Objective To determine which clinical, laboratory and imaging features most accurately distinguished gout from non-gout. Methods A cross-sectional study of consecutive rheumatology clinic patients with at least one swollen joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus aspirate microscopy by certified examiners in all patients. The sample was randomly divided into a model development (2/3) and test sample (1/3). Univariate and multivariate association between clinical features and MSU-defined gout was determined using logistic regression modelling. Shrinkage of regression weights was performed to prevent over-fitting of the final model. Latent class analysis was conducted to identify patterns of joint involvement. Results In total, 983 patients were included. Gout was present in 509 (52%). In the development sample (n=653), these features were selected for the final model (multivariate OR) joint erythema (2.13), difficulty walking (7.34), time to maximal pain < 24 hours (1.32), resolution by 2 weeks (3.58), tophus (7.29), MTP1 ever involved (2.30), location of currently tender joints: Other foot/ankle (2.28), MTP1 (2.82), serum urate level > 6 mg/dl (0.36 mmol/l) (3.35), ultrasound double contour sign (7.23), Xray erosion or cyst (2.49). The final model performed adequately in the test set with no evidence of misfit, high discrimination and predictive ability. MTP1 involvement was the most common joint pattern (39.4%) in gout cases. Conclusion Ten key discriminating features have been identified for further evaluation for new gout classification criteria. Ultrasound findings and degree of uricemia add discriminating value, and will significantly contribute to more accurate classification criteria.
Objectives To examine the performance of ultrasound for the diagnosis of gout using presence of monosodium urate (MSU) crystals as the gold standard. Methods We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multi-center observational cross-sectional study of consecutive subjects with at least one swollen joint who conceivably may have gout. All subjects underwent arthrocentesis; cases were subjects with MSU crystal confirmation. Rheumatologists or radiologists, blinded to the results of the MSU crystal analysis, performed ultrasound on one or more clinically affected joints. Ultrasound findings of interest were: double contour sign (DCS), tophus, and ‘snowstorm’ appearance. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated. Multivariable logistic regression models were used to examine factors associated with positive ultrasound results among subjects with gout. Results Ultrasound was performed in 824 subjects (416 cases and 408 controls). The sensitivity, specificity, PPV and NPV for the presence of any one of the features were 76.9%, 84.3%, 83.3% and 78.1% respectively. Sensitivity was higher among subjects with disease ≥2 years duration and among subjects with subcutaneous nodules on exam (suspected tophus). Associations with a positive ultrasound finding included suspected clinical tophus (odds ratio 4.77; 95% CI 2.23–10.21), any abnormal plain film radiograph (4.68; 2.68–8.17) and serum urate (1.31; 1.06–1.62). Conclusions Ultrasound features of MSU crystal deposition had high specificity and high positive predictive value but more limited sensitivity for early gout. The specificity remained high in subjects with early disease and without clinical signs of tophi.
Genetic and acquired factors are thought to be interrelated and imperative to estimate the risk and prognosis of oral squamous cell carcinoma (OSCC). HOX transcript antisense intergenic RNA ( HOTAIR) plays crucial roles in gene regulation and is regulated in a variety of cancers. Polymorphisms in HOTAIR have been recently linked to the predisposition to diverse malignancies. In the present study, we aimed to evaluate the influences of HOTAIR gene polymorphisms, combined with environmental triggers, on the susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms of the HOTAIR gene- rs920778, rs1899663, rs4759314, and rs12427129-were tested in 1,200 control participants and 907 patients with OSCC. We detected a significant association of rs1899663 with the risk of OSCC (adjusted odds ratio, 2.227; 95% confidence interval [95% CI], 1.197 to 4.146; P = 0.012) after adjustment for 3 potential confounders: smoking, betel quid chewing, and alcohol consumption. In further analyses where habitual exposure to each of 3 environmental factors was excluded, we found that, in addition to rs1899663, non-betel quid users who carried the polymorphic allele of rs920778 were more prone to develop OSCC than were those homozygous for wild-type allele (TC: odds ratio [OR], 1.472; 95% CI, 1.069 to 2.029; P = 0.018; TC+CC: OR, 1.448; 95% CI, 1.060 to 1.977; P = 0.020). Moreover, in exploring the relationship between HOTAIR gene polymorphisms and the clinical status of only patients with OSCC who were non-betel quid chewers (excluding the advanced clinical stage), we found that rs920778 and rs4759314 were correlated with the development of large-size tumors (OR, 1.891; 95% CI, 1.027 to 3.484; P = 0.04) and increased lymph node metastasis (OR, 4.140; 95% CI, 1.785 to 9.602; P = 0.001), respectively. Further functional assessments link rs920778 to the regulation of HOTAIR expression and epigenetic status. Our results reveal an interactive effect of HOTAIR gene polymorphisms and betel quid chewing on the development and progression of oral cancer.
Objective. To establish consensus for potential remission criteria to use in clinical trials of gout. Methods. Experts (n 5 88) in gout from multiple countries were invited to participate in a web-based questionnaire study. Three rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed by a discretechoice experiment using 1000Minds software. The exercises focused on identifying domains, definitions for each domain, and the timeframe over which remission should be defined.Results. There were 49 respondents (56% response) to the initial survey, with subsequent response rates ranging from 57% to 90%. Consensus was reached for the inclusion of serum urate (98% agreement), flares (96%), tophi (92%), pain (83%), and patient global assessment of disease activity (93%) as measurement domains in remission criteria. Consensus was also reached for domain definitions, including serum urate (<0.36 mm), pain (<2 on a 10-point scale), and patient global assessment (<2 on a 10-point scale), all of which should be measured at least twice over a set time interval. Consensus was not achieved in the Delphi exercise for the timeframe for remission, with equal responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment, there was a preference towards 12 months as a timeframe for remission. Conclusion. These consensus exercises have identified domains and provisional definitions for gout remission criteria. Based on the results of these exercises, preliminary remission criteria are proposed with domains of serum urate, acute flares, tophus, pain, and patient global assessment. These preliminary criteria now require testing in clinical data sets.
Existing classification criteria for gout have sensitivity of over 80% in early and established disease but currently available criteria that do not require synovial fluid analysis have inadequate specificity especially later in the disease. Classification criteria for gout with better specificity are required, although the findings should be cautiously applied to non-rheumatology clinic populations.
Down-regulation of Growth arrest-specific 5 (GAS5) is correlated with enhanced cell proliferation and poorer prognosis of prostate cancer. We aimed to investigate the effect of variant rs145204276 of GAS5 on the prostate cancer susceptibility and clinicopathologic characteristics. In this study, 579 prostate cancer patients who underwent robot-assisted radical prostatectomy and 579 healthy controls were included. The frequency of the allele del of rs145204276 were compared between the patients and the controls to evaluate the impact of tumor susceptibility and the correlation of clinicopathological variables. The results shown that patients who carries genotype ins/del or del/del at SNP rs145204276 showed decreased risk of pathological lymph node metastasis disease (OR=0.545, p=0.043) and risk of seminal vesicle invasion (OR=0.632, p=0.022) comparing to with genotype ins/ins. In the subgroup analysis of age, more significant risk reduction effects were noted over lymph node metastasis disease (OR=0.426, p=0.032) and lymphovascular invasion (OR=0.521, p=0.025). In conclusion, the rs145204276 polymorphic genotype of GAS5 can predict the risk of lymph node metastasis. This is the first study to report the correlation between GAS5 gene polymorphism and prostate cancer prognosis.
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