated by Mendelian randomization [BMI–gout: OR (odds ratio) = 1.66, 95% CI = 1.45, 1.88; WHR–gout: OR = 1.57, 95% CI = 1.37, 1.81]. Replacing the binary disease status of gout with its latent pathological measure, serum urate, a similar pattern of correlation, pleiotropy and causality was observed with even more pronounced magnitude and significance. Conclusion Our comprehensive genome-wide cross-trait analysis demonstrates a shared genetic basis and pleiotropic loci, as well as a causal relationship between obesity, serum urate, and gout, highlighting an intrinsic link underlying these complex traits. [ABSTRACT FROM AUTHOR]

Objectives The association of tea or coffee consumption with gout is inconsistently reported. Few prospective studies have explored their dose–response relationship. Therefore, we aimed to quantitatively investigate the association between tea, coffee and the risk of developing gout. Methods The study included 447 658 participants in the UK Biobank who were initially free of gout. Tea and coffee consumption were assessed at baseline. We used Cox proportional hazards models to estimate the associations between tea/coffee consumption and incident gout, with restricted cubic spline added to the Cox models to evaluate the dose–response relationships. Results During a median follow-up period of 13.42 years, we recorded 3,053 gout cases. The associations between tea, coffee and gout were nonlinear, with a significant reduction in the risk by ∼ six cups/day of tea and three cups/day of coffee. Compared with those who were not tea and coffee drinkers, those who consumed >6 cups/day of tea or coffee were associated with 23% (HR 0.77, 95% CI, 0.66, 0.91) and 40% (HR 0.60, 95% CI, 0.47, 0.77) lower risks of gout, respectively, and both caffeinated and decaffeinated coffee consumption were associated with a decreased risk. Moreover, hyperuricaemia may modify the association between coffee and gout. Compared with non-coffee consumers with hyperuricaemia, those with ≥4 cups/day coffee intake without hyperuricaemia had the lowest risk (HR 0.34, 95% CI, 0.28, 0.41). Conclusion Consumption of tea or coffee had a strong nonlinear association in gout risk reduction. Hyperuricaemia status had a potential effect modification on the association of coffee intake with gout. [ABSTRACT FROM AUTHOR]

Objective To describe factors associated with change in health-related quality of life (HRQOL) in people living with gout in primary care. Methods In a UK prospective cohort study, adults with a diagnosis of gout registered with 20 general practices completed the Gout Impact Scale (GIS; scale 0–100), 36-item Short Form Physical Function subscale (PF-10; 0–100) and HAQ Disability Index (HAQ-DI; 0–3) via postal questionnaires at baseline and 6, 12, 24 and 36 months. Linear mixed modelling was used to investigate factors associated with changes in HRQOL over 3 years. Results A total of 1184 participants responded at baseline (adjusted response 65.6%); 990 (83.6%) were male, with a mean age of 65.6 years (s. d. 12.5). A total of 818, 721, 696 and 605 responded at 6, 12, 24 and 36 months, respectively. Factors associated with worse disease-specific and generic HRQOL over 3 years were flare frequency (five or more flares; GIS subscales, PF-10), oligo/polyarticular flares (GIS subscales, PF-10, HAQ-DI), worse pain (GIS subscales, PF-10, HAQ-DI), body pain (GIS subscales, PF-10, HAQ-DI) and more severe depression (GIS subscales, PF-10, HAQ-DI) (P  ≤ 0.05). More severe anxiety was associated with worse disease-specific HRQOL only (GIS subscales). Older age (PF-10), being female (PF-10, HAQ-DI) and BMI (HAQ-DI) were associated with worse generic HRQOL (P  ≤ 0.05). Conclusion Gout-specific, comorbid and sociodemographic factors were associated with change in HRQOL over a 3-year period, highlighting people at risk of worse outcomes who could be targeted for interventions. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the therapeutic potential of fibroblast growth factor 21 (FGF21) for gout. Topics explored include the role of FGF21 in the regulation of urate metabolism, energy balance, and lipid homeostasis, the observed link between FGF21 signalling and lower urate levels, and the mechanistic pathway that demonstrate the influence of FGF21 on gout risk and serum urate levels.

Objective Gout flares during urate-lowering therapy (ULT) initiation are common, but predictors of these flares are poorly understood. The aim of this study was to determine whether serum CA72-4 is an independent predictor for gout flares during ULT initiation. Methods A prospective cohort study was conducted between March 2021 and January 2022. Men with gout, at least one gout flare in the past year, and at least three serum CA72-4 measurements in the previous six months were enrolled. Participants were grouped according to their highest recorded serum CA72-4 levels (above or within the normal range). All participants took oral febuxostat 20 mg daily without flare prophylaxis therapy, and attended face-to-face visits every four weeks until 24 weeks. The incidence of gout flare was compared between the two groups. Backward stepwise logistic regression analyses were used to identify risk factors associated with flares. Receiver operating characteristic curve analysis was used to evaluate prediction efficacy. Results A total of 193 completed the study (79 with high CA72-4; 114 with normal CA72-4). The cumulative incidence of at least one gout flare was 48.1% (62.1% in the high CA72-4 group, 38.4% in the normal CA72-4 group, P  = 0.001), and recurrent (≥2) flares was 33.0% (47.1% in the high CA72-4 group, 23.2% in the normal CA72-4, P  < 0.001). High CA72-4, disease duration, intra-articular tophus size, glucose, high-density lipoprotein-cholesterol and ESR were independent risk factors for gout flares. Serum CA72-4 alone predicted recurrent flares with an area under the curve of 0.63 (95% CI = 0.54, 0.71), and 0.78 (95% CI = 0.71, 0.85) when combined with other independent variables. Conclusion High serum CA72-4 predicts the risk of gout flares during ULT initiation. Trial registration ChiCTR; https://www.chictr.org.cn/ ; ChiCTR2100043573. [ABSTRACT FROM AUTHOR]

