Slowly melting the urate snow in joints: Explaining gout attacks to patients.
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ABSTRACT:
SUBMITTER: Shimizu T
PROVIDER: S-EPMC8126960 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC7511301 | biostudies-literature
Project description:Several 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.We 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.Our 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.These 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.
| S-EPMC4360969 | biostudies-literature
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.
2023-06-01 | GSE217561 | GEO
Project description:To examine the association between cardioprotective use of low-dose aspirin and the risk of recurrent gout attacks among gout patients.We 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.Of 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.Our 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.
| S-EPMC3902644 | biostudies-literature
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.
| S-EPMC6256332 | biostudies-literature
Project description:OBJECTIVE:To estimate the prevalence and distribution of asymptomatic monosodium urate monohydrate (MSU) crystal deposition in sons of patients with gout. METHODS:Patients with gout were mailed an explanatory letter with an enclosed postage-paid study packet to mail to their son(s) age ?20 years old. Sons interested in participating returned a reply form and underwent telephone screening. Subsequently, they attended a study visit at which blood and urine samples were obtained and musculoskeletal ultrasonography was performed, with the sonographer blinded with regard to the subject's serum urate level. Images were assessed for double contour sign, intraarticular or intratendinous aggregates/tophi, effusion, and power Doppler signal. Logistic regression was used to examine associations. Adjusted odds ratios (ORadj ) and 95% confidence intervals (95% CIs) were calculated. RESULTS:One hundred thirty-one sons (mean age 43.8 years, mean body mass index 27.1 kg/m2 ) completed assessments. The serum urate level was ?6 mg/dl in 64.1%, and 29.8% had either a double contour sign or intraarticular aggregates/tophi in ?1 joint. All participants with MSU deposition had involvement of 1 or both first metatarsophalangeal joints. Intratendinous aggregates were present in 21.4% and were associated with intraarticular MSU crystal deposits (ORadj 2.96 [95% CI 1.17-7.49]). No participant with a serum urate level of ?5 mg/dl had MSU crystal deposition seen on ultrasonography, and 24.2% of those with serum urate levels between 5 and 6 mg/dl had ultrasonographic MSU deposition. MSU crystal deposition was associated with increasing serum urate levels (ORadj 1.61 [95% CI 1.10-2.36] for each increase of 1 mg/dl). CONCLUSION:Asymptomatic sons of patients with gout frequently have hyperuricemia and MSU crystal deposits. In this study MSU crystal deposits were present in participants with serum urate levels of ?5 mg/dl. Evaluation of subjects without a family history of gout is needed to determine whether the threshold for MSU crystal deposition is also lower in the general population.
| S-EPMC6220843 | biostudies-other
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.
| S-EPMC5102948 | biostudies-literature
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 .
| S-EPMC8425059 | biostudies-literature
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.
| S-EPMC6739730 | biostudies-literature
Project description:To study the relationship between cherry intake and the risk of recurrent gout attacks among individuals with gout.We conducted a case-crossover study to examine the associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed up online for 1 year. Participants were asked to provide the following information regarding gout attacks: the onset date of the gout attack, symptoms and signs, medications (including antigout medications), and exposure to potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate OR 0.65 [95% CI 0.50-0.85]). Cherry extract intake showed a similar inverse association (multivariate OR 0.55 [95% CI 0.30-0.98]). The effect of cherry intake persisted across subgroups stratified by sex, obesity status, purine intake, alcohol use, diuretic use, and use of antigout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than during periods without either exposure (OR 0.25 [95% CI 0.15-0.42]).These findings suggest that cherry intake is associated with a lower risk of gout attacks.
| S-EPMC3510330 | biostudies-literature