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Estimation of Primary Prevention of Gout in Men Through Modification of Obesity and Other Key Lifestyle Factors.
McCormick, N, Rai, SK, Lu, N, Yokose, C, Curhan, GC, Choi, HK
JAMA network open. 2020;3(11):e2027421
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Gout is prevalent in most Western countries. Modifying the contributary factors such as obesity and alcohol intake could prevent gout, however the impact this could have on prevention is unknown. This cohort study of 44,654 men, aimed to estimate the proportion of gout cases that could be prevented through the modification of risk factors. The results showed that the most important risk factor for gout was body mass index (BMI) and modifying other risk factors did not prevent gout. 77% of gout cases could be prevented if all men had been of normal weight, had no alcohol intake, if they adhered to a diet known as the Dietary Approaches to Stop Hypertension (DASH) diet and if they didn't take drugs to increase urine output. It was concluded that weight loss in men determines their ability to prevent gout, regardless of whether they have modified other contributory factors. This study could be used by healthcare professionals to understand that unless weight loss is achieved in individuals who are overweight and have gout, then other interventions may have minimal impact. Recommending the DASH diet to achieve weight loss, may be more successful in the long-term management of gout.
Abstract
Importance: The population impact of modifying obesity and other key risk factors for hyperuricemia has been estimated in cross-sectional studies; however, the proportion of incident gout cases (a clinical end point) that could be prevented by modifying such factors has not been evaluated. Objective: To estimate the proportion of incident gout cases that could be avoided through simultaneous modification of obesity and other key risk factors. Design, Setting, and Participants: The Health Professionals Follow-up Study is a US prospective cohort study of 51 529 male health professionals enrolled in 1986 and followed up through questionnaires every 2 years through 2012. Self-reported gout cases were confirmed through June 2015. Clean and complete data used for this analysis were available in June 2016, with statistical analyses performed from July 2016 to July 2019. Exposures: From data collected in the validated questionnaires, men were categorized to low-risk groups according to combinations of the following 4 factors: normal body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; <25), no alcohol intake, adherence to Dietary Approaches to Stop Hypertension (DASH)-style diet (highest quintile of DASH diet score), and no diuretic use. Main Outcomes and Measures: Population attributable risks (PARs) for incident gout meeting the preliminary American College of Rheumatology survey criteria, overall and stratified by BMI. Results: We analyzed 44 654 men (mean [SD] age, 54.0 [9.8] years) with no history of gout at baseline. During 26 years of follow-up, 1741 (3.9%) developed incident gout. Among all participants, PAR for the 4 risk factors combined (BMI, diet, alcohol use, and diuretic use) was 77% (95% CI, 56%-88%). Among men with normal weight (BMI <25.0) and overweight (BMI 25.0-29.9), we estimated that more than half of incident gout cases (69% [95% CI, 42%-83%] and 59% [95% CI, 30%-75%], respectively) may have been prevented by the combination of DASH-style diet, no alcohol intake, and no diuretic use. However, among men with obesity (BMI ≥30), PAR was substantially lower and not significant (5% [95% CI, 0%-47%]). Conclusions and Relevance: The findings of this cohort study suggest that addressing excess adiposity and other key modifiable factors has the potential to prevent the majority of incident gout cases among men. Men with obesity may not benefit from other modifications unless weight loss is addressed.
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Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis.
