Gout Patients Research Articles

The association between gout and subsequent cardiovascular events: a retrospective cohort study with 132,000 using propensity score matching in primary care outpatients in Germany.

Both the risk of developing heart disease and the course of the disease are determined in particular by comorbidities. In this context, gout has recently been identified as an important factor in influencing the development of cardiovascular events such as heart failure or coronary artery disease. This retrospective cohort study compared the incidence of angina pectoris (AP) (ICD-10: I20), myocardial infarction (MI) (ICD-10: I21, I22), chronic coronary heart disease (CHD) (ICD-10: I25), atrial fibrillation (AF), and heart failure (HF) as a function of gout in Germany in a large collective of 66,000 gout patients in comparison to 66,000 individuals without gout between using propensity score matching (1:1) from January 2005 to December 2020. Within 10years after the index date, AP was diagnosed in 5.2% of gout and 2.9% of non-gout patients (p < 0.001), MI in 3.1% of gout and 2.2% of non-gout patients (p < 0.001), CHD in 16.5% of gout and 11.8% of non-gout patients, AF in 12.6% of gout and 8.4% of non-gout patients (p < 0.001), and HF in 14.7% of gout and 8.5% of non-gout patients (p < 0.001). For all diagnoses except CHD, the association was stronger in male than in female patients. The relationship shown between gout and cardiovascular disease indicates that gout could be one of a series of inflammatory conditions that increase the risk of cardiac disease. The association we have shown between gout and all major cardiac diseases suggests that there is a risk modifier, the treatment of which could help prevent these diseases. Further research is needed to determine whether treating gout can effectively reduce this risk.

Effect of low-purine diet on the serum uric acid of gout patients in different clinical subtypes: a prospective cohort study

BackgroundThe pathogenic causes of primary gout include urate overproduction and/or renal or extra-renal urate underexcretion. The aim of this study was to evaluate the association of gout subtypes with the response to low-purine diet (LPD).MethodsThis is a single-center prospective clinical study. Gout patients visiting from 2019 to 2022, from Shandong Gout Clinic Center at the Affiliated Hospital of Qingdao University, China, assigned to three groups according to clinical subtypes, were enrolled and all treated with 2-week low-purine diet. General characteristics, serum uric acid (sUA) and other clinical biochemical variables before and after the diet were evaluated.ResultsA total of 626 gout patients (age 41.20 ± 13.41 years, male 98.0%) were included. Of these, 69 (11.0%) were overproduction type, 428 (68.37%) were underexcretion type, and 129 (20.61%) were combined type. Overall, there was a substantial decrease in sUA after a 2-week LPD (p < 0.001). In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum triglycerides (TG), serum total cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) levels were lower than those at baseline (p < 0.05). On the other hand, there were significant differences in the reduction of sUA among different types, the rank order being overproduction type (− 88.81 ± 63.01 μmol/L) > combined type (− 65.22 ± 44.13 μmol/L) > underexcretion type (− 57.32 ± 61.19 μmol/L). After adjusting for age, BMI and baseline sUA and eGFR, there were still significant differences in the decline of serum uric acid among different types. Higher baseline sUA (95%CI − 0.285, − 0.191; p < 0.001) and BUN (95%CI − 6.751, − 0.602; p < 0.001) were correlated with greater decrease of sUA.ConclusionsOur findings support the protective role of low-purine diet on sUA levels in gout patients, especially overproduction type. Furthermore, LPD could exert a beneficial effect on gout patients’ blood pressure, BMI, blood lipid, BUN and Scr levels.Trial registration Registered with ChiCTR, No. ChiCTR1900022981 at 06/05/2019.

Is cardiac function associated with the clinical course of disease in patients with gout? A prospective study.

