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1.
J Craniovertebr Junction Spine ; 15(2): 133-140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957764

RESUMO

Background: Spinal gout, a rare and often underdiagnosed condition, significantly impacts patients' quality of life. Therefore, the aim of the research is to analyze cases of spinal gout, including clinical features, anatomical location of spinal gout, laboratory studies, imaging studies, treatment choices, and outcomes from various cases of spinal gout. Methods: The author conducted a systematic literature search in the PUBMED and Science Direct databases from 2013 to 2023. We included clinical case presentations of spinal cases in adults, published in English. The three researchers independently reviewed the title and abstract of each article, and any differences in opinions were resolved through consensus. The extracted data were subsequently analyzed descriptively. Results: A total of 88 cases of spinal gout were obtained and studied. Out of the total reviewed cases of spinal gout, 89.77% of the subjects were male, with an average age of 51.9 years (age range 16-87 years). Common symptoms include back/neck pain (78.41%) and lower extremity weakness (37.50%). The lumbar spine is the most frequently affected region (62.50%), diagnosed primarily through magnetic resonance imaging (MRI) scans. Surgery, performed in 61.36% of cases, commonly involves decompressive laminectomy. Posttreatment, symptoms resolve in 87.50% of cases. Conclusion: Cases of spinal gout present with a variety of symptoms, including back pain and weakness. Diagnosis typically involves an MRI examination and synovial fluid analysis for confirmation. Treatment varies and includes medication therapy and surgical interventions. A deeper understanding of these cases can assist healthcare practitioners in the management and diagnosis of spinal gout cases.

2.
Best Pract Res Clin Rheumatol ; : 101967, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38951047

RESUMO

The explosion in Mendelian randomization (MR) publications is hard to ignore and shows no signs of slowing. Clinician readers, who may not be familiar with jargon-ridden methods, are expected to discern the good from the many low-quality studies that make overconfident claims of causality or stretch the plausibility of what MR can investigate. We aim to equip readers with foundational concepts, contextualized using examples in rheumatology, to appraise the many MR papers that are or will appear in their journals. We highlight the importance of assessing whether exposures are under plausibly specific genetic influence, whether the hypothesized causal pathways make biological sense, and whether results stand up to replication and use of control outcomes. Quality of research can vary substantially using MR as with any design, and all methods have inherent limitations. MR studies have provided and can still contribute valuable insights in the context of evidence triangulation.

3.
Eur Radiol Exp ; 8(1): 69, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38862843

RESUMO

BACKGROUND: Dual-energy computed tomography (DECT) is useful for detecting gouty tophi. While iodinated contrast media (ICM) might enhance the detection of monosodium urate crystals (MSU), higher iodine concentrations hamper their detection. Calculating virtual noncontrast (VNC) images might improve the detection of enhancing tophi. The aim of this study was to evaluate MSU detection with VNC images from DECT acquisitions in phantoms, compared against the results with standard DECT reconstructions. METHODS: A grid-like and a biophantom with 25 suspensions containing different concentrations of ICM (0 to 2%) and MSU (0 to 50%) were scanned with sequential single-source DECT using an ascending order of tube current time product at 80 kVp (16.5-220 mAs) and 135 kVp (2.75-19.25 mAs). VNC images were equivalently reconstructed at 80 and 135 kVp. Two-material decomposition analysis for MSU detection was applied for the VNC and conventional CT images. MSU detection and attenuation values were compared in both modalities. RESULTS: For 0, 0.25, 0.5, 1, and 2% ICM, the average detection indices (DIs) for all MSU concentrations (35-50%) with VNC postprocessing were respectively 25.2, 36.6, 30.9, 38.9, and 45.8% for the grid phantom scans and 11.7, 9.4, 5.5, 24.0, and 25.0% for the porcine phantom scans. In the conventional CT image group, the average DIs were respectively 35.4, 54.3, 45.4, 1.0, and 0.0% for the grid phantom and 19.4, 17.9, 3.0, 0.0, and 0.0% for the porcine phantom scans. CONCLUSIONS: VNC effectively reduces the suppression of information caused by high concentrations of ICM, thereby improving the detection of MSU. RELEVANCE STATEMENT: Contrast-enhanced DECT alone may suffice for diagnosing gout without a native acquisition. KEY POINTS: • Highly concentrated contrast media hinders monosodium urate crystal detection in CT imaging • Virtual noncontrast imaging redetects monosodium urate crystals in high-iodinated contrast media concentrations. • Contrast-enhanced DECT alone may suffice for diagnosing gout without a native acquisition.