Objective To investigate associations between treat-to-target urate-lowering therapy (ULT) and hospitalizations for gout. Methods Using linked Clinical Practice Research Datalink and NHS Digital Hospital Episode Statistics data, we described the incidence and timing of hospitalizations for flares in people with index gout diagnoses in England from 2004–2020. Using Cox proportional hazards and propensity models, we investigated associations between ULT initiation, serum urate target attainment, colchicine prophylaxis, and the risk of hospitalizations for gout. Results Of 292 270 people with incident gout, 7719 (2.64%) had one or more hospitalizations for gout, with an incidence rate of 4.64 hospitalizations per 1000 person-years (95% CI 4.54, 4.73). There was an associated increased risk of hospitalizations within the first 6 months after ULT initiation, when compared with people who did not initiate ULT [adjusted Hazard Ratio (aHR) 4.54; 95% CI 3.70, 5.58; P  < 0.001]. Hospitalizations did not differ significantly between people prescribed vs not prescribed colchicine prophylaxis in fully adjusted models. From 12 months after initiation, ULT associated with a reduced risk of hospitalizations (aHR 0.77; 95% CI 0.71, 0.83; P  < 0.001). In ULT initiators, attainment of a serum urate <360 micromol/l within 12 months of initiation associated with a reduced risk of hospitalizations (aHR 0.57; 95% CI 0.49, 0.67; P  < 0.001) when compared with people initiating ULT but not attaining this target. Conclusion ULT associates with an increased risk of hospitalizations within the first 6 months of initiation but reduces hospitalizations in the long term, particularly when serum urate targets are achieved. [ABSTRACT FROM AUTHOR]

Objectives Gout prevalence is reportedly ∼20% higher in US Black adults than Whites, but racial differences in emergency department (ED) visits and hospitalizations for gout are unknown. We evaluated the latest US national utilization datasets according to racial/ethnic groups. Methods Using 2019 US National Emergency Department Sample and National Inpatient Sample databases, we compared racial/ethnic differences in annual population rates of ED visits and hospitalizations for gout (primary discharge diagnosis) per 100 000 US adults (using 2019 age- and sex-specific US census data). We also examined rates of ED visits and hospitalizations for gout among all US ED visits/hospitalizations and mean costs for each gout encounter. Results Compared with White patients, the per capita age- and sex-adjusted rate ratio (RR) of gout primary ED visits for Black patients was 5.01 (95% CI 4.96, 5.06), for Asian patients 1.29 (1.26, 1.31) and for Hispanic patients 1.12 (1.10, 1.13). RRs for gout primary hospitalizations were 4.07 (95% CI 3.90, 4.24), 1.46 (1.34, 1.58) and 1.06 (0.99, 1.13), respectively. Corresponding RRs among total US hospitalizations were 3.17 (95% CI 2.86, 3.50), 3.23 (2.71, 3.85) and 1.43 (1.21, 1.68) and among total ED visits were 2.66 (95% CI, 2.50, 2.82), 3.28 (2.64, 4.08), and 1.14 (1.05, 1.24), respectively. RRs were largest among Black women. Costs for ED visits and hospitalizations experienced by race/ethnicity showed similar disparities. Conclusions These first nationwide data found a substantial excess in both gout primary ED visits and hospitalizations experienced by all underserved racial/ethnic groups, particularly by Black women, revealing an urgent need for improved care to eliminate inequities in gout outcomes. [ABSTRACT FROM AUTHOR]

Objectives Prompt diagnosis of septic arthritis (SA) in acute native hot joints is essential for avoiding unnecessary antibiotics and hospital admissions. We evaluated the utility of synovial fluid (SF) and serum tests in differentiating causes of acute hot joints. Methods We performed a systematic literature review of diagnostic testing for acute hot joints. Articles were included if studying ≥1 serum or SF test(s) for an acute hot joint, compared with clinical assessment and SF microscopy and culture. English-language articles only were included, without date restriction. The following were recorded for each test, threshold and diagnosis: sensitivity, specificity, positive/negative predictive values and likelihood ratios. For directly comparable tests (i.e. identical fluid, test and threshold), bivariate random-effects meta-analysis was used to pool sensitivity, specificity, and areas under the curves. Results A total of 8443 articles were identified, and 49 were ultimately included. Information on 28 distinct markers in SF and serum, differentiating septic from non-septic joints, was extracted. Most had been tested at multiple diagnostic thresholds, yielding a total of 27 serum markers and 156 SF markers. Due to heterogeneity of study design, outcomes and thresholds, meta-analysis was possible for only eight SF tests, all differentiating septic from non-septic joints. Of these, leucocyte esterase had the highest pooled sensitivity [0.94 (0.70, 0.99)] with good pooled specificity [0.74 (0.67, 0.81)]. Conclusion Our review demonstrates many single tests, individually with diagnostic utility but suboptimal accuracy for exclusion of native joint infection. A combination of several tests with or without a stratification score is required for optimizing rapid assessment of the hot joint. [ABSTRACT FROM AUTHOR]

