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Gout flares have emerged as a significant public health concern. Colchicine (COL) is a first-line and standard drug for treating gout flares. However, its clinical use is limited due to various adverse effects. Besides, COL fails to adequately meet the needs of patients, particularly young patients. In this study, we investigate the therapeutic administration of Lactobacillus paracasei GY-1 (GY-1) to overcome the limitations of COL. Our results demonstrate that GY-1 attenuates COL toxicity in terms of body weight loss, decreased feed intake, mortality, reduced locomotor activity, colon shortening, increased oxidative stress, histological damage, and impaired gut permeability. Meanwhile, we demonstrate that GY-1 enhances the therapeutic effect for gout flares when combined with COL, as evidenced by the reduction in paw swelling, decreased levels of proinflammatory cytokines including IL-1β and TNF-α, and an increase in the anti-inflammatory cytokine IL-10. Additionally, the absolute quantification of the gut microbiota shows that GY-1 restores the gut microbiota imbalance caused by COL. Furthermore, GY-1 reduces the abundance of 4 Alistipes species and 6 Porphyromonadaceae species, which may be responsible for toxicity alleviation. At the same time, GY-1 increases the abundance of Bacteroides sartorii and Enterococcus sp., which may contribute to its therapeutic efficacy. This study demonstrates the feasibility of developing probiotic-based adjuvant therapy or bacteriotherapy for treating gout flares. To our knowledge, GY-1 is the first probiotic that could be used as an alternative synergetic agent with COL for the therapeutic treatment of gout flares.

Objectives: To assess whether the extent of monosodium urate (MSU) crystal deposition estimated by ultrasound could predict renal and cardiometabolic events during urate-lowering therapy (ULT)., Methods: A prospective study on gout patients from two referral centers initiating ULT who underwent baseline ultrasound and were followed for 1 year. Ultrasound scans assessed six joints for double-contour (DC) signs and tophi. A five-point change (mL/min/1.73 m 2 ) in the glomerular filtration rate at month 12 (M12) was considered significant. Outcomes of interest were renal function degraded versus improved and a composite cardiometabolic outcome (new hypertension, diabetes, atherosclerotic disease, and cardiovascular death). Homogeneity analyses and Cox regression models were performed., Results: One hundred sixty patients were recruited. At baseline, 81.1% of patients (n = 129) showed sonographic tophi with a mean number of 1.4 joints (±1.3) with a DC sign. At M12, 18 patients (11.3%) were lost to follow-up. The serum urate (SU) target (<6.0 mg/dL) was reached in 86 patients (69.9%). Regarding renal function, 15.9% of patients showed improvement, while in 31.0% it degraded. Fourteen new cardiometabolic events occurred in 12 patients. Neither the DC sign nor tophi showed any significant impact on the outcomes of interest. Baseline SU level was higher in those with renal improvement but not with renal decline, while achieving the SU target protected against new cardiometabolic events (HR = 0.2; 95% CI: 0.05-0.81)., Conclusions: Sonographic MSU crystal burden was unhelpful in predicting renal and cardiometabolic events during the first year of ULT. Reaching the SU target prevented cardiometabolic events, while its benefit in preserving/improving renal function is unclear., (© 2023 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: The main objective of the study was to see the concordance between the diagnosis of gout recorded in primary care electronic medical records and the ACR/EULAR 2015 classification criteria., Methods: A cross-sectional study was conducted using electronic medicals records in 7 primary care centres of Barcelona. Patients' data to study clinical diagnose and management was gathered from the primary care electronic medical records of the Catalonian health institute (Institut Català de la Salut, ICS) and phone interview. Patients were considered to have gout if they scored 8 or more points on the EULAR/ACR 2015 classification criteria for gout., Results: In total, 70.9% of the patients with a gout diagnosis met ACR/EULAR 2015 criteria. Adding a hyperuricemia in a blood test in the EMR increased the percentage to 78.9%. 29.8% of the gout patients were not receiving urate-lowering therapy. 62.3% of the treated patients did not achieve the target uricemia (< 6mg/dL)., Conclusions: The majority of gout patients from primary care electronic medical records fulfil ACR/EULAR gout criteria. This database can be used for observational studies. In most of the gout patients the urate target was not achieved., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background and Objective: HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor that is being developed for the treatment of hyperuricemia and gout. The primary aim of the present study was to study the pharmacokinetic drug‒drug interactions (DDIs) of HP501, febuxostat, and colchicine in hyperuricemic patients., Methods: Hyperuricemic patients were randomly divided into group A, receiving HP501 40 mg once daily on days 1 and 4-10, and group B, receiving febuxostat 40 mg once daily on day 1 and HP501 40 mg plus febuxostat 40 mg on days 4-10. All patients received 0.5 mg colchicine once daily from day 4 to 12. Blood samples were collected for measurement of drug concentrations and serum uric acid (sUA) levels., Results: Coadministration of colchicine with HP501 or HP501 plus febuxostat did not affect steady-state exposure to colchicine. Coadministration of HP501 and febuxostat did not significantly change the pharmacokinetic profiles of either drug. Following multiple administrations of HP501 40 mg once daily for 7 days, the maximal percent sUA change from baseline in group A was - 24.77%. The coadministration of HP501 40 mg and febuxostat 40 mg in group B for 7 days resulted in a - 55.82% maximal sUA reduction from baseline, and all patients achieved the goal of sUA < 360 μmol/L. All adverse events (AEs) were either mild or moderate, and the most frequently reported AEs were diarrhea and elevated alanine aminotransferase (ALT) levels., Conclusions: The concomitant use of HP501, febuxostat, and colchicine did not produce clinically meaningful DDIs in terms of their pharmacokinetic properties., Clinical Trial Registration: No. CTR20212261 ( http://www.chinadrugtrials.org.cn/ ) registered September 2021., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