To analyze the function of the left heart in patients with different courses of gout, the independent influencing factors for left heart functional changes, and interactions between left atrial and left ventricular functions. Patients with gout (n=171) were selected; 87 patients with a disease course <10 years were included in Group I, and 84 patients with a disease course ≥10 years were included in Group II. Ninety-four healthy volunteers comprised the control group. The intergroup differences in cardiac strain parameters were statistically significant (p<.05). Moreover, the differences gradually declined with disease progression. Multivariate logistic regression analysis showed that uric acid was an independent predictor of decreased left ventricular global longitudinal strain (LVGLS). Moreover, LVGLS had a positive effect on the left atrial systolic rate (LASr) and the left atrial systolic contraction time (LASct) but no interaction with the left atrial systolic contraction duration (LAScd). The course of the disease significantly affected the function of the left heart in gout patients, and uric acid was observed to be an independent predictor of decreased LVGLS in gout patients.

Anti-inflammatory effects of MerTK by inducing M2 macrophage polarization via PI3K/Akt/GSK-3β pathway in gout

Mer tyrosine kinase (MerTK) has been found to regulate the secretion of inflammatory factors and exert immunosuppressive effects, but its role in gout remains unclear. In this study, we aimed to clarify the immnue effects of MerTK in gout. MerTK in synovium or serum of gout patients was determined by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and real-time quantitative polymerase chain reaction (RT-qPCR). In monosodium urate (MSU)-induced gout mice, the effect of MerTK inhibitor (UNC2250) on inflammation and polarization was also assessed. After inhibition, knockdown or overexpression of MerTK, inflammatory response and polarization level in THP1-derived macrophages were evaluated by RT-qPCR and flow cytometry. Regulation of MerTK inhibitors on mitochondrial function and downstream pathway in THP1-derived macrophages were detected. MerTK in synovium and serum of gout patients were increased. MerTK inhibitor stimulated the inflammation and M1 polarization in MSU-induced gout mice. MerTK inhibition, knock-down, or overexpression affected inflammatory response, polarization and mitochondrial function in vitro in gout model. The PI3K/Akt/GSK-3β pathway was identified to reduce after MerTK inhibition and the relevant results were as expected, validated by knock-down or overexpressing MerTK. In conclusion, MerTK was detected to increase in both gout patients and model. MerTK influenced inflammatory response and polarization markers through PI3K/Akt/GSK-3β pathway. Interfering MerTK/PI3K/Akt/GSK-3β axis may provide a new therapeutic target for gout.

Muscle CT Radiomics is Feasible in the Identification of Gout.

The aim of this study was to investigate the feasibility of muscle CT radiomics in identifying gout. A total of 30 gout patients and 20 non-gout cases with CT examinations of ankles were analyzed by using the methods of CT radiomics. CT radiomics features of the soleus muscle were extracted using the software of a 3D slicer, and then gout cases and non-gout cases were compared. The radiomics features that were significantly different between the two groups were then processed with machine learning methods. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Five CT radiomics features were significantly different between gout cases and non-gout cases (P < 0.05). In the logic regression, the AUC, sensitivity, specificity, and accuracy were 0.738, 77% (46/60), 70% (28/40), and 74% (74/100), respectively. In the Random forest, Xgboost, and support vector machine analysis, the accuracy was 0.901, 0.833, and 0.875, respectively. From this study, it can be concluded that muscle CT radiomics is feasible in identifying gout.</p>.

Gout and erectile dysfunction: Increased carotid intima-media thickness is independently associated with greater likelihood for erectile dysfunction.