Assuntos
Meios de Contraste , Gota , Imagens de Fantasmas , Tomografia Computadorizada por Raios X , Ácido Úrico , Tomografia Computadorizada por Raios X/métodos , Ácido Úrico/análise , Gota/diagnóstico por imagem , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Animais , Suínos
4.
Clin Case Rep ; 12(6): e9033, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38868124

RESUMO

Hyperuricemic patients (≥7.8 mg/dL) can develop polyarticular tophaceous gout from intermittent arthritis if untreated. Acute flares and tophi development can be avoided by lowering blood urate levels with xanthine oxidase inhibitors.

5.
Clin Cardiol ; 47(6): e24297, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873862

RESUMO

BACKGROUND: Elevated serum uric acid (sUA) is associated with heart failure (HF). HYPOTHESIS: Urate-lowering therapy (ULT) in HF is associated with lower risk of HF hospitalization (hHF) and mortality. METHODS: Data on patients with HF and gout or hyperuricemia in the Clinical Practice Research Datalink database linked to the Hospital Episode Statistics and the Office for National Statistics in the United Kingdom were analyzed. Risks of hHF and all-cause mortality or cardiovascular-related mortality by ULT exposure (ULT initiated within ≤6 months of gout or hyperuricemia diagnosis) were analyzed in a propensity score-matched cohort using adjusted Cox proportional hazards regression models. RESULTS: Of 2174 propensity score-matched pairs, patients were predominantly male, aged >70 years, with mean ± standard deviation sUA 9.3 ± 1.8 (ULT-exposed) and 9.4 ± 1.9 mg/dL (ULT-unexposed). At 5 years, ULT-exposed patients had a 43% lower risk of hHF or all-cause mortality (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.51-0.65) and a 19% lower risk of hHF or cardiovascular-related mortality (adjusted HR: 0.81; 95% CI: 0.71-0.92) versus no ULT exposure. CONCLUSION: ULT was associated with reduced risk of adverse clinical outcomes in patients with HF and gout or hyperuricemia over 5 years.


Assuntos
Supressores da Gota , Insuficiência Cardíaca , Hiperuricemia , Ácido Úrico , Humanos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Hiperuricemia/complicações , Masculino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Feminino , Idoso , Reino Unido/epidemiologia , Estudos Retrospectivos , Ácido Úrico/sangue , Supressores da Gota/uso terapêutico , Fatores de Risco , Pessoa de Meia-Idade , Biomarcadores/sangue , Resultado do Tratamento , Gota/tratamento farmacológico , Gota/sangue , Gota/complicações , Gota/epidemiologia , Fatores de Tempo , Bases de Dados Factuais , Seguimentos
6.
Bioorg Chem ; 150: 107558, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38878755

