A Tale of Two Diagnoses; Gout Vs Chronic Osteomyelitis. A Case Report.

Gout can potentially be diagnosed clinically and treated, if classical symptoms are present. In some cases, gout and osteomyelitis can have similar presenting signs and symptoms and it may be difficult to differentiate just on clinical presentation, routine laboratory workup and imaging like radiography or ultrasound. Arthrocentesis can be crucial in such scenarios to differentiate the two entities as missed opportunity to treat infectious etiology can have detrimental outcomes. We present a case of patient with ankle pain and swelling treated as recurrent gout, as there were no risk factors for osteomyelitis. Arthrocentesis confirmed the diagnosis of osteomyelitis and patient was treated with intravenous antibiotics, resulting in resolution of symptoms.

Extensive Gouty Tophus in Neglected Femoral Neck Fracture: A Case Report.

Femoral neck fractures are extremely common injuries, especially in the elderly, who often have multiple associated comorbidities. Despite advances in surgical technique and implant technology, neglected fractures are still a reality in developing countries due to the lack of access to healthcare services or socioeconomic conditions of patients. This case report presents a 61-year-old male patient referred from a rural area to a trauma referral hospital with a neglected femoral neck fracture. The patient had multiple comorbidities, and during the surgical approach for total hip arthroplasty, the intraoperative finding of an extensive gouty tophus led to an increase in surgical time and modifications in the surgical procedure. The epidemiological profile of the patient in question fits the pattern of patients with diffuse gouty arthropathy, warranting suspicion of hip involvement when manifested in other joints. Performing complementary exams in patients preoperatively with proximal femur fractures and coxarthrosis can be an indispensable tool for the successful implementation of the therapeutic plan. This report presents these findings and the outcome of the method used.

Multimodal Machine Learning-Based Marker Enables Early Detection and Prognosis Prediction for Hyperuricemia.

Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.

Euphorbia factor L2 alleviated gouty inflammation by specifically suppressing both the priming and activation of NLRP3 inflammasome.

Euphorbia L. is a traditionally used herb and contains many newly identified compounds with novel chemical structures. Euphorbia factor L2 (EFL2), a diterpenoid derived from Euphorbia seeds, is reported to alleviate acute lung injury and arthritis by exerting anti-inflammatory effects. In this study, we aimed to test the therapeutic benefit and mechanisms of EFL2 in NLRP3 inflammasome-mediated gouty models and identified the potential molecular mechanism. A cell-based system was used to test the specific inhibitory effect of EFL2 on NLRP3-related inflammation. The gouty arthritis model and an air pouch inflammation model induced by monosodium urate monohydrate (MSU) crystals were used for in vivo experiments. Nlrp3-/- mice and in vitro studies were used for mechanistic exploration. Virtual molecular docking and biophysical assays were performed to identify the direct binding and regulatory target of EFL2. The inhibitory effect of EFL2 on inflammatory cell infiltration was determined by flow cytometry in vivo. The mechanism by which EFL2 activates the NLRP3 inflammasome signaling pathway was evaluated by immunological experiment and transmission electron microscopy. In vitro, EFL2 specifically reduced NLRP3 inflammasome-mediated IL-1ß production and alleviated MSU crystal-induced arthritis, as well as inflammatory cell infiltration. EFL2 downregulated NF-κB phosphorylation and NLRP3 inflammasome expression by binding to glucocorticoid receptors. Moreover, EFL2 could specifically suppress the lysosome damage-mediated NLRP3 inflammasome activation process. It is expected that this work may be useful to accelerate the development of anti-inflammatory drugs originated from traditional herbs and improve therapeutics in gout and its complications.

Association between oxidative balance score and risk of gout: The NHANES cross-sectional study, 2007-2018.

