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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]

Objective: Hyperuricemia can be stratified into four subtypes according to renal uric acid handling. The aim of this study was to comprehensively describe the biologic characteristics (including genetic background) of clinically defined hyperuricemia subtypes in two large geographically independent gout cohorts. Methods: Hyperuricemia subtype was defined as renal uric acid overload (ROL), renal uric acid underexcretion (RUE), combined, or renal normal. Twenty single nucleotide polymorphisms (SNPs) previously identified as gout risk loci or associated with serum urate (SU) concentration in the East Asian population were genotyped. Weighted polygenic risk scores were calculated to assess the cumulative effect of genetic risks on the subtypes. Results: Of the 4,873 participants, 8.8% had an ROL subtype, 60.9% RUE subtype, 23.1% combined subtype, and 7.2% normal subtype. The ROL subtype was independently associated with older age at onset, lower SU, tophi, and diabetes mellitus; RUE was associated with lower body mass index (BMI) and non–diabetes mellitus; the combined subtype was associated with younger age at onset, higher BMI, SU, estimated glomerular filtration rate (eGFR), and smoking; and the normal subtype was independently associated with older age at onset, lower SU, and eGFR. Thirteen SNPs were associated with gout with 6 shared loci and subtype‐dependent risk loci patterns. High polygenic risk scores were associated with ROL subtype (odds ratio [OR] = 9.63, 95% confidence interval [95% CI] 4.53–15.12), RUE subtype (OR = 2.18, 95% CI 1.57–3.03), and combined subtype (OR = 6.32, 95% CI 4.22–9.48) compared with low polygenic risk scores. Conclusion: Hyperuricemia subtypes classified according to renal uric acid handling have subtype‐specific clinical and genetic features, suggesting subtype‐unique pathophysiologic mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: This research aimed to replicate the Swinson, D., Snaith, J., Buckberry, J., & Brickley, M. (2010). High performance liquid chromatography (HPLC) in the investigation of gout in paleopathology. International Journal of Osteoarchaeology, 20, 135–143. https://doi.org/10.1002/oa.1009 method for detecting uric acid in archeological human remains to investigate gout in past populations and to improve the original High Performance Liquid Chromatography‐ultraviolet (HPLC‐UV) method by using HPLC‐mass spectrometry (HPLC‐MS), a more sensitive, compound‐specific detection method. Materials and Methods: We used reference samples of uric acid to create a dilution series to assess the limits of quantification and detection. Samples from individuals with and without gout lesions were taken from foot bones and ribs from the English cemeteries of Tanyard, Hickleton, Gloucester, and Lincoln. Results: We could not replicate the results of Swinson and colleagues using HPLC‐UV. Tests using a dilution series of uric acid showed HPLC‐MS was approximately 100× more sensitive than HPLC‐UV, with the additional benefit of being compound specific. A newly developed hydrophilic interaction chromatography (HILIC) method improved retention characteristics. Fourteen samples from eight individuals, five with skeletal lesions consistent with gout, were analyzed with the final method. None showed evidence of uric acid despite the newly developed method's improved sensitivity and specificity. Discussion: The lack of detectable uric acid extracted from these samples suggests that (1) urate crystals were not present in any of the bone samples, regardless of gout status; (2) urate crystals did not survive these specific archeological conditions; or (3) the concentration of uric acid in our bone extracts was low, and thus larger samples would be required. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to analyze and compare the effects of different urate-lowering agents on testicular functions in men with gout in a clinical setting. Methods: In this prospective cohort study (Clinical Trial Registration Number: NCT04213534), a total of 49 male patients aged 18–45 years with gout were enrolled. They were divided into three groups and received treatment with either allopurinol, febuxostat or benzbromarone for a duration of 3 months. Semen parameters, reproductive hormones and biochemical assessments were evaluated at baseline, month 1, and month 3. Results: Overall, 40 individuals (81.6%) completed the follow-up visits. In allopurinol group, there were no significant differences in semen parameters from baseline to month 3. Most of sperm parameters in febuxostat group did not show notable changes, except for a decrease in sperm motility at month 3(33.6%, [22.9–54.3] vs 48.4%, [27.4–67.6], p = 0.033). However, the total motile sperm count did not differ significantly after febuxostat treatment. Surprisingly, administration of benzbromarone resulted in improved sperm concentration (37.19 M/mL, [29.6–69.92] vs 58.5 M/mL, [49.8–116.6], p = 0.001). There were no significant changes observed in sperm DNA integrity and reproductive hormones in the three groups from baseline to month 3. The incidence of adverse events did not differ significantly among the three groups as well. Conclusion: This study is the first to demonstrate that urate-lowering agents, allopurinol and febuxostat, do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout, and benzbromarone presents improving sperm concentration. Results provide important preliminary guidance for the development of reproductive health management guidelines for patients RCID with gout. [ABSTRACT FROM AUTHOR]

Les arthropathies microcristallines recouvrent la goutte, le rhumatisme à dépôts de pyrophosphate de calcium (PPCa), et le rhumatisme à hydroxyapatite. Ces rhumatismes sont parmi les plus fréquemment rencontrés en pratique quotidienne. La goutte est une complication de l'hyperuricémie chronique, mais tous les patients ayant une hyperuricémie ne développeront pas de goutte. Dans les pays occidentaux, la prévalence de l'hyperuricémie peut atteindre 20 % de la population adulte, mais celle de la goutte est estimée entre 1 et 4 %. Les facteurs de risque de goutte sont ceux de l'hyperuricémie avec, au premier plan, des facteurs alimentaires et génétiques, mais aussi certains médicaments comme les diurétiques. La prévalence du rhumatisme à PPCa est moins bien connue, car les études se sont souvent concentrées sur sa manifestation radiographique, la chondrocalcinose, dont la prévalence est estimée à 4–7 % de la population adulte. Ses facteurs de risque principaux sont l'hyperparathyroïdie primitive, l'hémochromatose génétique, l'hypomagnésémie, et l'arthrose. Les données épidémiologiques concernant le rhumatisme à hydroxyapatite manquent, et ne permettent pas d'estimer précisément sa prévalence en population générale. Crystal-associated arthropathies include gout, calcium pyrophosphate deposition disease (CPPD) and basic calcium phosphate (BCP) crystal-associated arthropathies. These conditions are among the most frequently encountered in daily practice. Gout is a complication of chronic hyperuricaemia, but gout will not develop in all patients with hyperuricaemia. In Western countries, the prevalence of hyperuricaemia may be as high as 20% of the adult population, but the prevalence of gout is estimated to be between 1 and 4%. The risk factors for gout are the same as for hyperuricaemia, with dietary and genetic factors being the most important ones, along with diuretics. The prevalence of CPPD is less well known, as studies have often focused on chondrocalcinosis, its radiographic manifestation, the prevalence of which is estimated at 4–7% of the adult population. Its main risk factors are primary hyperparathyroidism, hereditary haemochromatosis, hypomagnesaemia and osteoarthritis. Epidemiological data on BCP crystal-associated arthropathies are lacking, and its prevalence in the general population is not precisely known. [ABSTRACT FROM AUTHOR]

