General and Abdominal Adiposity and Risk of Death in Europe

Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. This study examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). A Cox regression analysis was used, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height

Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet

Weight Loss with a Low-Carbohydrate, Mediterranean, or Low- Fat Diet (July 17, 2008;359:229-41). In Figure 3 (page 239), the y-axis in Panel D should have been labeled \u93Change\u94 rather than \u93Change (mg/dl).\u94 We regret the error. The article has been corrected at NEJM.org. Maternal and Neonatal Herpes Simplex Virus Infections (October 1, 2009;361:1376-85). An additional correction is described in the Correspondence section of this issue of the Journal (Maternal and Neonatal Herpes Simplex Virus Infections ([December 31, 2009;361:2678-9])

Maternal and Neonatal Herpes Simplex Virus Infections

To the Editor: In their informative review article on infection with herpes simplex virus (HSV), Corey and Wald (Oct. 1 issue)1 do not make it clear to readers that universal prenatal herpes screening is not recommended by any expert panel that has reviewed this topic, including the American College of Obstetricians and Gynecologists (2007),2 the Centers for Disease Control and Prevention (2006),3 and the U.S. Preventive Services Task Force (2009).4 Neonatal herpes can be a devastating disease. Yet, it should be made clear to providers who care for pregnant women that routine prenatal screening for HSV infection is not recommended and should not be part of a standard prenatal screening panel. New research findings may emerge, but, currently, routine prenatal screening for herpes continues to be a bad idea.5 Adam C. Urato, M.D

Dabigatran versus Warfarin in Patients with Atrial Fibrillation

To the Editor: Although Connolly et al. (Sept. 17 issue)1 have demonstrated a modest advantage for dabigatran over warfarin in atrial fibrillation, we think the benefit could be even greater. Warfarin has many adverse properties. Vitamin K content varies widely in foods. Warfarin inhibits the synthesis of sequential enzymes in the coagulation cascade, which imparts a drastically steep dose\u96response relationship. The binding of warfarin to plasma proteins and its metabolism by cytochrome P-450 enzymes facilitate drug interactions. These properties result in variability in anticoagulant control, which is associated with bleeding, thrombosis, and increased risk of death.2-5 Dabigatran lacks these undesirable properties. But the adoption of \u93one size fits all\u94 dosing has probably undermined the performance of dabigatran in the trial for the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY). Dabigatran appeared to be more efficacious in patients who weighed less and in patients with impaired renal function (in whom the drug accumulates), pointing to significant interpatient variability in response. Individualized dosing, based on weight and estimated creatinine clearance, might improve the drug\u92s risk\u96benefit ratio. Dosing could be further refined with the use of a single measurement of the drug level drawn at steady state, if necessary. Such an approach should be studied. Donald Stuart Houston, M.D., Ph.D. Ryan Zarychanski, M.D

Sex Hormone\u96Binding Globulin and Risk of Type 2 Diabetes

To the Editor: Ding et al. (Sept. 17 issue)1 found that sex hormone\u96binding globulin, which is predominantly expressed in hepatocytes, may protect against type 2 diabetes. What variables in the natural history of diabetes determine circulating levels of sex hormone\u96binding globulin? Recently, monosaccharide-induced hepatic lipogenesis, but not insulin, was shown to suppress hepatic production of sex hormone\u96binding globulin in animals.2 Because this pathway is involved in the pathogenesis of fatty liver, a major risk factor in type 2 diabetes,3 we hypothesized that levels of sex hormone\u96binding globulin decrease, particularly under hepatic steatosis. In subjects who underwent precise measurements of liver-fat and body-fat distribution4 we observed that besides sex and age, liver fat, but not visceral fat or total body fat, was an independent predictor of levels of sex hormone\u96binding globulin (Fig. 1A). During a lifestyle intervention, an increase in levels of sex hormone\u96binding globulin was more strongly associated with a decrease in liver fat

Human GM-CSF Autoantibodies and Reproduction of Pulmonary Alveolar Proteinosis

To the Editor: Idiopathic pulmonary alveolar proteinosis is a rare disease in which surfactant lipids and proteins accumulate in pulmonary alveolar macrophages and alveoli, resulting in respiratory insufficiency and, in severe cases, respiratory failure.1 Granulocyte\u96macrophage colonystimulating factor (GM-CSF) autoantibodies occur in these patients2 and may mediate the pathogenesis of this disease, but they are also present in healthy persons and in immune globulin prepared from plasma obtained from healthy persons. Since GM-CSF is required for surfactant catabolism by alveolar macrophages in mice, we hypothesized that high levels of GM-CSF autoantibodies (i.e., levels sufficient to eliminate endogenous GM-CSF priming of myeloid cells) could cause idiopathic pulmonary alveolar proteinosis by impairing surfactant clearance by alveolar macrophages.3 We previously found that high levels of GM-CSF autoantibodies are specifically associated with idiopathic pulmonary alveolar proteinosis4 and can be isolated in pure form from these patients.5 We administered highly purified GM-CSF autoantibodies derived from a patient with idiopathic pulmonary alveolar proteinosis to healthy nonhuman primates (Macaca fascicularis). These autoantibodies were administered intravenously, and serum levels of 40 \ub5g per milliliter or more were maintained for 10 months. A marked reduction in levels of GM-CSF\u96stimulated CD11b in blood leukocytes indicated that GM-CSF signaling was blocked; these results were identical to those in patients with idiopathic pulmonary alveolar proteinosis.

AIDS - medical and prevention studies

An article from The New England Journal of Medicine discussing recent medical progress in discovering how the human immunodeficiency virus (HIV) is transmitted and the groups that are at risk to become infected with the virus that progresses into the acquired immunodeficiency syndrome (AIDS)