Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias

Robert Clarke and colleagues conduct a meta-analysis of unpublished datasets to examine the causal relationship between elevation of homocysteine levels in the blood and the risk of coronary heart disease. Their data suggest that an increase in homocysteine levels is not likely to result in an increase in risk of coronary heart disease

The CORTES Study: corneal transplant indications and graft survival in an italian cohort of patients

Purpose: To describe the corneal transplantation activity in Italy, to assess the long-term graft survival, and to begin to outline the potential risk factors for graft outcome. Methods: We followed a consecutive series of penetrating (PK) and lamellar (LK) keratoplasties performed with corneas procured and distributed by the Veneto Eye Bank Foundation, which provides about one third of the corneas grafted in Italy each year. Results: Data on 4415 PKs and 489 LKs performed in 174 clinical centers are reported. Keratoconus was the major transplant indication (47% and 66%, respectively, for the 2 groups), followed by regraft (14%) and bullous keratopathy (14%) in the PK group and keratitis (8%) and refractive reasons (4%) for the LKs. In the 2 groups, graft survival, after 1 year, was estimated to be 95% and 93%, respectively, showing a decrease of the survival rate during the second and third years of the study. Graft survival in patients with keratoconus indication was 98% in the PK group and 95% in the LK group for the whole period of observation, whereas the patients with other indications reported a survival rate ranging from 92% after 1 year to 52% after 3 years (PK) and from 89% to 85% (LK). Conclusions: CORTES is the most extensive survey on corneal transplantation in Italy that involves a large cohort of patients and a significant number of surgeons with corneal tissues processed and distributed by a single eye bank. In the first 3 years, a picture of the epidemiology of the corneal transplant has been defined. The graft survival rates were comparable to those reported by other studies for the same follow-up period. However, the follow-up of a sample of this cohort for a farther 3 years will allow us to precisely estimate the long-term graft survival and to better evaluate the risk factors related to graft failure

Clinical, histological and genetic characterisation of patients with tubular aggregate myopathy caused by mutations in STIM1

Tubular aggregate myopathies (TAMs) are muscle disorders characterised by abnormal accumulations of densely packed single-walled or double-walled membrane tubules in muscle fibres. Recently, STIM1, encoding a major calcium sensor of the endoplasmic reticulum, was identified as a TAM gene

Predicting heart failure outcome from cardiac and comorbid conditions: The 3C-HF score.

BACKGROUND: Prognostic stratification in heart failure (HF) is crucial to guide clinical management and treatment decision-making. Currently available models to predict HF outcome have multiple limitations. We developed a simple risk stratification model, based on routinely available clinical information including comorbidities, the Cardiac and Comorbid Conditions HF (3C-HF) Score, to predict all-cause 1-year mortality in HF patients. METHODS: We recruited in a cohort study 6274 consecutive HF patients at 24 Cardiology and Internal Medicine Units in Europe. 2016 subjects formed the derivation cohort and 4258 the validation cohort. We entered information on cardiac and comorbid candidate prognostic predictors in a multivariable model to predict 1-year outcome. RESULTS: Median age was 69years, 35.8\% were female, 20.6\% had a normal ejection fraction, and 65\% had at least one comorbidity. During 5861 person-years follow-up, 12.1\% of the patients met the study end-point of all-cause death (n=750) or urgent transplantation (n=9). The variables that contributed to outcome prediction, listed in decreasing discriminating ability, were: New York Heart Association class III-IV, left ventricular ejection fraction <20\%, no beta-blocker, no renin-angiotensin system inhibitor, severe valve heart disease, atrial fibrillation, diabetes with micro or macroangiopathy, renal dysfunction, anemia, hypertension and older age. The C statistic for 1-year all-cause mortality was 0.87 for the derivation and 0.82 for the validation cohort. CONCLUSIONS: The 3C-HF score, based on easy-to-obtain cardiac and comorbid conditions and applicable to the 1-year time span, represents a simple and valuable tool to improve the prognostic stratification of HF patients in daily practice

Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: The ASTRONAUT randomized trial

Importance: Hospitalizations for heart failure (HHF) represent a major health burden, with high rates of early postdischarge rehospitalization and mortality. Objective: To investigate whether aliskiren, a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular (CV) death or HF rehospitalization among HHF patients. Design, Setting, and Participants: International, double-blind, placebo-controlled study that randomized hemodynamically stable HHF patients a median 5 days after admission. Eligible patients were 18 years or older with left ventricular ejection fraction (LVEF) 40% or less, elevated natriuretic peptides (brain natriuretic peptide [BNP] 65400 pg/mL or N-terminal pro-BNP [NT-proBNP] 651600 pg/mL), and signs and symptoms of fluid overload. Patients were recruited from 316 sites across North and South America, Europe, and Asia between May 2009 and December 2011. The follow-up period ended in July 2012. Intervention: All patients received 150 mg (increased to 300 mg as tolerated) of aliskiren or placebo daily, in addition to standard therapy. The study drug was continued after discharge for a median 11.3 months. Main Outcome Measures: Cardiovascular death or HF rehospitalization at 6 months and 12 months. Results: In total, 1639 patients were randomized, with 1615 patients included in the final efficacy analysis cohort (808 aliskiren, 807 placebo). Mean age was 65 years; mean LVEF, 28%; 41% of patients had diabetes mellitus, mean estimated glomerular filtration rate, 67 mL/min/1.73 m2. At admission and randomization, median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL, respectively. At randomization, patients were receiving diuretics (95.9%), \u3b2-blockers (82.5%), angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (84.2%), and mineralocorticoid receptor antagonists (57.0%). In total, 24.9% of patients receiving aliskiren (77 CV deaths, 153 HF rehospitalizations) and 26.5% of patients receiving placebo (85 CV deaths, 166 HF rehospitalizations) experienced the primary end point at 6 months (hazard ratio [HR], 0.92; 95% CI, 0.76-1.12; P=.41). At 12 months, the event rates were 35.0% for the aliskiren group (126 CV deaths, 212 HF rehospitalizations) and 37.3% for the placebo group (137 CV deaths, 224 HF rehospitalizations; HR, 0.93; 95% CI, 0.79-1.09; P=.36). The rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo. Conclusion and Relevance: Among patients hospitalized for HF with reduced LVEF, initiation of aliskiren in addition to standard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge. Trial Registration: clinicaltrials.gov Identifier: NCT00894387. \ua92013 American Medical Association. All rights reserved