BACKGROUND: The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. The association between OBS and gout has not been reported previously. We conducted a cross-sectional study to investigate the complex association between OBS and gout in US adults. METHODS: In all, 10 492 participants were included in this study. The exposure variable was OBS, which was scored by 16 dietary and four lifestyle factors. Multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were used to analyze the association between OBS and gout. RESULTS: Compared with the lowest OBS quartile group (Q1), the multivariate corrected odds ratio (OR) (95% confidence interval [C]) for the highest quartile of OBS (Q4) was 0.72 (0.52-1.00) (p = .13 for trend); furthermore, the RCS showed a negative linear relationship between OBS and gout (p-nonlinear = .606). CONCLUSION: In conclusion, the risk of gout is higher with high OBS. The prevalence of gout decreased with higher OBS. Diabetes may alter this negative correlation.

A study on the antioxidant, anti-inflammatory, and xanthine oxidase inhibitory activity of the Artemisia vulgaris L. extract and its fractions.

ETHNOPHARMACOLOGICAL RELEVANCE: Vietnamese people use mugwort (Artemisia vulgaris L.) to treat arthritis and gout. Our previous research shows that mugwort contains flavonoids, and its extract possesses antibacterial and anti-inflammatory activities. However, no publications have been on the xanthine oxidase inhibitory activity of mugwort and acute anti-inflammatory activity in vivo. AIM OF THE STUDY: The study aimed to verify the antioxidant, xanthine oxidase inhibitory, and anti-inflammatory capabilities of mugwort extract in vitro and in vivo, isolate phyto-compounds from potential bioactive fractions, and then evaluate their potential in inhibiting xanthine oxidase. METHODS: According to established methods, the extract and the active flavonoids were obtained using different chromatographic techniques. DPPH, ABTS, reducing power, and H2O2 elimination were used to evaluate antioxidant activity. The model of LPS-induced RAW264.7 cells was used to measure the inhibition of NO production. The carrageenan-induced paw oedema model was used to assess acute inflammation in mice. In vitro, xanthine oxidase inhibition assay was applied to investigate the effects of extract/compounds on uric acid production. Chemical structures were identified by spectral analysis. RESULTS: The assessment of the acute inflammatory model in mice revealed that both the 96% ethanol and the 50% ethanol extracts significantly decreased oedema in the mice's feet following carrageenan-induced inflammation. 96% ethanol extract exhibited a better reduction in oedema at the low dose. The analysis revealed that the ethyl acetate fraction had the highest levels of total polyphenols and flavonoids. Additionally, this fraction demonstrated significant antioxidant activity in various assays, such as DPPH, ABTS, reducing power, and H2O2 removal. Furthermore, it displayed the most potent inhibition of xanthine oxidase, an anti-inflammatory activity. Five phytochemicals were isolated and determined from the active fraction such as luteolin (1), rutin (2), apigenin (3), myricetin (4), and quercetin (5). Except for rutin, the other compounds demonstrated the ability to inhibit effective xanthine oxidase compared to standard (allopurinol). Moreover, quercetin (5) inhibited NO production (IC50 21.87 µM). CONCLUSION: The results indicate that extracts from A. vulgaris effectively suppressed the activity of xanthine oxidase and exhibited antioxidant and anti-inflammatory properties, potentially leading to a reduction in the production of uric acid in the body and eliminating ROS. The study identified mugwort extract and bioactive compounds derived from Artemisia vulgaris, specifically luteolin, apigenin, and quercetin, as promising xanthine oxidase inhibitors. These findings suggest that further development of these compounds is warranted. At the same time, the above results also strengthen the use of mugwort to treat gout disease in Vietnam.

Understanding spinal gout: A comprehensive study of 88 cases and their clinical implications.

