Gout Patients Research Articles

Evaluation of continued 2-monthly or annual urate monitoring in gout: an extension of the GoutSMART randomised controlled feasibility trial

Aim: Improved outcomes for patients with gout are associated with reduced urate levels and many guidelines recommend regular urate monitoring. There is no consensus on how frequently monitoring should be performed, and so we have used a supported self-management approach which incorporates urate self-testing to evaluate 2-monthly urate monitoring compared to annual monitoring. Methods: This study was an extension of a 12-month feasibility trial in 60 gout patients randomised 2:1 to support gout self-management or usual care. Participants exiting the self-management arm were offered 2-monthly urate monitoring, with usual care participants offered annual monitoring. Additional participants were randomised 1:1 to either arm. All participants were offered initial dose titration to a urate target of 0.3 mmol/L. The primary outcome was the proportion of participants with urate ≤ 0.36 mmol/L at 24 months with an intention-to-treat analysis. Results: Between September 2020, and September 2021, 67 patients were enrolled. The mean age was 55.5 (SD 14.0) years. 61 (91%) self-reported as cisgender male, 5 (7.5%) as cisgender female and 1 (1.5%) as transgender female. 62 (92.5%) were White, 4 (6.0%) were Asian and 1 (1.5%) was Black. 40 participants were allocated to 2-monthly monitoring (including 10 new participants), and 27 participants to annual monitoring (including 12 new participants). The primary study outcome of urate ≤ 0.36 mmol/L at 24 months was achieved by 38 (95%) 2-monthly monitoring participants, compared to 17 (62.9%) annual monitoring participants (risk difference 0.32 [95% CI 0.13 to 0.52]; p = 0.0021). 5 (7.5%) participants withdrew with 4 allocated to annual monitoring. 2 annual monitoring participants died. Conclusions: 2-monthly monitoring of urate is associated with improved maintenance of urate targets after 2 years compared to annual monitoring, a result influenced by an increased withdrawal rate amongst annual monitoring participants. Further trials evaluating the cost-effectiveness and optimal frequency of urate monitoring are now needed (ClinicalTrials.gov identifier: NCT03274063).

Causal relationship between gout and liver cancer: A Mendelian randomization and transcriptome analysis.

Gout is an inflammatory arthritis resulting from urate crystal deposition, now recognized as part of metabolic syndrome. Hyperuricemia, a hallmark of gout, is associated with various health complications, including liver cancer. Observational studies indicate a link between gout and increased cancer incidence. However, the causal relationship between gout and hepatocellular carcinoma remains uncertain. This study utilizes Mendelian randomization (MR) to explore this connection, minimizing confounding factors commonly present in observational studies. Genome-wide association study data for gout and liver cancer were sourced from the UK Biobank. We selected single nucleotide polymorphisms that are strongly associated with gout and liver cancer as instrumental variables for the analysis. We conducted 2-sample MR analysis using multiple MR methods (MR-Egger, weighted median, inverse variance weighting, and weighted mode) to evaluate causality. Co-localization and transcriptomic analyses were employed to identify target genes and assess their expression in hepatocellular carcinoma tissues. The 2-sample MR analysis indicated a significant causal relationship between gout and heightened liver cancer risk (P_IVW = .014). Co-localization analysis identified phosphatidylethanolamine N-methyltransferase (PEMT) as a crucial gene associated with gout (pH4 = 0.990). Transcriptomic data showed that PEMT expression was significantly higher in normal liver tissues compared to malignant samples (P < .001), and higher PEMT levels correlated with improved survival outcomes (P = .045). Immunohistochemical analysis revealed lower PEMT expression in hepatocellular carcinoma from patients with concurrent gout compared to those without (P < .05). The results indicate that gout increases the risk of hepatocellular carcinoma, with PEMT potentially playing a key role. Although this study focused on European populations, indicating a need for further research in diverse groups, the results emphasize the potential for liver cancer screening in newly diagnosed gout patients. Understanding the relationship between these conditions may inform future clinical practices and cancer prevention strategies.

