Project description:Urate in the fingernails of gout patients and healthy volunteers was successfully detected by high-performance liquid chromatography (HPLC) with ultraviolet (UV) in our previous research. This study aimed to further investigate whether nail urate could be a proxy for the burden of monosodium urate (MSU) crystals deposits in gout. To this end, we conducted a study in two parts. Firstly, we successfully detected urate in the nail by HPLC-UV and evaluated nail urate concentrations in control subjects and patients with gout. As expected, we found that levels of nail urate were significantly higher in patients with gout than in healthy controls, and the nail urate level was significantly correlated with the volume of MSU crystals deposits measured by dual-energy CT (DECT). Secondly, we found that nail urate can reflect changes in urate levels in the body during urate lowering therapy through a 3-month follow-up study. Our results provide the possibility of quantification of urate in human fingernails as a non-invasive alternative for assessing MSU crystals deposits in gout.
Project description:ObjectiveSeveral plausible mechanisms and anecdotal descriptions suggest that gout attacks often occur at night, although there are no scientific data supporting this. We undertook this study to evaluate the hypothesis that gout attacks occur more frequently at night.MethodsWe conducted a case-crossover study to examine the risk of acute gout attacks in relation to the time of the day. Gout patients were prospectively recruited and followed up via the internet for 1 year. Participants were asked about the following information concerning their gout attacks: the date and hour of attack onset, symptoms and signs, medication use, and purported risk factors during the 24- and 48-hour periods prior to the gout attack. We calculated the odds ratios (ORs) of gout attacks (with 95% confidence intervals [95% CIs]) according to three 8-hour time blocks of the day (i.e., 12:00 AM to 7:59 AM, 8:00 AM to 3:59 PM [reference], and 4:00 PM to 11:59 PM) using conditional logistic regression.ResultsOur study included 724 gout patients who experienced a total of 1,433 attacks (733, 310, and 390 attacks during the first, second, and third 8-hour time blocks, respectively) over 1 year. The risk of gout flares in the 8-hour overnight time block (12:00 AM to 7:59 AM) was 2.36 times higher than in the daytime (8:00 AM to 3:59 PM) (OR 2.36 [95% CI 2.05-2.73]). The corresponding OR in the evening (4:00 PM to 11:59 PM) was 1.26 (95% CI 1.07-1.48). These associations persisted among those with no alcohol use and in the lowest quintile of purine intake in the 24 hours prior to attack onset. Furthermore, these associations persisted in subgroups according to sex, age group, obesity status, diuretic use, and use of allopurinol, colchicine, and nonsteroidal antiinflammatory drugs.ConclusionThese findings provide the first prospective evidence that the risk of gout attacks during the night and early morning is 2.4 times higher than in the daytime. Further, these data support the purported mechanisms and historical descriptions of the nocturnal onset of gout attacks and may have implications for antigout prophylactic measures.
Project description:BackgroundUltrasound (US) has a high sensitivity in detecting monosodium urate (MSU) deposition in gout patients. However, the value of US in predicting gout flares has been reported only in a few monocentric studies.ObjectiveTo investigate the association between gout flares in the previous year and US-detected MSU burden using two different US scores.DesignA retrospective study.MethodsPatients with gout were consecutively recruited to undergo musculoskeletal US examinations of their knees, ankles, and feet. The score derived from Outcome Measure in Rheumatology (hereinafter referred to as MSU score) and musculoskeletal US features-based (hereinafter referred to as MSKF score) were used to quantify the MSU burden of gout. Odds ratios for frequent gout flares were calculated.ResultsWe enrolled 1894 patients with gout (mean age: 45 years; gout duration: 5 years; males: 96.1%), experiencing a median of three flares over the past year. Of these, 428 (22.6%) patients reported frequent (⩾7) gout flares. The MSU and MSKF median scores were 6 and 9, respectively. For each five-point increase in MSU and MSKF score, the odds ratio of frequent gout flares increased 1.13-fold and 1.24-fold, respectively. The area under the curve (AUC) for the MSU and MSKF score was 0.635 [95% confidence interval (CI): 0.604-0.665] and 0.688 (95% CI: 0.659-0.718), respectively, (AUC difference 0.054, p value for AUC difference < 0.001).ConclusionThe MSU and MSKF scores were significantly associated with the number of gout flares in the previous year. The MSKF score outperformed the MSU score in terms of frequent gout flare discrimination.
