New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study

Rationale &amp; objectiveThe clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.Study designA multicenter, prospective, cohort study.Setting &amp; participantsWe evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC) study.ExposuresBaseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography-tandem mass spectrometry (LC-MS/MS).OutcomesIncident heart failure, myocardial infarction, and stroke events.Analytical approachWe used Cox regression to evaluate associations of baseline secretory solute clearances with incident study outcomes adjusting for estimated GFR (eGFR) and other confounders.ResultsParticipants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m2. Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR.LimitationsExclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances.ConclusionsIn a national cohort study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD

Bacterial Meningitis in Infants

Neonatal bacterial meningitis is an uncommon but devastating infection. Although the incidence and mortality have declined over the last several decades, morbidity among survivors remains high. The types and distribution of causative pathogens are related to birth gestational age, postnatal age, and geographic region. Confirming the diagnosis of meningitis can be difficult. Clinical signs are often subtle, and the lumbar puncture is frequently deferred in clinically unstable infants. When obtained, confirmatory testing with cerebrospinal fluid (CSF) culture is often compromised by antepartum or postnatal antibiotic exposure. While blood cultures and CSF parameters may be helpful in cases where the diagnosis is uncertain, bacterial meningitis occurs in infants without bacteremia and with normal CSF parameters. Newer tests such as the polymerase chain reaction are promising but require further study. Prompt treatment with appropriate antibiotics is essential to optimize outcomes. Successful efforts to prevent meningitis in infants have included the use of intrapartum antibiotic prophylaxis against Group B Streptococcus (GBS). Clinical trials investigating the use of a GBS vaccine for the prevention of neonatal GBS disease are ongoing