SHR4640 is a novel, selective urate reabsorption inhibitor. As the mode of action of SHR4640 differs from that of a xanthine oxidase inhibitor, such as febuxostat, coadministration of these drugs may be a treatment option for patients with primary hyperuricemia. We assessed the potential drug-drug interaction between SHR4640 and febuxostat. In this single-center, open-label, randomized, drug-drug interaction study, subjects received 80 mg febuxostat or 10 mg SHR4640 alone daily in the first week, whereas during the second week a combination of SHR4640 and febuxostat was administered daily to all subjects. Plasma concentrations of SHR4640 and febuxostat were analyzed. We compared their pharmacokinetic and pharmacodynamic parameters and assessed both safety and tolerability. Compared with febuxostat alone, the geometric mean ratios (90%CIs) of the maximum concentration (C max ) and the area under the plasma concentration-time curve over the dosing interval τ (AUC 0-τ ) for febuxostat after coadministration were 1.284 (1.016 to 1.621) and 0.984 (0.876 to 1.106), respectively. The geometric mean ratios (90%CIs) of C max and AUC 0-τ for SHR4640 after coadministration compared with SHR4640 alone were 0.910 (0.839 to 0.988) and 0.929 (0.893 to 0.966), respectively. Febuxostat had no effect on SHR4640 pharmacokinetic parameters, as the 90%CIs of the geometric mean ratios were all within the range of 0.80 to 1.25. The coadministration of febuxostat and SHR4640 was well tolerated. The coadministration of SHR4640 with febuxostat was not associated with any clinically relevant pharmacokinetic drug interactions. SHR4640 combined with febuxostat had a synergistic effect on reducing uric acid in the pharmacodynamics, with the AUC decreasing from 7440 to 3170 h μmol/L compared with febuxostat alone and from 5730 to 2960 h μmol/L compared with SHR4640 alone., (© 2022, The American College of Clinical Pharmacology.)

&lt;b&gt;Background and Objective:&lt;/b&gt; Hyperuricemia is a disease triggered by disorders of uric acid metabolism. Therefore, this study evaluated the potential of leaves ethanolic extract of &lt;i&gt;Etlingera hemisphaerica&lt;/i&gt; (LE3H) and fruits ethanolic extract &lt;i&gt;E. hemisphaerica&lt;/i&gt; (FE3H) to restore hyperuricemia in mice. &lt;b&gt;Materials and Methods:&lt;/b&gt; Six groups (A0, A1, A2, A3, A4 and A5) each consisted of four male mice. Hyperuricemia in mice was induced by giving 0.3 mL of fresh chicken liver juice (FCLJ) for seven days (A1, A2, A3, A4 and A5). The condition of hyperuricemia in A1 is not neutralized. Meanwhile, hyperuricemia conditions in A2, A3, A4 and A5 were neutralized for seven days by giving 0.01 mg g&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt; body weight (BW) allopurinol, 0.13, 0.26 and 0.36 mg g&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt; BW LE3H. The control group (A0) only received double-distilled water in the same way. Blood uric acid levels were measured with the GCU Meter Device before and after the induction of hyperuricemia and after efforts to neutralize the hyperuricemia condition. Six groups (B0, B1, B2, B3, B4, B5) each consisting of four male mice were also provided to test the potential of FE3H. The recovery potential FE3H against hyperuricemia was tested separately in the same way as was done for LE3H. &lt;b&gt;Results:&lt;/b&gt; Giving FCLJ significantly increased (140.00-187.00%) uric acid compared to the control, so hyperuricemia was achieved. Doses of 0.13, 0.26 and 0.36 mg g&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt; BW LE3H significantly recovered hyperuricemia as much as 54.09, 56.14 and 60.88%, respectively. Meanwhile, doses of 0.13, 0.26 and 0.36 mg g&lt;sup&gt;&lt;/sup&gt;&lt;sup&gt;1&lt;/sup&gt; FE3H significantly recovered hyperuricemia as much as 60.37, 62.24 and 65.572%, respectively. The LE3H and FE3H at the same dose showed that FE3H had a higher potential to restore hyperuricemia than LE3H. &lt;b&gt;Conclusion:&lt;/b&gt; Leave and fruit ethanolic extract of &lt;i&gt;E. hemisphaerica&lt;/i&gt; can potentially restore hyperuricemia in mice.