Objective Oxylipins modulate inflammation via complex pathways. The oxylipin profile in gout remains unexplored. In this study, we systemically profiled oxylipins in young men and identified new oxylipin biomarkers for clinical use in differentiating gout from hyperuricaemia. Material and methods Oxylipin profiling was performed in 90 men (30 very early onset gout, 30 asymptomatic hyperuricaemia [HU] and 30 normouricaemia [NU], all aged <20 years) divided into discovery and validation sample sets. The dataset was analysed based on orthogonal projection to latent structure-discriminant analysis. Correlation network and pathway enrichment were conducted to reveal potential oxylipin-involved pathways of gout. Candidate oxylipins were further evaluated and optimized in the validation cohort, and differential oxylipin biomarkers combined with or without serum urate were applied to construct diagnostic models. Results In discovery stage, 21 differential oxylipins in the gout vs HU comparisons and 14 differential oxylipins in the gout vs NU comparisons were discovered. Correlation network analysis was performed and 14(S)-HDHA (14 S -hydroxy-4 Z ,7 Z ,10 Z ,12 E ,16 Z ,19 Z -docosahexaenoic acid) was identified as a hub metabolite in both comparisons. Seven down-regulated oxylipins in the gout vs HU group and five down-regulated oxylipins in the gout vs NU group were validated. Diagnostic models were constructed with the above oxylipins, with 14(S)-HDHA alone having an area under the curve of 1 (95% CI, 1, 1) in both comparisons. Conclusions Young men with very early onset gout have distinct oxylipin spectrums, especially those derived from arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid. Differential oxylipins could serve as candidate serum biomarkers in differentiating gout from hyperuricaemia. [ABSTRACT FROM AUTHOR]

Objectives The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) vs dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new-onset gout remains unknown. This study aims to compare the effects of SGLT2I against DPP4I on gout risks. Methods This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between 1 January 2015 and 31 December 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression models were conducted. Competing risks models and multiple approaches based on the propensity score were applied. Results This study included 43 201 patients [median age: 63.23 years old (Interquartile range, IQR): 55.21–71.95, 53.74% males; SGLT2I group: n  = 16 144; DPP4I group: n  = 27 057] with a median follow-up of 5.59 years (IQR: 5.27–5.81 years) since initial drug exposure. The incidence rate of developing gout [Incidence rate (IR): 2.5; 95% CI: 2.2, 2.9] among SGLT2I users was significantly lower than DPP4I users (IR: 5.2; 95% CI: 4.8, 5.8). SGLT2I was associated with 51% lower risks of gout (HR: 0.49; 95% CI: 0.42, 0.58; P -value < 0.0001) and 51% lower risks of all-cause mortality (HR: 0.49; 95% CI: 0.42, 0.58; P -value < 0.0001) after adjusting for significant demographics, past comorbidities, medications and laboratory results. The results remained consistent on competing risk and other propensity score approaches. Conclusions SGLT2I use was associated with lower risks of new gout diagnosis compared with DPP4I use. [ABSTRACT FROM AUTHOR]

Objectives To determine an US scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligo-arthritis of unknown origin. Methods Patients with acute mono/oligo-arthritis in whom a joint aspiration at the most clinically involved joint (target joint) was requested were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated. Results A total of 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92–0.96) and CPPD (0.90–0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1 joints; CPPD: knees, wrists) plus the target joint had an excellent diagnostic sensitivity (gout: 0.91, CPPD: 0.93) and specificity (gout: 0.91, CPPD: 0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared with the US evaluation of the target joint [gout area under the curve (AUC) 0.91 vs 0.84, P  = 0.03; CPPD AUC 0.93 vs 0.84, P  = 0.04] unless the target joint was the knee or the MTP1 joint in gout and the knee or the wrist in CPPD. Conclusions A targeted US scanning protocol of two joints bilaterally plus the target joint showed an excellent accuracy (>90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis.   A video abstract is available for this article and can be viewed at https://doi.org/10.1093/rheumatology/keac479. [ABSTRACT FROM AUTHOR]

The field of rheumatology has advanced significantly in recent years to provide rheumatologists with an extensive array of medications to combat rheumatic joint conditions. In contrast to an older era, when NSAIDs and other nephrotoxic agents were the mainstay of treatment, modern DMARDs vary considerably in their nephrotoxic potential and their use is not always precluded in populations with pre-existing chronic kidney disease (CKD). This review will explore in detail the safety and efficacy profiles of medications used to treat rheumatologic disease, specifically in the setting of CKD. Specifically, we discuss both traditional agents used, i.e. NSAIDs, CSs and conventional synthetic DMARDs, as well as novel biologic DMARDs and targeted synthetic DMARDs. Anti-gout prescribing in CKD is also reviewed. We aim to provide practical guidance to rheumatologists, nephrologists and general physicians when prescribing these medications in the setting of CKD. [ABSTRACT FROM AUTHOR]

Objectives To evaluate whether US findings indicating MSU deposits and US-detected inflammation (i.e. power Doppler signal) predict gout flares over 12 months. Methods Gout patients on urate-lowering therapy for at least the preceding 6 months were enrolled consecutively in this 12-month prospective, observational, single-centre study. A nested case–control analysis was performed. Cases were participants with at least one flare in the follow-up period, while controls did not self-report any gout flare. The US assessment included elbows, wrists, second MCP joints, knees, ankles, and first MTP joints. The US findings indicating MSU deposits [i.e. aggregates, double contour (DC) sign and tophi] were identified as present/absent according to the Outcome Measure in Rheumatology definitions. Power Doppler signal was scored semiquantitatively. Summated scores were calculated for each US finding. Results Eighty-one gout participants were enrolled, and 71 completed the study. Thirty (42.3%) of 71 participants experienced at least one flare over 12 months, with a median of 2.0 flares. Cases had a greater US burden of MSU deposits (6.7 ± 4.7 vs 2.9 ± 2.6, P  = 0.01) and power Doppler signal (3.73 ± 3.53 vs 0.82 ± 1.44, P  < 0.01) than controls, at baseline. The baseline US scores indicating MSU deposits and US-detected inflammation were significantly associated with the occurrence (total MSU score, adjusted odds ratio:1.75, 95% CI: 1.26, 2.43; power Doppler score, adjusted odds ratio: 1.63, 95% CI: 1.12, 2.40) and the number (total MSU score, adjusted incidence risk ratio: 1.17, 95% CI: 1.08, 1.26; power Doppler score, adjusted incidence risk ratio: 1.29, 95% CI: 1.19, 1.40) of flares over 12 months in multivariate analyses. Conclusions Baseline US findings indicating MSU deposits and US-detected inflammation are independent predictors of gout flares over 12 months. [ABSTRACT FROM AUTHOR]