Background: Spinal gout, a rare and often underdiagnosed condition, significantly impacts patients' quality of life. Therefore, the aim of the research is to analyze cases of spinal gout, including clinical features, anatomical location of spinal gout, laboratory studies, imaging studies, treatment choices, and outcomes from various cases of spinal gout. Methods: The author conducted a systematic literature search in the PUBMED and Science Direct databases from 2013 to 2023. We included clinical case presentations of spinal cases in adults, published in English. The three researchers independently reviewed the title and abstract of each article, and any differences in opinions were resolved through consensus. The extracted data were subsequently analyzed descriptively. Results: A total of 88 cases of spinal gout were obtained and studied. Out of the total reviewed cases of spinal gout, 89.77% of the subjects were male, with an average age of 51.9 years (age range 16-87 years). Common symptoms include back/neck pain (78.41%) and lower extremity weakness (37.50%). The lumbar spine is the most frequently affected region (62.50%), diagnosed primarily through magnetic resonance imaging (MRI) scans. Surgery, performed in 61.36% of cases, commonly involves decompressive laminectomy. Posttreatment, symptoms resolve in 87.50% of cases. Conclusion: Cases of spinal gout present with a variety of symptoms, including back pain and weakness. Diagnosis typically involves an MRI examination and synovial fluid analysis for confirmation. Treatment varies and includes medication therapy and surgical interventions. A deeper understanding of these cases can assist healthcare practitioners in the management and diagnosis of spinal gout cases.

Associations of oxidative balance score with hyperuricemia and gout among American adults: a population-based study.

Objective: The current study aimed to assess the relationships between oxidative balance score (OBS) and OBS subclasses (dietary and lifestyle OBS) with risks of hyperuricemia (HUA) and gout among American adults. Methods: Participants in the National Health and Nutrition Examination Survey from 2007 to 2018 were initially recruited and then the final sample was restricted to adults without missing values about serum uric acid, gout, OBS, and covariates. Rao-Scott adjusted chi-square test and analysis of variance were utilized to compare the baseline characteristics in adults of different quartiles of OBS, while the weighted stepped logistic regression models were used to explore the associations of overall, dietary, and lifestyle OBS with the risks of HUA and gout. Weighted restricted cubic spline analyses were conducted to explore the nonlinear dose-response associations. Results: The final sample consisted of 22,705 participants aged 20 years and older, which was representative of approximately 197.3 million non-institutionalized American adults. HUA and gout prevalence decreased with OBS quartiles. Compared with adults in the first quartile of OBS, those in the second (OR: 0.85, 95% CI: 0.72-0.99), third (OR: 0.71, 95% CI: 0.58-0.85), and fourth (OR: 0.48, 95% CI: 0.38-0.61) quartiles of OBS had reduced risks of hyperuricemia. Similarly, adults in the second (OR: 0.70, 95% CI: 0.51-0.97) quartile of OBS was associated with lower gout risk in comparison to adults in the lowest quartile. Regarding OBS subclasses, dietary and lifestyle OBS were both negatively correlated with the risk of HUA, and only higher lifestyle OBS was significantly associated with lower gout risk. Furthermore, the subgroup analyses and interaction effects also substantiated similar effects. Significant nonlinear dose-response relationships were observed between overall, dietary, and lifestyle OBS with HUA risk as well as that of lifestyle OBS with gout risk. Conclusion: This study strongly suggests the significant negative associations of OBS with HUA and gout in American adults and provides a dietary and lifestyle guideline to reduce the risks.