The study aimed to compare gout patients and healthy subjects in terms of erectile dysfunction, carotid intima-media thickness (CIMT), and other variables and to investigate the relationship between CIMT and erectile dysfunction. This cross-sectional study was conducted with 134 male gout patients (median age: 56 years; range, 48 to 62 years) and 104 healthy males (median age: 47 years; range, 40.5 to 54.5 years) between September 2022 and June 2023. Age, comorbidities, height, weight, laboratory results, gout treatment data, insulin resistance evaluated by the homeostatic model assessment for insulin resistance, presence and severity of erectile dysfunction evaluated by the six-item International Index of Erectile Function erectile function domain (IIEF-EF), and CIMT measured by ultrasound were assessed. Hypertension, hyperlipidemia, greater insulin resistance, erectile dysfunction, and bilaterally increased CIMT were significantly more common in the gout group. The mean IIEF-EF score of gout patients was significantly lower than that of controls. Multivariable logistic regression revealed increased CIMT as the sole parameter independently associated with erectile dysfunction (p=0.010). When both groups were categorized into CIMT-based subsets, erectile dysfunction was present in 97.9% of patients with coexistence of gout and increased CIMT (≥0.9 mm), a significantly higher proportion compared to the other three subsets (p<0.001). Increased CIMT was the only factor independently associated with a greater likelihood of erectile dysfunction in patients with and without gout; however, coexistence of gout and increased CIMT appears to result in a significantly elevated risk for erectile dysfunction.

Statin use associated with a reduced risk of hip fracture in patients with gout

Studies show that statins users are at reduced risk of fracture and improved bone mineral density. However, the clinical effectiveness of statin use in patients with gout has not been investigated. This retrospective cohort study used data from Taiwan's National Health Insurance Research Database, consisting of 3443 patients with gout using statins aged 50 years and above and 6886 gout patients of non-statin users matched by sex, age and propensity score. The Cox proportional hazards regression analysis showed that statin use was associated with a reduced risk of hip fracture (adjusted hazard ratio [aHR] = 0.78, 95 % confidence interval [CI] = 0.64–0.94) after controlling for potential confounding factors. The association was significant in both genders aged 50–64 years, with aHRs of near 0.35, but not in the elderly. In addition, women aged 50–64 years who used statins also exhibited a lower risk of vertebral fracture (aHR = 0.70, 95 % CI = 0.50–0.99), but not men. In conclusion, the stating use in gout patients could reduce fracture risk for younger patients. Further research is warranted to confirm these findings.

Association of rare and common genetic variants in MOCOS with inadequate response to allopurinol.

The minor allele of the common rs2231142 ABCG2 variant predicts inadequate response to allopurinol urate lowering therapy. We hypothesize that additional variants in genes encoding urate transporters and allopurinol-to-oxypurinol metabolic enzymes also predict allopurinol response. This study included a subset of participants with gout from the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients, whose whole genome was sequenced (n = 563). Good responders had a 4:1 or 5:1 ratio of good (serum urate (SU) <0.36 mmol/l on allopurinol ≤300 mg/day) to poor (SU ≥ 0.36 mmol/l despite allopurinol >300 mg/day) responses over 5-6 timepoints, while inadequate responders had a 1:4 or 1:5 ratio of good to poor responses. Adherence to allopurinol was determined by pill counts, and for a subgroup (n = 303), by plasma oxypurinol >20μmol/l. Using the sequence kernel association test (SKAT) we estimated the combined effect of rare and common variants in urate secretory (ABCC4, ABCC5, ABCG2, SLC17A1, SLC17A3, SLC22A6, SLC22A8) and reuptake genes (SLC2A9, SLC22A11) and in allopurinol-to-oxypurinol metabolic genes (AOX1, MOCOS, XDH) on allopurinol response. There was an association of rare and common variants in the allopurinol-to-oxypurinol gene group (PSKAT-C = 0.019), and in MOCOS, encoding molybdenum cofactor sulphurase, with allopurinol response (PSKAT-C = 0.011). Evidence for genetic association with allopurinol response in the allopurinol-to-oxypurinol gene group (PSKAT-C = 0.002) and MOCOS (PSKAT-C < 0.001) was stronger when adherence to allopurinol therapy was confirmed by plasma oxypurinol. We provide evidence for common and rare genetic variation in MOCOS associating with allopurinol response.

Association of serum 25-hydroxyvitamin D concentrations with all-cause and cause-specific mortality among individuals with gout and hyperuricemia

BackgroundWe aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA).MethodsThe study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007–2018 and 2001–2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models.ResultsAmong participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses.ConclusionsSerum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.

Analysis of risk factors for changes of renal artery resistance indexes in gout patients by ultrasound colour Doppler.

Gout may disturb renal hemodynamics by promoting uric acid deposition; however, this relationship has not been elucidated with adequate clinical evidence. In this study, we measured the renal artery resistance index (ARI) in patients with gout to identify the risk factors and establish predictive models for elevated renal ARI in these patients. Renal artery ultrasound examination was performed in 235 primary gout patients and 50 healthy controls (HCs); subsequently, their renal interlobar ARI (RIARI), renal segmental ARI (RSARI) and overall intrarenal ARI (OIARI) were recorded. Each ARI > 0.7 was considered elevated. RIARI, RSARI and OIARI were higher in patients with gout than in HCs (all P < 0.001). Nineteen (8.1%), 24 (10.2%) and 18 (7.7%) patients had elevated RIARI, RSARI and OIARI scores, respectively. Multivariate logistic regression analyses disclosed that: age ≥ 60 years (P = 0.000), abnormal beta2 microglobulin (β2MG) (P = 0.028), and abnormal high-density lipoprotein cholesterol (HDLC) (P = 0.030) were independently associated with elevated RIARI; age ≥ 60 years (P = 0.000), and abnormal β2MG (P = 0.013) were independently related to elevated RSARI; abnormal total protein (TP) (P = 0.014) were independently linked with elevated OIARI in gout patients. Consequently, predictive models for elevated ARI were established using nomograms based on the aforementioned independent risk factors, which showed a satisfactory value for estimating elevated RIARI [area under the curve (AUC):0.929], RSARI (AUC: 0.926) and OIARI (AUC: 0.660) in patients with gout, as validated by receiver operating characteristic curves. Renal ARI were elevated in patients with gout, whose independent risk factors included older age and abnormal β2MG, HDLC and TP levels.

Relationships between obesity and prevalence of gout in patients with type 2 diabetes mellitus: a cross-sectional population-based study

BackgroundThe purpose of this study was to investigate the relationships between generalized, abdominal, and visceral fat obesity and the prevalence of gout in patients with type 2 diabetes mellitus (T2DM).MethodsData were obtained from the electronic medical databases of the National Metabolic Management Center (MMC) of Yuhuan Second People’s Hospital and Taizhou Central Hospital (Taizhou University Hospital) between September 2017 and June 2023. Four obesity indicators were analyzed: waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and visceral fat area (VFA). The relationships between these parameters and gout prevalence were analyzed using multivariate logistic regression and restricted cubic spline (RCS) analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of the four parameters for gout.ResultsThis cross-sectional study enrolled 10,535 participants (600 cases and 9,935 controls). Obesity was more common in patients with gout, and the obesity indicators were markedly higher in this group. After adjustment for confounders, obesity, as defined by BMI, WC, WHR, and VFA, was found to be associated with greater gout prevalence, with odds ratios (OR) of 1.775, 1.691, 1.858, and 1.578, respectively (P < 0.001). The gout odds ratios increased markedly in relation to the obesity indicator quartiles (P-value for trend < 0.001), and the obesity indicators were positively correlated with gout prevalence, as shown using RCS. The area under the ROC curve values for BMI, WC, WHR, and VFA were 0.629, 0.651, 0.634, and 0.633, respectively.ConclusionObesity—whether general, abdominal, or visceral fat obesity—was positively linked with elevated gout risk. But uncovering the causality behind the relationship requires further prospective study. Obesity indicators (BMI, WC, WHR, and VFA) may have potential value for diagnosing gout in clinical practice.

Total Hip Arthroplasty Outcomes in Patients with Gout: A Retrospective Analysis of Matched Large Cohorts.