Background: Gout remains a leading cause of inflammatory arthritis worldwide, and the main risk factor for gout is persistent hyperuricemia. The clinical management of gout is mostly drug-based, and other treatment options are often ignored. This research proposal will explore whether exergames combined with ice therapy can help patients with gout to lose weight, relieve pain, improve the range of movement, improve quality of life, decrease uric acid level, decrease kinesiophobia and improve mental health of patients with gout. Methods: This experiment will use a two-arm randomized controlled design. The study setting is at the Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia (USM). Obese patients with gout (N = 30) will be randomly assigned to the control group (receive an exergames intervention) and intervention group (receive an exergames intervention combined with ice therapy). The outcomes measurement will be conducted before (baseline) and after intervention (4 weeks). Then, it will be followed up at 12 weeks. Discussion: To our knowledge, no study has investigated the effect of exergames and ice therapy among gout patients. This study is expected to demonstrate that exercise rehabilitation facilitated by exergames with ice therapy is more effective in gout management compared to a conventional rehabilitation intervention. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300070029). Registered on 31 March 2023. [ABSTRACT FROM AUTHOR]

The aim of this study was to validate the preventive effects of koumine (KM), a monoterpene indole alkaloid, on gouty arthritis (GA) and to explore its possible mechanisms. C57BL/6 mice were intraperitoneally administered KM (0.8, 2.4 or 7.2 mg/kg), colchicine (3.0 mg/kg) or sterile saline. One hour later, a monosodium urate (MSU) suspension was injected into the right hind paws of the mice to establish an acute gout model. Inflammation symptoms were evaluated at 0, 3, 6, 12 and 24 h, and the mechanical withdrawal threshold was evaluated at 0, 6 and 24 h. After 24 h, the mice were euthanized, and the joint tissue, kidney and blood were collected for subsequent experiments. Histological examination and antioxidant enzyme, kidney index and serum uric acid (UA) measurements were taken. The expression levels of the signalling pathway components were determined. KM effectively alleviated the symptoms of redness, swelling and pain; counteracted inflammatory cell infiltration; and increased antioxidant enzyme levels, reduced kidney index and seru UA levels through regulating UA excretion in MSU‐induced mice. The expression of toll‐like receptor 4 (TLR4)/nuclear factor kappa‐B (NF‐κB)/nucleotide‐binding oligomerization domain, leucine‐rich repeat and pyrin domain‐containing 3 (NLRP3) signalling pathway proteins and mRNA were reduced in the KM group. These results suggest that KM may be effective in alleviating GA through the TLR4/NF‐κB/NLRP3 pathway. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to investigate the diagnostic values of different musculoskeletal ultrasound (MSUS) signs, serum uric acid (SUA), and their combined detection for gouty arthritis (GA). Patients and methods: In this retrospective study, 70 patients (62 males, 8 females; mean age: 46.1±14.1 years; range, 25 to 86 years) diagnosed with GA (the GA group) between August 2022 and March 2023 and 70 patients (54 females, 16 males; mean age: 49.0±14.1 years; range, 21 to 75 years) diagnosed with rheumatoid arthritis and osteoarthritis during the same period (the non-GA group) were included. The positive rate of MSUS signs and SUA in both groups was recorded to compare the differences. The correlations of MSUS signs and SUA with GA were analyzed using Spearman's rank correlation analysis. The diagnostic values of different MSUS signs, SUA, and their combined detection for GA were analyzed using a receiver operating characteristic, the area under the curve (AUC), sensitivity, specificity, and the Youden index. Results: The positive rate of the double contour (DC) sign (chi-squared [Χ²]=102.935, p<0.001), hyperechoic spots (Χ²=56.395, p<0.001), bone erosions (Χ²=10.080, p<0.001), and SUA (Χ²=41.117, p<0.001) were higher in the GA group than in the non-GA group. The positive rate of the DC sign (rs=0.829, p=0.001), hyperechoic spots (rs=0.631, p<0.001), bone erosion (rs=0.268, p=0.001), and SUA (rs=0.542, p<0.001) were positively correlated with GA. Among the single-indicator measures, the DC sign exhibited the highest diagnostic value (AUC=0.907, sensitivity=81.4%, specificity=100%, p<0.001). Among the combined-indicator measures, the DC sign combined with SUA exhibited the highest diagnostic value (AUC=0.929, sensitivity=91.4%, specificity=94.3%, p<0.001), higher than DC sign detection alone. Conclusion: The DC sign combined with SUA yielded a high diagnostic value and can thus provide a reliable basis for effectively and efficiently diagnosing GA. [ABSTRACT FROM AUTHOR]

The ninth annual international G-CAN research symposium was held in La Jolla, CA on the 7th and 8th of November 2023. This hybrid meeting, a live face-to-face and virtual live symposium, was attended by 191 participants. Over 20 research abstract submissions were received from early-career investigators, for plenary oral and poster presentations. Here, we present the 20 accepted, lightly edited abstracts from the early-career presenters consenting to have their materials published. We thank and congratulate the presenters for their work and contributions to the meeting. [ABSTRACT FROM AUTHOR]