Co-regulated ceRNA network mediated by circRNA and lncRNA in patients with gouty arthritis

Numerous studies have demonstrated the involvement of messenger RNAs (mRNAs) and non-coding RNAs, including long non-coding RNAs (lncRNA), circular RNAs (circRNAs) and microRNA (miRNAs), in gouty arthritis onset; however, the regulatory mechanism has not yet been elucidated. Here, we applied whole-transcriptome sequencing to identify the differentially expressed circRNAs, lncRNAs, miRNAs and mRNAs between the gout patients and normal people, and constructed co-regulated networks of circRNAs and lncRNAs according to the competitive endogenous RNA (ceRNA) theory for gouty arthritis onset to improve our understanding of the pathogenesis of this disease. The most significant finding of this study is the co-regulated ceRNA network of circRNAs and lncRNAs in gouty arthritis. The circRNA novel_circ_0030384 and the lncRNAs AAMP, TRIM16, PKN1, XLOC_184579 and XLOC_189826 were upstream genes in the co-regulated network. These upstream genes upregulated miR550a-5p and miR550a-3-5p, which downregulated PSME1 and FERMT3 expression. These mRNAs participated in proteasome dynamics, antigen processing and presentation, and platelet activation, which are associated with inflammation in gouty arthritis. In addition, the circRNA and lncRNAs upregulated miR550a-5p, which downregulated GRK2 and OS9 expression. Also, it proved that the down-regulated of PSME1, FERMT3, GRK2 and OS9 can aggravate gouty arthritis in vitro. In summary, these genes mediate inflammation in gouty arthritis through chemokine signaling to regulate neutrophil function.

Assessing Changes in Vascular Inflammation and Urate Deposition in the Vasculature of Gout Patients After Administration of Pegloticase Using Positron Emission Tomography and Dual-Energy Computed Tomography—A Pilot Study

We assessed changes in vascular inflammation and monosodium urate (MSU)-coded deposits after administration of Pegloticase in the vasculature of tophaceous gout patients using 18F-fluorodeoxyglucose (18F-FDG) Positron emission tomography/computed tomography (PET/CT) and dual-energy CT (DECT). Ten patients with tophaceous gout, intolerant or refractory to urate-lowering therapy (ULT), were treated with Pegloticase every two weeks for six months. 18F-FDG PET/CT and DECT were performed at baseline and after Pegloticase therapy to detect vessel wall inflammation (Standard uptake value, SUVmean, and SUVmax) and vascular MSU-coded deposition (MSU volume). Data were summarized using means and standard deviations. Baseline and follow-up values were compared for each variable using mixed-effect models. Significant decreases in SUVmean (p = 0.0003) and SUVmax (p = 0.009) were found with a trend towards a decrease in vessel wall MSU volume after treatment. There was a significant decrease in serum urate, correlating with reduction in SUVmean (R2 = 0.65), with a trend towards a decrease in CRP and blood pressure in all patients. Despite the small sample size, we were able to demonstrate a decrease in vessel wall inflammation and a trend towards a decrease in MSU volume by intensively lowering serum urate. These findings suggest that MSU-coded deposits and hyperuricemia may play a role in vascular wall inflammation. It remains to be seen whether this correlates with a decrease in adverse cardiovascular outcomes.

Differential expression of ferroptosis-related proteins in urinary exosomes: potential indicators for monitoring acute gout attack