Objective To examine the expression of Free fatty acid receptor 2 (FFAR2) and Suppressor of cytokine signalling 3 (SOCS3) genes in asymptomatic hyperuricaemia (AH), AH with MSU crystal deposition, inter-critical gout and gout flare. Methods Study participants (n  = 120) comprised 34 people with serum urate (SU) <360 μmol/l, 69 with AH ± MSU crystal deposition and 17 with a gout flare. Sixteen of the 17 patients with a gout flare attended a second visit 6–12 weeks later. Gene expression levels were assessed using RT-qPCR and results computed as fold changes (FC) after normalization to the reference gene. Results FFAR2 was significantly upregulated during gout flares (FC = 2.9) compared with normal SU, AH, and AH + MSU crystal deposition (FC = 1.1, P  < 0.0001 for each comparison). FFAR2 was also significantly upregulated during inter-critical gout (FC = 1.8) compared with normal SU, AH and AH + MSU (FC = 1.1, P  < 0.001 for each comparison). SOCS3 was significantly upregulated during gout flares (FC = 3.4) compared with normal SU, AH, and AH + MSU crystal deposition (FC = 1.1, 1.1 and 1.2, respectively, P  < 0.0001 for each comparison). SOCS3 was also upregulated during inter-critical gout (FC = 2.1) compared with normal SU (P  = 0.02) and AH (P  = 0.006) (FC = 1.1 and 1.2, respectively). FFAR2 expression was upregulated during gout flare compared with inter-critical gout and SOCS3 expression showed negative correlation with flare duration (r = –0.49, P  < 0.05). Conclusion FFAR2 upregulation is associated with gout and may trigger gout flares. SOCS3 may have a role in amelioration of gout flares. [ABSTRACT FROM AUTHOR]

Objectives To identify genetic variants and polygenic risk score (PRS) relating to female gout and asymptomatic hyperuricaemia (AH) in a genome-wide association study (GWAS). Methods Gout, AH and normouricemia controls were included from Taiwan biobank and China Medical University Hospital. All participants were divided into discovery and replication cohorts for GWAS. PRS was estimated according to whether the variant exhibited a protective effect on the phenotypes or not. Each cohort was separated into two groups by the age of 50 years old. Results A total of 59 472 females were enrolled, and gout and AH occupied 1.60% and 19.59%, respectively. Six variants located in genes SLC2A9 , C5orf22 , CNTNAP2 and GLRX5 were significantly predictors of female gout in those aged ≥50. For those aged <50 years old, only the variant rs147750368 (SPANXN1) on chromosome X was found. Most variants located in genes SLC2A9 , ZNF518B , PKD2 and ABCG2 were found to be significantly related to AH in both age groups. The PRS could explain ∼0.59% to 0.89% of variance of gout in variants with protective effects, which showed 6.2 times of mean PRS in the risk variants, but only 1.2 times in the AH phenotype. Moreover, the PRS also revealed a dose-response trend between AH rates and quartile scores. Conclusion The variants in gene SLC2A9 are the major genetic factors for females associated with gout in those aged ≥50. PRS can provide a more robust prediction of the gout/AH under a homogeneous selection of variants that show effects on the traits. [ABSTRACT FROM AUTHOR]

ObjectiveLesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.MethodsSafety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).ResultsIn the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.ConclusionAt the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.

Objectives To explore trends in risk factor control (hypertension, diabetes mellitus, hyperlipidaemia) in patients with gout and medication use among those whose risk factor control targets were not achieved. Methods We used the data from National Health and Nutrition Examination Survey (NHANES) between 2007–2008 and 2017–2018 for analyses. The study samples were weighted so that they could be representative of the non-institutionalized US population. We conducted a cross-sectional analysis to assess trends in risk factor control and medication use, and employed logistic regression analyses to explore patient characteristics associated with risk factor control. Results The prevalence of participants in whom blood pressure control target was achieved decreased from 64.6% in 2007–2008 to 55.3% in 2017–2018 (P -value for trend = 0.03). The percentage of participants whose glycaemic, lipid or all three risk factor control targets were achieved remained stable temporally (P  > 0.05). Some patient characteristics were significantly related to risk factor control, including age 45–64, age ≥65, Asian Americans, non-Hispanic Blacks, higher family income, and being overweight and obese. A trend towards increased use of glucose-lowering medication was found (from 71.0% in 2007–2008 to 94.7% in 2017–2018, P  < 0.01), while the prevalence of taking blood pressure-lowering and lipid-lowering medications remained stable (P  > 0.05). Conclusion Based on NHANES data, a significant trend towards decreased blood pressure control was observed in patients with gout, while glycaemic and lipid control levelled off. These findings emphasize that more endeavours are needed to improve management of cardiovascular risk factors in patients with gout. [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were (i) to evaluate the responsiveness of gout-specific US lesions representing urate deposition in patients receiving treat-to-target urate-lowering therapy using a binary and the OMERACT-defined semi-quantitative scoring systems; (ii) to determine the most responsive US measure for urate deposition and the optimal joint/tendon set for monitoring this. Methods US (28 joints, 14 tendons) was performed in microscopically verified gout patients initiating/increasing urate-lowering therapy and repeated after 6 and 12 months. Static images/videos of pathologies were stored and scored binarily and semi-quantitatively for tophus, double contour sign (DC) and aggregates. Lesion scores were calculated at patient level, as were combined crystal sum scores. Responsiveness of lesions—scored binarily and semi-quantitatively—was calculated at both patient and joint/tendon levels. Results Sixty-three patients underwent longitudinal evaluation. The static images/videos assessed retrospectively showed statistically significant decreases in tophus and DC, when scored binarily and semi-quantitatively, whereas aggregates were almost unchanged during follow-up. The responsiveness of the semi-quantitative tophus and DC sum scores were markedly higher than when using binary scoring. The most responsive measure for urate deposition was a combined semi-quantitative tophus-DC-sum score. A feasible joint/tendon set for monitoring included knee and first–second MTP joints and peroneus and distal patella tendons (all bilateral), representing the most prevalent and responsive sites. Conclusion The OMERACT consensus-based semi-quantitative US gout scoring system showed longitudinal validity with both tophus and DC being highly responsive to treatment when assessed in static images/videos. A responsive US measure for urate deposition and a feasible joint/tendon set for monitoring were proposed and may prove valuable in future longitudinal studies. [ABSTRACT FROM AUTHOR]