Jutras, BL, Lochhead, RB, Kloos, ZA, Biboy, J, Strle, K, Booth, CJ, Govers, SK, Gray, J, Schumann, P, Vollmer, W, et al
Proceedings of the National Academy of Sciences of the United States of America. 2019;116(27):13498-13507
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Lyme disease is a varied, multisystem disorder caused by the spiral-shaped bacteria Borrelia burgdorferi (Bb). Advanced stages of the disease can present with oligoarthritis, most commonly involving the knee joints. Peptidoglycan (PG) is a compound that makes up the cell envelope of Bb and other bacteria. It acts as a microbe-associated molecular pattern, which can trigger the immune system and induces pro-inflammatory responses. This article summarises a series of cell, human, and animal studies supporting the theory that PG is a contributor to persistent Lyme’s arthritis (LA) far beyond the eradication of the pathogen. Significantly elevated inflammatory markers as well as antibodies to PG and Bb itself have been found in patients with LA before and after antibiotic therapy. The inflammatory response to Bb PG seems to be particularly high when compared to other bacteria. In summary, the authors suggest that PG accumulation in the joints and subsequent persistent inflammation contribute to LA and that targeting the specific inflammatory pathways involved may yield potential therapeutic interventions. This article could be of interest to those looking to understand more about the mechanisms and specific inflammatory responses involved in LA.
Abstract
Lyme disease is a multisystem disorder caused by the spirochete Borrelia burgdorferi A common late-stage complication of this disease is oligoarticular arthritis, often involving the knee. In ∼10% of cases, arthritis persists after appropriate antibiotic treatment, leading to a proliferative synovitis typical of chronic inflammatory arthritides. Here, we provide evidence that peptidoglycan (PG), a major component of the B. burgdorferi cell envelope, may contribute to the development and persistence of Lyme arthritis (LA). We show that B. burgdorferi has a chemically atypical PG (PGBb) that is not recycled during cell-wall turnover. Instead, this pathogen sheds PGBb fragments into its environment during growth. Patients with LA mount a specific immunoglobulin G response against PGBb, which is significantly higher in the synovial fluid than in the serum of the same patient. We also detect PGBb in 94% of synovial fluid samples (32 of 34) from patients with LA, many of whom had undergone oral and intravenous antibiotic treatment. These same synovial fluid samples contain proinflammatory cytokines, similar to those produced by human peripheral blood mononuclear cells stimulated with PGBb In addition, systemic administration of PGBb in BALB/c mice elicits acute arthritis. Altogether, our study identifies PGBb as a likely contributor to inflammatory responses in LA. Persistence of this antigen in the joint may contribute to synovitis after antibiotics eradicate the pathogen. Furthermore, our finding that B. burgdorferi sheds immunogenic PGBb fragments during growth suggests a potential role for PGBb in the immunopathogenesis of other Lyme disease manifestations.
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Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention.
Abbaoui, B, Lucas, CR, Riedl, KM, Clinton, SK, Mortazavi, A
Molecular nutrition & food research. 2018;62(18):e1800079
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Worldwide, almost 400,000 cases of bladder cancer are diagnosed each year, with 150,000 deaths, a high rate of recurrence and a high treatment cost. This review article evaluates the literature regarding the potential role of cruciferous vegetables (broccoli, cauliflower, cabbages, pak choi, watercress, wasabi are all examples of cruciferous vegetables) in bladder cancer prevention and as an adjunct to current treatment protocols. In vitro studies have shown inhibition of bladder cancer cell reproduction, stalled cancer cell cycles, and cancer cell death by compounds in cruciferous vegetables, in particular sulphoraphane (known to be high in broccoli and broccoli sprouts) and erucin (available in rocket for example). Studies show an inverse relationship between cruciferous vegetable intake and risk of bladder cancer, with those consuming 2 or more portions per week having a 39% lower risk of bladder cancer than those who consume less than 1 portion per week. The review also looks at cooking method, with steaming, stir-frying and sauteeing protecting the important nutrients when compared to boiling. The authors call for pre-clinical studies to be performed, examining multiple formulations of cruciferous vegetables in a variety of bladder cancer models, looking at prevention in high risk groups and adjuvant to standard treatment protocols. Nutrition Practitioners may want to consider including regular intake of cruciferous vegetables in their client protocols.
Abstract
Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although not yet completely understood, many mechanisms of anticancer activity at the steps of cancer initiation, promotion, and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro-growth, pro-survival, pro-inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their antitumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden.