Association between oxidative balance score and risk of gout: The NHANES cross-sectional study, 2007-2018.

BACKGROUND: The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. The association between OBS and gout has not been reported previously. We conducted a cross-sectional study to investigate the complex association between OBS and gout in US adults. METHODS: In all, 10 492 participants were included in this study. The exposure variable was OBS, which was scored by 16 dietary and four lifestyle factors. Multivariate logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were used to analyze the association between OBS and gout. RESULTS: Compared with the lowest OBS quartile group (Q1), the multivariate corrected odds ratio (OR) (95% confidence interval [C]) for the highest quartile of OBS (Q4) was 0.72 (0.52-1.00) (p = .13 for trend); furthermore, the RCS showed a negative linear relationship between OBS and gout (p-nonlinear = .606). CONCLUSION: In conclusion, the risk of gout is higher with high OBS. The prevalence of gout decreased with higher OBS. Diabetes may alter this negative correlation.

Gout: A Rapid Review of Presentation, Diagnosis and Management.

Gout is inflammatory arthritis caused by monosodium urate crystal deposition in articular and non-articular structures. Acute gout flares are often monoarticular/polyarticular involving lower extremity joints characteristically involving 1st metatarsophalangeal joint. However, gout flares can also be polyarticular, involving upper extremity joints, especially in patients with multiple comorbidities and contraindications to urate-lowering therapies (ULT). Risk factors exacerbating gout flares include obesity, high alcohol and purine-rich food consumption, and the use of diuretics. Diagnosis requires synovial fluid analysis with direct visualization of monosodium urate crystals. Acute flares are managed with steroids, non-steroidal anti-inflammatory drugs, or colchicine. Long-term management includes lifestyle modifications including a heavy emphasis on weight loss, avoidance of alcohol, purine-rich foods, and diuretics. ULT is indicated in patients with 2 or more gout flares/year, tophi, or radiographic evidence of gouty arthropathy. Although allopurinol is the first-line ULT agent, it does carry a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and patients harboring the HLA-B*5801 allele. Other ULT agents include febuxostat and probenecid. ULT is usually titrated to achieve goal serum uric acid (SUA) levels below 6 mg/dL. However, in patients with tophi, a lower SUA target of less than 5 mg/dL should be implemented for prompt urate crystal dissolution.

Concomitant septic and crystal arthropathy: a single-centre 10-year retrospective observational study in New Zealand.

AIM: To quantify and characterise patients with coexistent septic arthritis (SA) and crystal arthritis (CA) (SACA) in an emergency department (ED) setting. METHODS: A single-centre, retrospective, 10-year observational study was conducted at a major referral centre. Patients with a positive joint aspirate for CA or SA carried out in ED, were included. The Newman criteria were utilised to define SA. RESULTS: Of the 567 patients included in the final analysis, 427 had CA and 140 had a final diagnosis of SA. Twenty-three point six percent of patients diagnosed with SA had concomitant CA, while 7.2% of patients diagnosed with CA had concomitant SA. The greatest predisposing factors for SACA were previous history of gout, rheumatoid arthritis, being immunocompromised or having joint metalware. Synovial fluid (SF) white cell count (WCC) showed excellent predictive capability for joint infection with the area under the receiver operating characteristic curves (AUROCs) of 0.81 and 0.87 for SA and SACA respectively. The receiver operating characteristic curves (ROCs) reported a SF WCC cutoff of 32,000/mm3 allowed for 100% sensitivity and approximately 50% specificity. CONCLUSIONS: SACA remains a small but important sub-group of patients at risk of misdiagnosis of CA alone. SF WCC of 32,000/mm3 may be a better cutoff than the traditionally accepted 50,000/mm3, possibly warranting inpatient admission for investigation and management of presumed SA.

Imaging of Rheumatic Diseases Affecting the Lower Limb.