Objectives Pegloticase rapidly lowers serum urate in uncontrolled/refractory gout patients, with ≥1 tophus resolution in 70% of pegloticase responders and 28% of non-responders. Dual-energy computed tomography (DECT) non-invasively detects MSU deposition, including subclinical deposition, quantifies MSU volumes and depicts bone erosions. This report presents DECT findings in MIRROR open-label trial participants receiving pegloticase+MTX co-therapy. Methods Serial DECT scans were obtained during pegloticase (8 mg biweekly infusions)+oral MTX (15 mg/week) co-therapy. Bilateral hand/wrist, elbow, foot/ankle and knee images were analysed with default post-processing settings. MSU volumes were quantified and bone erosions were identified and evaluated for remodelling (decreased size, sclerosis, new bone formation). DECT and physical examination findings were compared. Results 2 patients underwent serial DECT. Patient 1 (44-year-old male) completed 52 weeks of pegloticase+MTX co-therapy (26 infusions). Baseline examination detected 4 tophus-affected joints while DECT identified 73 MSU-affected joints (total MSU volume: 128.76 cm3). At end-of-treatment, there were no clinically-affected joints and 4 joints with DECT-detected MSU deposition. MSU volume decreased by 99% and bone erosion remodelling was evident. Patient 2 (51-year-old male) had 10 weeks of therapy (5 infusions), discontinuing because of urate-lowering response loss. Baseline examination detected 7 tophus-affected joints while DECT identified 55 MSU-affected joints (total MSU volume: 59.20 cm3). At end-of-treatment, there were 5 clinically affected joints and 42 joints with DECT-detected MSU deposition. MSU volume decreased by 58% and bone erosion remodelling was evident. Conclusion DECT detected subclinical MSU deposition and quantified changes over time. Rapid tophus resolution and bone erosion remodelling occurred during pegloticase+MTX co-therapy. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03635957. [ABSTRACT FROM AUTHOR]

Objectives Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout. Methods We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3–G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex. Results Overall, 3085 patients with CKD progression were matched to 11   715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3. Conclusion Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the heritability estimates of gout, including its subtypes, in Japanese populations via genome-wide association study (GWS) meta-analyses. Cited are the findings of the investigation on single nucleotidepolymorphism (SNP)-based heritability of three major subtypes of gout, the estimated polygenetic contributions to the heritability of gout, and results indicating that genetic factors are contributors to individual variability in gout.

Objective Interleukin (IL)-37 is a natural suppressor of inflammation. Macrophages play an important role in acute gout flare by dominating the inflammation and spontaneous relief. We have reported that IL-37 could limit runaway inflammation in gout. Here we focus on whether IL-37 inhibits gouty inflammation by altering macrophage functions, and how it does so. Methods Macrophage functions were evaluated in terms of phagocytosis, pyroptosis, polarization and metabolism. Phagocytosis and polarization of macrophages were detected by side scattering and double-labelling induced nitrogen monoxide synthase (iNOS)/arginase-1 (Arg-1) using flow cytometry, respectively. Transcription of pyroptosis-related molecules was detected by qPCR. Metabolomics was performed by liquid chromatograph mass spectrometer. Human IL-37 knock-in mice and a model with point mutation (S9A) at mouse Gsk3b locus were created by CRISPR/Cas-mediated genome engineering. MSU was injected into the paws and peritoneal cavity to model acute gout. Vernier calliper was used to measure the thickness of the paws. The mice paws and human synovium tissues or tophi were collected for pathological staining. Peritoneal fluid of mice was used to enrich macrophages to detect polarization. Results IL-37 promoted non-inflammatory phagocytic activity of macrophages by enhancing phagocytosis of MSU, reducing transcription of pyroptosis-related proteins and release of inflammatory cytokines, protecting mitochondrial function, and mediating metabolic reprogramming in MSU-treated THP-1 cells. These multifaceted roles of IL-37 were partly depended on the mediation of glycogen synthase kinase-3β (GSK-3β). Conclusions Our study revealed that IL-37 could shape macrophages into a 'silent' non-inflammatory phagocytic fashion. IL-37 may become a potentially valuable treatment option for patients of chronic gout, especially for those with tophi. [ABSTRACT FROM AUTHOR]

Objectives Previous studies have indicated that a sizeable proportion of patients with inflammatory arthritis present with features characteristic of central pain sensitization. However, this has not yet been examined in patients with gout. The objective of this study was to explore the presence of generalized pain hypersensitivity and associated factors in patients with diagnosed gout. Methods A cross-sectional survey was performed in outpatients with crystal proven gout using the generalized pain questionnaire (GPQ) to screen for the presence of generalized pain hypersensitivity. Additional self-reported socio-demographic and medical information was collected and several patient-reported outcome measures were completed. Univariable logistic regressions and multivariable LASSO regression analysis with 10-fold cross-validation was used to explore relationships with patient characteristics, clinical features and PROMs. Results Of the 97 included patients (84.5% male; mean (s. d.) age: 68.9 ± 11.9 years), 20 patients (20.6%, 95% CI: 13.0, 30.0) reported possible generalized pain hypersensitivity defined as a GPQ score ≥11 (range: 0–28; mean (s. d.) GPQ: 6.3 ± 5.3). Lower age, concomitant fibromyalgia and more experienced difficulties in performing their social role were independently associated with generalized pain hypersensitivity. Notably, use of urate lowering therapy was significantly lower in those with generalized pain hypersensitivity. Conclusions Generalized pain hypersensitivity appears to be quite common in gout, despite its more intermittent nature compared with other inflammatory arthritides. As this kind of pain does not respond well to regular treatment, screening for non-inflammatory pain may be important for improving pain management in gout. [ABSTRACT FROM AUTHOR]

