Pulse pressure is an age-independent predictor of stroke development after cardiac surgery

Chronologic age is a strong predictor of adverse outcomes after cardiac surgery. The variability in age-related cardiovascular changes suggests that age may not be the most accurate predictor of adverse perioperative outcomes. Vascular stiffness has emerged as an important surrogate of vascular aging. In a retrospective review, we investigated the value of vascular stiffness, as assessed by brachial pulse pressure (PP) measurements, in predicting stroke in 703 patients (63.4% men and 36.6% women). Patients were followed for 348+/-215 days after cardiac surgery. We used a multivariable logistic model and unadjusted and adjusted Cox proportional-hazard models to assess the probability of stroke and the hazards of stroke over time. Stroke patients had a significantly higher PP (81.2 mm Hg versus 64.5 mm Hg; P=0.0006). In the logistic regression model, PP was an independent predictor of stroke development (unadjusted odds ratio: 1.35; 95% CI: 1.13 to 1.62, for every 10-mm Hg increase in PP; P=0.001). In the unadjusted and adjusted Cox models, PP again predicted stroke (hazard ratio: 1.32; 95% CI: 1.12 to 1.57; hazard ratio: 2.62; 95% CI: 1.49 to 4.60, respectively; P=0.001 for both) for every 10 mm Hg increase in PP. Age, gender, and diabetes were not independent predictors of stroke. Ejection fraction was inversely related to stroke in the adjusted model. Kaplan-Meier estimates and corresponding log-rank test indicated that the probability of stroke-free survival function was significantly lower (P=0.0067) in patients with PP >72 mm Hg versus <72 mm Hg. This analysis suggests that indices of vascular stiffness could be important predictors of neurologic complications.     

Influence of fat/carbohydrate ratio on progression of fatty liver disease and on development of osteopenia in male rats fed alcohol via total enteral nutrition (TEN)

Alcohol abuse is associated with the development of fatty liver disease and also with significant osteopenia in both genders. In this study, we examined ethanol-induced pathology in response to diets with differing fat/carbohydrate ratios. Male Sprague-Dawley rats were fed intragastrically with isocaloric liquid diets. Dietary fat content was either 5% (high carbohydrate, HC) or 45% (high fat, HF), with or without ethanol (12–13 g/kg/day). After 14, 28, or 65 days, livers were harvested and analyzed. In addition, bone morphology was analyzed after 65 days. HC rats gained more weight and had larger fat pads than HF rats with or without ethanol. Steatosis developed in HC + ethanol (HC + EtOH) compared to HF + ethanol (HF + EtOH) rats, accompanied by increased fatty acid (FA) synthesis and increased nuclear carbohydrate response element binding protein (ChREBP) (p < 0.05), but in the absence of effects on hepatic silent mating type information regulation 2 homolog (SIRT-1) or nuclear sterol regulatory binding element protein (SREBP-1c). Ethanol reduced serum leptin (p < 0.05) but not adiponectin. Over time, HC rats developed fatty liver independent of ethanol. FA degradation was significantly elevated by ethanol in both HC and HF groups (p < 0.05). HF + EtOH rats had increased oxidative stress from 28 days, increased necrosis compared to HF controls and higher expression of cytochromes P450, CYP2E1, and CYP4A1 compared to HC + EtOH rats (p < 0.05). In contrast, HC + EtOH rats had no significant increase in oxidative stress until day 65 with no observed increase in necrosis. Unlike liver pathology, no dietary differences were observed on ethanol-induced osteopenia in HC compared to HF groups. These data demonstrate that interactions between diet composition and alcohol are complex, dependent on the length of exposure, and are an important influence in development of fatty liver injury. Importantly, it appears that diet composition does not affect alcohol-associated skeletal toxicity.     

Measuring Women’s Cumulative Neighborhood Deprivation Exposure Using Longitudinally Linked Vital Records: A Method for Life Course MCH Research

A life course conceptual framework for MCH research demands new tools for understanding population health and measuring exposures. We propose a method for measuring population-based socio-environmental trajectories for women of reproductive age. We merged maternal longitudinally-linked births to Georgia-resident women from 1994 to 2007 with census economic and social measures using residential geocodes to create woman-centered socio-environmental trajectories. We calculated a woman’s neighborhood deprivation index (NDI) at the time of each of her births and, from these, we calculated a cumulative NDI. We fit Loess curves to describe average life course NDI trajectories and binomial regression models to test specific life course theory hypotheses relating cumulative NDI to risk for preterm birth. Of the 1,815,944 total live births, we linked 1,000,437 live births to 413,048 unique women with two or more births. Record linkage had high specificity but relatively low sensitivity which appears non-differential with respect to maternal characteristics. Georgia women on average experienced upward mobility across the life course, although differences by race, early life neighborhood quality, and age at first birth produced differences in cumulative NDI. Adjusted binomial models found evidence for modification of the effect of history of prior preterm birth and advancing age on risk for preterm birth by cumulative NDI. The creation of trajectories from geocoded maternal longitudinally-linked vital records is one method to carry out life course MCH research. We discuss approaches for investigating the impact of truncation of the life course, selection bias from migration, and misclassification of cumulative exposure.     

Esophageal atresia/tracheoesophageal fistula and proximal symphalangism in a patient with a NOG nonsense mutation

Esophageal atresia and tracheoesophageal fistula (EA/TEF) are relatively common malformations of the human foregut. The etiology remains incompletely understood with genetic causes identified in a small minority of affected patients. We present the case of a newborn with type C EA/TEF along with proximal symphalangism found to have a de novo NOG nonsense mutation. Patients with chromosome 17q deletions including the NOG gene have previously been reported to have EA/TEF but mutations in the gene have not been identified in patients with this malformation. This case provides evidence that haploinsufficiency for NOG may be the cause for EA/TEF in the 17q deletion syndrome and suggests that the clinical spectrum of NOG-related symphalangism spectrum disorders may include EA/TEF.