Background/objective: Diabetes mellitus is a common "non-gout" disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that in healthy individuals, and is accompanied by severe albuminuria and high serum creatinine (Scr). Recent clinical studies have found that uric acid-lowering therapy (such as allopurinol) could reduce urinary albumin excretion rates (UAER) and Scr, increase eGFR, and thus reduce kidney damage in patients with diabetes. Therefore, this meta-analysis [PROSPERO CRD42021274465] intended to evaluate the efficacy and safety of allopurinol in patients with diabetes mellitus., Methods: We thoroughly searched five electronic resource databases for randomized controlled trials (RCTs) that compared the efficacy and safety of allopurinol versus conventional treatment or placebo for the treatment of patients with diabetes mellitus. Predetermined outcomes were considered continuous variables, mean difference (MD) was used for the determination of effect size (standardized mean difference [SMD] was used to determine the effect size when there were different evaluation criteria in different articles), and the corresponding 95% confidence interval (CI) was calculated. All outcome measures were analyzed using a random-effects model for data analysis., Results: Ten eligible trials with a total of 866 participants were included in the meta-analysis. Allopurinol was more effective in decreasing serum uric acid (SUA) levels compared with conventional treatment ( p  = 0.0001) or placebo ( p  < 0.00001). Moreover, the levels of 24-hour urine protein were significantly lower in the allopurinol group ( p  < 0.00001). The subgroup analysis of Scr showed that the Scr of patients with an allopurinol treatment duration of fewer than six months was significantly lower than that of the control group ( p  = 0.03). No significant difference in adverse events (AEs) was identified between the treatment and control groups., Conclusions: Our meta-analysis of RCTs showed that oral administration of allopurinol effectively reduced SUA levels in patients with diabetes, and patients' renal function was protected. More RCTs with larger sample sizes and higher quality are needed to clarify the role of allopurinol use in decreasing blood pressure, maintaining blood glucose levels, and improving renal function in patients with diabetes.

Objective: The predominant mechanism driving hyperuricemia in gout is renal uric acid underexcretion; however, the standard urate-lowering therapy (ULT) recommendation is first-line xanthine oxidase inhibitor (XOI), irrespective of the cause of hyperuricemia. This comparative effectiveness clinical trial was undertaken to compare first-line nontitrated low-dose benzbromarone (LDBen) uricosuric therapy to XOI ULT with low-dose febuxostat (LDFeb) in gout patients with renal uric acid underexcretion., Methods: We conducted a prospective, randomized, single-center, open-label trial in men with gout and renal uric acid underexcretion (defined as fractional excretion of urate <5.5% and uric acid excretion ≤600 mg/day/1.73 m 2 ). A total of 196 participants were randomly assigned to receive LDBen 25 mg daily or LDFeb 20 mg daily for 12 weeks. All participants received daily urine alkalization with oral sodium bicarbonate. The primary end point was the rate of achieving the serum urate target of <6 mg/dl., Results: More participants in the LDBen group achieved the serum urate target than those in the LDFeb group (61% compared to 32%, P < 0.001). Rates of adverse events, including gout flares and urolithiasis, did not differ between groups, with the exception of greater transaminase elevation in the LDFeb group (4% for LDBen compared to 15% for LDFeb, P = 0.008)., Conclusion: Compared to LDFeb, LDBen has superior urate-lowering efficacy and similar safety in treating relatively young and healthy patients with renal uric acid underexcretion-type gout., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Hyperuricemia is a purine metabolism disorder, with increasing prevalence worldwide. Here, a high throughput cell model for screening of antihyperuricemic compounds was set up. Human kidney cells (HK2 cells) were stimulated with adenosine and the resulting supernatant and lysate were then analyzed using high performance liquid chromatography (HPLC). The results showed that hypoxanthine content was increased in both HK2 cells supernatant and xanthine oxidase (XO)-overexpressing HK2 cells lysate, but no uric acid was detected due to lower endogenous XO content in these cells. Exogenous XO was added to the supernatant, and then used to evaluate the antihyperuricemic activity of Febuxostat and two the previously identified peptides, Pro-Gly-Ala-Cys-Ser-Asn (PGACSN) and Trp-Met-Leu (WML). By adding exogenous XO, this combined-adenosine-XO-induced hyperuricemia model was optimized and established, and the Febuxostat and peptides were confirmed to significantly reduce uric acid production in the HK2 cells supernatant ( p < 0.05). Therefore, this cell model could be recommended for screening potential bioactive antihyperuricemic compounds.