RESUMO

Lathyrane-based diterpenoid is one of the critical bioactive elements of Euphorbia lathyris L., a widely used traditional Chinese medicine for the treatment of inflammation and infection. In this study, we introduced and evaluated seven synthetic or natural lathyrane-based diterpenoids with the same core structure but notable structural variations at specific positions, for their anti-inflammatory and gout-alleviating properties. There was no significant cytotoxicity below 10 µM among the initial test of the cell counting kit 8 of the seven candidate derivatives (compounds 13 to 19) in this work. Furthermore, maintaining the acyloxy group at 15-C position and the strongly hydrophobic aryl structure at 3-C and 5-C positions, compounds 15 (Euphorbia factor L3, EFL3) and 17 strikingly inhibited the production of IL-1ß related to the actuation of the inflammasome in our study. The ELISA assay indicated that the anti-inflammatory effects of EFL3 were better associated with MSU stimulation than other second-line pathways triggered by inflammasome. Further examinations on the acute paw gout model in C57BL/6 mice showed that EFL3 had a significantly inflammatory retarding effect by intraperitoneal injection. It decreased swelling volume as well as the cleavage and activation of local IL-1ß and casepas-1 in the paw. To conclude, our findings reveal several potential key structure-activity relationships that govern the anti-inflammatory effects of lathyrane-type diterpenoids, the dispensable acyl group at the 15-C position, the importance of maintaining the spatial structure of the B-ring, and the potential importance of hydrophobic substituents at the 3-C position. These insights may provide guidance for the structural design of lathyrane-type agents in the future; furthermore, we found that the lathyrane-based diterpenoid EFL3 is a potential agent for gout that is expected to provide a novel therapeutic strategy for inflammation intervention.

7.
Diagn Cytopathol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38881518

RESUMO

We report two patients with pancreatic tophaceous gout diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of presumed cystic mass lesions. The first case involved a patient who had a recent episode of acute pancreatitis 6 months prior, with subsequent imaging concerning for a pseudocyst or mass lesion. The second case involved a patient with epigastric pain associated with a pancreatic head cystic mass and an erroneous original diagnosis of a mucinous pancreatic neoplasm on EUS-FNA. Diff-Quik stained direct smears on fresh material obtained from EUS-FNA of the lesions showed chalky debris with needle shaped negatively birefringent crystals consistent with gout. For the first case, the chalky material was not present on the H&E stained paraffin embedded formalin fixed cellblock slides. The importance of inclusion of cytologic specimen preparations to examine monosodium urate crystals is emphasized.

8.
BMC Surg ; 24(1): 186, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877436

RESUMO

BACKGROUND/PURPOSE: Patients with gout are at risk for increased serum uric acid (SUA) levels and gout attacks in the short term after undergoing bariatric surgery, and the purpose of this study was to evaluate the benefits of short-term treatment with uric acid-lowering medication after bariatric surgery for the control of gout attacks and SUA levels in patients with gout. METHODS: 71 patients who underwent SG from January 2020 to December 2022 were prospectively included. These patients were diagnosed with hyperuricemia before surgery and had a history of gout attacks. Patients were classified into a drug-treatment group (DTG, n = 32) and a non-drug-treatment group (NDTG, n = 39) according to whether they took uric acid-lowering medication after surgery. Changes in the number of gout attacks, body mass index (BMI), and SUA levels at 1 week, 1 month, 3 months, and 6 months after bariatric surgery were measured in both groups. RESULTS: In the DTG, 22 patients (68.8%) experienced an increase in SUA within 1 week, 3 patients (9.4%) had an acute attack of gout within the first month, and no patients had a gout attack thereafter. In the NDTG, 35 patients (89.7%) experienced an increase in SUA within 1 week, 7 patients (17.9%) had an acute gout attack within the first month, and 4 patients (10.3%) experienced gout attacks between month 1 and month 3 postoperatively. Both groups were free of gout attacks between the 3rd and 6th postoperative month and showed a significant decrease in SUA and BMI by the sixth month. CONCLUSION: In patients with gout, continued use of uric acid-lowering medication after bariatric surgery is beneficial in reducing the number of gout attacks and the risk of rising SUA.