Imaging methods capable of detecting inflammation, such as MR imaging and ultrasound, are of paramount importance in rheumatic disease management, not only for diagnostic purposes but also for monitoring disease activity and treatment response. However, more advanced stages of arthritis, characterized by findings of cumulative structural damage, have traditionally been accomplished by radiographs and computed tomography. The purpose of this review is to provide an overview of imaging of some of the most prevalent inflammatory rheumatic diseases affecting the lower limb (osteoarthritis, rheumatoid arthritis, and gout) and up-to-date recommendations regarding imaging diagnostic workup.

Comparison of the therapeutic effects of febuxostat combined with a low-purine diet and allopurinol combined with a low-purine diet on the improvement of gout patients.

OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1ß), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 µmol/L ± 17.23 µmol/L vs. S198.32 µmol/L ± 18.34 µmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025). CONCLUSION: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.

Investigating gout flares: beyond a definition.

PURPOSE OF REVIEW: Gout flares are a paramount component of disease burden inflicted by gout onto the patient. Furthermore, they are included in the core domain set for long-term gout studies recognized by Outcome Measures in Rheumatology. Along with a validated classification criterion for gout, gout investigators have turned their efforts into defining and characterizing the gout flare. This brief review will summarize the efforts that have been done to define and characterize a gout flare in clinical studies. RECENT FINDINGS: Recent findings include a validated definition of a gout flare that has been utilized in novel clinical studies, use of technology to monitor for gout flares and their effects on patient life, and qualitative analyses into the disease burden that a patient undergoes. SUMMARY: Although guidelines for core outcome domains have been well established, there is question in methods of measuring and reporting gout flares in long-term trials. Furthermore, there is question as to the effectiveness of the agreed upon instruments' abilities to fully capture the disease burden experienced by patients with gout. A combination of outcome measurements including binary data (gout flare present or absent) along with a comprehensive measurement of disease burden over time would theoretically provide a more accurate description of the disease and serve as a basis for intervention development.

Creating machine learning models that interpretably link systemic inflammatory index, sex steroid hormones, and dietary antioxidants to identify gout using the SHAP (SHapley Additive exPlanations) method.

Background: The relationship between systemic inflammatory index (SII), sex steroid hormones, dietary antioxidants (DA), and gout has not been determined. We aim to develop a reliable and interpretable machine learning (ML) model that links SII, sex steroid hormones, and DA to gout identification. Methods: The dataset we used to study the relationship between SII, sex steroid hormones, DA, and gout was from the National Health and Nutrition Examination Survey (NHANES). Six ML models were developed to identify gout by SII, sex steroid hormones, and DA. The seven performance discriminative features of each model were summarized, and the eXtreme Gradient Boosting (XGBoost) model with the best overall performance was selected to identify gout. We used the SHapley Additive exPlanation (SHAP) method to explain the XGBoost model and its decision-making process. Results: An initial survey of 20,146 participants resulted in 8,550 being included in the study. Selecting the best performing XGBoost model associated with SII, sex steroid hormones, and DA to identify gout (male: AUC: 0.795, 95% CI: 0.746- 0.843, accuracy: 98.7%; female: AUC: 0.822, 95% CI: 0.754- 0.883, accuracy: 99.2%). In the male group, The SHAP values showed that the lower feature values of lutein + zeaxanthin (LZ), vitamin C (VitC), lycopene, zinc, total testosterone (TT), vitamin E (VitE), and vitamin A (VitA), the greater the positive effect on the model output. In the female group, SHAP values showed that lower feature values of E2, zinc, lycopene, LZ, TT, and selenium had a greater positive effect on model output. Conclusion: The interpretable XGBoost model demonstrated accuracy, efficiency, and robustness in identifying associations between SII, sex steroid hormones, DA, and gout in participants. Decreased TT in males and decreased E2 in females may be associated with gout, and increased DA intake and decreased SII may reduce the potential risk of gout.

Prednisolone Versus Colchicine for Acute Gout in Primary Care: statistical analysis plan for the pragmatic, multicenter, randomized, and double-blinded COPAGO non-inferiority trial.

