Diastolic and systolic blood pressure and gout: a Mendelian randomization study.

Background: Although there is solid epidemiological evidence supporting the connection between hypertension and gout, little has been said about the relationship between diastolic and systolic blood pressure and gout, the causal relationship and direction associated are uncertain, so we aim to research the causal relationship between diastolic and systolic blood pressure and gout. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect between 2 blood pressure phenotypes (including diastolic blood pressure and systolic blood pressure) and 5 gout phenotypes (including gout, drug-induced gout, idiopathic gout, unspecified gout, and strictly defined gout) using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. Results: After the screening, we found a causal relationship between diastolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout, and a causal relationship between systolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout. Conclusion: From a genetic predisposition, controlling blood pressure may reduce the risk of gout.

Single-cell and genome-wide Mendelian randomization identifies causative genes for gout.

BACKGROUND: Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis. METHODS: The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout. RESULTS: We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A. CONCLUSION: According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.

Health literacy in patients with gout: A latent profile analysis.

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.

Hyperuricemia and intravenous fat emulsion are risk factors for gout flares during active gastrointestinal bleeding: a case control study.

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.

Association between colchicine use and the risk of dementia among patients with gout: A nationwide retrospective cohort study.

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.

Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. RESULTS: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31-1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, p = 0.042). CONCLUSION: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.Systematic review registration: PROSPERO CRD42021272591.

Creating machine learning models that interpretably link systemic inflammatory index, sex steroid hormones, and dietary antioxidants to identify gout using the SHAP (SHapley Additive exPlanations) method.

Background: The relationship between systemic inflammatory index (SII), sex steroid hormones, dietary antioxidants (DA), and gout has not been determined. We aim to develop a reliable and interpretable machine learning (ML) model that links SII, sex steroid hormones, and DA to gout identification. Methods: The dataset we used to study the relationship between SII, sex steroid hormones, DA, and gout was from the National Health and Nutrition Examination Survey (NHANES). Six ML models were developed to identify gout by SII, sex steroid hormones, and DA. The seven performance discriminative features of each model were summarized, and the eXtreme Gradient Boosting (XGBoost) model with the best overall performance was selected to identify gout. We used the SHapley Additive exPlanation (SHAP) method to explain the XGBoost model and its decision-making process. Results: An initial survey of 20,146 participants resulted in 8,550 being included in the study. Selecting the best performing XGBoost model associated with SII, sex steroid hormones, and DA to identify gout (male: AUC: 0.795, 95% CI: 0.746- 0.843, accuracy: 98.7%; female: AUC: 0.822, 95% CI: 0.754- 0.883, accuracy: 99.2%). In the male group, The SHAP values showed that the lower feature values of lutein + zeaxanthin (LZ), vitamin C (VitC), lycopene, zinc, total testosterone (TT), vitamin E (VitE), and vitamin A (VitA), the greater the positive effect on the model output. In the female group, SHAP values showed that lower feature values of E2, zinc, lycopene, LZ, TT, and selenium had a greater positive effect on model output. Conclusion: The interpretable XGBoost model demonstrated accuracy, efficiency, and robustness in identifying associations between SII, sex steroid hormones, DA, and gout in participants. Decreased TT in males and decreased E2 in females may be associated with gout, and increased DA intake and decreased SII may reduce the potential risk of gout.

The experiences and perspectives of people with gout on urate self-monitoring.

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.

Limb salvage and systemic management of gouty tophi: Case series.

INTRODUCTION: Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice. PATIENT CONCERNS: In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management. DIAGNOSIS: Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities. INTERVENTIONS: In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management. OUTCOMES: Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions. LESSONS: We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.

Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

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.

Deficiency of histone deacetylases 3 in macrophage alleviates monosodium urate crystals-induced gouty inflammation in mice.

BACKGROUND: Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation. METHODS: Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein. RESULTS: Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1ß release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge. CONCLUSIONS: Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.

Adherence to Healthy and Unhealthy Plant-Based Diets and the Risk of Gout.