BackgroundGout is the most prevalent form of inflammatory arthritis, characterized by significant pain during acute episodes. Current diagnostic and monitoring techniques are invasive and fail to predict the onset of acute attacks. Recent studies have implicated ferroptosis-related proteins in the pathogenesis of inflammation and gout; however, their clinical relevance in gout patients remains largely unexplored. This study aimed to evaluate the expression of these proteins in urinary exosomes from gout patients and to investigate their potential as noninvasive biomarkers.MethodsUtilizing data-independent acquisition (DIA) mass spectrometry and advanced bioinformatics techniques, we assessed the expression of ferroptosis-related proteins in the urinary exosomes of three groups: acute gout patients (AD group), intermittent gout patients (ID group), and normal controls (NC group). We constructed receiver operating characteristic (ROC) curves to determine the clinical utility of these proteins in monitoring acute gout attacks.ResultsOur analysis of urinary exosome proteomics identified 13 ferroptosis-related proteins. Notably, in comparison to the ID group, the proteins ACSL4, VDAC2, GPX4, and GSS were significantly upregulated in the AD group. ROC curve analysis revealed that the presence of ACSL4, VDAC2, and GPX4 in urinary exosomes possesses substantial predictive value for acute gout attacks.ConclusionIn patients with gout, numerous protein alterations occur within urinary exosomes. Specifically, changes in ferroptosis-related proteins such as ACSL4, VDAC2, GPX4, and GSS may serve as promising biomarkers for the monitoring of acute gout attacks.

Hyperuricemia suppresses lumican, exacerbating adverse remodeling after myocardial infarction by promoting fibroblast phenotype transition

BackgroundHyperuricemia is independently associated with a poor prognosis in patients with myocardial infarction (MI). Furthermore, MI induces activation of the repair response in local fibroblasts, resulting in extracellular matrix accumulation that generates a stable fibrotic scar in the infarcted area. However, researchers have not determined whether hyperuricemia affects fibroblast activation and its involvement in postinfarction cardiac remodeling.ObjectivesWe aimed to trigger hyperuricemia by administering potassium oxonate in a mouse model of MI to evaluate the role of hyperuricemia in MI pathogenesis.MethodsMicroarray datasets and single-cell sequencing data from gout patients, heart failure patients, and model mice were used to identify the underlying mechanisms responsible for the effect of hyperuricemia on MI progression. A hyperuricemia-related MI mouse model was established. Cardiac function was assessed, followed by sample collection and a uric acid assay. We conducted an enzyme-linked immunosorbent assay, histological detection, immunofluorescence, sequencing data processing, single-cell RNA-seq, and functional enrichment analysis. We then isolated and cultured cardiac fibroblasts and performed Western blotting, quantitative real-time polymerase chain reaction, and shRNA-mediated lumican knockdown assays.ResultsHyperuricemia decreased cardiac function, increased mortality, and aggravated adverse fibrosis remodeling in mice after MI. These outcomes were closely related to reduced levels of fibroblast-derived lumican. This reduction activated the TGF-β/SMAD signaling pathway to induce aberrant myofibroblast activation and extracellular matrix deposition in the infarcted area. Furthermore, lumican supplementation or uric acid-lowering therapy with allopurinol alleviated hyperuricemia-mediated abnormal cardiac remodeling.ConclusionHyperuricemia aggravates postinfarction cardiac remodeling by reducing lumican expression and promoting fibroblast phenotype transition. We highlight the clinical importance of lowering uric acid levels in hyperuricemia-related MI to prevent adverse ventricular remodeling.

Footwear and Foot Health: Unveiling the Role of Proper Shoe Fit in Preventing Podiatric Issues and Enhancing Well-Being

Background: The appropriate choice of footwear is crucial for foot health, yet its impact on different populations and medical conditions remains understudied. This review explores the effect of shoe fit on the prevention of podiatric disorders and overall well-being. Methods: The research included major academic databases such as MEDLINE, Cochrane Central, Scopus, and PEDro, using specific keywords. A scoping review was conducted following the Joanna Briggs Institute methodology, encompassing studies on shoe fit across diverse populations and conditions. Medical databases and grey literature were also included. Results: Five studies were included, covering topics such as footwear advice for women over 50, the effect of shoes in preventing calluses under the metatarsals, the effectiveness of a shoe-related intervention for gout patients, and the impact of custom-fitted shoes on physical activity in children with Down syndrome. Results showed that well-fitting shoes can prevent callus formation, but the efficacy of custom-fitted shoes for increasing physical activity requires further research. Conclusions: The choice of appropriate footwear should not be solely based on aesthetic considerations but rather on the specific needs of each individual. Physicians should consider providing advice on appropriate shoe characteristics as a primary intervention

Gout diagnoses uncertain when made by general practitioners without serum uric acid testing: an observational study.