BACKGROUND: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. STUDY DESIGN: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. STATISTICAL ANALYSIS PLAN: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes. DISCUSSION: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).

Development and validation of a self-updating gout register from electronic health records data.

OBJECTIVE: To develop an automatic gout register from electronic health records (EHRs) data. METHODS: We analysed the EHR of all patients >18 years old from a tertiary academic hospital (2013-2022) based on six criteria: International Classification of Diseases 10 gout diagnosis, urate-lowering therapy prescription, monosodium urate crystals in joint aspiration and gout-related terms in problem lists, clinical or imaging reports. We assessed the positive and negative predictive value (PPV and NPV) of the query by chart reviews. RESULTS: Of 2 110 902 outpatients and inpatients, 10 289 had at least one criterion for gout. The combination of joint aspiration OR diagnostic in the problem list OR≥2 other criteria created a register of 5138 patients, with a PPV of 92.4% (95% CI 88.5% to 95.0%) and an NPV of 94.3% (95% CI 91.9% to 96.0%). PPV and NPV were similar among outpatients and inpatients. Incidence was 2.9 per 1000 person-year and dropped by 30% from the COVID-19 pandemic onward. Patients with gout were on average 71.2 years old (SD 14.9), mainly male (76.5%), overweight (69.5%) and polymorbid (mean number of comorbidities of 3, IQR 1-5). More than half (57.4%) had received a urate-lowering treatment, 6.7% had a gout that led to a hospitalisation or ≥2 flares within a year and 32.9% received a rheumatology consultation. CONCLUSION: An automatic EHR-based gout register is feasible, valid and could be used to evaluate and improve gout management. Interestingly, the register uncovered a marked underdiagnosis or under-reporting of gout since the COVID-19 pandemic.

High-performance liquid chromatography (HPLC) as a means of assessing the presence of uric acid in archeological human remains: Challenges and future directions.

OBJECTIVES: This research aimed to replicate the Swinson, D., Snaith, J., Buckberry, J., & Brickley, M. (2010). High performance liquid chromatography (HPLC) in the investigation of gout in paleopathology. International Journal of Osteoarchaeology, 20, 135-143. https://doi.org/10.1002/oa.1009 method for detecting uric acid in archeological human remains to investigate gout in past populations and to improve the original High Performance Liquid Chromatography-ultraviolet (HPLC-UV) method by using HPLC-mass spectrometry (HPLC-MS), a more sensitive, compound-specific detection method. MATERIALS AND METHODS: We used reference samples of uric acid to create a dilution series to assess the limits of quantification and detection. Samples from individuals with and without gout lesions were taken from foot bones and ribs from the English cemeteries of Tanyard, Hickleton, Gloucester, and Lincoln. RESULTS: We could not replicate the results of Swinson and colleagues using HPLC-UV. Tests using a dilution series of uric acid showed HPLC-MS was approximately 100× more sensitive than HPLC-UV, with the additional benefit of being compound specific. A newly developed hydrophilic interaction chromatography (HILIC) method improved retention characteristics. Fourteen samples from eight individuals, five with skeletal lesions consistent with gout, were analyzed with the final method. None showed evidence of uric acid despite the newly developed method's improved sensitivity and specificity. DISCUSSION: The lack of detectable uric acid extracted from these samples suggests that (1) urate crystals were not present in any of the bone samples, regardless of gout status; (2) urate crystals did not survive these specific archeological conditions; or (3) the concentration of uric acid in our bone extracts was low, and thus larger samples would be required.

Gout and its management.

Gout is a common and treatable chronic disease of monosodium urate crystal deposition. It is experienced as extremely painful episodes of joint inflammation that impact all aspects of the person's life. This Clinical Perspectives article provides an update on gout diagnosis, medications and strategies to improve the quality of gout care.

Estimation of the spatial pattern of gout prevalence across China by wastewater-based epidemiology.