A relationship between metabolic disorders and hyperuricemia is well established. The nature of the relationship—risk factor, causal agent, or byproduct—remains unclear. Recent studies of sodium–glucose transporter 2 inhibitors (SGLT2i's) have established that this pharmacological intervention is beneficial to patients with hyperglycemia and type 2 diabetes mellitus (T2D) and also against the common cardio and renal comorbidities associated with diabetes. Hyperuricemia, or high plasma uric acid levels, is one of the comorbidities mitigated with SGLT2i treatment, raising the potential for using SGLT2i's as part of the treatment for gout and hyperuricemia. However, the mechanisms underlying the lower plasma urate levels and increased uricosuria produced with SGLT2i's remains poorly understood. Here, we review the renal physiology of glucose and uric acid transport, the renal consequences of hyperglycosuria and diabetes, the benefits and physiology of SGLT2i use, and discuss several potential mechanisms that may be responsible for the favorable uricosuric effect observed in those treated with SGLT2i's. [ABSTRACT FROM AUTHOR]

Population-based databases in Nordic countries offer unique opportunities for large-scale population-based epidemiological studies. The personal identity number enables researchers to link different registers at the individual level, which can be used for large-scale epidemiological population-based studies. This review outlines how these opportunities have been used so far in the field of gout research, as well as the potential challenges and limitations. Their major advantage is that they cover the entire population, minimizing problems such as selection bias and loss to follow-up. This has enabled us to provide information on gout regarding risk factors; occurrence; association with comorbidities in relation to gout onset; treatment patterns; as well as its effect on other outcomes, such as sick leave and mortality. Validity issues, missing data, and legal issues are some of the challenges that researchers need to deal with. Choosing the most appropriate combination of databases to use for a specific question is crucial in order to maximize validity and adjust for confounders. Despite challenges and potential limitations, the Swedish registers have provided valuable epidemiological results and will continue to play an important role in the years to come. [ABSTRACT FROM AUTHOR]

Gout, an inflammatory disease orchestrated by interleukin-1β activation and release, is more prevalent in men. The clinical profiles of patients with gout report differences by sex. This study aims to investigate sex-specific cytokine profiles in circulation and in stimulated peripheral blood mononuclear cells (PBMCs) of patients with gout and controls. Participants included in the gout group met the criteria of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR). The control group included individuals with varying levels of serum urate and absence of gout. PBMCs were stimulated in vitro for 24 h with various TLR ligands. Cytokines were determined in culture supernatants and plasma. Plasma IL-1Ra and high-sensitivity C-reactive protein (hsCRP) were higher in men with gout compared to men without gout whereas no significant differences in circulating cytokines were observed in women. PBMCs of patients with gout showed higher cytokine production of IL-1β, IL-1Ra, and TNF-α following 24 h stimulation, predominantly observed in women. We identified sex-specific cytokine production in gout in response to in vitro stimulation. While men with gout had higher levels of circulating cytokines, stimulated PBMCs of women with gout show an enhanced capacity for cytokine production. These data may suggest potentially different regulatory mechanisms of inflammation in men and women with gout. [ABSTRACT FROM AUTHOR]

The use of ultrasonography (US) has considerable potential for the diagnosis and monitoring of gout due to its capacity to detect monosodium urate deposits. In the last decade, a critical amount of scientific data has become available. Consensus-based definitions for ultrasonographic elementary lesions in gout have been developed, tested, and validated, as well as a semiquantitative scoring system for their quantification. Many scanning protocols have been proposed in different clinical scenarios. In this review, we formulate a set of practical suggestions for the use of the US in daily practice. We discuss the current knowledge to indicate which joints and structures are to be scanned and which elementary findings are to be evaluated according to the clinical scenario. While for some clinical settings, a quite definite scanning protocol can be indicated, others still need to be further investigated, and how to obtain the best out of the US is still entrusted to the individual experience. [ABSTRACT FROM AUTHOR]

Gout, recognized as the most common form of inflammatory arthritis, arises from the accumulation of uric acid crystals, leading to intense pain, particularly in the big toe. This condition has traditionally been associated with the overproduction or reduced clearance of uric acid. Recent studies, however, have underscored the significant role of the gut microbiota in uric acid metabolism, impacting both its production and elimination. This emerging understanding suggests that maintaining gut health could offer innovative approaches to treating gout, complementing traditional dietary and pharmacological interventions. It highlights the potential of probiotics or microbiome-based therapies, indicating a future where treatments are tailored to an individual's microbiome. This offers a fresh perspective on gout management and underscores the broader influence of the microbiota on health and disease. [ABSTRACT FROM AUTHOR]