Assuntos
Cirurgia Bariátrica , Supressores da Gota , Gota , Ácido Úrico , Humanos , Gota/sangue , Cirurgia Bariátrica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Ácido Úrico/sangue , Supressores da Gota/uso terapêutico , Adulto , Estudos Prospectivos , Hiperuricemia/sangue , Hiperuricemia/etiologia , Índice de Massa Corporal , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
9.
Trials ; 25(1): 404, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907256

RESUMO

BACKGROUND: Gout remains a leading cause of inflammatory arthritis worldwide, and the main risk factor for gout is persistent hyperuricemia. The clinical management of gout is mostly drug-based, and other treatment options are often ignored. This research proposal will explore whether exergames combined with ice therapy can help patients with gout to lose weight, relieve pain, improve the range of movement, improve quality of life, decrease uric acid level, decrease kinesiophobia and improve mental health of patients with gout. METHODS: This experiment will use a two-arm randomized controlled design. The study setting is at the Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia (USM). Obese patients with gout (N = 30) will be randomly assigned to the control group (receive an exergames intervention) and intervention group (receive an exergames intervention combined with ice therapy). The outcomes measurement will be conducted before (baseline) and after intervention (4 weeks). Then, it will be followed up at 12 weeks. DISCUSSION: To our knowledge, no study has investigated the effect of exergames and ice therapy among gout patients. This study is expected to demonstrate that exercise rehabilitation facilitated by exergames with ice therapy is more effective in gout management compared to a conventional rehabilitation intervention. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300070029). Registered on 31 March 2023.


Assuntos
Terapia por Exercício , Gota , Obesidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Jogos de Vídeo , Humanos , Gota/complicações , Gota/terapia , Terapia por Exercício/métodos , Obesidade/complicações , Obesidade/terapia , Obesidade/diagnóstico , Obesidade/fisiopatologia , Resultado do Tratamento , Qualidade de Vida , Crioterapia/métodos , Malásia , Masculino , Pessoa de Meia-Idade , Terapia Combinada , Feminino , Adulto , Ácido Úrico/sangue , Redução de Peso
10.
Poult Sci ; 103(8): 103869, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38909510

RESUMO

Goose astrovirus (GoAstV) is an emerging avian pathogen that induces gout in goslings with a mortality of up to 50%. Organ damage caused by GoAstV infection was considered the cause of gout, but it is still unclear whether other factors are involved. Human and murine studies have linked the gut microbiome-derived urate and gout, thus we hypothesized that gut microbiome may also play an important role in gout induced by GoAstV infection. This study tested the pathogenicity of our isolated GoAstV genotype 2 strain on goslings, while the appearance of clinical signs, histopathological changes, viral distribution and the blood level of cytokines were monitored for 18 d postinfection (dpi). The dynamics in the gut microbiome were profiled by 16S sequencing and then correlated with GoAstV infection. Results showed that this study successfully developed an experimental infection model for studying the pathogenicity of the GoAstV infection which induces typical symptoms of gout. GoAstV infection significantly altered the gut microbiome of goslings with the enrichment of potential proinflammatory bacteria and depletion of beneficial bacteria that can produce short-chain fatty acids. More importantly, the microbial pathway involved in urate production was significantly increased in goslings infected with GoAstV, suggesting that gut microbiome-derived urate may also contribute to the gout symptoms. Overall, this study demonstrated the role of gut microbiome in the pathogenesis of GoAstV infection, highlighting the potential of gut microbiome-based therapeutics against gout symptoms.

11.
Korean J Intern Med ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910514

RESUMO

Background/Aims: The Gout Impact Scale (GIS), a part of the Gout Assessment Questionnaire 2.0, is used to measure gout-specific health-related quality of life (HRQOL). Although several studies have been conducted on the factors affecting the HRQOL of patients with gout, few have focused on lifestyle factors. This study aimed to investigate the correlation between lifestyle habits and HRQOL using the GIS in patients with gout. Methods: We used data from the Urate-Lowering TheRApy in Gout (ULTRA) registry, a prospective cohort of Korean patients with gout treated at multiple centers nationwide. The patients were aged ≥18 years and met the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria. They were asked to complete a GIS and questions regarding their lifestyle habits at enrollment. Results: The study included 232 patients. 'Gout concern overall' scores in the GIS were significantly lower in patients who exercised more frequently and consumed soft drinks and meat less, and 'well-being during attack' scores were significantly lower in patients who consumed vegetables and exercised more frequently. The frequency of vegetable consumption had a negative linear relationship with the 'well-being during attack' and 'gout concern during attack' scores (p = 0.01, p = 0.001, respectively). The frequency of exercise had a negative linear relationship with the 'gout concern overall' and 'gout concern during attack' scores (p = 0.04 and p = 0.002, respectively). Conclusions: Patients with gout who frequently consumed vegetables and exercised regularly experienced less impact of gout, exhibiting a better GIS that represented HRQOL.