Project description:BackgroundThis study aimed to explore the clinical characteristics of perioperative acute gout attacks in patients with varying uric acid levels undergoing orthopedic surgery, identify the risk factors for gout recurrence within the first postoperative year, and provide a disease prevention and diagnostic reference.MethodsThis hospital-based retrospective study was conducted between January 2018 and December 2020. According to the blood uric acid levels at admission, the patients were grouped into either the normal uric acid level group or the hyperuricemia group. Patient comorbidities, serum uric acid levels, inflammatory indicators, follow-up recurrence rates, and other indicators were compared.ResultThe uric acid decline ratio and the inflammatory indexes (white blood cell count and C-reactive protein level) at the time of the attack were significantly higher in the normal uric acid level group than in the hyperuricemia group (P < 0.05). Patients in the hyperuricemia group with diabetes and tophi and those administered diuretics were more prone to acute gout attacks than those in the normal uric acid level group (P < 0.05). In the normal uric acid level group, 22 patients (84.6%) exhibited single joint involvement, whereas only 18 patients (47.4%) in the hyperuricemia group demonstrated single joint involvement (P < 0.05). After 1 year of follow-up, the gout recurrence rate in the hyperuricemia group was 44.7%, which was significantly higher that the recurrence rate in the normoglycemic group (11.5%; P < 0.05). Presenting tophi in perioperative orthopedic surgery patients was found to be an independent risk factor for gout recurrence within 1 year (RR = 4.80; P = 0.029).ConclusionThe recurrence rate of gout in patients with hyperuricemia during perioperative period increased 1 year after operation. Therefore, it is crucial to monitor the uric acid level to prevent acute gout attacks during the perioperative period and recurrence during the 1-year follow-up period. Moreover, the risk of an acute gout recurrence 1 year after operation increased in patients who presented tophi; therefore, it is necessary to maintain appropriate blood uric acid level during perioperative period among patients undergoing orthopedic surgery.
Project description:As a prominent feature of gout, monosodium urate (MSU) crystal deposition can induce gout flare, yet its impact on blood immune in gout remission patients still remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) is used to compare the gene expression profiling of peripheral blood mononuclear cells (PBMCs) among intercritical gout remission patients, advanced gout remission patients and healthy volunteers. The increase of HLA-DQA1high classical monocytes, and their important role in immune inflammatory responses and osteoclast differentiation are discovered in advanced gout remission patients. Moreover, the differentiation level of CD8+T cells are found to elevate in advanced gout remission patients, which is further validated via flow cytometry. It is also observed that pathways related to bone metabolism and inflammatory responses are overactive in advanced gout remission patients. By analysis on intercellular communication network, immune-related cell-cell interactions among PBMCs are shown to enhance in both intercritical and advanced gout remission patients. The analyses on gene expression and LC-MS/MS together indicate the increased metabolic level of arachidonic acid in gout remission patients with MSU deposition at the intercritical and advanced stage. The study reveals distinctive blood immune characteristics in gout remission with MSU deposition, which provides more sights into its pathogenesis.