Gout is a metabolic arthritis caused by hyperuricemia. In recent years, the prevalence of gout has been increased significantly in China due to the improvement of the living standards, and gout has become another common metabolic disease following diabetes mellitus. Gout severely affects the health status and life quality of human. In order to monitor the near real-time prevalence of gout, a wastewater-based epidemiology (WBE) approach was carried out in 257 Chinese cities using febuxostat as the biomarker. Febuxostat in wastewater was measured by a LC-MS/MS method with satisfactory results of method validation. The average concentration of febuxostat in wastewater was 53.05 ± 31.76 ng/L, with the estimated per capita consumption of 124.40 ± 73.37 mg/day/1000 inhabitant. The calculated prevalence of febuxostat was 0.41 % ± 0.24 %, and the prevalence of gout was finally estimated to be 1.30 % ± 0.77 % (0.60 % to 2.11 %), which was nearly consistent with value of 1.10 % obtained from the Guideline for the diagnosis and management of hyperuricemia and gout in China (2019). The results indicated that the febuxostat-based WBE approach might be reasonable to assess the near real-time gout prevalence in China.

Middle Ear Tophi: A Case Series of Two Unusual Lesions and a Report of Facial Weakness and Review of the Literature.

OBJECTIVE: Tophaceous lesions of the middle ear from calcium pyrophosphate deposition disease (CPPD, or pseudogout) and gout are infrequently reported. Recognizing its characteristic findings will allow clinicians to accurately narrow the differential diagnosis of bony-appearing middle ear lesions and improve management. PATIENTS: Two consecutive cases of tophaceous middle ear lesions presenting to a tertiary care center between January 2021 and December 2021. Neither with previous rheumatologic history. INTERVENTIONS: Surgical excision of tophaceous middle ear lesions. MAIN OUTCOME MEASURE: Improvements in facial weakness and conductive hearing loss. RESULTS: The first case was a 66-year-old gentleman with progressive conductive loss, ipsilateral progressive facial weakness over years, and an opaque, irregular-appearing tympanic membrane anterior to the malleus found to have CPPD on surgical pathology, with immediate postoperative improvement of facial function. The second was a 75-year-old gentleman with progressive conductive loss and similar appearing tympanic membrane as case 1, previously diagnosed with tympanosclerosis, found to have gout on surgical pathology. In both cases, the CT showed a heterogenous, bony-appearing lesion in the middle ear, and both tophaceous lesions were a of gritty, chalky consistency intraoperatively. CONCLUSION: Tophaceous lesions of the middle ear are rare but have similar findings. Notably, the tympanic membrane can appear opaque and irregular, and the CT demonstrates a radiopaque, heterogeneous appearance. Facial weakness is an unusual finding. Specimens of suspected tophi must be sent to pathology without formalin for accurate diagnosis.

Describing calcium pyrophosphate deposition: undoing the tower of Babel!

PURPOSE OF REVIEW: In 1977, McCarty astutely observed, 'The variety of names suggested for the condition associated with deposits of calcium pyrophosphate dihydrate crystals is exceeded only by the variations of its clinical presentation'. Fast forward to 2024, a standardized nomenclature for calcium pyrophosphate deposition (CPPD) is still lacking. This review aims to delineate the challenges in characterizing CPPD through nomenclature and imaging. RECENT FINDINGS: Despite the effort of nomenclature standardization in 2011 by the EULAR, confusion persists in the literature and clinical practice, with pseudo-forms and obscure abbreviations. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) has launched a project to redefine CPPD nomenclature and formulate a user-friendly language for effective communication with patients and other stakeholders. Additionally, recent advancements in imaging, have shed light on various aspects of the disorder. SUMMARY: Almost 60 years from the first description of a clinical manifestation related to calcium pyrophosphate crystals, a common language describing the disorder is still lacking. A redefined CPPD nomenclature, together with lay-friendly terminology, would significantly contribute to the uniformity of CPPD research, enhance public understanding and awareness and improve doctor-patient communication and therefore disease outcomes. Imaging can provide deep insights into CPPD elements, promoting comprehension of this disorder.