12.
J Control Release ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906421

RESUMO

Improving the activity of uricase and lowering its immunogenicity remain significant challenges in the enzyme replacement management of hyperuricemia and related inflammatory diseases. Herein, an immunogenicity-masking strategy based on engineered red blood cells (RBCs) was developed for effective uricase delivery against both hyperuricemia and gout. The dynamic membrane of RBCs enabled high resistance to protease inactivation and hydrogen peroxide accumulation. Benefiting from these advantages, a single infusion of RBC-loaded uricase (Uri@RBC) performed prolonged blood circulation and sustained hyperuricemia management. Importantly, RBCs masked the immunogenicity of uricase, leading to the maintenance of UA-lowering performance after repeated infusion through reduced antibody-mediated macrophage clearance. In an acute gout model, Uri@RBC profoundly alleviated joint edema and inflammation with minimal systemic toxicity. This study supports the employment of immunogenicity-masking tools for efficient and safe enzyme delivery, and this strategy may be leveraged to improve the usefulness of enzyme replacement therapies for managing a wide range of inflammatory diseases.

13.
Am J Kidney Dis ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906504

RESUMO

RATIONALE & OBJECTIVE: We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). STUDY DESIGN: Prespecified sub cohort analysis of a randomized controlled trial. SETTING: & Participants: A sub study of the STOP Gout trial in participants with CKD. CKD was defined as an eGFR 30-59 mL/min/1.73 m2 at baseline. EXPOSURE: Trial participants with CKD and gout and serum urate (sUA) concentration ≥6.8 mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal sUA of <6.0 mg/dl (<5.0 mg/dl with tophi) (Phase 1) and maintained during weeks 25-48 (Phase 2). Gout flare was assessed between weeks 49-72 (Phase 3). OUTCOME: Gout flare between weeks 49-72 (Phase 3) was the primary outcome. Secondary outcomes included sUA goal achievement and ULT dosing at end of Phase 2, and serious adverse events (SAEs). ANALYTICAL APPROACH: Outcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm. RESULTS: 351 of 940 participants (37.3%) had CKD; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; p=0.02) despite similar attainment of sUA goal (79% vs. 81%; p=0.6) by the end of Phase 2. Acute kidney injury (AKI) was more common in participants with stage 3 CKD randomized to allopurinol compared to febuxostat. LIMITATIONS: Limited power to assess infrequent safety events, largely male, older population. CONCLUSIONS: Allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen.

14.
Med ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38834074

RESUMO

BACKGROUND: This study aims to estimate the burden, trends, forecasts, and disparities of early musculoskeletal (MSK) disorders among individuals ages 15 to 39 years. METHODS: The global prevalence, years lived with disabilities (YLDs), disability-adjusted life years (DALYs), projection, and inequality were estimated for early MSK diseases, including rheumatoid arthritis (RA), osteoarthritis (OA), low back pain (LBP), neck pain (NP), gout, and other MSK diseases (OMSKDs). FINDINGS: More adolescents and young adults were expected to develop MSK disorders by 2050. Across five age groups, the rates of prevalence, YLDs, and DALYs for RA, NP, LBP, gout, and OMSKDs sharply increased from ages 15-19 to 35-39; however, these were negligible for OA before age 30 but increased notably at ages 30-34, rising at least 6-fold by 35-39. The disease burden of gout, LBP, and OA attributable to high BMI and gout attributable to kidney dysfunction increased, while the contribution of smoking to LBP and RA and occupational ergonomic factors to LBP decreased. Between 1990 and 2019, the slope index of inequality increased for six MSK disorders, and the relative concentration index increased for gout, NP, OA, and OMSKDs but decreased for LBP and RA. CONCLUSIONS: Multilevel interventions should be initiated to prevent disease burden related to RA, NP, LBP, gout, and OMSKDs among individuals ages 15-19 and to OA among individuals ages 30-34 to tightly control high BMI and kidney dysfunction. FUNDING: The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation. The project is funded by the Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