Gout renal injury has an insidious onset, no obvious symptoms, and laboratory abnormalities in the early stages of the disease. The injury is not easily detected, and in many cases, the patients have entered the renal failure stage at the time of diagnosis. Therefore, the detection of gout renal injury-related risk factors and early diagnostic biomarkers of gout renal injury is essential for the prevention and early diagnosis of the disease. This article reviews the research progress in risk factors and early diagnostic biomarkers of gout renal injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhang, Hao, Wang, Liu, Niu, Mi, Peng and Gao.)

Introduction: Tumor lysis syndrome is an oncologic emergency characterized by hyperuricemia. Previous studies have demonstrated that a fixed-dose strategy of rasburicase is as effective as the FDA approved weight-based dose. Albany Medical Center employs rasburicase 1.5 mg in patients with a uric acid (UA) between 8 and 12 mg/dL and 3 mg for UA above12 mg/dL.We aimed to evaluate the UA lowering effectiveness and provider adherence to the institutional protocol, as well as the cost-efficiency of this dosing strategy., Methods: This is a single center, retrospective, cohort study. The electronic medical record was used to identify patients receiving rasburicase and to collect baseline demographic and laboratory data. The fixed-dose strategies of rasburicase 1.5 mg and 3 mg were compared in their degree of UA reduction and clinical outcomes. Cost-savings of fixed-dosing was compared to the FDA-approved weight-based dose., Results: Mean UA reduction in the 1.5 mg group (n = 49) from baseline to 24 hours was 2.88 ± 0.88 mg/dL (p < 0.0001) and 4.83 ± 1.39 mg/dL (p < 0.0001) in the 3 mg group (n = 105). A subgroup analysis of patients who received per protocol initial doses of rasburicase showed a mean reduction in UA from baseline to 24 hours of 2.83 ± 0.62 mg/dL in the 1.5 mg group (n = 42) and 6.12 ± 1.87 mg/dL in the 3 mg group (n = 42). Using a low fixed-dose approach resulted in a cost-savings of $138,077.30 annually., Conclusion: Low fixed-dose rasburicase was an effective treatment, with a dose of 1.5 mg being sufficient to reach a goal UA of less than 8 mg/dL for serum UA levels below 12 mg/dL, while a 3 mg dose is appropriate for levels above 12 mg/dL. Cost analysis indicates this strategy is more cost-efficient than the FDA-approved weight-based dose.

Objective: To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial., Methods: Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100-mg increments from 200-400 mg or 300-600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV-related cause. The latter subgroup included patients who died due to non-CV causes and those who did not die due to any cause., Results: Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow-up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient-years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient-years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV-related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of >50%., Conclusion: In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Febuxostat is recommended by the American College of Rheumatology Gout Management Guidelines as a first-line therapy for lowering the level of urate in patients with gout. At present, this drug is being prescribed mainly based on the clinical experience of doctors. The potential effects of clinical and demographic variables on the bioavailability and therapeutic effectiveness of febuxostat are not being considered. In this study a physiologically based pharmacokinetic (PBPK) model of febuxostat was developed, thereby providing a theoretical basis for the individualized dosing of this drug in gout patients. The plasma concentration-time profiles corresponding to healthy subjects and gout patients with normal kidney function were simulated and validated; then, the model was used to predict the pharmacokinetic (PK) data of the drug in gout patients suffering from varying degrees of impaired kidney function. The error values (the predicted value/observed value) were used to validate the simulated PK parameters predicted by the PBPK model, including the area under the plasma concentration-time curve, the maximum plasma concentration, and time to maximum plasma concentration. Considering that to all error fold changes were smaller than 2, the PBPK model was. In subjects suffering from mild kidney impairment, moderate kidney impairment, severe kidney impairment, and endstage kidney disease (ESRD), the predicted AUC 0-24h values increased by 1.62, 1.74, 2.27, and 2.65-fold, respectively, compared to gout patients with normal kidney function. Overall, the results showed that the PBPK model constructed in this study predict the pharmacokinetic changes in gout patients suffering from varying degrees of impaired kidney function., (© 2022 John Wiley & Sons Ltd.)