The article describes the case of a 77-year-old woman with arterial hypertension and a history of stroke and with a three-month history of slowly progressive gait impairment due to muscle weakness and hypotesthesia of the lower limbs. Topics include finding on physical examination, a diagnosis of tophaceous gout, and the need to recognize the clinical signs of gout and acknowledge the potential formation of monosodium urate (MSU) crystals in the spine as a cause of neurological symptoms.

Objectives Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. Methods Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. Results Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13–96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. Conclusion No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to characterize the systemic lipid profile of patients with asymptomatic hyperuricemia (HUA) and gout using lipidomics, and to find potential underlying pathological mechanisms therefrom. Methods Sera were collected from Affiliated Hospital of Nanjing University of Chinese Medicine as centre 1 (discovery and internal validation sets) and Suzhou Hospital of Traditional Chinese Medicine as centre 2 (external validation set), including 88 normal subjects, 157 HUA and 183 gout patients. Lipidomics was performed by ultra high performance liquid chromatography plus Q-Exactive mass spectrometry (UHPLC-Q Exactive MS). Differential metabolites were identifed by both variable importance in the projection ≥1 in orthogonal partial least-squares discriminant analysis mode and false discovery rate adjusted P ≤ 0.05. Biomarkers were found by logistic regression and receiver operating characteristic (ROC) analysis. Results In the discovery set, a total of 245 and 150 metabolites, respectively, were found for normal subjects vs HUA and normal subjects vs gout. The disturbed metabolites included diacylglycerol, triacylglycerol (TAG), phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, etc. We also found 116 differential metabolites for HUA vs gout. Among them, the biomarker panel of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 could differentiate well between HUA and gout. The area under the receiver operating characteristic ROC curve was 0.8288, the sensitivity was 82% and the specificity was 78%, at a 95% CI 0.747, 0.9106. In the internal validation set, the predictive accuracy of TAG 18:1-20:0-22:1 and TAG 14:0-16:0-16:1 panel for differentiation of HUA and gout reached 74.38%, while it was 84.03% in external validation set. Conclusion We identified serum biomarkers panel that have the potential to predict and diagnose HUA and gout patients. [ABSTRACT FROM AUTHOR]

Objectives There is a lack of large longitudinal studies of urate deposition measured by dual-energy CT (DECT) during urate lowering therapy (ULT) in people with gout. We explored longitudinal changes in DECT urate depositions during a treat-to-target strategy with ULT in gout. Methods Patients with a recent gout flare and serum-urate (sUA) >360 µmol/l attended tight-control visits during escalating ULT. The treatment target was sUA <360 µmol/l, and <300 µmol/l if presence of tophi. A DECT scanner (General Electric Discovery CT750 HD) acquired data from bilateral forefeet and ankles at baseline and after one and two years. Images were scored in known order, using the semi-quantitative Bayat method, by one experienced radiologist who was blinded to serum urate and clinical data. Four regions were scored: the first metatarsophalangeal (MTP1) joint, the other joints of the toes, the ankles and midfeet, and all tendons in the feet and ankles. Results DECT was measured at baseline in 187 of 211 patients. The mean (s. d.) serum urate level (μmol/l) decreased from 501 (80) at baseline to 311 (48) at 12 months, and 322 (67) at 24 months. DECT scores at all locations decreased during both the first and the second year (P <0.001 for all comparisons vs baseline), both for patients achieving and not achieving the sUA treatment target. Conclusions In patients with gout, urate depositions in ankles and feet as measured by DECT decreased both in the first and the second year, when patients were treated using a treat-to-target ULT strategy. [ABSTRACT FROM AUTHOR]

Objectives To develop and validate a gout flare risk stratification tool for people with gout hospitalized for non-gout conditions. Methods The prediction rule for inpatient gout flare was derived from a cohort of 625 hospitalized people with comorbid gout from New Zealand. The rule had four items: no pre-admission gout flare prophylaxis, no pre-admission urate-lowering therapy, tophus and pre-admission serum urate >0.36 mmol/l within the previous year (GOUT-36 rule). Two or more items are required for the classification of high risk for developing inpatient gout flares. The GOUT-36 rule was validated in a prospective cohort of 284 hospitalized people with comorbid gout from Thailand and China. Results The GOUT-36 rule had a sensitivity of 75%, specificity of 67% and area under the curve of 0.71 for classifying people at high risk for developing inpatient gout flares. Four risk groups were developed: low (no items), moderate (one item), high (two items) and very high risk (three or four items). In a population with frequent (overall 34%) in-hospital gout flares, 80% of people with very high risk developed inpatient flares while 11% with low risk had inpatient flares. Conclusion The GOUT-36 rule is simple and sensitive for classifying people with high risk for inpatient gout flares. The rule may help inform clinical decisions and future research on the prevention of inpatient gout flares. [ABSTRACT FROM AUTHOR]