General practitioners (GPs) diagnose the majority of all gout patients. They make their diagnosis clinically. Serum uric acid (SUA) level >0.35mmol/l is largely determinative for the clinical diagnosis of gout. We aimed to assess to what extent GPs test SUA when making a first gout diagnosis, and to consider consequences regarding diagnostic certainty of not testing it. We calculated proportions of patients from 87 Dutch general practices (1-1-2013 to 1-1-2022) with a first gout diagnosis and a recorded SUA test, evaluated if SUA testing was punctually timed with respect to the diagnosis date, whether SUA levels were >0.35mmol/L, and whether diagnoses corresponded with diagnoses according to the 'Acute Gout Diagnosis Rule' (AGD-rule). In 43.0% of 7782 patients (mean age 64.4 years; 68.8% male) no SUA test result was recorded, with substantial variation among practices: median 41.9% (IQR 20.2%). 'Gout very likely' according to the AGD-rule was seen in all males and in 83.1% of females when a punctually timed SUA >0.35mmol/L was present. When such SUA level was lacking, 'Questionable or indeterminate gout diagnosis' was seen in all males and in 67.1% of females, and 'Arthritis diagnosis other than gout' in 32.9% of females. GPs diagnosed gout without testing SUA in ~40% of cases. This implies avoidable diagnostic uncertainty with impact for the clinical care of many patients as well as for studies that include primary care patients with gout. Key Points • Serum uric acid (SUA) level > 0.35mmol is determinative when diagnosing gout: however, it is unknown how often SUA testing is applied as such. • More than 40% of patients with a first gout diagnosis according to general practitioners (GPs) had no SUA test result registered in their medical record. • Gout diagnosing by GPs without SUA testing appeared to lead to avoidable diagnostic uncertainty, as diagnoses are often questionable or sometimes even wrong. • Researchers investigating gout need to take into account diagnostic uncertainty if they include gout patients who are diagnosed in primary care in their studies without SUA information.

Imaging human coronary cholesterol/urate crystals with cross-polarized micro-optical coherence tomography.

Birefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-µOCT) for visualizing individual birefringent crystals in human coronary arteries. Human cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-µOCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-µOCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-µOCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (p < 0.05), and thus were MSU. CP-µOCT was three-dimensionally volume-rendered for counting MSU and CCs in 79 regions of interest sized [750 (x) × 500 (y) × 400 (z) µm]. Crystal counts were normalized by the total coronary length utilized. The relationship between CP-µOCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-µOCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (R = 0.98, p < 0.01), and with histology-derived intimal thickening (R = 0.51, p < 0.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (p < 0.05). These results demonstrate a significant increase in CP-µOCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.

Modifiable risk factors and incident cardiovascular events in gout patients

Abstract Background Gout is associated with increased risks of cardiovascular events. However, it remains uncertain whether achieving the control targets for risk factors can attenuate this risk. This study evaluated the association between the attainment of targeted seven risk factors and the incidence of major adverse cardiovascular events (MACCE) among patients with gout. Methods From the UK Biobank database, we analyzed data from participants diagnosed with gout at baseline (2006-2010). These individuals were followed to monitor the incidence of MACCE. Gout patients were stratified based on the achievement of seven predefined risk factor targets at baseline: body mass index 18.5-24.9, adherence to a high-quality diet, engagement in regular exercise, non-smoking status, abstention from alcohol, hemoglobin A1c &amp;lt;48 mmol/mol, and serum urate &amp;lt; 360 μmol/L. The primary outcome was the incidence of MACCE, encompassing all-cause death, stroke, or myocardial infarction. Cox model was used to identify independent predictors of MACCE. Results After a median follow-up of 14.1 years, 1,318 of 6,273 gout patients developed MACCE. Among individuals with gout, the risk of MACCE decreased stepwise with the number of optimally managed modifiable risk factors. For participants exhibiting 1, 2, 3, and ≥4 optimal modifiable factors, the hazard ratios (HRs) were 0.39 (95% confidence interval (CI): 0.26-0.58), 0.30 (95%CI: 0.20-0.44), 0.28 (95%CI: 0.19-0.41), and 0.24 (95%CI: 0.16-0.36) respectively, showing a significant trend towards risk reduction (Ptrend &amp;lt;0.001). Conclusion Among individuals with gout, there is a stepwise decrease in the risk of MACCE with every additional risk factor that is optimally controlled.Study flowStratified analysis for adjusted HRs