Introduction: Gout management remains suboptimal despite safe and effective urate‐lowering therapy. Self‐monitoring of urate may improve gout management, however, the acceptability of urate self‐monitoring by people with gout is unknown. The aim of this study was to explore the experiences of urate self‐monitoring in people with gout. Methods: Semistructured interviews were conducted with people taking urate‐lowering therapy (N = 30) in a 12‐month trial of urate self‐monitoring in rural and urban Australia. Interviews covered the experience of monitoring and its effect on gout self‐management. Deidentified transcripts were analysed thematically. Results: Participants valued the ability to self‐monitor and gain more understanding of urate control compared with the annual monitoring ordered by their doctors. Participants indicated that self‐monitoring at home was easy, convenient and informed gout self‐management behaviours such as dietary modifications, hydration, exercise and medication routines. Many participants self‐monitored to understand urate concentration changes in response to feeling a gout flare was imminent or whether their behaviours, for example, alcohol intake, increased the risk of a gout flare. Urate concentrations were shared with doctors mainly when they were above target to seek management support, and this led to allopurinol dose increases in some cases. Conclusion: Urate self‐monitoring was viewed by people with gout as convenient and useful for independent management of gout. They believed self‐monitoring achieved better gout control with a less restricted lifestyle. Urate data was shared with doctors at the patient's discretion and helped inform clinical decisions, such as allopurinol dose changes. Further research on implementing urate self‐monitoring in routine care would enable an evaluation of its impact on medication adherence and clinical outcomes, as well as inform gout management guidelines. Patient or Public Contribution: One person with gout, who was not a participant, was involved in the study design by providing feedback and pilot testing the semistructured interview guide. In response to their feedback, subsequent modifications to the interview guide were made to improve the understandability of the questions from a patient perspective. No additional questions were suggested. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the link between dietary vitamin C intake and hyperuricemia/gout, utilizing Mendelian randomization to assess causality. Methods: We analyzed cross‐sectional data from the National Health and Nutrition Examination Survey (2007–2018) to investigate the association. Mendelian randomization studies, using genetic data from genome‐wide association surveys, were conducted to infer causality between vitamin C intake and hyperuricemia/gout. The weighted logistic regression analysis and the instrumental variable based on the inverse‐variance weighting served as the primary analytical tool, with sensitivity analyses to ensure robustness. Results: After adjusting for covariates, a stable association was observed between vitamin C intake and hyperuricemia/gout risk. Those consuming >111.75 mg of vitamin C generally had a lower risk. Vitamin C intake recommendations of 75–525 mg and 75–225 mg appeared effective for hyperuricemia and gout, respectively. Mendelian randomization analysis revealed a negative association between vitamin C intake and hyperuricemia (OR = 0.985, 95% CI = 0.973–0.997, p =.015) and gout (OR = 0.857, 95% CI = 0.797–0.921, p <.001). Reverse Mendelian randomization indicated no reverse causality. Conclusion: We hypothesize that a dietary vitamin C intake of 75–525 mg or 75–225 mg may reduce the risk of hyperuricemia and gout, respectively. Further research with larger samples is required to confirm this. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have reported controversial results on the association between gout and the risk of cancer. This study aimed to investigate the relationship between gout and the incidence of head and neck cancer (HNC). Methods: The data of participants who underwent health checkups in 2009 were analyzed using the National Health Insurance Database in South Korea. A total of 14,348 HNC patients and 57,392 control participants were analyzed for a prior history of gout. Overlap weighting was applied, and odds ratios (ORs) of gout for HNC patients were analyzed. The overlap-weighted model adjusted for demographic, socioeconomic, and lifestyle factors and comorbidities. HNC sites were classified as oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity/sinus cancer, larynx cancer, or salivary gland cancer, and the ORs of gout were estimated for each site. Results: Overall, patients with HNC had 1.12-fold greater odds of having gout (95% confidence intervals [CIs] = 1.04–1.20). According to the site of HNC, oral cavity cancer, oropharynx cancer, and larynx cancer demonstrated high odds of having gout (OR = 1.25, 95% CI = 1.16–1.34 for oral cavity cancer; OR = 1.08, 95% CI = 1.01–1.15 for oropharynx cancer; and OR = 1.12, 95% CI = 1.06–1.20 for larynx cancer). On the other hand, nasal cavity/sinus cancer, nasopharynx cancer, and salivary gland cancer presented low odds of having gout (OR = 0.78, 95% CI = 0.72–0.84 for nasal cavity/sinus cancer; OR = 0.89, 95% CI = 0.83–0.96 for nasopharynx cancer; and OR = 0.88, 95% CI = 0.81–0.96 for salivary gland cancer). Conclusions: A prior history of gout was associated with a high overall incidence of HNC. Oral cavity cancer, oropharynx cancer, and larynx cancer have a high incidence in gout patients. However, nasal cavity/sinus cancer, nasopharyngeal cancer, and salivary gland cancer have low incidences in gout patients. The impact of gout on HNC risk should be specifically considered according to the site of the HNC. [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]

A subset of gout patients developed persistent joint pain after flares. Analysis of this clinical phenomenon may shed further light on the factors related to worsening gout and even provide clues to its pathogenesis. We analyzed the clinical, laboratory, and ultrasound data of gout patients to explore the associations of these data with persistent joint pain after gout flares. A total of 1029 gout patients were included: 182 (17.7%) patients with persistent joint pain and 847 (82.3%) patients with nonpersistent joint pain. Patients with persistent joint pain had more total involved joints, more gout flares in the past year, and more joints with simultaneous gout flares (P < 0.01). Among the ultrasound-detected lesions, patients with persistent joint pain had a higher incidence of tophus (36.4% vs. 21.1%) and bone erosion (18.6% vs. 8.6%) (P < 0.05). Higher UA and lower TBil were found in patients with persistent joint pain (P < 0.001). Hypertension (54.9% vs. 38.7%) and metabolic syndrome (58.8% vs. 46.4%) were both more frequent in patients with persistent joint pain (P < 0.05). TBil was negatively correlated with the incidence of persistent joint pain (P < 0.001, r = −0.190), UA values (P < 0.001, r = −0.125), and metabolic syndrome scores (P < 0.001, r = −0.192). A correlation curve was fitted using LOESS (locally weighted region). Persistent joint pain after gout flares is a marker of increased disease burden in gout. The significance of the level of total bilirubin for the exacerbation of gout deserves further study. [ABSTRACT FROM AUTHOR]

Objectives: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. Methods: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. Results: In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24 h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow–derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. Conclusions: Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage. [ABSTRACT FROM AUTHOR]

The knee is one of the most commonly affected joints in the course of inflammatory arthropathies, such as crystal-induced and autoimmune inflammatory arthritis. The latter group includes systemic connective tissue diseases and spondyloarthropathies. The different pathogenesis of these entities results in their varied radiologic images. Some lead quickly to joint destruction, others only after many years, and in the remaining, destruction will not be a distinguishing radiologic feature. Radiography, ultrasonography, and magnetic resonance imaging have traditionally been the primary modalities in the diagnosis of noninflammatory and inflammatory arthropathies. In the case of crystallopathies, dual-energy computed tomography has been introduced. Hybrid techniques also offer new diagnostic opportunities. In this article, we discuss the pathologic findings and imaging correlations for crystallopathies and inflammatory diseases of the knee, with an emphasis on recent advances in their imaging diagnosis. [ABSTRACT FROM AUTHOR]

Gout is a metabolic condition characterized by the accumulation of urate crystals in the synovial joints. These crystal depositions result in joint swelling and increased concentration of serum uric acid in blood. The commercially available drugs lower serum uric acid levels and reduce inflammation, but these standard therapies have many side effects. This study aimed to investigate anti-gout and anti-inflammatory properties of curcumin nanoparticles (CNPs). For this purpose, CNPs were prepared by dissolving curcumin into dichloromethane. Then, gout was induced by injecting monosodium urate crystals (MSU) in the ankle joint and in the intra-peritoneal cavity which caused ankle swelling and increased blood uric acid levels. CNPs in different concentrations (5, 10, and 20 ppm) and allopurinol were orally administered. The MSU crystals increased the xanthine oxidase levels both in serum and the liver. Moreover, MSU crystals increased the serum levels of interleukin 1β, interleukin-6, tumor necrosis factor-alpha, liver function tests markers, renal function tests markers, and lipid profiles. However, the administration of CNPs decreased the levels of all these variables. CNPs increased the serum high-density lipoprotein and interleukin-10 levels. Moreover, CNPs also reduced ankle swelling significantly. Hence, the levels of xanthine oxidase, uric acid and ankle swelling were reduced significantly by oral administration of CNPs. Our findings indicate that CNPs through their anti-inflammatory properties significantly alleviate gouty arthritis. Thus, the study concluded that CNPs can be developed as an efficient anti-gout agent with minimal side effects. [ABSTRACT FROM AUTHOR]

Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. We conducted a nationwide, population-based case-crossover study of all Danes ≥ 18 years of age with first-time gout during 1997–2020, who experienced a cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel–Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85–0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88–0.97) and naproxen (OR = 0.85, 95% CI: 0.74–0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90–1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac. [ABSTRACT FROM AUTHOR]

The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro‐inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age‐related macular degeneration (AMD), a sight‐threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro‐oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal‐induced and non‐crystal‐induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations. [ABSTRACT FROM AUTHOR]

Background: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. Results: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. Conclusions: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout. [ABSTRACT FROM AUTHOR]

Background: Gout prediction is essential for the development of individualized prevention and treatment plans. Our objective was to develop an efficient and interpretable machine learning (ML) model using the SHapley Additive exPlanation (SHAP) to link dietary fiber and triglyceride-glucose (TyG) index to predict gout. Methods: Using datasets from the National Health and Nutrition Examination Survey (NHANES) (2005–2018) population to study dietary fiber, the TyG index was used to predict gout. After evaluating the performance of six ML models and selecting the Light Gradient Boosting Machine (LGBM) as the optimal algorithm, we interpret the LGBM model for predicting gout using SHAP and reveal the decision-making process of the model. Results: An initial survey of 70,190 participants was conducted, and after a gradual exclusion process, 12,645 cases were finally included in the study. Selection of the best performing LGBM model for prediction of gout associated with dietary fiber and TyG index (Area under the ROC curve (AUC): 0.823, 95% confidence interval (CI): 0.798–0.848, Accuracy: 95.3%, Brier score: 0.077). The feature importance of SHAP values indicated that age was the most important feature affecting the model output, followed by uric acid (UA). The SHAP values showed that lower dietary fiber values had a more pronounced effect on the positive prediction of the model, while higher values of the TyG index had a more pronounced effect on the positive prediction of the model. Conclusion: The interpretable LGBM model associated with dietary fiber and TyG index showed high accuracy, efficiency, and robustness in predicting gout. Increasing dietary fiber intake and lowering the TyG index are beneficial in reducing the potential risk of gout. [ABSTRACT FROM AUTHOR]

Objectives: Understanding the health literacy status of patients with gout diagnosis is essential for improving the health of this population. Our study aimed to investigate the latent profiles of health literacy in patients with gout and to analyze differences in characteristics across potential profiles. Methods: This was a cross-sectional study. Eligible participants attended the Shandong Gout Medical Center, from March 2023 to May 2023 and self-reported gout diagnosis. We used the Health Literacy Scale for Patients with Gout designed and validated by our team. The scale had good reliability and validity among patients with gout. 243 patients completed the Demographic Information Questionnaire and the Health Literacy Scale for Patients with Gout. We used latent profile analysis to identify the latent profiles of gout patients' health literacy. We used Chi-square tests with Bonferroni correction to analyze differences in demographics and illness characteristics across identified profiles. Results: Three profiles of patients with gout emerged (prevalence): the low literacy-low critical group (21.81%), the moderate literacy group (42.79%), and the high literacy-stable group (35.39%). The three groups differed in age, education level, monthly income, disease duration, and place of residence (P<0.01). Conclusions: The health literacy of patients with gout was heterogeneous. Healthcare professionals should adopt targeted interventions based on the characteristics of each latent health literacy profile to improve the health literacy level of patients with gout. [ABSTRACT FROM AUTHOR]

This essay examines the depiction of French ragout in eighteenth-century English literature, arguing that the dish reflects social apprehension regarding ideological, cultural, and military conflicts between England and France. This essay first traces a brief history of ragout, along with an overview of the dish’s cultural connotation and complexity, in eighteenth-century English society. It next delves into the concept of eighteenth-century English Francophobia, demonstrating that this sentiment was a mixture of national pride and anxiety amid England’s identity crisis under the potential French cultural threat. Finally, the essay examines ragout in eighteenth-century English literature and identifies the dish as the target of French pretension and cultural invasion. This research highlights the fact that eighteenth-century English authors’ satirical portrait of ragout underscored xenophobic gastronomy and cautioned against a simple interpretation of the dish. The caricature and representation of ragout as a feminized, artificial, and laughable dish reinforces eighteenth-century English writers’ concern for the invasion of foreign culture by emphasizing the contrast between authentic ‛Anglo’ meat consumption and ‛Franco’ sophistication. [ABSTRACT FROM AUTHOR]

Background: The relationship between gout and gut microbiota has attracted significant attention in current research. However, due to the diverse range of gut microbiota, the specific causal effect on gout remains unclear. This study utilizes Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and gout, aiming to elucidate the underlying mechanism of microbiome-mediated gout and provide valuable guidance for clinical prevention and treatment. Materials and Methods: The largest genome-wide association study meta-analysis conducted by the MiBioGen Consortium (n=18,340) was utilized to perform a two-sample Mendelian randomization investigation on aggregate statistics of intestinal microbiota. Summary statistics for gout were utilized from the data released by EBI. Various methods, including inverse variance weighted, weighted median, weighted model, MR-Egger, and Simple-mode, were employed to assess the causal relationship between gut microbiota and gout. Reverse Mendelian randomization analysis revealed a causal association between bacteria and gout in forward Mendelian randomization analysis. Cochran's Q statistic was used to quantify instrumental variable heterogeneity. Results: The inverse variance weighted estimation revealed that Rikenellaceae exhibited a slight protective effect on gout, while the presence of Ruminococcaceae UCG_011 is associated with a marginal increase in the risk of gout. According to the reverse Mendelian Randomization results, no significant causal relationship between gout and gut microbiota was observed. No significant heterogeneity of instrumental variables or level pleiotropy was detected. Conclusion: Our MR analysis revealed a potential causal relationship between the development of gout and specific gut microbiota; however, the causal effect was not robust, and further research is warranted to elucidate its underlying mechanism in gout development. Considering the significant association between diet, gut microbiota, and gout, these findings undoubtedly shed light on the mechanisms of microbiota-mediated gout and provide new insights for translational research on managing and standardizing treatment for this condition. [ABSTRACT FROM AUTHOR]