Objective: To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout., Methods: We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points., Results: Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups., Conclusion: Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout., (© 2021 American College of Rheumatology.)

Uric acid is the final product of purine metabolism in human. The increase of serum uric acid is tightly related to the incidence of hyperuricemia and gout. Also, it has been reported that the intake of purine-rich foods like meat and seafood is associated with an increased risk of gout. Therefore, the reduction of purine absorption is one of therapeutic approaches to prevent hyperuricemia and gout. Currently, probiotics are being studied for the management of hyperuricemia and gout. In this study, we aimed to investigate the effect of Lactobacillus brevis MJM60390 on hyperuricemia induced by a high-purine diet and potassium oxonate in a mouse model. L. brevis MJM60390 among 24 lactic acid bacteria isolated from fermented foods showed the highest ability to assimilate inosine and guanosine in vitro and typical probiotic characteristics, like the absence of bioamine production, D-lactate production, hemolytic activity, as well as tolerance to simulated orogastrointestinal conditions and adherence to Caco-2 cells. In an in vivo animal study, the uric acid level in serum was significantly reduced to a normal level after oral administration of L. brevis MJM60390 for 2 weeks. The activity of xanthine oxidase catalyzing the formation of uric acid was also inhibited by 30%. Interestingly, damage to the glomerulus, Bowman's capsule, and tubules in the hyperuricemia model were reversed by supplementation with this strain. Fecal microbiome analysis revealed that L. brevis MJM60390 supplementation enhanced the relative abundance of the Rikenellaceae family, which produces the short-chain fatty acid butyrate and helps to maintain good gut condition. Therefore, these results demonstrated that L. brevis MJM60390 can be a probiotic candidate to prevent hyperuricemia.

Objective: To evaluate demographic characteristics, care encounters, comorbidities, and clinical differences in Hmong and non-Hmong patients with gout., Methods: Using retrospective chart review, all inpatient encounters (Hmong versus non-Hmong) were reviewed from 2014 to 2017. Acute or chronic gout was the primary or secondary diagnosis for the encounter., Results: Hmong gout patients were on average 11 years younger than non-Hmong patients, but after adjustment for age, sex, and type of encounter, they had similar rates of hypertension, diabetes mellitus, and heart disease. Hmong patients had significantly decreased renal function at the time of presentation; the odds ratio of chronic kidney disease for Hmong patients was 2.33 versus 1.48 for non-Hmong patients (P < 0.05), the mean creatinine level was 3.3 mg/dl versus 2.0 mg/dl (β = 1.35, P < 0.001), and the glomerular filtration rate was 44.8 ml/minute versus 49.3 ml/minute (β = -6.95, P < 0.001). Hmong gout patients were more likely to use emergency care versus elective or urgent care, they were less likely to be using medications for the treatment of gout prior to admission (32.3% versus 58.2%), and the length of hospital stay was increased (8.8 versus 5.2 days; P < 0.05)., Conclusion: Hmong gout patients who had a tertiary care encounter were 11 years younger than non-Hmong patients with similar rates of comorbidities but had worse renal function despite the age differences. They were more likely to use emergency services, to be insured through Medicaid, and not to use preventive medications for gout prior to their encounter. Intensive efforts are needed in the Hmong population for culturally appropriate preventive care management of gout along with diabetes mellitus, hypertension, heart disease, and kidney disease., (© 2020 American College of Rheumatology.)