NUMB dysfunction defines a novel mechanism underlying hyperuricemia and gout

Defective renal excretion and increased production of uric acid engender hyperuricemia that predisposes to gout. However, molecular mechanisms underlying defective uric acid excretion remain largely unknown. Here, we report a rare genetic variant of gout-unprecedented NUMB gene within a hereditary human gout family, which was identified by an unbiased genome-wide sequencing approach. This dysfunctional missense variant within the conserved region of the NUMB gene (NUMBR630H) underwent intracellular redistribution and degradation through an autophagy-dependent mechanism. Mechanistically, we identified the uric acid transporter, ATP Binding Cassette Subfamily G Member 2 (ABCG2), as a novel NUMB-binding protein through its intracellular YxNxxF motif. In polarized renal tubular epithelial cells (RTECs), NUMB promoted ABCG2 trafficking towards the apical plasma membrane. Genetic loss-of-function of NUMB resulted in redistribution of ABCG2 in the basolateral domain and ultimately defective excretion of uric acid. To recapitulate the clinical situation in human gout patients, we generated a NUMBR630H knock-in mouse strain, which showed marked increases of serum urate and decreased uric acid excretion. The NUMBR630H knock-in mice exhibited clinically relevant hyperuricemia. In summary, we have uncovered a novel NUMB-mediated mechanism of uric acid excretion and a functional missense variant of NUMB in humans, which causes hyperuricemia and gout.

Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators

Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p < 0.05) in clustering and proteome networks in sera and peripheral blood mononuclear cells. Sera demonstrated altered complement activation and regulatory gene ontology biologic processes. In both cohorts, a treatment-emergent serum interactome included key gouty inflammation mediators (C5, IL-1B, CXCL8, IL6). Last, febuxostat treatment decreased complement activation biologic process proteins in cultured BMDMs. Reduced gout flares are linked with a XOI treatment-emergent serum protein interactome that includes inflammation regulators, associated with altered complement activation and regulatory biologic processes. Serum and leukocyte proteomics could help identify when gouty inflammatory processes begin to subside in response to ULT.Trial Registration: ClinicalTrials.gov Identifier NCT02579096, posted October 19, 2015.

6741 Serum Urate-Lowering Effects Of Sodium-Glucose Transport Protein 2 Inhibitors Compared To Dipeptidyl Peptidase-4 Inhibitors In Gout Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study