Aims: Dose escalation at the initiation of allopurinol therapy can be protracted and resource intensive. Tools to predict the allopurinol doses required to achieve target serum urate concentrations would facilitate the implementation of more efficient dose‐escalation strategies. The aim of this research was to develop and externally evaluate allopurinol dosing tools, one for use when the pre‐urate‐lowering therapy serum urate is known (Easy‐Allo1) and one for when it is not known (Easy‐Allo2). Methods: A revised population pharmacokinetic‐pharmacodynamic model was developed using data from 653 people with gout. Maintenance doses to achieve the serum urate target of <0.36 mmol L−1 in >80% of individuals were simulated and evaluated against external data. The predicted and observed allopurinol doses were compared using the mean prediction error (MPE) and root mean square error (RMSE). The proportion of Easy‐Allo predicted doses within 100 mg of the observed was quantified. Results: Allopurinol doses were predicted by total body weight, baseline urate, ethnicity and creatinine clearance. Easy‐Allo1 produced unbiased and suitably precise dose predictions (MPE 2 mg day−1 95% confidence interval [CI] −13‐17, RMSE 91%, 90% within 100 mg of the observed dose). Easy‐Allo2 was positively biased by about 70 mg day−1 and slightly less precise (MPE 70 mg day−1 95% CI 52‐88, RMSE 131%, 71% within 100 mg of the observed dose). Conclusions: The Easy‐Allo tools provide a guide to the allopurinol maintenance dose requirement to achieve the serum urate target of <0.36 mmol L−1 and will aid in the development of novel dose‐escalation strategies for allopurinol therapy. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to estimate adherence to urate‐lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient‐reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day). Methods: Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12‐month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%. We measured the correlation between the two methods of calculating PDC using a Wilcoxon signed rank test. Agreement between ULT‐taking status (self‐reports) and ULT‐dispensed status (PBS records) was tested with Cohen's kappa (κ), and positive and negative percent agreement. Results: Allopurinol was prescribed in 93.5% of participants taking ULT. Their self‐reported mean daily dose (SD) was 291 (167) mg/day. Mean PDC (SD) for allopurinol was 83% (21%) calculated using self‐reported dose, and 63% (24%) using WHO's DDD. Sixty‐three percent of allopurinol users were identified as adherent (PDC ≥80%) using self‐reported dose. There was good agreement between self‐reported ULT use and PBS dispensing claims (κ = 0.708, P <.001; positive percent agreement = 90%, negative percent agreement = 82%). Conclusions: Participant‐reported allopurinol daily doses, in addition to PBS dispensing claims, may enhance confidence in estimating PDC and adherence compared to using DDD. This approach improves adherence estimations from pharmaceutical claims datasets for medications where daily doses vary between individuals or where there is a wide therapeutic dose range. [ABSTRACT FROM AUTHOR]

Research examining migrant homemaking is multi-disciplinary and well-developed, providing evidence that 'home' exists in multiple places. However, only a small component of this work examines the role of the senses. This paper draws on research conducted between 2015 and 2019 in Glasgow, a city in Scotland, UK, with migrant, refugee and asylum-seeking women that used photo elicitation interviews, to bridge the gap between scholarship on migrant homemaking and the senses. The paper empirically demonstrates how the senses allow migrants to cultivate the embodied experience of physically being elsewhere by drawing on sensory memories, practices, and material cultures, specifically engaging taste and smell. The paper analyses the experience of four participants who described this sensation, and addresses the impact of the security of migrant status and financial resources in sensory homemaking. The concluding discussion proposes the concept of 'sensory space-time compression' as a novel way of understanding the sensory experiences of home in the context of migration. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the impact of triggers for gout flares on individuals with gout. The study reveals that gout flares are characterized by intense inflammation and pain, and identifies various triggers such as physical activity, medical illness, vaccinations, diet, alcohol, and medications. The research aims to understand how these triggers affect the daily lives of individuals with gout, including their adoption of trigger avoidance behaviors and the impact on their psychological well-being. The study emphasizes the importance of urate-lowering therapy and trigger avoidance behaviors in effectively managing gout in the long term. The study also sheds light on the challenges faced by individuals with gout in managing their condition and the need for improved management strategies. [Extracted from the article]

Objective: To compare the clinical efficacy of febuxostat combined with a low‐purine diet versus allopurinol combined with a low‐purine diet in the treatment of gout. Method s : In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low‐purine diet) and the control group (allopurinol combined with a low‐purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor‐a (TNF‐a), cytokine interleukin‐1beta (IL‐1β), and interleukin (IL)‐18 (IL‐18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. Results: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p =.027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 μmol/L ± 17.23 μmol/L vs. S198.32 μmol/L ± 18.34 μmol/L, p <.001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p =.014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p <.001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p <.001) compared to the control group, with statistically significant differences (p <.05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p <.05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p =.025). Conclusion: Febuxostat combined with a low‐purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first‐line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. Methods: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. Results: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01–2.32) compared to the nonuser group. Conclusions: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia. [ABSTRACT FROM AUTHOR]

Objectives: Cellular NAD+ declines in inflammatory states associated with increased activity of the leukocyte-expressed NADase CD38. In this study, we tested the potential role of therapeutically targeting CD38 and NAD+ in gout. Methods: We studied cultured mouse wild type and CD38 knockout (KO) murine bone marrow derived macrophages (BMDMs) stimulated by monosodium urate (MSU) crystals and used the air pouch gouty inflammation model. Results: MSU crystals induced CD38 in BMDMs in vitro, associated with NAD+ depletion, and IL-1β and CXCL1 release, effects reversed by pharmacologic CD38 inhibitors (apigenin, 78c). Mouse air pouch inflammatory responses to MSU crystals were blunted by CD38 KO and apigenin. Pharmacologic CD38 inhibition suppressed MSU crystal-induced NLRP3 inflammasome activation and increased anti-inflammatory SIRT3–SOD2 activity in macrophages. BMDM RNA-seq analysis of differentially expressed genes (DEGs) revealed CD38 to control multiple MSU crystal-modulated inflammation pathways. Top DEGs included the circadian rhythm modulator GRP176, and the metalloreductase STEAP4 that mediates iron homeostasis, and promotes oxidative stress and NF-κB activation when it is overexpressed. Conclusions: CD38 and NAD+ depletion are druggable targets controlling the MSU crystal- induced inflammation program. Targeting CD38 and NAD+ are potentially novel selective molecular approaches to limit gouty arthritis. [ABSTRACT FROM AUTHOR]

