In patients with advanced heart failure and LBBB, baseline SPWMD is a strong predictor of the occurrence of reverse remodeling after CRT, thus suggesting its usefulness in identifying patients likely to benefit from biventricular pacing.

Background-Brugada syndrome is associated with a high risk of sudden cardiac death and is caused by mutations in the cardiac voltage-gated sodium channel gene. Previously, the R282H-SCN5A mutation in the sodium channel gene was identified in patients with Brugada syndrome. In a family carrying the R282H-SCN5A mutation, an asymptomatic individual had a common H558R-SCN5A polymorphism and the mutation on separate chromosomes. Therefore, we hypothesized that the polymorphism could rescue the mutation. Methods and Results-In heterologous cells, expression of the mutation alone did not produce sodium current. However, coexpressing the mutation with the polymorphism produced significantly greater current than coexpressing the mutant with the wild-type gene, demonstrating that the polymorphism rescues the mutation. Using immunocytochemistry, we demonstrated that the R282H-SCN5A construct can traffic to the cell membrane only in the presence of the H558R-SCN5A polymorphism. Using fluorescence resonance energy transfer and protein fragments centered on H558R-SCN5A, we demonstrated that cardiac sodium channels preferentially interact when the polymorphism is expressed on one protein but not the other. Conclusions-This study suggests a mechanism whereby the Brugada syndrome has incomplete penetrance. More importantly, this study suggests that genetic polymorphisms may be a potential target for future therapies aimed at rescuing specific dysfunctional protein channels. (Circulation. 2006;114:368-376.)

Background and objective Serum uric acid may predict the onset and progression of kidney disease, but it is unclear whether uric acid is an independent risk factor for diabetic nephropathy. Our aim was to study the relationship between uric acid levels and the development of CKD components in patients with type 2 diabetes.Design, setting, participants, & measurements Longitudinal study of a cohort of patients with type 2 diabetes from the database of the Italian Association of Clinical Diabetologists network. From a total of 62,830 patients attending the diabetes centers between January 1, 2004, and June 30, 2008, we considered those with baseline eGFR values $60 ml/min per 1.73 m 2 and normal albumin excretion (n=20,142). Urinary albumin excretion, GFR, and serum uric acid were available in 13,964 patients. We assessed the association of serum uric acid quintiles with onset of CKD components by multinomial logistic regression model adjusting for potential confounders. We calculated the relative risk ratios (RRRs) for eGFR ,60 ml/min per 1.73 m 2 , albuminuria, and their combination at 4 years.Results At 4-year follow-up, 1109 (7.9%) patients developed GFR ,60 ml/min per 1.73 m 2 with normoalbuminuria, 1968 (14.1%) had albuminuria with eGFR $60 ml/min per 1.73 m 2 , and 286 (2.0%) had albuminuria with eGFR ,60 ml/min per 1.73 m 2 . The incidence of eGFR ,60 ml/min per 1.73 m 2 increased in parallel with uric acid quintiles: Compared with the lowest quintile, RRRs were 1.46 (95% confidence interval [CI], 1.14 to 1.88; P=0.003), 1.44 (95% CI, 1.11 to 1.87; P=0.006), 1.95 (95% CI, 1.48 to 2.58; P,0.001), and 2.61 (95% CI, 1.98 to 3.42; P,0.001) for second, third, fourth, and fifth quintiles, respectively. Serum uric acid was significantly associated with albuminuria only in presence of eGFR ,60 ml/min per 1.73 m 2 .Conclusions Mild hyperuricemia is strongly associated with the risk of CKD in patients with type 2 diabetes.

In a large population of outpatients with diabetes, low HDL-C and high TG levels were independent risk factors for the development of DKD over 4 years.

Symptoms, malignancy, overall morbidity, hypoparathyroidism, RLN palsy and hematoma are increased in cases of substernal goiter.

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In CHF patients TSH levels even slightly above normal range are independently associated with a greater likelihood of heart failure progression. This supports the need for prospective studies aimed at clarifying the most appropriate therapeutic approach to sub-clinical hypothyroidism in such patients.