Abstract Disclosure: R.K. Shariff: None. C. Chung: None. P. Huang: None. S. Mon: None. K. Ma: None. Background/Purpose: Effective management of gout in patients requiring long-term urate-lowering therapy involves maintaining serum rate levels within specific ranges. Hyperuricemia and gout have been associated with an increased risk of Type 2 Diabetes Mellitus (T2DM), with a reported prevalence of 16% in gout patients. Pharmacological approaches to glycemic control, including Sodium-glucose Transport Protein 2 Inhibitors inhibitor (SGLT2i) and Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), have showed potential serum urate lowering effects. However, a direct comparison of these effects in patients with gout and concomitant T2DM is lacking. This study aims to evaluate the serum urate-lowering effects of SGLT2i compared to DPP-4i in this patient population. Methods: This was a population-based cohort study of patients with gout diagnosed following the 2015 Gout classification criteria in the American College of Rheumatology/European League Against Rheumatism collaborative initiative and T2DM diagnosed following the American Diabetes Association criteria, respectively. Subjects treated between 2008 and 2023 at 92 United States hospitals were screened. Propensity score matching was used to balance the baseline differences in age of gout onset, sex, comorbidities, and past medical history between the two groups. The primary predictor variable was the use of therapies of SGLT2i and DPP-4i. The primary outcome of interest was the serum urate more than 6 mg/dL during the follow-up period. Kaplan-Meier analysis and log-rank tests were utilized to compare if the numbers of serum urate were higher than 6 mg/dL in both arms. A Cox proportional hazards model was utilized to estimate the association between the use of SGLT2i versus DPP-4i and the numbers of serum urate higher than 6 mg/dL. Inclusion criteria include patients with gout and concomitant T2DM, age over 18, and must have serum uric acid level data available. Results: Of the 11,495 gout patients, including 3,593 users of SGLT2i users, were propensity score-matched to 3593 DPP-4i users. Among gout patients with T2DM on SGLT2i, 598 experienced serum urate levels exceeding than 6 mg/dL, while in the DPP-4i group, 920 patients had serum urate higher than 6 mg/dL. The use of SGLT2i was associated with significantly lower odds of serum uric acid exceeding 6 mg/dl compared to DPP-4i. (OR: 0.580 [0.517-0.651]). Conclusion: Our study suggests that SGLT2i may offer a more effective means of managing serum uric acid levels in gout patients with concomitant T2DM compared to DPP-4i. Clinical trials are required to validate the findings. For clinical practice, the dosage for SGLT2i to cause the urate-lowering effect needs to be investigated. With further studies and clinical trials, the rationale of choosing SGLT2i over DPP-4i may be incorporated into the management of T2DM in gout patients with T2DM. Presentation: 6/1/2024

Associations of Dietary Magnesium Intake with All-Cause and Cause-Specific Mortality Among Individuals with Gout and Hyperuricemia.

We aimed to evaluate the relationship of dietary magnesium intake with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). We analyzed data of 1171 gout patients and 6707 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. Dietary intake data were obtained from 24-h dietary recall interviews. Mortality status was determined using the NHANES public-use linked mortality fill. We used Cox regression model and restricted cubic spline analysis to probe the association of dietary magnesium intake and mortality among gout and HUA patients. During 7081 person-years of follow-up, 257 deaths were documented in gout patients, among which 74 died from cardiovascular disease (CVD) and 48 died from cancer. For HUA patients followed up for 58,216 person-years, 1315 all-cause deaths occurred, including 411 CVD deaths and 224 cancer deaths. After multifactorial adjustments, higher dietary magnesium intake was associated with lower risk of all-cause mortality. Nonlinear negative associations were found between dietary magnesium intake and CVD mortality among gout and HUA patients, with inflection points of 152.5mg/day and 303mg/day, respectively, and cancer mortality among HUA patients, with the inflection point of 232mg/day. The results were robust in subgroup and sensitivity analyses. High dietary magnesium intake is linearly related to all-cause mortality, and nonlinearly associated with cause-specific mortality among gout and HUA patients.

Subclinical carotid atherosclerosis in gouty patients: relation to musculoskeletal ultrasonographic findings and serum sclerostin level

Objectives. To detect subclinical carotid atherosclerosis in gout patients and its relation to musculoskeletal ultrasound (MSK US) manifestations and serum sclerostin (SCL) levels. Patients and methods. Thirty Egyptian gouty patients were classified into two groups: Group A included 15 patients with diagnostic MSK US manifestations of gout (double contour sign), and Group B included 15 patients without MSK US findings. MSK US was done for both knees and the first MTP joints. Carotid duplex ultrasonography was done to evaluate carotid intima-media-thickness (CIMT) and serum SCL level was measured in all patients by ELISA technique. Results. Gouty patients with MSK US findings had a significantly higher increase in serum SCL levels than those without MSK US findings (p &lt;0.01). Group A patients had a significantly greater CIMT than patients of group B (p &lt;0.01). Serum uric acid and SCL levels were found to be significantly positively correlated. The ROC curve revealed that the optimal SCL cutoff value for detecting positive MSK US findings in gout patients was &gt;25.05 ng/ml. At this level, there was a significant difference between the patients with a CIMT &gt;0.9 mm and the patients with a CIMT ≤0.9 mm (p &lt;0.05). Conclusions. Patients with MSK US manifestations of gout are more liable to have subclinical carotid atherosclerosis than patients without these manifestations. SCL at a certain level &gt;25.05 ng/ml in gout patients might predispose patients to radiographic findings of MSK US of gout and subclinical atherosclerosis.