Gout is a common and treatable chronic disease of monosodium urate crystal deposition. It is experienced as extremely painful episodes of joint inflammation that impact all aspects of the person's life. This Clinical Perspectives article provides an update on gout diagnosis, medications and strategies to improve the quality of gout care. [ABSTRACT FROM AUTHOR]

Objective: Despite scarce evidence, guidelines recommend weight loss as a management strategy for patients with gout. We investigated the effect of an intensive dietary intervention on body weight and clinical measures of gout severity in individuals with obesity and gout. Methods: We conducted a 16‐week randomized nonmasked parallel‐group trial in Denmark, randomly assigning (one‐to‐one) individuals with obesity and gout to a low‐energy diet or a control diet. The primary outcome was change in body weight. Key secondary outcomes were changes in serum urate (SU) level and visual analog scale–assessed pain and fatigue. Results: Between December 1, 2018, and June 1, 2019, 61 participants were included in the intention‐to‐treat population and randomly assigned to the intensive diet group (n = 29) or control diet group (n = 32). Participants had a mean age of 60.3 (SD 9.9) years and mean body mass index of 35.6 (SD 5.0), and 59 (97%) were men. After 16 weeks, there was a significant difference in change in body weight between the diet and control groups (−15.4 vs −7.7 kg; difference −7.7 kg [95% confidence interval −10.7 to −4.7], P < 0.001). Despite results being potentially in favor of a low‐energy diet, we could not confirm differences in SU level changes and fatigue between groups. No differences in pain and gout flares were observed between groups. No serious adverse events or deaths occurred during the trial. Conclusion: An intensive dietary intervention was safe and effectively lowered body weight in people with obesity and gout, but the weight loss did not directly translate into effects on SU level, fatigue, and pain. [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G‐PROB) has been developed to aid diagnosis has not yet been tested in a real‐world setting. Our aim was to assess whether G‐PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. Methods: Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G‐probabilities (0%–100%) were created for each patient based on known disease‐associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or "other diseases." Performance of the G‐probabilities compared with clinician diagnosis was assessed. Results: We tested G‐PROB on 1,047 patients. Calibration of G‐probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G‐probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84–0.86). G‐probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G‐probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G‐probability corresponded to clinician diagnosis. Conclusion: G‐PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting. [ABSTRACT FROM AUTHOR]

Objective To observe the expression of NOD-like receptor family 3 (NLRP3) protein, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the process of gout inflammation induced by macrophage monosodium urate (MSU) crystals in macrophages differentiated from leukemia cells overexpressing purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) . Methods THP-1 cell line were taken and randomly divided into the overexpression group, empty vector group, model group and control group, respectively. Cells in the overexpression group and empty vector group were transfected with P2X7R overexpression plasmid and empty vector plasmid for five days, respectively. THP-1 cells in the vector group, empty vector group and model group were stimulated with 100 ng/mL PMA for three hours and then were differentiated into macrophages. In addition, MSU crystals were dissolved with sodium hydroxide to prepare MSU chyle suspension at a concentration of 100 μg/mL and were incubated in the culture medium for six hours. Cells in the control group were cultured normally. The mRNA and protein of P2X7R in macrophages were measured by RT-PCR and Western blotting, respectively. IL-1β and TNF-α in the supernatant of macrophages were detected by ELISA, and the NLRP3 protein in macrophages was measured by Western blotting. Results Compared with the control group, the relative expression levels of P2X7R mRNA and protein, IL-1β and TNF-α in cell supernatant and NLRP3 protein all increased in the overexpression group, empty vector group and model group (all P<0. 05) . Compared with the model group and empty vector group, the relative expression levels of P2X7R mRNA and protein, IL-1β and TNF-α in cell supernatant and NLRP3 protein all increased in the overexpression group (all P<0. 05) . Conclusion The expression of IL-1β, TNF-α and NLRP3 increases and the levels of IL-1β and TNF-α levels increase in the process of gout inflammation induced by MSU crystals of macrophages differentiated from leukemia cells with P2X7R overexpression, which may be achieved by activating NLRP3 protein. [ABSTRACT FROM AUTHOR]

Introduction: This study investigates the biological activities of Lavandula pinnata essential oil (LPEO), an endemic lavender species from the Canary Islands, traditionally used in treating various ailments. Methods: LPEO was extracted by hydrodistillation and analyzed using GC-MS. Antioxidant activity was assessed by DPPH radical scavenging and total antioxidant capacity assays. Antimicrobial activity was evaluated by disc diffusion, MIC, MBC, and MFC determination against bacterial (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Pseudomonas aeruginosa) and fungal (Candida glabrata, Rhodotorula glutinis, Aspergillus niger, Penicillium digitatum) strains. Antidiabetic and anti-gout potential were investigated through α-amylase, α-glucosidase, and xanthine oxidase inhibition assays. Antityrosinase activity was determined using a modified dopachrome method. Cytotoxicity was assessed by MTT assay against breast (MCF-7, MDA-MB-468), liver (HepG2), colon (HCT-15) cancer cells, and normal cells (PBMCs). Results and discussion: LPEO exhibits potent antiradical activity (IC50 = 148.33 ± 2.48 μg/mL) and significant antioxidant capacity (TAC = 171.56 ± 2.34 μg AA/mg of EO). It demonstrates notable antibacterial activity against four strains (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, and Pseudomonas aeruginosa) with inhibition zones ranging from 18.70 ± 0.30mm to 29.20 ± 0.30 mm, along with relatively low MIC and MBC values. LPEO displays significant antifungal activity against four strains (Candida glabrata, Rhodotorula glutinis, Aspergillus niger, and Penicillium digitatum) with a fungicidal effect at 1 mg/mL, surpassing the positive control (cycloheximide), and MIC and MFC values indicating a fungicidal effect. It exhibits substantial inhibition of xanthine oxidase enzyme (IC50 = 26.48 ± 0.90 μg/mL), comparable to allopurinol, and marked inhibitory effects on α-amylase (IC50 = 31.56 ± 0.46 μg/mL) and α-glucosidase (IC50 = 58.47 ± 2.35 μg/mL) enzymes.The enzyme tyrosinase is inhibited by LPEO (IC50 = 29.11 ± 0.08 mg/mL). LPEO displays moderate cytotoxic activity against breast, liver, and colon cancer cells, with low toxicity towards normal cells (PBMC). LPEO exhibits greater selectivity than cisplatin for breast (MCF-7) and colon (HCT-15) cancer cells but lower selectivity for liver (HepG2) and metastatic breast (MDA-MB-468) cancer cells. These findings suggest the potential of LPEO as an antioxidant, antimicrobial, antigout, antidiabetic, and anticancer agent. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionGout is a chronic inflammatory diseases caused by monosodium urate crystal deposition. However, the role of interleukin (IL)-36 in gout has not dbeen elucidated.We enrolled 75 subjects, including 20 healthy controls (HC), 30 patients with acute gout attack and 25 patients in remission. Baseline data were obtained through clinical interrogation and laboratory data were obtained through tests of blood samples. Serum levels of IL-36α were detected using enzyme-linked immunosorbent assay. Spearman correlation analysis was used to investigate the correlation of IL-36α with other parameters. The diagnostic value of IL-36α was demonstrated using a receiver operating characteristic curve.The serum IL-36α level of gout patients in acute attack and remission stage was significantly higher than that of HC. Serum IL-36α was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST). Serum amyloid A (SAA) levels positively correlated with C-reactive protein levels and erythrocyte sedimentation rates. Glutamyl transpeptidase levels positively correlated with AST and ALT levels.In conclusion, serum IL-36α levels were elevated in patients with gout and correlated with the clinical markers of inflammation. Our findings suggest that IL-36α may be a novel inflammatory indicator for gout. [ABSTRACT FROM AUTHOR]