Objectives Hospital admissions for gout flares have increased dramatically in recent years, despite widely available, effective medications for the treatment and prevention of flares. We conducted a systematic review to evaluate the effectiveness and implementation of interventions in patients hospitalized for gout flares. Methods A search was conducted in MEDLINE, Embase and the Cochrane library, from database inception to 8 April 2021, using the terms 'gout' and 'hospital' and their synonyms. Studies were included if they evaluated the effectiveness and/or implementation of interventions during hospital admissions or emergency department attendances for gout flares. Risk of bias assessments were performed for included studies. Results Nineteen articles were included. Most studies were small, retrospective analyses performed in single centres, with concerns for bias. Eleven studies (including five randomized controlled trials) reported improved patient outcomes following pharmacological interventions with known efficacy in gout, including allopurinol, prednisolone, NSAIDs and anakinra. Eight studies reported improved outcomes associated with non-pharmacological interventions: inpatient rheumatology consultation and a hospital gout management protocol. No studies to date have prospectively evaluated strategies designed to prevent re-admissions of patients hospitalized for gout flares. Conclusion There is an urgent need for high-quality, prospective studies of strategies for improving uptake of urate-lowering therapies in hospitalized patients, incorporating prophylaxis against flares and treat-to-target optimization of serum urate levels. Such studies are essential if the epidemic of hospital admissions from this treatable condition is to be countered. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to compare the prophylactic effect of regular-dose (RD, 1.2 mg/day) vs low-dose (LD, 0.6 mg/day) colchicine on gout flare when initiating urate-lowering therapy. Methods In this retrospective cohort study, we included gout patients who were initiated on either allopurinol or febuxostat, in combination with colchicine therapy and followed them up for 3 months. We analysed the rates of gout flare and adverse events according to the dose of colchicine. We performed the inverse probability of treatment weighting (IPTW) and weighted logistic regression analysis to assess the treatment effect. Analysis of gout flares and adverse events was performed on an intention-to-treat (ITT) and per-protocol (PP) basis. Results Of the total of 419 patients with gout, 177 patients (42.2%) received LD colchicine, whereas 242 patients (57.8%) received RD colchicine. Lower BMI and estimated glomerular filtration rate, and higher incidence of cardiovascular disease were seen in the LD group than in the RD group. In IPTW-adjusted analysis, events of gout flare were not significantly different between the LD and RD groups [ITT: 14.3% vs 11.3%; odds ratio (OR): 1.309, 95% CI: 0.668, 2.566, P  = 0.432; PP: 15.3% vs 10.0%; OR: 1.623, 95% CI: 0.765, 3.443, P  = 0.207]. However, LD colchicine was associated with a lower rate of adverse events than RD colchicine [ITT: 8.2% vs 17.9%; OR: 0.410, 95% CI: 0.217, 0.777; P  < 0.05; PP: 8.4% vs 17.2%; OR: 0.442, 95% CI: 0.223, 0.878; P  < 0.05]. Conclusion Our data suggest that LD colchicine can adequately prevent gout flare with fewer adverse events compared with RD colchicine. [ABSTRACT FROM AUTHOR]

Objective To investigate the onset of comorbidities and pattern of flares over 5 years according to baseline comorbidity clusters in people with gout. Methods In a prospective primary care-based cohort study, adults aged ≥18 years with gout were identified from primary care medical records in 20 general practices across the West Midlands, UK and followed up over 5 years. Four clusters of participants have been defined previously according to baseline comorbidity status. The associations of (i) incident comorbidities and (ii) gout flares with baseline cluster membership were estimated using age and sex-adjusted Poisson regression and mixed effects ordinal logistic regression, respectively. Results The comorbidity with the highest incidence was coronary artery disease (39.2%), followed by hypertension (36.7%), chronic kidney disease stage ≥3 (18.1%), obesity (16.0%), hyperlipidaemia (11.7%), diabetes (8.8%) and cancer (8.4%). There were statistically significant associations observed between cluster membership and incidence of coronary artery disease, hyperlipidaemia, heart failure and hypertension. In each cluster, nearly one-third of participants reported two or more gout flares at each time-point. History of oligo/polyarticular flares (odds ratio [OR]= 2.16, 95% confidence interval [CI]: 1.73, 2.70) and obesity (1.66, 95% CI: 1.21, 2.25) were associated with increasing flares whereas current use of allopurinol was associated with lower risk (0.42, 95% CI: 0.34–0.53). Cluster membership was not associated with flares. Conclusion Substantial numbers of people in each cluster developed new comorbidities that varies by cluster membership. People also experienced multiple flares over time, but these did not differ between clusters. Clinicians should be vigilant for the development of new comorbidities in people with gout. [ABSTRACT FROM AUTHOR]

Objectives Gout, caused by chronic elevation of serum uric acid levels, is the commonest form of inflammatory arthritis. The causative effect of common and rare variants of ATP-binding cassette transporter G2 (ABCG2/BCRP) on gout risk has been studied, but little attention has been paid to the effect of common (rs121907892, p.W258X) and rare variants of urate transporter 1 (URAT1/SLC22A12) on gout, despite dysfunctional variants of URAT1 having been identified as pathophysiological causes of renal hypouricaemia. Methods To address this important but overlooked issue, we investigated the effects of these URAT1 variants on gout susceptibility, using targeted exon sequencing on 480 clinically defined gout cases and 480 controls of Japanese males in combination with a series of functional analyses of newly identified URAT1 variants. Results Our results show that both common and rare dysfunctional variants of URAT1 markedly decrease the risk of gout (OR 0.0338, reciprocal OR 29.6, P = 7.66 × 10−8). Interestingly, we also found that the URAT1 -related protective effect on gout eclipsed the ABCG2 -related causative effect (OR 2.30–3.32). Our findings reveal only one dysfunctional variant of URAT1 to have a substantial anti-gout effect, even in the presence of causative variants of ABCG2 , a 'gout gene'. Conclusion Our findings provide a better understanding of gout/hyperuricaemia and its aetiology that is highly relevant to personalized health care. The substantial anti-gout effect of common and rare variants of URAT1 identified in the present study support the genetic concept of a 'Common Disease, Multiple Common and Rare Variant' model. [ABSTRACT FROM AUTHOR]