Importance: Plant-based diets are increasing in popularity due, in part, to their health benefits for selected cardiometabolic diseases as well as favorable environmental impact. Little is known about how such a diet is related to gout risk. Objective: To examine associations between adherence to a plant-based diet (including healthy and unhealthy versions of this diet), as well as its 18 individual food groups, and incident gout. Design, Setting, and Participants: This prospective cohort study used data from population-based cohorts of US men and women enrolled in the Health Professionals Follow-Up Study (1986-2012) and Nurses' Health Study (1984-2010). Participants were men and women free of gout at baseline. Statistical analyses were performed over March 2020 to August 2023. Exposures: An overall plant-based diet index (PDI), as well as healthy (hPDI) and unhealthy (uPDI) versions of this index that emphasize healthy and less healthy plant-based foods, respectively. These diet indices were comprised of 18 food groups, assessed using a validated semiquantitative food frequency questionnaire. Main Outcomes and Measures: Incident cases of gout that were confirmed with a supplementary questionnaire to meet the preliminary American College of Rheumatology survey criteria for gout. Cox proportional hazards regression models were used to evaluate multivariable-adjusted associations of all 3 PDIs with incident gout using quintiles (Q) of adherence. Results: Among a total of 122 679 participants (mean [SD] age, 53.8 [9.8] years among 43 703 men; mean [SD] age, 50.9 [7.2] years among 78 976 women) over 2 704 899 person-years of follow-up, 2709 participants experienced incident gout. The overall PDI was not significantly associated with gout in either cohort (Q5 vs Q1 pooled hazard ratio [HR], 1.02 [95% CI, 0.89-1.17]; P for trend = .63). In the pooled analysis, hPDI was significantly inversely associated with risk of gout (Q5 vs Q1 HR, 0.79 [95% CI, 0.69-0.91]; P for trend = .002), while the uPDI was positively associated with risk of gout (Q5 vs Q1 HR, 1.17 [95% CI, 1.03-1.33]; P for trend = .02), particularly in women (Q5 vs Q1 HR, 1.31 [95% CI, 1.05-1.62]; P for trend = .01). In analysis of individual food groups, higher intakes of certain healthy plant foods, such as whole grains (pooled HR per 1 serving/d, 0.93 [95% CI, 0.89-0.97]) and tea and coffee (pooled HR per 1 serving/d, 0.95 [95% CI, 0.92-0.97]), as well as dairy (pooled HR per 1 serving/d, 0.86 [95% CI, 0.82-0.90]), were independently associated with a lower risk of gout, while selected unhealthy plant foods, such as fruit juice (pooled HR per 1 serving/d, 1.06 [95% CI, 1.00-1.13]) and sugar-sweetened beverages (pooled HR per 1 serving/d, 1.16 [95% CI, 1.07-1.26]) were associated with increased risk of gout. Conclusions and Relevance: The findings of this prospective cohort study of PDIs and gout support current dietary recommendations to increase consumption of healthy plant foods while lowering intake of unhealthy plant foods to mitigate gout risk.

Antigout effects and mechanisms of total flavonoids from prunus tomentosa.

BACKGROUND: In recent years, hyperuricemia and acute gouty arthritis have become increasingly common, posing a serious threat to public health. Current treatments primarily involve Western medicines with associated toxic side effects. OBJECTIVE: This study aims to investigate the therapeutic effects of total flavones from Prunus tomentosa (PTTF) on a rat model of gout and explore the mechanism of PTTF's anti-gout action through the TLR4/NF-κB signaling pathway. METHODS: We measured serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) levels using an enzyme-linked immunosorbent assay (ELISA). Histopathological changes were observed using HE staining, and the expression levels of relevant proteins were detected through Western blotting. RESULTS: After PTTF treatment, all indicators improved significantly. PTTF reduced blood levels of UA, Cr, BUN, IL-1ß, IL-6, and TNF-α, and decreased ankle swelling. CONCLUSIONS: PTTF may have a therapeutic effect on animal models of hyperuricemia and acute gouty arthritis by reducing serum UA levels, improving ankle swelling, and inhibiting inflammation. The primary mechanism involves the regulation of the TLR4/NF-κB signaling pathway to alleviate inflammation. Further research is needed to explore deeper mechanisms.

Investigating gout flares: beyond a definition.

PURPOSE OF REVIEW: Gout flares are a paramount component of disease burden inflicted by gout onto the patient. Furthermore, they are included in the core domain set for long-term gout studies recognized by Outcome Measures in Rheumatology. Along with a validated classification criterion for gout, gout investigators have turned their efforts into defining and characterizing the gout flare. This brief review will summarize the efforts that have been done to define and characterize a gout flare in clinical studies. RECENT FINDINGS: Recent findings include a validated definition of a gout flare that has been utilized in novel clinical studies, use of technology to monitor for gout flares and their effects on patient life, and qualitative analyses into the disease burden that a patient undergoes. SUMMARY: Although guidelines for core outcome domains have been well established, there is question in methods of measuring and reporting gout flares in long-term trials. Furthermore, there is question as to the effectiveness of the agreed upon instruments' abilities to fully capture the disease burden experienced by patients with gout. A combination of outcome measurements including binary data (gout flare present or absent) along with a comprehensive measurement of disease burden over time would theoretically provide a more accurate description of the disease and serve as a basis for intervention development.

Current updates for hyperuricemia and gout in age-related macular degeneration.

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.