OBJECTIVESome obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk.RESEARCH DESIGN AND METHODSFifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m2; obese: ≥30 kg/m2) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant ≥2.5).RESULTSObese insulin-sensitive subjects represented 11% (95% CI 8.1–14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08–1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46–2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects.CONCLUSIONSIn contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study.

High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.

Background: In ST-segment–elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. Methods: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. Results: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P =0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P =0.53). Conclusions: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.

Although vaccination against influenza is recommended for elderly and high-risk patients in many countries, efficacy in the elderly has been suboptimal. The MF59 adjuvanted trivalent inactivated vaccine (ATIV) was developed to increase the immune response of elderly subjects to influenza vaccination, but its effectiveness has not yet been well documented. This prospective, observational study evaluated the relative effectiveness of ATIV versus nonadjuvanted trivalent inactivated vaccine (TIV) in individuals at least 65 years of age in Lombardy, northern Italy. Hospitalizations for influenza or pneumonia (International Classification of Diseases, Ninth Revision, Clinical Modification, codes 480–487) during the 2006–2007, 2007–2008, and 2008–2009 influenza seasons were identified from administrative databases. Stratified and regression analyses, including the propensity score to adjust for confounding, as well as generalized estimating equations to account for repeated vaccination, were used. Overall, 107,661 records were evaluated, contributing 170,988 person-seasons of observation. Since ATIV is preferentially recommended for more frail individuals, subjects vaccinated with ATIV were older and had more functional impairment and comorbidities. In the primary analysis, risk of hospitalization for influenza or pneumonia was 25% lower for ATIV relative to TIV (relative risk = 0.75, 95% confidence interval: 0.57, 0.98). To the extent that there is residual bias, ATIV is likely to be even more protective than this result suggests.

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