Objective To study subclinical inflammation in intercritical gout patients and its relation to the estimated size of monosodium urate crystal deposition and cardiovascular risk factors. Methods We performed a secretome analysis and the quantification of cytokine and adipokine plasma levels [IL-1β, IL-18, IL-6, soluble IL-6 receptor (sIL-6R), TNF-α, C-X-C motif chemokine 5, RANTES (Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted), leptin, resistin and adiponectin] to analyse subclinical inflammation in intercritical gout patients. Since it is currently not feasible to determinate the whole body deposit of monosodium urate crystals, we created an indirect clinical classification to estimate it. Then we compared cytokine levels in controls and gout patients and in patients with different crystal deposition sizes. We also studied the association between cytokine-levels and the number of cardiovascular risk factors. Results Ninety consecutive patients attending a crystal arthritis unit were studied. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in intercritical gout patients than in controls. An association was observed between IL-18, sIL6-R and RANTES levels and the size of crystal deposition. IL-18, sIL6-R, RANTES and leptin were higher in patients with no cardiovascular risk factors compared with controls with no risk factors. Conclusion Our results showed that the levels of some pro-inflammatory cytokines and metabolic proteins are elevated in intercritical gout patients. The levels of certain cytokines were related to the estimated size of the monosodium urate crystal deposition and to the number of cardiovascular risk factors. These cytokine changes may help to explain the increase in cardiovascular events in gout patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients. Methods A total of 983 gout patients on fenofibrate treatment who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020 were retrospectively enrolled from the electronic records system. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during the treatment period were assessed by a generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr. Results A total of 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dl within 6 months after fenofibrate initiation. The median change of SCr in the whole cohort was 0.11 mg/dl [interquartile range (IQR) 0.03–0.20], whereas it was 0.36 (0.33–0.45) in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) [odds ratio (OR) 2.39 (95% CI 1.48, 3.86)] and tophus [OR 2.29 (95% CI 1.39, 3.78)] were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily increased, serum urate and triglyceride concentrations decreased using the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, the SCr increase in 65% of patients was reversed after an average of 49 days off the drug. Conclusions This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout needs additional research. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor, in Chinese subjects with hyperuricaemia. Methods This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid (sUA) levels were ≥480 µmol/l with gout, ≥480 µmol/l without gout but with comorbidities, or ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg, 5 mg, 10 mg of SHR4640, 50 mg of benzbromarone or placebo, respectively. The primary end point was the proportion of subjects who achieved target sUA level of ≤360 µmol/l at week 5. Results 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects who achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in the 5 mg, 10 mg SHR4640 and benzbromarone groups, respectively, significantly higher than the placebo group (0%; P < 0.05 for 5 mg and 10 mg SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg SHR4640 and benzbromarone, respectively, vs placebo (5.9%; P < 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. Conclusions The present study indicated a superior sUA-lowering effect and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as compared with placebo in Chinese subjects with hyperuricaemia. Trial registration ClinicalTrials.gov number, NCT03185793 [ABSTRACT FROM AUTHOR]

Objectives During the COVID-19 pandemic, much communication occurred online, through social media. This study aimed to provide patient perspective data on how the COVID-19 pandemic impacted people with rheumatic and musculoskeletal diseases (RMDs), using Twitter-based patient-generated health data (PGHD). Methods A convenience sample of Twitter messages in English posted by people with RMDs was extracted between 1 March and 12 July 2020 and examined using thematic analysis. Included were Twitter messages that mentioned keywords and hashtags related to both COVID-19 (or SARS-CoV-2) and select RMDs. The RMDs monitored included inflammatory-driven (joint) conditions (ankylosing spondylitis, RA, PsA, lupus/SLE and gout). Results The analysis included 569 tweets by 375 Twitter users with RMDs across several countries. Eight themes emerged regarding the impact of the COVID-19 pandemic on people with RMDs: (i) lack of understanding of SARS-CoV-2/COVID-19; (ii) critical changes in health behaviour; (iii) challenges in healthcare practice and communication with healthcare professionals; (iv) difficulties with access to medical care; (v) negative impact on physical and mental health, coping strategies; (vi) issues around work participation; (vii) negative effects of the media; and (viii) awareness-raising. Conclusion The findings show that Twitter serves as a real-time data source to understand the impact of the COVID-19 pandemic on people with RMDs. The platform provided 'early signals' of potentially critical health behaviour changes. Future epidemics might benefit from the real-time use of Twitter-based PGHD to identify emerging health needs, facilitate communication and inform clinical practice decisions. [ABSTRACT FROM AUTHOR]

Objectives Microcrystal-induced arthritis is still an unresolved paradigm for medicine. Overt inflammation may be absent even when crystals occur in SF. Recently, the production of neutrophil extracellular traps (NETs) embedding MSU crystals has been proposed as a possible mechanism of the auto-resolution of the inflammatory phase during gout. We aimed to verify and quantify the release of NETs in SFs during gout and pseudogout attacks and to compare any differences with respect to crystals and neutrophils number, and to analyse activation of necroptosis pathway in SF from crystal-induced arthritis. Methods SF samples were obtained by arthrocentesis from 22 patients presenting acute crystal-induced arthritis, gout or pseudogout (n  = 11 each group), and from 10 patients with acute non-crystal arthritis as controls. NETosis was quantified in SF by nucleic acid stain and by quantification of human neutrophil elastase. Activation of phosphorylated MLKL was assessed by western blot. Results We observed that SF neutrophils encountering MSU and CPPD crystals during episodes of gout and pseudogout release NETs in relation to the number of crystals in SF and irrespective of neutrophil density and type of crystal. This release was accompanied by necroptosis through the activation of the MLKL pathway. Conclusions Our findings suggest that a role of NETs in crystal-induced arthritis is to 'trap extracellular particles', including microcrystals. Embedding crystals in aggregates of NETs may be the basis of tophi and CPPD deposition, and may have implications for disease evolution rather than for spontaneous resolution of the acute attack. [ABSTRACT FROM AUTHOR]