Gout arthritis commonly affects joint regions by deposition of crystals, promoting functional damage mainly during periods of exacerbation. Cryotherapy is a commonly used resource to contain inflammatory processes, however, its use during a gout crisis is not yet well understood. Therefore, the objective was to evaluate the parameters of Wistar rats submitted to an experimental gout model and treated with dual cryotherapy protocol. Twenty-one male Wistar rats were used, separated into three groups: control group (CG), lesion group (LG), and lesion + cryotherapy group (LCG). Gout model induction was through intra-articular injection, with urate crystal solution, in the right knee and cryoimmersion treatment was performed for 20 minutes at a temperature of 5° ± 2°C. Seven evaluations and two treatment moments were performed, and the following parameters were analyzed: joint edema, grip strength, joint disability, motor function, and leukocyte migration through synovial lavage. In the statistical analysis we used SPSS 20.0 with Generalized Linear Models, with least significant difference posttest, always with 5% significance level. The treatment reduced edema, promoted strength recovery, and was effective in reducing total leukocytes in the synovial fluid. No difference was observed between the injured groups for joint disability and motor function. Cryotherapy promoted edema reduction and increased pelvic limb grip strength in Wistar rats during the acute period.

Objective: Determine the real-world incidence of acute gout prophylaxis (AGP) prescribing when a xanthine oxidase inhibitor (XOI) is initiated and describe characteristics of AGP prescribing., Methods: Retrospective cohort analysis from 2007 to 2017 using medical and prescription claims from an administrative database (IQVIA™ Health Plan Claims Database) among adult patients with a diagnosis of gout. Primary endpoint was the proportion of patients receiving AGP among all patients newly initiated on XOI therapy. Secondary endpoints included incidence proportions of acute flare and of XOI discontinuation among patients who received AGP compared to those who did not. Chi-square and Fisher's exact tests were used in univariate analysis of proportions between treatment groups., Results: A total of 7414 patients were included for analysis. There were 697 patients (9.4%) who received AGP with XOI initiation and colchicine alone was the most common medication used among patients who received prophylaxis (n = 303, 43.4%). The incidence proportion of patients with an acute gout flare within 3 months of index was 21.5% in the AGP cohort and 12.7% in the no prophylaxis cohort (p < 0.001). The proportion of patients who discontinued XOI within 12 months of initiation was 38.7% in the AGP cohort and 46.2% in the no prophylaxis cohort (p < 0.001)., Conclusion: In the real world, the proportion of patients who receive AGP with initiation of XOI therapy is low and discontinuation of XOI within 12 months of initiation is significant. In this analysis, use of AGP was not associated with a lower risk of acute gout flare after initiation of XOI therapy. Key Points • Real-world acute gout prophylaxis (AGP) prescribing with xanthine oxidase inhibitor (XOI) initiation is very low despite current guideline recommendations • More than one third of patients discontinue XOIs within 12 months of initiation regardless of AGP prescribing.

Objectives: The aim was to evaluate the efficacy, defined as achieving target serum urate <6.0 mg/dl, and safety of urate-lowering therapies (ULTs) for people with gout and chronic kidney disease (CKD) stages 3-5., Methods: PubMed, The Cochrane Library and EMBASE were searched from 1 January 1959 to 31 January 2018 for studies that enrolled people with gout, who had an estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) of <60 ml/min and exposure to allopurinol, febuxostat, probenecid, benzbromarone, lesinurad or pegloticase. All study designs other than case reports were included, except for people on dialysis, for whom we did include case reports., Results: There were 36 reports with an analysis of efficacy and/or safety based upon renal function: allopurinol ( n  = 12), febuxostat ( n  = 10), probenecid ( n  = 3), benzbromarone ( n  = 5), lesinurad ( n  = 5) and pegloticase ( n  = 1). There were 108 reports that involved people with gout and renal impairment but did not contain any analysis on efficacy and/or safety based upon renal function: allopurinol ( n  = 84), febuxostat ( n  = 14), benzbromarone ( n  = 1), lesinurad ( n  = 3) and pegloticase ( n  = 6). Most studies excluded people with more severe degrees of renal impairment (eGFR or CrCl of <30 ml/min). For allopurinol, in particular, there was significant variability in the dose of drug used and the efficacy in terms of urate lowering, across all levels of renal impairment., Conclusion: There is a lack of evidence regarding the efficacy and/or safety of currently used ULTs according to different levels of renal function. Future studies should include patients with CKD and should report study outcomes stratified by renal function., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2021. This work is written by US Government employees and is in the public domain in the US.)

Hyperuricemia (HU) and gout are strongly associated with CVD, associations that are most likely due to shared etiologies rather than causality. HU is for example causally related to the metabolic syndrome and in particular to obesity. Gout and HU can both be caused by and lead to decreased kidney function. On the other hand, there are observational data suggesting that HU may protect against neurodegenerative diseases such as Alzheimer and Parkinson's disease. Ongoing RCTs with urate and urate lowering therapy (ULT) will help to resolve some of these controversies. Nevertheless, gout is a "curable disease" by ULT, a treatment which in adequate doses may also have positive effect on several associated co-morbidities.

