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Concept: Gout

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BACKGROUND: Research involving more representative samples is needed to extend our understanding of the broader impact of obesity in hip or knee joint disease (arthritis and OA) beyond clinical settings. Although population-based research has been conducted in the United States, how these findings translate to other countries is unclear. Using a national approach, this study explored associations between obesity and the burden of hip and knee joint disease in Australia (in terms of prevalence, pain, stiffness, function, Health-Related Quality of Life (HRQoL) and disease severity). METHODS: A random sample of 5000 Australians (>=39 years) from the federal electoral roll was invited to complete a mailed questionnaire to identify doctor-diagnosed hip arthritis, hip OA, knee arthritis and knee OA and evaluate the burden of these conditions. Validated questionnaires included the WOMAC Index, Assessment of Quality of Life instrument and Multi-Attribute Prioritisation Tool. Body Mass Index (BMI) was classified into underweight/normal weight (<=24.99 kg/m2), overweight (25--29.99) or obese (>=30). Multiple logistic regression was used to estimate odds of arthritis and OA, with demographic and socioeconomic variables included in the models. Associations between BMI and other variables were investigated using analysis of covariance, with adjustment for age and sex. RESULTS: Data were available from 1,157 participants (23%). Overweight participants had increased odds of knee arthritis (adjusted OR (AOR) 1.87, 95%CI 1.14-3.07) and knee OA (AOR 2.11, 95%CI 1.07-4.15). Obesity was associated with higher prevalence of hip arthritis (AOR 2.18, 95%CI 1.17-4.06), knee arthritis (AOR 5.47, 95%CI 3.35-8.95) and knee OA (AOR 7.35, 95%CI 3.85-14.02). Of those with arthritis or OA, obese individuals reported more pain (for hip arthritis, hip OA and knee OA), greater stiffness (for hip arthritis, knee arthritis and knee OA), worse function (all diagnoses), lower HRQoL (for hip arthritis and hip OA) and greater disease severity (all diagnoses). CONCLUSIONS: This national study has demonstrated that the odds of arthritis and OA was up to 7 times higher for obese individuals, compared with those classified as underweight/normal weight. Concurrent obesity and joint disease had a marked impact on several key aspects of wellbeing, highlighting the need for public health interventions.

Concepts: Cancer, Obesity, Quality of life, Osteoarthritis, Body mass index, Gout, Waist-hip ratio, Body shape

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Objective To prospectively examine the relation between the Dietary Approaches to Stop Hypertension (DASH) and Western diets and risk of gout (ie, the clinical endpoint of hyperuricemia) in men.Design Prospective cohort study.Setting The Health Professionals Follow-up Study.Participants 44 444 men with no history of gout at baseline. Using validated food frequency questionnaires, each participant was assigned a DASH dietary pattern score (based on high intake of fruits, vegetables, nuts and legumes, low fat dairy products, and whole grains, and low intake of sodium, sweetened beverages, and red and processed meats) and a Western dietary pattern score (based on high intake of red and processed meats, French fries, refined grains, sweets, and desserts).Main outcome measure Risk of incident gout meeting the preliminary American College of Rheumatology survey criteria for gout, adjusting for potential confounders, including age, body mass index, hypertension, diuretic use, and alcohol intake.Results During 26 years of follow-up, 1731 confirmed cases of incident gout were documented. A higher DASH dietary pattern score was associated with a lower risk for gout (adjusted relative risk for extreme fifths 0.68, 95% confidence interval 0.57 to 0.80, P value for trend <0.001). In contrast, a higher Western dietary pattern score was associated with an increased risk for gout (1.42, 1.16 to 1.74, P=0.005).Conclusion The DASH diet is associated with a lower risk of gout, suggesting that its effect of lowering uric acid levels in individuals with hyperuricemia translates to a lower risk of gout. Conversely, the Western diet is associated with a higher risk of gout. The DASH diet may provide an attractive preventive dietary approach for men at risk of gout.

Concepts: Nutrition, Metabolic syndrome, Gout, Diuretic, Uric acid, Hyperuricemia, Diets, Fast food

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Dietary fructose is implicated in metabolic syndrome, but intervention studies are confounded by positive caloric balance, changes in adiposity, or artifactually high amounts. This study determined whether isocaloric substitution of starch for sugar would improve metabolic parameters in Latino (n = 27) and African-American (n = 16) children with obesity and metabolic syndrome.

Concepts: Nutrition, Enzyme, Glucose, Obesity, Metabolic syndrome, Gout, Fructose, Sucrose

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Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans.

Concepts: Metabolism, Enzyme, Triglyceride, Gout, Fructose, Uric acid, Hyperuricemia, Xanthine oxidase

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Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1β (IL-1β) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases β-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1β in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout.