Clinical implications of persistent joint pain after gout flare.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Investigating the involvement of the NLRP3/ASC/caspase-1 and NF-κb/MAPK pathways in the pathogenesis of gouty arthritis: Insights from irradiated and non-irradiated Trifolium alexandrium L. extracts and some metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: Trifolium alexandrinum L. (TA), has traditionally been used in folk medicine for its anti-inflammatory properties against hyperuricemia and gout. However, the specific mechanisms of action of TA have not been thoroughly studied. AIM OF THE WORK: This study aimed to evaluate the protective effects of irradiated (TR25) and non-irradiated (TR0) Trifolium alexandrinum L. aqueous extract (TAAE), along with two isolated compounds, caffeine (CAF) and saponin (SAP), in a rat model of acute gouty arthritis (GA). MATERIALS AND METHODS: The GA model was established by injecting a monosodium urate (MSU) suspension into the knee joint. Synovial tissue pathology was assessed, and levels of TNF-α, IL-6, IL-1ß, NF-κB, mTOR, AKT1, PI3K, NLRP3, and ASC were measured by ELISA. mRNA expression of ERK1, JNK, and p-38 MAPK was detected using qRT-PCR, and Caspase-1 protein expression was assessed by immunohistochemical analysis. Knee swelling, uric acid levels, liver and kidney function, and oxidative stress markers were also evaluated. RESULTS: TAAE analysis identified 170 compounds, with 73 successfully identified using LC-HR-MS/MS, including caffeine citrate and theasapogenol B glycoside as the main constituents. The studied materials demonstrated significant protective effects against GA. TR25 administration significantly mitigated knee joint circumference compared to other treatments. It demonstrated potential in alleviating hyperuricemia, renal and hepatic impairments induced by MSU crystals. TR25 also alleviated oxidative stress and reduced levels of IL1ß, IL-6, TNF-α, and NF-κB. Weak Caspase-1 immune-positive staining was observed in the TR25 group. TR25 decreased NLRP3 and ASC expression, reducing inflammatory cytokine levels in GA. It effectively inhibited the PI3K, AKT, and mTOR signaling pathways, promoting autophagy. Additionally, TR25 suppressed ERK1, JNK, and p-38 MAPK gene expression in synovial tissue. These effects were attributed to various components in TAAE, such as flavonoids, phenolic acids, tannins, alkaloids, and triterpenes. CONCLUSION: Importantly, irradiation (25 KGy) enhanced the antioxidant effects and phtchemical contents of TAAE. Additionally, TR0, TR25, CAF, and SAP exhibited promising protective effects against GA, suggesting their therapeutic potential for managing this condition. These effects were likely mediated through modulation of the NLRP3/ASC/Caspase-1 and ERK/JNK/p-38 MAPK signaling pathways, as well as regulation of the PI3K/AKT/mTOR pathway. Further research is warranted to fully elucidate the underlying mechanisms and optimize their clinical applications.

Meta-analysis and systematic review of gout prevalence in the heart/lung transplantation population.

Introduction: Gout may complicate solid organ transplantation with potentially serious consequences. An accurate prevalence of gout in this population is unknown. Objectives: This study aimed to estimate the prevalence of gout in the heart and/or lung transplantation population through a systematic review and meta-analysis. Methods: MEDLINE, Embase, PsycINFO, CENTRAL and Cochrane Library (inception to February 2022) were searched for studies that reported the prevalence and/or incidence of gout in heart and/or lung transplant recipients. Two authors extracted outcomes data. Data were pooled using a random effects model. Overall quality of evidence was assessed using GRADE. Primary outcomes were the prevalence of pre- or post-transplant gout expressed as a prevalence rate (95% CI). Secondary outcomes included risk factors for gout, adverse events, and therapeutic complications of gout treatment. Results: Ten studies were included. Gout prevalence (PR) was 8% pre-transplant (PR = 0.08; 95% CI: 0.05-0.12; 4 studies n = 651) and 6% post-transplant (PR = 0.06; 95% CI: 0.06-0.06; 10 studies n = 45,298). Post-transplant gout prevalence in heart transplant recipients was almost three times higher than lung transplant recipients (PR = 0.16; 95% CI: 0.13-0.20 vs. PR = 0.06; 95% CI: 0.05-0.06 respectively). Patients with a pre-transplant history of gout had a higher risk of developing post-transplant gout than patients without (RR = 3.61; 95% CI: 2.19-5.95). Factors associated with gout and outcomes for heart and/or lung transplant recipients with gout were comprehensively reviewed from the included studies. Conclusion: Gout is highly prevalent in heart and/or lung transplant patients. Pre-transplant gout is predictive of developing symptomatic post-transplant gout. This has significant implications for management of heart/lung transplant patients. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42020190632).

Psychometric evaluation of the Adherence to Refills and Medications Scale (ARMS) in Australians living with gout.

This study aimed to examine psychometric properties of the Adherence to Refills and Medications Scale (ARMS) in people with gout. We conducted exploratory factor analysis (EFA) and tested internal consistency (ordinal and Cronbach's alpha coefficients) and agreement (intraclass correlation coefficient (2,1)) in ARMS scores across three timepoints (baseline, 6, and 12 months) in 487 people with gout. The Kruskal-Wallis test, Spearman's rank, Kendall's tau-b correlations, and logistic regression were used to examine the criterion-related validity of the ARMS and factors associated with the ARMS. EFA suggested a one-factor structure, explaining 43.2% of total variance. High internal consistency (ordinal alpha = 0.902 at baseline) and moderate agreement in ARMS scores over time (ICCs > 0.5; p < 0.001) were observed. Lower ARMS scores (indicating better adherence) predicted achieving target serum urate (OR, 0.89; 95% CI, 0.83-0.95; p < 0.001), but not urate-lowering therapy (ULT) adherence (Proportion of Days Covered (PDC) ≥ 80%) (OR, 0.93; 95% CI, 0.81-1.05; p = 0.261). Negative correlations between ARMS and PDC were not statistically significant (Kendall's tau-b, r = - 0.126, p = 0.078; Spearman's rho = - 0.173, p < 0.073). Differences in median ARMS scores (IQR) of 16 (14-20), 13 (12-15), and 17.5 (15-21) in three groups of participants who reported (1) not taking ULT, (2) taking ULT and adherent, and (3) taking ULT but not adherent, respectively, were statistically significant (p < 0.001). Age was the only patient factor independently associated with optimal adherence (ARMS score = 12) (OR, 1.91; 95% CI, 1.50-2.43; p < 0.001). The ARMS is a reliable and valid measure of medication adherence behaviours in people with gout, justifying its use in gout medication adherence research.

Transdermal delivery of iguratimod and colchicine ethosome by dissolving microneedle patch for the treatment of recurrent gout.

This study introduces a novel approach of repetitive modeling to simulate the pathological process of recurrent gout attacks in humans. This methodology addresses the instability issues present in rat models of gout, providing a more accurate representation of the damage recurrent gout episodes inflict on human skeletal systems. A soluble nanoneedle system encapsulating colchicine and iguratimod ethosomal formulations was developed. This system aims to modulate inflammatory cytokines and inhibit osteoclast activity, thereby treating inflammatory pain and bone damage associated with recurrent gout. Additionally, a comprehensive evaluation of the microneedles' appearance, morphology, mechanical properties, and penetration capability confirmed their effectiveness in penetrating the stratum corneum. Dissolution tests and skin irritation assessments demonstrated that these microneedles dissolve rapidly without irritating the skin. In vitro permeation studies indicated that transdermal drug delivery via these microneedles is more efficient and incurs lower drug loss compared to traditional topical applications. In vivo pharmacodynamic assessments conducted in animal models revealed significant analgesic and anti-inflammatory effects when both types of microneedles were used together. Further analyses, including X-ray imaging, hematoxylin and eosin (H&E) staining, Safranin-O/fast green staining, tartrate-resistant acid phosphatase staining, and quantification of osteoclasts, confirmed the bone-protective effects of the microneedle combination. In conclusion, the findings of this research underscore the potential of this novel therapeutic approach for clinical application in the treatment of recurrent gout.

Burden of gout among different WHO regions, 1990-2019: estimates from the global burden of disease study.

The global incidence of gout has increased rapidly, likely secondary to the increase in the prevalence of conditions that predispose to gout, such as obesity. Depending on the population studied, the prevalence of gout ranges from less than 1 to 6.8%. Thus, gout can be a significant burden on healthcare systems. The objective of this study is to observe the trends in the incidence, prevalence, and disability-adjusted life years (DALYs) of gout between 1990 and 2019 globally and in the European Union (EU) 15+ nations. We extracted data from the Global Burden of Disease Study database based on the International Classification of Diseases (ICD) versions 10 and 9. Incidence, prevalence, and disability-adjusted life years (DALYs) were extracted for individual EU15+ countries and globally in males and females between 1990 and 2019. Joinpoint regression analysis was used to describe trends. Between 1990 and 2019, gout prevalence, incidence, and DALYs increased in both males (+ 21.42%, + 16.87%, + 21.49%, respectively) and females (+ 21.06%, + 18.75%, + 20.66%, respectively) globally. The United States of America had the highest increase in prevalence (males: + 90.6%; females + 47.1%), incidence (males: + 63.73%; females: + 39.11%) and DALYs (males: + 90.43%; females: + 42.75%). Incidence, prevalence, and DALYs from gout are increasing worldwide and in most of the EU15+ countries for males and females. Studies have reported the association of gout with comorbidities such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. Health policies and resource allocation are required to increase awareness and modify risk factors globally.

Effects of the concentration of seeds, finite time-dependent supersaturations, and viscosity on the crystallization kinetics of monosodium urate monohydrate.

CONTEXT: Although the crystallization of monosodium urate monohydrate (MSUM) has a crucial role in the occurrence of gout, which is an inflammatory arthritis disease, theoretical models have not been able to describe all features observed in its seeded growth kinetics. In contrast to previous modeling approaches, we show that our model can reproduce qualitative features typically observed in experiments. In particular, our results show that the higher the initial supersaturation and the lower the viscosity, the faster the crystallization kinetics, and they also indicate that there are distinct growth regimes for low and high concentrations of seeds. METHODS: In this work, we introduce an alternative approach based on a master equation that allows us to incorporate hypotheses for the seeded growth crystallization of MSUM in a more transparent way. Such an approach includes not only effects that are related to the finite time-dependent supersaturation and concentration of seeds, but it can also be used to determine how the viscosity of the solution can affect the crystallization kinetics of MSUM molecules.

Controversies and practical management of patients with gout and chronic kidney disease.

Uric acid is a toxin retained with advancing kidney disease. Clinical manifestations of hyperuricemia include gout and systemic inflammation that are associated with increased risk for cardiovascular mortality. As many as one third of all patients with chronic kidney disease (CKD) have a history of gout, yet <25% of these patients are effectively treated to target serum urate levels of ≤6 mg/dL. A major reason for ineffective management of gout and hyperuricemia is the complexity in managing these patients, with some medications contraindicated, others requiring special dosing, potential drug interactions, and other factors. Consequently, many nephrologists do not primarily manage gout despite it being a common complication of CKD, leaving management to the primary physician or rheumatologist. We believe that kidney specialists should consider gout as a major complication of CKD and actively manage it in their patients. Here, we present insights from nephrologists and rheumatologists on a team approach to gout management that includes the nephrologist.

Causal impact of human blood metabolites and metabolic pathways on serum uric acid and gout: a mendelian randomization study.