15.
Rheumatol Ther ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836994

RESUMO

INTRODUCTION: Gout, a common comorbidity of chronic kidney disease (CKD), is associated with high morbidity and healthcare utilization. However, a large proportion of gout remains undermanaged or untreated which may lead to worse patient outcomes and greater healthcare costs. This study estimates the present and future health and economic burden of controlled and uncontrolled gout in a virtual United States (US) CKD population. METHODS: A validated microsimulation model was used to project the burden of gout in patients with CKD in the USA through 2035. Databases were utilized to build a virtual CKD population of "individuals" with controlled or uncontrolled gout. Modelling assumptions were made on the basis of the literature, which was sparse in some cases. Health and economic outcomes with the current care (baseline) scenario were evaluated, along with potential benefits of urate-lowering intervention scenarios. RESULTS: The prevalence of comorbid gout and CKD in the USA was projected to increase by 29%, from 7.9 million in 2023 to 9.6 million in 2035 in the baseline scenario. Gout flares, tophi, and comorbidity development were also projected to increase markedly through 2035, with the economic burden of gout in the CKD population subsequently increasing from $38.9 billion in 2023 to $47.3 billion in 2035. An increased use of oral urate-lowering therapies in undermanaged patients, and pegloticase use in patients refractory to oral urate-lowering therapies were also project to result in 744,000 and 353,000 fewer uncontrolled gout cases, respectively, by 2035. Marked reductions in complications and costs ensued. CONCLUSIONS: This study projected a substantial increase in comorbid gout and CKD. However, improved use of urate-lowering interventions could mitigate this growth and reduce the health and economic burdens of gout.

16.
Arthritis Res Ther ; 26(1): 114, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831441

RESUMO

BACKGROUND: Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis. METHODS: The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout. RESULTS: We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A. CONCLUSION: According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Gota , Análise da Randomização Mendeliana , Locos de Características Quantitativas , Análise de Célula Única , Gota/genética , Humanos , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla/métodos , Predisposição Genética para Doença/genética , Locos de Características Quantitativas/genética , Análise de Célula Única/métodos , Metilação de DNA/genética , Polimorfismo de Nucleotídeo Único , Mapas de Interação de Proteínas/genética , Álcool Desidrogenase
17.
Rheum Dis Clin North Am ; 50(3): 463-482, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38942580

RESUMO

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.


Assuntos
Artrite Reumatoide , Gota , Extremidade Inferior , Imageamento por Ressonância Magnética , Doenças Reumáticas , Humanos , Imageamento por Ressonância Magnética/métodos , Extremidade Inferior/diagnóstico por imagem , Gota/diagnóstico por imagem , Gota/diagnóstico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/diagnóstico , Doenças Reumáticas/diagnóstico por imagem , Doenças Reumáticas/diagnóstico , Tomografia Computadorizada por Raios X , Ultrassonografia/métodos , Osteoartrite/diagnóstico por imagem , Osteoartrite/diagnóstico
18.
Artigo em Inglês | MEDLINE | ID: mdl-38895877

RESUMO

OBJECTIVE: To develop a machine learning-based prediction model for identifying hyperuricemic participants at risk of developing gout. METHODS: A retrospective nationwide Israeli cohort study used the Clalit Health Insurance database of 473 124 individuals to identify adults 18 years or older with at least two serum urate measurements exceeding 6.8 mg/dl between January 2007 and December 2022. Patients with a prior gout diagnosis or on gout medications were excluded. Patients' demographic characteristics, community and hospital diagnoses, routine medication prescriptions and laboratory results were used to train a risk prediction model. A machine learning model, XGBoost, was developed to predict the risk of gout. Feature selection methods were used to identify relevant variables. The model's performance was evaluated using the receiver operating characteristic area under the curve (ROC AUC) and precision-recall AUC. The primary outcome was the diagnosis of gout among hyperuricemic patients. RESULTS: Among the 301 385 participants with hyperuricemia included in the analysis, 15 055 (5%) were diagnosed with gout. The XGBoost model had a ROC-AUC of 0.781 (95% CI 0.78-0.784) and precision-recall AUC of 0.208 (95% CI 0.195-0.22). The most significant variables associated with gout diagnosis were serum uric acid levels, age, hyperlipidemia, non-steroidal anti-inflammatory drugs and diuretic purchases. A compact model using only these five variables yielded a ROC-AUC of 0.714 (95% CI 0.706-0.723) and a negative predictive value (NPV) of 95%. CONCLUSIONS: The findings of this cohort study suggest that a machine learning-based prediction model had relatively good performance and high NPV for identifying hyperuricemic participants at risk of developing gout.

19.
Front Endocrinol (Lausanne) ; 15: 1367621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841306

RESUMO

Background: Although there is solid epidemiological evidence supporting the connection between hypertension and gout, little has been said about the relationship between diastolic and systolic blood pressure and gout, the causal relationship and direction associated are uncertain, so we aim to research the causal relationship between diastolic and systolic blood pressure and gout. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect between 2 blood pressure phenotypes (including diastolic blood pressure and systolic blood pressure) and 5 gout phenotypes (including gout, drug-induced gout, idiopathic gout, unspecified gout, and strictly defined gout) using genome-wide association study statistics. The inverse variance weighting method was used to generate the main results, while sensitivity analyses using MR-Egger, weighted median, Cochran's Q test, Egger intercept test, and leave-one-out analysis, were performed to assess the stability and reliability of the results. Results: After the screening, we found a causal relationship between diastolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout, and a causal relationship between systolic blood pressure and gout, idiopathic gout, unspecified gout, and strictly defined gout. Conclusion: From a genetic predisposition, controlling blood pressure may reduce the risk of gout.


Assuntos
Pressão Sanguínea , Estudo de Associação Genômica Ampla , Gota , Hipertensão , Análise da Randomização Mendeliana , Humanos , Gota/genética , Gota/epidemiologia , Pressão Sanguínea/genética , Hipertensão/genética , Hipertensão/epidemiologia , Predisposição Genética para Doença , Diástole , Sístole , Polimorfismo de Nucleotídeo Único , Fatores de Risco
20.
Rheumatol Adv Pract ; 8(3): rkae069, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855627

RESUMO

Objectives: PsA and gout are two prevalent rheumatic diseases, that can be associated as part of a rheumatism known as 'Psout'. Both conditions are associated with cardiovascular (CV) risk, thus their co-occurrence could have significant implications for the management of CV risks and patient care. This study aimed to determine the prevalence of gout within a PsA patient cohort and, consequently, to identify factors associated with this pathological association. Methods: This is an observational, descriptive, cross-sectional, single-center study, including patients diagnosed with PsA. Demographic, clinical, biological and imaging data were collected. We identified the proportion of patients simultaneously affected by PsA and gout and compared characteristics between those with and without gout. Results: The prevalence of gout among PSA patients was 9.8% (12/122), with a prevalence of 23% for asymptomatic hyperuricemia and 7.4% presenting with specific US signs of gout. Significant associated factors in the univariate analysis included weight, hypertension, diabetes, certain medications (diuretics, aspirin, lipid-lowering agents), impaired renal function, elevated fasting blood glucose, lipid abnormalities and specific US signs of gout. Conclusion: Our study has described the existence of patients simultaneously affected by PsA and gout ('Psout'). Performing joint US along with uric acid level measurements in PsA patients can enable personalized therapeutic care.

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