Concepts: Immune system, Inflammation, White blood cell, Monocyte, Bacteria, Infection, Macrophage, Gout

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More than 14 years of clinical practice in rheumatology led the author to discover the prognostic role of anti-citrullinated protein antibody (ACPA) as well as the erosions found by MRI, in detecting the RA patients resulting in establishing a new set of criteria by revising the 1987 ACR classification-Iran Criteria for Rheumatoid Arthritis. Medical records of 243 patients at the outpatient Rheumatology Clinic of the author (private sector) were reviewed for the data on the criteria of the 1987 ACR, 2010 ACR/European League against Rheumatism (EULAR), and Iran Criteria for RA. In addition to modifying the 1987 ACR classification, Iran Criteria for RA adds some additional information to the ACR criteria (including ACPA and bony erosions detected by MRI), and any patient who satisfies 6 out of 12 points is considered as a definite RA patient. Sensitivity of the three classifications was calculated considering the clinical diagnosis by a single rheumatologist as the gold standard. A total of 63 male and 180 female patients with a mean follow-up duration of 28.24 ± 50.19 months were considered. Mean age at diagnosis and mean disease duration were 49.16 ± 15.38 years and 7.04 ± 6.87 months, respectively. The sensitivity for Iran Criteria for RA, 1987 ACR classification, and 2010 ACR/EULAR criteria were calculated as 98.4, 59.7, and 66.3%, respectively. Comparing Iran Criteria for RA with ACR and ACR/EULAR criteria, it was concluded that our newly introduced criteria is a more sensitive instrument in determining RA patients in the early stages of the disease.

Concepts: Medical terms, Rheumatoid arthritis, Rheumatology, Vasculitis, Gout, Arthritis, Rheumatism, European League Against Rheumatism

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Gout is a consequence of an innate immune reaction to monosodium urate crystals deposited in joints. Acute gout attacks can be triggered by dietary factors that are themselves associated with serum urate levels. Tomato consumption is an anecdotal trigger of gout flares. This study aimed to measure the frequency of tomato consumption as a self-reported trigger of gout attacks in a large New Zealand sample set, and to test the hypothesis that tomato consumption is associated with serum urate levels.

Concepts: Immune system, Sample, Sample size, Innate immune system, Real number, Gout, Uric acid, Trigger pad

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In this case report, we review the experience of a patient who presented with early stage pancreatic cancer (Stage IIb) who underwent a Whipple procedure and adjuvant chemoradiation. The patient’s past medical history included early stage colon cancer in remission, post-traumatic-stress-disorder, hypertension, hyperlipidemia, osteoarthritis, gout, and pre-diabetes. Chemotherapy initially consisted of weekly gemcitabine. The patient developed acute gouty attacks after his second dose of gemcitabine, which brought him to the emergency room for emergent treatment on several occasions. Gemcitabine was held and treatment began with fluorouracil and concurrent radiation. After completion of his chemoradiation with fluorouracil, he was again treated with weekly gemcitabine alone. As soon as the patient started gemcitabine chemotherapy the patient developed gouty arthritis again, requiring discontinuation of chemotherapy. The patient received no additional treatment until his recent recurrence 8 months later where gemcitabine chemotherapy was again introduced with prophylactic medications consisting of allopurinol 100 mg by mouth daily and colchicine 0.6 mg by mouth daily throughout gemcitabine chemotherapy, and no signs of gouty arthritis occurred. To our knowledge, this is the first case report describing gout attacks associated with gemcitabine therapy. There is limited data available describing the mechanism that gouty arthritis may be precipitated from gemcitabine chemotherapy. Further monitoring and management may be required in patients receiving gemcitabine chemotherapy with underlying gout.

Concepts: Cancer, Obesity, Rheumatology, Gout, Pancreatic cancer, Arthritis, Allopurinol, Colchicine

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We report the case of a 36-year-old man with psoriatic arthritis and miliary tuberculosis, whose serum uric acid (SUA) level increased after the initiation of antituberculosis treatment, which included pyrazinamide. Most strikingly and paradoxically, the patient’s SUA level increased after treatment with allopurinol. On cessation of allopurinol, his SUA level decreased substantially, and complete normalisation was observed following the discontinuation of pyrazinamide treatment.

Concepts: Tuberculosis, Gout, Arthritis, Uric acid, Hyperuricemia, Miliary tuberculosis, Psoriatic arthritis

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Prevention of recurrent calcium stone disease includes treatment with thiazide and thiazide-type diuretics to reduce urinary calcium (UCa) levels, with the reduction in UCa correlating with risk of stone recurrence. There has been a recent trend of using lower doses of these medications and change from chlorthalidone (CTL) use to hydrochlorothiazide (HCTZ) use. It is unknown whether low doses of HCTZ are effective in lowering UCa levels to target levels. We hypothesize that HCTZ is associated with less reduction in UCa than is CTL when comparing currently used doses. Retrospective observational study of stone-formers was seen in metabolic stone clinic during a 3 years period. Data included patient demographics, co-morbidities, and 24 h urine electrolyte composition. Primary outcome was the change in 24 h UCa. 322 patients were identified with 112 meeting criteria and used in analysis. The majority were placed on HCTZ (n = 42) or CTL (n = 47) 25 mg QD. Patients on CTL 25 mg had a greater reduction in UCa (164 mg; 41 %) than those on HCTZ (85 mg; 21 %), p = 0.01. Neither CTL nor HCTZ at 12.5 mg QD significantly lowered UCa. There was a decrease in serum [K] of 0.5 Meq/L (p = 0.001) in patients on CTL 25 mg daily, but no significant difference in severe hypokalemia or arrhythmia compared to HCTZ. Our data show that CTL is associated with greater reduction in 24 h UCa compared to similarly dosed HCTZ.

Concepts: Kidney, Observational study, Urinary bladder, Urethra, Gout, Diuretic, Hydrochlorothiazide, Hypokalemia