Genetic variability at the TREX1 locus is not associated with natural resistance to HIV-1 infection

Three prime repair exonuclease 1 (TREX1) degrades excess HIV-1 DNA, thereby preventing recognition by innate immunity receptors and type I interferon responses. Analyses performed in two HIV-exposed seronegative (HESN) cohorts did not show any differences in TREX1 sequence, single nucleotide polymorphisms frequency, or expression in HESN compared to controls, suggesting that, despite its central role in the HIV-1 infection process, genetic diversity at TREX1 is not a major determinant of susceptibility to infection in humans.     

Long-term follow-up of hemodynamic responders to pharmacological therapy after variceal bleeding

Although it is assumed that hemodynamic responders to pharmacological therapy after a variceal hemorrhage are adequately protected from rebleeding, there is no evidence that either this response or its protective effect extend beyond the usual 2-year follow-up featured in available studies. We aimed to assess the maintenance of hemodynamic response and its impact on outcomes in a large cohort of hemodynamic responders during a long follow-up. One hundred three patients with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were prospectively evaluated. The hepatic venous pressure gradient (HVPG) was determined 5 days after the bleeding and repeated 5-7 days after maximal tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG ≤ 12 mm Hg or ≥ 20% decrease from baseline) were maintained on drugs and followed up with annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders. The median follow-up was 48 months (range, 2-108 months). Long-term HVPG evaluations could not be performed in eight patients (four deaths, two rebleedings, two follow-ups <1 year). Among the remaining 40 patients, hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were no baseline differences between the two subgroups. However, 100% of alcoholic patients who remained abstinent maintained long-term response, compared with 36% of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients with loss of hemodynamic response rebled more during follow-up and showed a higher incidence of death or liver transplantation. Conclusions: After variceal bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of this long-term response carries worse clinical outcomes.     

Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels

Introduction Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF‐I, GH‐binding protein (GHBP), IGF‐binding proteins (IGFBPs) and acid‐labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet. Aim of the study To explore whether GH secretion and/or levels of IGF‐I, IGFBP‐3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis. Materials and methods A total of 115 obese patients (BMI > 30) were enrolled in the protocol (65 patients with liver steatosis and 50 age‐ and BMI‐matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF‐I, GHBP, IGFBP‐3, ALS and GH after GHRH and arginine stimulation test. Results As expected, patients with NAFLD had blood glucose, insulin, HOMA‐R significantly higher than controls, indicating a more severe insulin‐resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP‐3 and lower GH peak and IGF‐I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF‐1 was negatively associated with hepatic steatosis. Conclusions This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF‐I axis is significantly altered probably leading to reduced IGF‐I bioavailability at tissue level.     

Improved outcomes and complications of atrial fibrillation catheter ablation over time: learning curve, techniques, and methodology

Introduction and objectives

The outcomes of atrial fibrillation ablation procedures vary widely between different centers. Our objective was to analyze the results and complications of this procedure in our center and identify factors predicting the efficacy and safety of atrial fibrillation ablation.

Methods

In total, 726 atrial fibrillation ablation procedures were performed in our center between 2002 and 2009. Beginning in January 2008, a protocol for anticoagulation and conscious sedation was systematically applied. Outcomes and complications could therefore be compared in 2 well-differentiated groups: group A included 419 procedures performed prior to 2008 and group B included 307 procedures completed after 2008 using the new protocol.

Results

During an average follow-up of 8.7 months, 60.9% of patients were arrhythmia-free after one or repeat procedures. After only 1 procedure, the success rate was 41% and significantly higher in group B (51.6% vs 35.2% in group A; P=.001). There were 31 major complications (4.2%), 26 in group A (6.2%) and 5 in group B (1.6%) (P=.002). The implementation of the new protocol was an independent predictor of the absence of complications (odds ratio=0.406; 95% confidence interval, 0.214-0.769; P<.006).

Conclusions

Systematic application of an anticoagulation and conscious sedation protocol is associated with improved results and fewer complications of atrial fibrillation ablation. Factors not evaluated in the present study, such as operator experience and ongoing improvements in atrial fibrillation ablation technology, could have influenced these findings.Full English text available from:www.revespcardiol.org     

Influence of obesity and malnutrition on acute heart failure

Introduction and objectives

Obesity is an independent risk factor for the development of heart failure. Several recent studies have found better outcomes of heart failure for obese patients, an observation termed as the “obesity paradox.” On the other hand, the negative effect of malnutrition on the evolution of heart failure has also been clearly established.

Methods

Data from the Minimum Basic Data Set were analyzed for all patients discharged from all the departments of internal medicine in hospitals of the Spanish National Health System between the years 2006 and 2008. The information was limited to those patients with a primary or secondary diagnosis of heart failure. Patients with a diagnosis of obesity or malnutrition were identified. The mortality and readmission indexes of obese and malnourished patients were compared against the subpopulation without these diagnoses.

Results

A total of 370 983 heart failure admittances were analyzed, with 41 127 (11.1%) diagnosed with obesity and 4105 (1.1%) with malnutrition. In-hospital global mortality reached 12.9% and the risk of readmission was 16.4%. Obese patients had a lower in-hospital mortality risk (odds ratio [OR]: 0.65, 95% confidence interval [95%CI]: 0.62-0.68) and early readmission risk (OR: 0.81, 95%CI: 0.78-0.83) than nonobese patients. Malnourished patients had a much higher risk of dying while in hospital (OR: 1.83 95%CI: 1.69-1.97) or of being readmitted within 30 days after discharge (OR: 1.39, 95%CI: 1.29-1.51), even after adjusting for possible confounding factors.

Conclusions

Obesity in patients admitted for HF substantially reduces in-hospital mortality risk and the possibility of early readmission, whereas malnutrition is associated with important increases in in-hospital mortality and risk of readmission in the 30 days following discharge.Full English text available from:www.revespcardiol.org