ObjectivesCOVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination.MethodsA clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates.ResultsWe enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare.ConclusionCOVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.

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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.

IntroductionAchieving a goal of serum urate levels in patients with gout is an important way to prevent gout and its complications while it remains difficult with a low targeting rate worldwidely. Currently, hyperuricemia classification has not been widely applied to the management of gout owing to insufficient clinical evidences. This study aimed to evaluate the effectiveness of achieving target urate based on hyperuricemia classification in Chinese patients with gout.MethodsIn this prospective study, patients with gout receiving urate lowering therapy with benzbromarone were assigned to two groups, a renal underexcretion and an unclassified type. The primary endpoint was the proportion of patients achieving the serum urate target (&lt;360 μmol/L) during the 12-week study. The frequency of acute gout attacks as well as physical and chemical indicators were secondary endpoints.ResultsTarget serum urate level was achieved in 60.5% of underexcretors compared with 39.0% of patients of the unclassified type at week 12 (P = 0.002). Blood glucose and cholesterol levels were lower in the underexcretor group compared with the unclassified type group at the end of the trial, without significant different frequencies in gout flare during the study. In subgroup analysis, stratified by body mass index and estimated glomerular filtration rate, the proportion of patients with serum urate &lt;360 μmol/L was greater in the underexcretion compared with the unclassified type group.ConclusionsThe increased achievement of target serum urate in the underexcretion group supports the use of a clinical hyperuricemia typing treatment strategy for gout.

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Objectives The deposition of monosodium urate (MSU) crystals within synovial joints and tissues is the initiating factor for gout arthritis. Thus, MSU crystals are a vital tool for studying gout’s molecular mechanism in animal and cellular models. This study mainly compared the excellence and worseness of MSU crystals prepared by different processes and the degree of inflammation induced by MSU crystals. Methods MSU crystals were prepared using neutralization, alkali titration, and acid titration methods. The crystals’ shape, length, quality, and uniformity were observed by polarized light microscopy and calculated by the software Image J. The foot pad and air pouch models were used to assess the different degrees of inflammation induced by the MSU crystals prepared by the three different methods at different time points. Paw swelling was evaluated by caliper. In air pouch lavage fluid, inflammatory cell recruitment was measured by hemocytometer, and the level of IL-1β, TNF-α, and IL-18 by ELISA. Inflammatory cell infiltration was assayed by immunohistochemistry of air pouch synovial slices. Results For the preparation of MSU crystals with the same uric acid, the quantity acquired by the alkalization method was highest, followed by neutralization, with the acid titration method being the lowest. The crystals prepared by neutralization were the longest. The swelling index of the foot pad induced by MSU crystals prepared by acid titration was significantly lower than that of the other methods at 24 h. The inflammatory cell recruitment and level of IL-1β, TNF-α, and IL-18 in air pouch lavage fluid were lowest in animals with crystals prepared by acid titration. IL-1β secretion induced by MSU crystals prepared by acid titration was significantly lower than that of the other two groups, but there was no significant difference in IL-18 secretion between the three groups in THP-1 macrophages and BMDMs. Conclusions All three methods can successfully prepare MSU crystals, but the levels of inflammation induced by the crystals prepared by the three methods were not identical. The degree of inflammation induced by MSU crystals prepared by neutralization and alkalization is greater than by acid titration, but the quantity of MSU crystals obtained by the alkalization method is higher and less time-consuming. Apparently, the window of inflammation triggered by acid titration preparation is shorter compared to other forms of crystal preparation. Overall, MSU crystals prepared by the alkaline method should be recommended for studying the molecular mechanisms of gout in animal and cellular models.

ObjectivesTo assess post‐COVID‐19 vaccination gout flare risk with differing baseline flare burden.MethodsWe prospectively studied gout patients with infrequent or frequent flares, defined as ≤1 flare/year, or ≥2 flares/year, respectively. COVID‐19 vaccine‐naïve patients managed with urate‐lowering therapy between February‐June 2021were included, and voluntarily decided on vaccination. Participants were followed for 12 weeks after enrollment or first vaccine dose. Gout flares and risk factors were compared between groups.ResultsOf 530 participants, 308 (58.1%) had infrequent flares, and 222 (41.9%) had frequent flares at baseline, with 248 (142 infrequent, 106 frequent) receiving two‐dose COVID‐19 vaccination. Vaccination increased cumulative flare incidence at 12 weeks in the infrequent but not the frequent flare group (26.1% vs. 10.8%, P=0.001, compared to 60.4% vs.65.5%, P=0.428). Flare incidence in the final 4 weeks of observation decreased significantly only in the vaccinated infrequent flare group (4.3% vs. 12.0%, P=0.017). Multivariable analyses showed that vaccination (OR=2.82, 95%CI 1.50‐5.30, P=0.001), flare in the preceding year (OR=1.95, 95%CI 1.03‐3.71, P=0.04) and BMI (OR=1.09, 95%CI 1.01‐1.19, P=0.03) were independently associated with increased flare risk in the infrequent flare group. Baseline serum urate (mg/dL) was an independent risk factor in the frequent flare group (OR=1.23, 95%CI 1.05‐1.45, P=0.012).ConclusionCOVID‐19 vaccination was associated with increased early gout flares only in patients with previously infrequent flares.image

LDFeb group (15% compared to 4% for LDBen). There was no significant difference in the rates of gout flares and urolithiasis, and the authors recommended low-dose benzbromarone in this situation. I have some comments about their study.Another randomized controlled study from China (2) compared the efficacy and safety of the 2 urate-lowering drugs at the same doses and duration of treatment as used in Yan et al. There was no significant difference in the rates of achieving the serum urate target and adverse events in the Liang et al study (2). Those authors mentioned that serum urate level and renal function might become key factors for selecting either LDBen or LDFeb. I understand that there is an ethnic difference in the rate of renal uric acid underexcretion in gout patients. In the Liang et al study (2), the incidence of gout flares in the LDFeb and LDBen groups was 22.85% and 33.94%, respectively, and the mean age of participants was >50 years. I think that continuous surveys are needed to specify the safety and efficacy of 2 different types of medication.Regarding the effect of clinical hyperuricemia typing (CHT) on the efficacy of urate-lowering therapy, Xue et al reported that percentages of gout patients with the underexcretion type and those with the unclassified type achieved 60.5% and 39.0% of the target serum urate level, respectively, following treatment with LDBen (3). In addition, blood glucose and cholesterol levels were lower in those with the underexcretion type compared to those with the unclassified type at the end of the trial. Since the prognosis was better in gout patients with the underexcretion type in the Xue et al study, CHT may be important for specifying the superiority of medication for gout.Finally, the data from the Xue et al study were derived from Chinese male participants. Ethnic and sex differences in the efficacy of urate-lowering therapy should be examined using randomized controlled studies. Furthermore, Xue et al focused on gout patients with the underexcretion type, and there was an advantage of LDBen treatment over LDFeb treatment.