Serum ionized magnesium acts as an independent protective factor against bone erosion in patients with gouty arthritis: a cross-sectional study.

Gouty arthritis is a common inflammatory arthritis. The recurrent gout attacks severely damage the joint's function, lead to bone erosion, and affect bone metabolism. The role of magnesium (Mg) ions in bone homeostasis has been recognized, whereas its specific relationship with gouty bone erosion remains unclear. This study examined the association between serum ionized Mg levels and bone erosion in patients with gout arthritis. A total of 769 patients with gout arthritis were included in the study. Participants were classified into four groups based on the quartiles of the serum ionized Mg level. Logistic regression analysis assessed the association between serum ionized Mg and bone erosion. Compared to patients without bone erosion, serum ionized Mg levels were lower in gout patients with bone erosion (p<0.001). When dividing serum ionized Mg into quartiles, the prevalence rate of bone erosion in group Q1, representing the patients with the lowest serum ionized Mg levels, was notably higher than in Q2, Q3, and Q4 (60.2% vs. 43.6%, 45.6%, 40.3%, p<0.001). Multiple logistic regression analysis revealed that patients in Q2-Q4 had a lower odds ratio (OR) of bone erosion compared to those in Q1 (ORs were 0.520, 0.533, and 0.411 in Q2-Q4, respectively, p<0.001). The incidence of bone erosion is higher in gout arthritis patients with lower serum ionized Mg levels. High serum ionized Mg levels may be an independent protective factor for bone erosion in gout arthritis. Thus, Mg supplementation may be a promising approach to prevent or slow down the development of bone erosion in gouty arthritis.

Integrating transcriptomics, eQTL, and Mendelian randomization to dissect monocyte roles in severe COVID-19 and gout flare.

There are considerable similarities between the pathophysiology of gout flare and the dysregulated inflammatory response in severe COVID-19 infection. Monocytes are the key immune cells involved in the pathogenesis of both diseases. Therefore, it is critical to elucidate the molecular basis of the function of monocytes in gout and COVID-19 in order to develop more effective therapeutic approaches. The single-cell RNA sequencing (scRNA-seq), large-scale genome-wide association studies (GWAS), and expression quantitative trait loci (eQTL) data of gout and severe COVID-19 were comprehensively analyzed. Cellular heterogeneity and intercellular communication were identified using the scRNA-seq datasets, and the monocyte-specific differentially expressed genes (DEGs) between COVID-19, gout and normal subjects were screened. In addition, the correlation of the DEGs with severe COVID-19 and gout flare was analyzed through GWAS statistics and eQTL data. The scRNA-seq analysis exhibited that the proportion of classical monocytes was increased in both severe COVID-19 and gout patient groups compared to healthy controls. Differential expression analysis and MR analysis showed that NLRP3 was positively associated with the risk of severe COVID-19 and involved 11 SNPs, of which rs4925547 was not significantly co-localized. In contrast, IER3 was positively associated with the risk of gout and involved 9 SNPs, of which rs1264372 was significantly co-localized. Monocytes have a complex role in gout flare and severe COVID-19, which underscores the potential mechanisms and clinical significance of the interaction between the two diseases.

Whole-genome sequencing reveals rare variants associated with gout in Taiwanese males.