Urate lowering therapy (ULT) should, according to recent guidelines, be initiated in the majority of cases already after the first attack of gout. Allopurinol is the first line choice of ULT and should be started with low dose, which is increased until the treatment target is reached. The treatment target should be a blood urate of < 360 µmol/l or < 300 µmol/l (in the presence of topfi), which should be maintained until topfi have resolved. NSAID/cox-inhibitors, colchicine and glucocorticoids are all valid short-term treatments of gout attacks. ULT should not be paused/terminated during attacks and can be initiated during an attack that is adequately treated. Recent RCTs of ULT treatment have demonstrated the importance of thorough and adequate information to the patient and regular follow-up until treatment targets are reached. Such a strategy improve both compliance and outcomes of ULT treatment.

The treat to target strategy looks attractive for management of gout because it removes the causal mechanism inducing formation, growth, and aggregation of urate crystals. Further reduction of serum urate (sUA) levels below the threshold may dissolve crystals more rapidly. It is generally agreed that sUA less than 6 mg/dL is acceptable as a therapeutic and long-term preventive target, with <5 mg/dL for the most severe cases. The challenges that this approach in gout is facing include whether proposed targets are the best for desired outcomes, whether they fit patient-related outcomes, and whether they adequately balance effectiveness and safety., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Light and Shadow of Hyperuricemia - Neuroprotection, Comorbidities and Therapeutic Strategies Abstract. Hyperuricemia can lead to gout but also favor the appearance of comorbidities like hypertension, kidney insufficiency, type 2 diabetes, myocardial infarction and strokes. Uric acid does not only have, however, negative impact on the body, but seems to influence positively certain inflammatory and degenerative neurological diseases. The inflammatory reaction at the center of a gout attack is mediated by interleukin 1. Therefore, antagonists against interleukin 1 or IL-1 receptors can be used for treatment if colchicine, steroids or nonsteroidal anti-inflammatory drugs are ineffective or contraindicated. First-line drug for urate-lowering therapy is allopurinol that positively influences comorbidities as well.

Nowadays, there is increased interest in the connection of gout and asymptomatic hyperuricemia with comorbid conditions such as diabetes mellitus, cardiovascular diseases, hypertension, chronic kidney disease and other. Studies conducted over the past few decades suggest that not only gout, but also asymptomatic hyperuricemia can significantly worsen the prognosis in patients with cardiovascular diseases, as the deposition of urate crystals can be both an immediate cause and a factor in the progression of renal failure. In that way, the timely appointment of urate - lowering therapy and achieving the target serum uric acid level can not only affect joint damage, but also can significantly slow the progression of life - threatening comorbid conditions.

Objective: To provide helpful continued medical education (CME) for physicians and improve gout treatment, we conducted a questionnaire survey to investigate physicians' knowledge in nine districts of Beijing. Methods: A questionnaire survey including ten gout-related questions was conducted among 298 physicians in Beijing. Demographic data and previous gout CME experience were collected. Chi-square test or Student's t test, univariate analysis and logistic regression analysis were used to evaluate the relevant factors of physicians' knowledge level. Results: A total of 250 valid copies were collected including 127 from community service centers (CSC), 123 from tertiary hospitals. The correct answer rate of gout etiology, pathogenesis and attack symptoms were over 70% in both groups. 45.5% (56/123) CSC doctors and 57.4% (66/115) tertiary doctors answered right drugs to control acute gout attack ( P= 0.067). Only 42.3% (52/123) in CSC and 53.4% (63/118) in hospitals chose allopurinol as a urate-lowering drug (ULT), while 46.3% (57/123) and 32.2% (38/118) doctors considered colchicine as a ULT drug ( P= 0.084) respectively. Near half doctors considered that gout patients should take long-term ULT [40.5% (51/126) vs. 57.6%(68/118)respectively, P= 0.007]. Univariate analysis showed that CME training could improve gout-related knowledge in CRC doctors. Conclusion: Most CSC doctors generally understand basic knowledge of gout, while confusion of treatment is still significant. CME especially including standard gout treatment should be performed by doctors in tertiary hospitals.

Rhein, an anthraquinone drug, is a widely used traditional Chinese medicine. Rhein is a major bioactive metabolite of diacerein which has been approved for treating osteoarthritis with a good safety profile in humans. Gouty arthritis is an inflammatory disease characterized by urate crystal-induced NLRP3 inflammasome activation with up-regulated caspase-1 protease and IL-1 β in macrophages. Inhibition of the NLRP3 inflammasome formation has been considered as a potential therapeutic avenue for treating or preventing many inflammatory diseases. This study aimed to evaluate the anti-inflammatory effects of rhein on gouty arthritis. Rhein within the physiological levels of humans showed no toxicity on the cell viability and differentiation, but significantly decreased the production of IL-1 β , TNF- α and caspase-1 protease in urate crystal-activated macrophages. Compared to medium controls, rhein at the therapeutic concentration (2.5 μ g/mL) effectively inhibited IL-1 β production by 47% ( P = 0 . 0 0 2 ). Rhein did not affect the mRNA levels of CASP1, NLRP3 and ASC, but suppressed the protein expression and enzyme activity of caspase-1. Immunofluorescence confocal microscopy further revealed that rhein suppressed the aggregation of ASC speck and inhibited the formation of NLRP3 inflammasome. Rhein of 5 μ g/mL significantly decreased the ASC speck to 36% ( P = 0 . 0 0 1 1 ), and reduced the NLRP3 aggregates to 37.5% ( P = 0 . 0 1 4 ). Our data demonstrate that rhein possesses pharmacological activity to suppress caspase-1 protease activity and IL-1 β production by interfering with the formation of NLRP3 multiprotein complex. These results suggest that rhein has therapeutic potential for treating NLRP3 inflammasome-mediated diseases such as gouty arthritis.

Gout is the most common form of inflammatory arthropathy, and is associated with excruciating pain, major impairment of quality of life, and increased risk of comorbidities and mortality. Although gout has somehow been neglected by researchers and clinicians in the past, in more recent times there has been a renewed interest in this disease, which has led to major improvements in its management. This article reviews the new clinical and experimental evidence about gout that emerged in 2017 and in the first half of 2018.

Hyperuricemia is the main risk factor for gout. Although the threshold of hyperuricemia has been recommended, the reference levels of serum urate for gout have not been clarified. In the present study, we estimated the reference levels of serum urate for gout. A study has shown the association between serum urate and incidence of gout during 5-15 years of follow-up. We calculated the reference levels of serum urate for gout based on the previous published data by using the benchmark dose (BMD) method. The subjects were divided into six groups according to serum urate levels (6.0, 6.5, 7.5, 8.5, 9.5, and 10 mg/dL). Gamma, LogLogistic, and LogProbit models were used in BMD calculation. If the benchmark response (BMR) was set at 5%, the 95% lower confidence bounds of BMD (BMDL) of serum urate for the total population were 8.09-8.14 mg/dL during 5 years of follow-up, 7.27-7.30 mg/dL during 10 years of follow-up, and 6.73-6.99 mg/dL during 15 years of follow-up. If the BMR was set at 1%, the BMDL further decreased by 1.4 mg/dL. They were 6.68-6.85 mg/dL, 5.97-6.03 mg/dL, and 5.25-5.36 mg/dL, respectively. Similar results were observed in men and women. A threshold of 7.0 mg/dL of serum urate may be not a sufficient goal for protection against gout. A stricter threshold of serum urate (< 6.0 mg/dL) should be made.

Aim: Febuxostat is an active xanthine oxidase (XO) inhibitor which is widely used in the treatment of hyperuricaemia. We aimed to evaluate the predictive performance of a pharmacokinetic-pharmacodynamic (PK-PD) model of the hypouricaemic effects of febuxostat., Methods: Previously, we formulated a PK-PD model for predicting the hypouricaemic effects of febuxostat as a function of baseline serum urate levels, body weight, renal function and drug dose, using datasets reported in preapproval studies. Using an updated model with a sensitivity analysis, we examined the predictive performance of the PK-PD model, using datasets obtained from the medical records of patients who received febuxostat from March 2011 to December 2015 at Tokyo Women's Medical University Hospital. Multivariate regression analysis was performed to explore clinical variables to improve the predictive performance of the model., Results: A total of 1199 serum urate values were retrieved from 168 patients (age: 60.5 ± 17.7 years; 71.4% male) who were receiving febuxostat as a treatment for hyperuricaemia. There was a significant correlation (r = 0.68; P < 0.01) between the serum urate levels observed and those predicted by the modified PK-PD model. A multivariate regression analysis revealed that the predictive performance of the model could be improved further by considering comorbidities (such as diabetes mellitus), estimated glomerular filtration rate (eGFR) and the coadministration of loop diuretics (r = 0.77, P < 0.01)., Conclusions: The PK-PD model may be useful for predicting individualized maintenance doses of febuxostat in real-world patients., (© 2018 The British Pharmacological Society.)