Gout affects 15%–30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate‐lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half‐life of 18–30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady‐state oral clearance (CL/F), elimination half‐life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%–60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate‐lowering therapy. [ABSTRACT FROM AUTHOR]

For the past few years, sweat analysis for health monitoring has attracted increasing attention benefiting from wearable technology. In related research, the sensitive detection of uric acid (UA) in sweat with complex composition based on surface-enhanced Raman spectroscopy (SERS) for the diagnosis of gout is still a significant challenge. Herein, we report a visualized and intelligent wearable sweat platform for SERS detection of UA in sweat. In this wearable platform, the spiral channel consisted of colorimetric paper with Ag nanowires (AgNWs) that could capture sweat for SERS measurement. With the help of photos from a smartphone, the pH value and volume of sweat could be quantified intelligently based on the image recognition technique. To diagnose gout, SERS spectra of human sweat with UA are collected in this wearable intelligent platform and analyzed by artificial intelligence (AI) algorithms. The results indicate that the artificial neural network (ANN) algorithm exhibits good identification of gout with high accuracy at 97%. Our work demonstrates that SERS-AI in a wearable intelligent sweat platform could be a feasible strategy for diagnosis of gout, which expands research on sweat analysis for comfortable and noninvasive health monitoring. [ABSTRACT FROM AUTHOR]

Background: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. Study design: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. Statistical analysis plan: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0–10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes. Discussion: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. Trial registration: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered). [ABSTRACT FROM AUTHOR]

The NOD‐, LRR‐, and Pyrin domain‐containing protein 3 (NLRP3) inflammasome plays key roles in regulating inflammation. Numerous studies show that the abnormal activation of NLRP3 associates with the initiation and progression of various diseases. Hence, the NLRP3 inflammasome may be a promising therapeutic target for these diseases. Octyl gallate (OG) is a small molecule with antioxidant, antimicrobial, antifungal, and anti‐inflammatory activities; however, the mechanism underlying its anti‐inflammatory activity is still unclear. Here, we developed a screening system for NLRP3‐inflammasome inhibitors. A total of 3287 small molecules were screened for inhibitors of nigericin‐induced NLRP3 oligomerization. OG was identified as a novel inhibitor. We show that OG directly targets the LRR domain of NLRP3 and thereby blocks the inflammatory cascade of the NLRP3 inflammasome. This contrasts with the mode‐of‐action of other direct NLRP3 inhibitors, which all bind to the NACHT domain of NLRP3. Interestingly, OG also inhibits the priming step by downregulating the Raf‐MEK1/2‐ERK1/2 axis. Thus, OG inhibits the NLRP3 inflammasome by two distinct mechanisms. Importantly, OG injection ameliorated the inflammation in mouse models of foot gout and sepsis. Our study identifies OG as a potential therapeutic agent for NLRP3‐associated diseases. [ABSTRACT FROM AUTHOR]

Gout is a self-limiting form of inflammatory arthropathy caused by the formation of urate crystals due to hyperuricemia. The resolution of gout involves the transition of proinflammatory M1-type macrophages to anti-inflammatory M2-type macrophages, as well as neutrophil-mediated extracellular trap (NET) formation. However, the underlying mechanisms of these changes are not clear. Studies have confirmed that high expression of CD39 on macrophages and neutrophils can trigger the polarization of macrophages from a proinflammatory state to an anti-inflammatory state. Recent studies have shown that the pathogenesis of gout involves extracellular ATP (eATP), and the synergistic effect of MSU and extracellular ATP can cause gout. CD39 is a kind of ATP hydrolysis enzyme that can degrade eATP, suggesting that CD39 may inhibit the aggravation of inflammation in gout and participate in the remission mechanism of gout. To confirm this hypothesis, using data mining and flow cytometry, we first found that CD39 expression was significantly upregulated on CD14 + monocytes and neutrophils in gout patients during the acute phase. Inhibition of CD39 by lentivirus or a CD39 inhibitor in acute gout models aggravated gouty arthritis and delayed gout remission. Apyrase, a functional analog of CD39, can significantly reduce the inflammatory response and promote gout remission in acute gout model mice. Our findings confirm that the upregulation of CD39 during gout flare-ups promotes spontaneous remission of acute gouty inflammation. [ABSTRACT FROM AUTHOR]

The article offers information on crystal arthritis, focusing on gout and calcium pyrophosphate deposition disease (CPPD). Topics include the presentation of crystal arthritis as acute monoarthritis caused by the deposition of crystals in joints, the importance of accurate diagnosis through synovial fluid analysis and clinical features, and the management of gout with urate-lowering therapy and anti-inflammatory drugs.

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]