To identify rare variants (RVs) of gout, we sequenced the whole genomes of 321 male gout patients and combined these with those of 64 male gout patients and 682 normal controls at Taiwan Biobank. We performed ACAT-O to identify 682 significant RVs (p < 3.8 × 10-8) clustered on chromosomes 1, 7, 10, 16, and 18. To prioritize causal variants effectively, we sifted them by Combined Annotation-Dependent Depletion score >10 or |effect size| ≥ 1.5 for those without CADD scores. In particular, to the best of our knowledge, we identified the rare variants rs559954634, rs186763678, and 13-85340782-G-A for the first time to be associated with gout in Taiwanese males. Importantly, the RV rs559954634 positively affects gout, and its neighboring gene NPHS2 is involved in serum urate and expressed in kidney tissues. The kidneys play a major role in regulating uric acid levels. This suggests that rs559954634 may be involved in gout. Furthermore, rs186763678 is in the intron of NFIA that interacts with SLC2A9, which has the most significant effect on serum urate. Note that gene-gene interaction NFIA-SLC2A9 is significantly associated with serum urate in the Italian MICROS population and a Croatian population. Moreover, 13-85340782-G-A significantly affects gout susceptibility (odds ratio 6.0; P = 0.038). The >1% carrier frequencies of these potentially pathogenic (protective) RVs in cases (controls) suggest the revealed associations may be true; these RVs deserve further studies for the mechanism. Finally, multivariate logistic regression analysis shows that the rare variants rs559954634 and 13-85340782-G-A jointly are significantly associated with gout susceptibility.

Support needs of gout patients and suitability of eHealth to address these needs.

To investigate the support needs of patients with gout regarding information, communication, treatment and disease monitoring, and patients' views on and preferences for eHealth applications to address these needs. A focus group study using purposive sampling was conducted. Three focus group sessions with a duration of 2 h per group were held with in total of 23 patients using urate-lowering therapy, recruited from primary and secondary care. Audio recordings were transcribed, and data were analysed using thematic analysis. Eight themes were identified. Five themes addressed support needs of gout patients and suitability of eHealth in addressing those needs: (1) Timely access to healthcare, especially during flares; (2) (personalized) information regarding diagnosis, medication, and diet; (3) insight into uric acid levels and medication side effects through blood monitoring; (4) better coordination across primary and secondary care; and (5) self-management and shared responsibility over care for maintaining health. Three themes addressed eHealth in general: (1) receptive towards eHealth in gout care; (2) the preference for eHealth to have a complementary role (i.e. not replacing face-to-face) contact with healthcare providers; and (3) preferences on eHealth use and functionalities. Patients expressed various needs regarding their disease management and projected a supporting role for eHealth in (self)management of gout. Addressing the needs and preferences of patients could enhance their understanding of the disease and treatment, self-management, and possibly health outcomes.

Untargeted metabolomics analysis of the urinary metabolic signature of acute and chronic gout

BackgroundGout is a common kind of inflammatory arthritis with metabolic disorders. However, the detailed pathogenesis of gout is complex and not fully clear. We investigated the urine metabolic profiling of gout patients by ultra-performance liquid chromatograph quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). MethodUrine metabolites were extracted from 26 acute gout patients, 31 chronic gout patients, and 32 healthy controls. Metabolite extracts were analyzed by UPLC-Q-TOF-MS for untargeted metabolomics. The peak area of creatinine was used to correct the content variations of urine samples for the semi-quantitative analysis. The value of variable importance in the projection (VIP) was obtained through the orthogonal partial least squares-discrimination analysis (OPLS-DA), and several differential metabolites were screened out. ResultsThe potential metabolic markers of gout in different stages were found based on the t-test. Finally, 18 different metabolites were identified through Human Metabolome Database (HMDB) and Targeted-MS/MS. The receiver operating characteristic (ROC) curve results revealed that all the screened biomarkers exerted high accuracy and diagnostic value. Pathway analysis indicated that the significantly different metabolites were mainly involved in purine metabolism and amino acid metabolism. ConclusionThe identified potential biomarkers are mainly involved in purine metabolism and amino acid metabolism, which leads us to further explore the pathogenesis of gout. This will lead us to further explore the pathogenesis of gout and provide the basis and ideas for the prevention and treatment of gout.