Gout is the most prevalent form of inflammatory arthritis in the world. Total hip arthroplasty (THA) has emerged as a widely sought-after and highly effective surgical procedure for advanced hip diseases. However, there is a lack of research on the impact of gout on primary THA outcomes in large cohorts. This study aimed to address this gap by primarily investigating complications following THA in patients with or without gout. Patients with records of gout in the 2 years leading up to their primary THA and who also have at least 2 years of follow-up were identified using a national insurance database and compared to a 5:1 matched control. A total of 32,466 patients with gout and 161,514 patients without gout undergoing THA were identified. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. In addition, 90-day emergency department (ED) visits and inpatient readmission were also documented. Patients with gout demonstrated higher rates of medical complications including deep vein thrombosis, transfusion, acute kidney injury, and urinary tract infection than non-gout patients (p < 0.001). Gout patients also showed higher rates of pulmonary embolism (p = 0.017). Increased incidences of surgical complications were identified in gout patients, specifically wound complications and periprosthetic joint infection (p < 0.001). There was an increased risk of revision for gout patients up to 90 days (p = 0.003), 1 year (p = 0.027), and 2 years (p = 0.039). There was also an increased risk of dislocation for gout patients up to 90 days (p = 0.022) and 1 year (p = 0.047), but not at 2 years. No significant difference was observed in aseptic loosening or periprosthetic fracture. Additionally, gout patients also demonstrated a higher likelihood of 90-day ED visits and readmission (p < 0.001). Primary THA in gout patients is associated with increased risks of multiple medical and surgical complications. Our findings provide insights into the planning and expectation of THA for patients with gout. These insights have the potential to benefit the decision-making process for gout patients considering THA.

Managing Gout in Patients with Metabolic Syndrome.

Gout is characterized by monosodium urate (MSU) crystal deposition secondary to hyperuricemia. Gout is associated with metabolic syndrome (MetS) and its related comorbid conditions such as cardiovascular disease (CVD). Major advances have been made in the comprehension of the link between MetS and gout. Despite observational studies suggesting an association between MetS-related conditions and hyperuricemia, there is no proof of causality. Most studies using Mendelian randomization did not find hyperuricemia as a causal factor for MetS-related conditions. In contrast, these conditions were found associated with hyperuricemia, which suggests a reverse causality. Among patients with gout, this high CVD risk profile implies the need for systematic screening for MetS-related conditions. Most international guidelines recommend systematic screening for and care of CVD and related risk factors in patients with gout. Some anti-hypertensive agents, such as losartan and calcium channel blockers, are able to decrease serum urate (SU) levels. However, there are potential interactions between gout management therapies and the treatment of metabolic diseases. Some data suggest that anti-inflammatory drugs used for gout flare treatment, such as colchicine or canakinumab, might have benefits for CVD. Regarding the impact of urate-lowering therapies on CVD risk, recent studies found a similar CVD safety profile for allopurinol and febuxostat. Finally, sodium-glucose cotransporter-2 inhibitors are promising for gout because of their ability to decrease SU levels and risk of recurrent flares. In this review, we focus on the clinical challenge of managing MetS in patients with gout, particularly older patients with co-medications.

Ultrasound Features in Gout: An Overview.

The accurate diagnosis of gout frequently constitutes a challenge in clinical practice, as it bears a close resemblance to other rheumatologic conditions. An undelayed diagnosis and an early therapeutic intervention using uric acid lowering therapy (ULT) is of the utmost importance for preventing bone destruction, the main point of managing gout patients. Advanced and less invasive imaging techniques are employed to diagnose the pathology and ultrasonography (US) stands out as a non-invasive, widely accessible and easily reproducible method with high patient acceptability, enabling the evaluation of the full clinical spectrum in gout. The 2023 EULAR recommendations for imaging in diagnosis and management of crystal-induced arthropathies in clinical practice state that US is a fundamental imagistic modality. The guidelines underline its effectiveness in detecting crystal deposition, particularly for identifying tophi and the double contour sign (DCS). Its utility also arises in the early stages, consequent to synovitis detection. US measures of monosodium urate (MSU) deposits are valuable indicators, sensitive to change consequent to even short-term administration of ULT treatment, and can be feasibly used both in current daily practice and clinical trials. This paper aimed to provide an overview of the main US features observed in gout patients with reference to standardized imaging guidelines, as well as the clinical applicability both for diagnosis accuracy and treatment follow-up. Our research focused on summarizing the current knowledge on the topic, highlighting key data that emphasize gout as one of the few rheumatological conditions where US is recognized as a fundamental diagnostic and monitoring tool, as reflected in the most recent classification criteria.

SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum

PurposeThis study aimed to evaluate the relative association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1Ra) with the incidence of gout in patients with type 2 diabetes (T2D) using real-world data. MethodsWe conducted a cohort study using data from TriNetX (an international federated database). We included patients commenced on metformin or insulin, either alone or with an SGLT2i or GLP-1Ra, at least 2 years prior to date of analysis. We propensity score matched (PSM) (1:1) for 26 relevant characteristics. Time to event analysis was performed to assess the incidence of gout, all-cause mortality (positive control), and herpes zoster infection (negative control) at 5 years following drug initiation. FindingsPrior to PSM, the cohort numbers were as follows: metformin control, 1,111,449; SGLT2i with metformin, 101,706; GLP-1Ra with metformin, 110,180, insulin control, 1,398,066; SGLT2i with insulin, 68,697; and GLP-1Ra with insulin, 99,693. SGLT2i with metformin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the metformin control cohort (HR 0.75 [95% CI 0.69-0.82], P < 0.0001). Similarly, SGLT2i with insulin demonstrated a statistically significant decreased incidence of gout at 5 years compared to the insulin control cohort (HR 0.83 [95% CI 0.74–0.92], P < 0.0001). Conversely, no significant disparity in gout incidence was observed between the use of GLP-1Ra and matched controls. Subgroup analysis showed an associated reduced incidence of gout with SGLT2i use compared to GLP-1Ra, in groups using metformin (HR 0.77 [95% CI 0.70-0.86], P < 0.0001) or insulin (HR 0.82 [95% CI 0.73-0.91)], P < 0.0001). ImplicationsIn this large-scale real-world study, SGLT2i use was associated with a lower incidence of gout in patients with T2D compared to both insulin and metformin controls. These findings suggest the potential of SGLT2i as a promising therapeutic option for treating gout in this population.

Association between physical activity and the prevalence of gout among patients with type 2 diabetes mellitus and hyperuricemia: a two-center population-based cross-sectional study

IntroductionDiabetes mellitus (DM) and gout cohabitation severely reduces patient life quality while raising financial burden on individual and society. The aim of this study was to elucidate the association between physical activity (PA) and the prevalence of gout among type 2 DM (T2DM) and hyperuricemia (HUA) patients.MethodsIn all, we recruited 2291 T2DM patients with HUA. Among them, 448 had gout and 1843 did not. We collected patient data, such as anthropometry, laboratory reports, and medical history, for our analyses. The PA assessment was based on the Chinese version of International PA Questionnaire-short (IPAQ). Moreover, the relationship between PA and gout risk was examined using multivariate logistic regression models.ResultsTotal PA was markedly low among gout patients, relative to controls (p < 0.05). Based on the IPAQ categorical score, 38.2% exhibited “low,” 26.8% “moderate,” and 35.0% “high” PA among gout patients. In comparison, 12.4% performed “low,” 53.8% “moderate,” and 33.8% “high” PA among controls. Multivariate analysis revealed that, after adjustment of confounding factors, both low (OR 6.382) and high PA (OR 2.048) had a higher prevalence of gout, as compared to moderate PA. Moreover, we revealed that the male sex, age, HUA duration, serum uric acid, glycated hemoglobin, dyslipidemia history, and drinking status were also independent indicators of the prevalence of gout. Furthermore, stratification analyses revealed results consistent with our prior results.ConclusionsPA intensity was associated with the prevalence of gout among T2DM and HUA patients, and the lowest prevalence was achieved from moderate intensity PA.Key Points• PA intensity was associated with the prevalence of gout among T2DM and HUA patients.• The lowest prevalence of gout was achieved from moderate intensity PA.