Project description:ObjectiveTo examine the association between cardioprotective use of low-dose aspirin and the risk of recurrent gout attacks among gout patients.MethodsWe conducted an online case-crossover study of individuals with gout over 1 year. The following information was obtained during gout attacks: the onset dates, symptoms and signs, medications, and exposure to potential risk factors, including daily aspirin use and dosage, during the 2-day hazard period prior to the gout attacks. The same exposure information was also obtained over 2-day control periods.ResultsOf the 724 participants analysed, 40.5% took aspirin ≤325 mg/day during either a hazard or a control period. Compared with no aspirin use, the adjusted OR of gout attacks increased by 81% (OR=1.81, 95% CI 1.30 to 2.51) for ≤325 mg/day of aspirin use on two consecutive days. The corresponding ORs were stronger with lower doses (eg, OR=1.91 for ≤100 mg, 95% CI 1.32 to 2.85). These associations persisted across subgroups by sex, age, body mass index categories and renal insufficiency status. Concomitant use of allopurinol nullified the detrimental effect of aspirin.ConclusionsOur findings suggest that the use of low-dose aspirin on two consecutive days is associated with an increased risk of recurrent gout attacks. Recommended serum urate monitoring with concomitant use and dose adjustment of a urate-lowering therapy among patients with gout may be especially important to help avoid the risk of gout attacks associated with low-dose aspirin.
Project description:ObjectivesTo examine whether gout is an independent risk factor for total joint replacement (TJR) and whether urate-lowering treatment (ULT) reduces this risk.MethodsUsing the Taiwan National Health Insurance database and the UK Clinical Practice Research Datalink, 74 560 Taiwan patients and 34 505 UK patients with incident gout were identified and age and sex matched to people without gout. Cox proportional hazards models and condition logistic regression were used to examine the risk of TJR in gout patients and the association between cumulative defined daily dose (cDDD) of ULT and TJR.ResultsThe prevalence rates of TJR in the patients at the time of diagnosis of gout and in people without gout were 1.16% vs 0.82% in Taiwan and 2.61% vs 1.76% in the UK. After a gout diagnosis, the incidence of TJR was higher in the patients with gout compared with those without (3.23 vs 1.91 cases/1000 person-years in Taiwan and 6.87 vs 4.61 cases/1000 person-years in the UK), with adjusted HRs of 1.56 (95% CI 1.45, 1.68) in Taiwan and 1.14 (1.05, 1.22) in the UK. Compared with patients with gout with <28 cDDD ULT, the adjusted ORs for TJR were 0.89 (95% CI 0.77, 1.03) for 28-90 cDDD, 1.03 (0.85, 1.24) for 90-180 cDDD and 1.12 (0.94, 1.34) for >180 cDDD ULT in Taiwan. In the UK, the respective ORs were 1.09 (0.83, 1.42), 0.93 (0.68, 1.27) and 1.08 (0.94, 1.24).ConclusionThis population-based study provides evidence from two nation populations that gout confers significant TJR risk, which was not reduced by current ULT.
Project description:The aim of this study was to systematically review the literature on effect of initiating urate-lowering treatment (ULT) during an acute attack of gout on duration of index attack and persistence on ULT. OVID (Medline), EMBASE and AMED were searched to identify randomized controlled trials (RCTs) of ULT initiation during acute gout attack published in English language. Two reviewers appraised the study quality and extracted data independently. Standardized mean difference (SMD) and relative risk (RR) were used to pool continuous and categorical data. Meta-analysis was carried out using STATA version 14. A total of 537 studies were selected. A total of 487 titles and abstracts were reviewed after removing duplicates. Three RCTs were identified. There was evidence from two high-quality studies that early initiation of allopurinol did not increase pain severity at days 10-15 [SMDpooled (95 % CI) 0.18 (-0.58, 0.93)]. Data from three studies suggested that initiation of ULT during an acute attack of gout did not associate with dropouts [RRpooled (95 % CI) 1.16 (0.58, 2.31)]. There is moderate-quality evidence that the initiation of ULT during an acute attack of gout does not increase pain severity and risk of ULT discontinuation. Larger studies are required to confirm these findings so that patients with acute gout can be initiated on ULT with confidence.