Objective: Hyperuricaemia and gout are common metabolic disorders. However, the causal relationships between blood metabolites and serum urate levels, as well as gout, remain unclear. A systematic evaluation of the causal connections between blood metabolites, hyperuricemia, and gout could enhance early screening and prevention of hyperuricemia and gout in clinical settings, providing novel insights and approaches for clinical treatment. Methods: In this study, we employed a bidirectional two-sample Mendelian randomization analysis utilizing data from a genome-wide association study involving 7,286 participants, encompassing 486 blood metabolites. Serum urate and gout data were sourced from the Chronic Kidney Disease Genetics consortium, including 288,649 participants for serum urate and 9,819 African American and 753,994 European individuals for gout. Initially, LDSC methodology was applied to identify blood metabolites with a genetic relationship to serum urate and gout. Subsequently, inverse-variance weighting was employed as the primary analysis method, with a series of sensitivity and pleiotropy analyses conducted to assess the robustness of the results. Results: Following LDSC, 133 blood metabolites exhibited a potential genetic relationship with serum urate and gout. In the primary Mendelian randomization analysis using inverse-variance weighting, 19 blood metabolites were recognized as potentially influencing serum urate levels and gout. Subsequently, the IVW p-values of potential metabolites were corrected using the false discovery rate method. We find leucine (IVW P FDR = 0.00004), N-acetylornithine (IVW P FDR = 0.0295), N1-methyl-3-pyridone-4-carboxamide (IVW P FDR = 0.0295), and succinyl carnitine (IVW P FDR = 0.00004) were identified as significant risk factors for elevated serum urate levels. Additionally, 1-oleoylglycerol (IVW P FDR = 0.0007) may lead to a substantial increase in the risk of gout. Succinyl carnitine exhibited acceptable weak heterogeneity, and the results for other blood metabolites remained robust after sensitivity, heterogeneity, and pleiotropy testing. We conducted an enrichment analysis on potential blood metabolites, followed by a metabolic pathway analysis revealing four pathways associated with serum urate levels. Conclusion: The identified causal relationships between these metabolites and serum urate and gout offer a novel perspective, providing new mechanistic insights into serum urate levels and gout.

Health-related quality of life in gout patients in Madinah Region, Saudi Arabia.

Background: Gout can significantly impact health-related quality of life (HRQoL) due to excruciating pain, chronic arthropathy, and associated comorbidities. The objective of our study was to evaluate HRQoL among patients diagnosed with gout in the Madinah region of Saudi Arabia. Materials and Methods: The research took place in the Madinah Region, where eligible adult participants aged 18 years or older, having a confirmed history, or present diagnosis of gout were enrolled using medical records from 2016 to 2022. To gather data, patients were invited to participate in telephone-based interviews and complete the Short Form-36 (SF-36) questionnaire. Results: The majority of participants were male (81.5%), and 31-39 years form the largest group (37.0%). Most participants were married (86.4%), and the majority possess university and postgraduate education (70.4%). The respondents' self-reported assessments were as follows: physical function (69.9), limitation due to physical health (74.1), emotional problem (75.8), energy or fatigue (61.6), emotional well-being (68.9), social functioning (76.6), pain (78.9), and general health (63.8). Conclusions: HRQoL among patients with gout was not significantly affected.

Use of Mendelian randomization to assess the causal status of modifiable exposures for rheumatic diseases.

The explosion in Mendelian randomization (MR) publications is hard to ignore and shows no signs of slowing. Clinician readers, who may not be familiar with jargon-ridden methods, are expected to discern the good from the many low-quality studies that make overconfident claims of causality or stretch the plausibility of what MR can investigate. We aim to equip readers with foundational concepts, contextualized using examples in rheumatology, to appraise the many MR papers that are or will appear in their journals. We highlight the importance of assessing whether exposures are under plausibly specific genetic influence, whether the hypothesized causal pathways make biological sense, and whether results stand up to replication and use of control outcomes. Quality of research can vary substantially using MR as with any design, and all methods have inherent limitations. MR studies have provided and can still contribute valuable insights in the context of evidence triangulation.

Current Challenges and Emerging Therapies in the Treatment of Gout.

Gout is a common form of inflammatory arthritis characterized by the deposition of MSU in the joints and surrounding tissues, which results in inflammation and recurrent painful attacks. Currently, xanthine oxidase inhibitors, i.e., Allopurinol and Febuxostat, are used in the therapy. Recently, nanoparticles (NPs) containing metal oxides and non-metal oxides have also been developed to better manage gout. This comprehensive review summarizes the pathophysiology of gout, currently used drugs in the treatment, followed by emerging therapies for gout.