Efficacy and safety of wet cupping in the management of Gout: An open labeled, randomized standard control study

BackgroundThe most prevalent form of inflammatory arthritis is Gouty arthritis. Wet cupping, a traditional regimental therapy of Greco-Arab and Chinese medicine, has been proven an effective and safe alternative treatment for multiple disorders especially in musculoskeletal ailments. Aims and objectivesTo study the efficacy and safety of wet cupping in Gouty arthritis. MethodsIn an open-labeled, randomized and standard controlled trial 60 patients of gout fulfilling the inclusion criteria were randomly allocated in test group (n=30) receiving wet cupping and the control group (n=30) receiving allopurinol for a period of 60 days. Patients were assessed at every 15th day for subjective parameters/symptoms, whereas for objective parameters (serum uric acid, inflammatory markers) assessment was done at 0th day and on 61st day of the study protocol. The data was analyzed statistically using student t-test to obtain the results. ResultsBoth the test and control groups showed a significant improvement in subjective parameters (p<0.001). Serum uric acid gets significantly improved after the treatment (p<0.001) in both the groups, however among inflammatory markers, better improvement in ESR was seen in test group (p< 0.05) than control group (p=0.37) but there was no considerable improvement in CRP either in test or control group. All the safety parameters (LFT, KFT) were found to remain undisturbed after completion of study protocol. ConclusionWet cupping has a considerable impact in improving the symptoms of gout and serum uric acid levels. It is much safer and could prove a better alternative for gout management.

Unraveling the pathological biomineralization of monosodium urate crystals in gout patients

Crystallization of monosodium urate monohydrate (MSU) leads to painful gouty arthritis. Despite extensive research it is still unknown how this pathological biomineralization occurs, which hampers its prevention. Here we show how inflammatory MSU crystals form after a non-inflammatory amorphous precursor (AMSU) that nucleates heterogeneously on collagen fibrils from damaged articular cartilage of gout patients. This non-classical crystallization route imprints a nanogranular structure to biogenic acicular MSU crystals, which have smaller unit cell volume, lower microstrain, and higher crystallinity than synthetic MSU. These distinctive biosignatures are consistent with the template-promoted crystallization of biotic MSU crystals after AMSU at low supersaturation, and their slow growth over long periods of time (possibly years) in hyperuricemic gout patients. Our results help to better understand gout pathophysiology, underline the role of cartilage damage in promoting MSU crystallization, and suggest that there is a time-window to treat potential gouty patients before a critical amount of MSU has slowly formed as to trigger a gout flare.

Peripheral neuropathy in patients with gout, beyond focal nerve compression: a cross-sectional study.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

Anti-Inflammatory Effect of Atorvastatin and Rosuvastatin on Monosodium Urate-Induced Inflammation through IL-37/Smad3-Complex Activation in an In Vitro Study Using THP-1 Macrophages.

Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on the monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of the target molecules IL-1β, IL-37, caspase-1, and Smad3 were measured in THP-1 macrophages stimulated with MSU, atorvastatin, or rosuvastatin using a real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1β or Smad3 siRNA in THP-1 macrophages was used to verify the pharmaceutical effect of statins in uric-acid-induced inflammation. Results: Serum IL-37 levels in gout patients were significantly higher than in controls (p < 0.001) and was associated with the serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and the transition of IL-37 from the cytoplasm to the nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1β in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1β expression but augmented translocation of IL-37 from the cytoplasm to the nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from the cytoplasm to the nucleus in THP-1 macrophages transfected with Smad3 siRNA compared to cells with negative control siRNA. Conclusions: This study revealed that statins inhibit the MSU-induced inflammatory response through phosphorylated Smad3-mediated IL-37 expression in THP-1 macrophages.