Project description:BackgroundPrevious studies have noted significant variation in serum urate (sUA) levels, and it is unknown how this influences the accuracy of hyperuricemia classification based on single data points. Despite this known variability, hyperuricemic patients are often used as a control group in gout studies. Our objective was to determine the accuracy of hyperuricemia classifications based on single data points versus multiple data points given the degree of variability observed with serial measurements of sUA.MethodsData was analyzed from a cross-over clinical trial of urate-lowering therapy in young adults without a gout diagnosis. In the control phase, sUA levels used for this analysis were collected at 2-4 week intervals. Mean coefficient of variation for sUA was determined, as were rates of conversion between normouricemia (sUA ≤6.8 mg/dL) and hyperuricemia (sUA > 6.8 mg/dL).ResultsMean study participant (n = 85) age was 27.8 ± 7.0 years, with 39% female participants and 41% African-American participants. Mean sUA coefficient of variation was 8.5% ± 4.9% (1 to 23%). There was no significant difference in variation between men and women, or between participants initially normouricemic and those who were initially hyperuricemic. Among those initially normouricemic (n = 72), 21% converted to hyperuricemia during at least one subsequent measurement. The subgroup with initial sUA < 6.0 (n = 54) was much less likely to have future values in the range of hyperuricemia compared to the group with screening sUA values between 6.0-6.8 (n = 18) (7% vs 39%, p = 0.0037). Of the participants initially hyperuricemic (n = 13), 46% were later normouricemic during at least one measurement.ConclusionSingle sUA measurements were unreliable in hyperuricemia classification due to spontaneous variation. Knowing this, if a single measurement must be used in classification, it is worth noting that those with an sUA of < 6.0 mg/dL were less likely to demonstrate future hyperuricemic measurements and this could be considered a safer threshold to rule out intermittent hyperuricemia based on a single measurement point.Trial registrationData from parent study ClinicalTrials.gov Identifier: NCT02038179 .
Project description:ImportanceThe prevalence of gout has increased in recent decades. Several clinical studies have demonstrated an association between gout and coronary heart disease, but direct cardiovascular imaging of monosodium urate (MSU) deposits by using dual-energy computed tomography (DECT) has not been reported to date.ObjectiveTo compare coronary calcium score and cardiovascular MSU deposits detected by DECT in patients with gout and controls.Design, setting, and participantsThis prospective Health Insurance Portability and Accountability Act-compliant study included patients with gout and controls who presented to a rheumatologic clinic from January 1, 2017, to November 1, 2018. All consecutive patients underwent DECT to assess coronary calcium score and MSU deposits in aorta and coronary arteries. In addition, cadavers were assessed by DECT for cardiovascular MSU deposits and verified by polarizing microscope. Analysis began in January 2017.Main outcomes and measuresDetection rate of cardiovascular MSU deposits using DECT in patients with gout and control group patients without a previous history of gout or inflammatory rheumatic diseases.ResultsA total of 59 patients with gout (mean [SD] age, 59 [5.7] years; range, 47-89 years), 47 controls (mean [SD] age, 70 [10.4] years; range, 44-86 years), and 6 cadavers (mean [SD] age at death, 76 [17] years; range, 56-95 years) were analyzed. The frequency of cardiovascular MSU deposits was higher among patients with gout (51 [86.4%]) compared with controls (7 [14.9%]) (χ2 = 17.68, P < .001), as well as coronary MSU deposits among patients with gout (19 [32.2%]) vs controls (2 [4.3%]) (χ2 = 8.97, P = .003). Coronary calcium score was significantly higher among patients with gout (900 Agatston units [AU]; 95% CI, 589-1211) compared with controls (263 AU; 95% CI, 76-451; P = .001) and also significantly higher among 58 individuals with cardiovascular MSU deposits (950 AU; 95% CI, 639-1261) compared with 48 individuals without MSU deposits (217 AU; 95% CI, 37-397; P < .001). Among 6 cadavers, 3 showed cardiovascular MSU deposits, which were verified by polarizing light microscope.Conclusion and relevanceDual-energy computed tomography demonstrates cardiovascular MSU deposits, as confirmed by polarized light microscopy. Cardiovascular MSU deposits were detected by DECT significantly more often in patients with gout compared with controls and were associated with higher coronary calcium score. This new modality may be of importance in gout population being at risk from cardiovascular disease.