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[This corrects the article DOI: 10.1371/journal.pone.0208540.].

Hyperglycemia during sepsis is associated with increased organ dysfunction and higher mortality. The role of the host immune response in development of hyperglycemia during sepsis remains unclear. We performed a retrospective analysis of critically ill adult septic patients requiring mechanical ventilation (n = 153) to study the relationship between hyperglycemia and ten markers of the host injury and immune response measured on the first day of ICU admission (baseline). We determined associations between each biomarker and: (1) glucose, insulin, and c-peptide levels at the time of biomarker collection by Pearson correlation; (2) average glucose and glycemic variability in the first two days of ICU admission by linear regression; and (3) occurrence of hyperglycemia (blood glucose>180mg/dL) by logistic regression. Results were adjusted for age, pre-existing diabetes mellitus, severity of illness, and total insulin and glucocorticoid dose. Baseline plasma levels of ST2 and procalcitonin were positively correlated with average blood glucose and glycemic variability in the first two days of ICU admission in unadjusted and adjusted analyses. Additionally, higher baseline ST2, IL-1ra, procalcitonin, and pentraxin-3 levels were associated with increased risk of hyperglycemia. Our results suggest associations between the host immune response and hyperglycemia in critically ill septic patients particularly implicating the interleukin-1 axis (IL-1ra), the interleukin-33 axis (ST2), and the host response to bacterial infections (procalcitonin, pentraxin-3).

The relationship between cardiovascular disease and abnormalities in sleep architecture is complex and bi-directional. Sleep disordered breathing (SDB) often confounds human studies examining sleep in the setting of heart failure, and the independent impact of isolated right or left heart failure on sleep is difficult to assess. We utilized an animal model of right heart failure using pulmonary artery banding (PAB) in mice to examine the causal effect of right heart failure on sleep architecture. Four weeks after PAB or sham (control) surgery, sleep was measured by polysomnography for 48 hours and right ventricular (RV) hypertrophy confirmed prior to sacrifice. PAB resulted in right ventricular hypertrophy based on a 30% increase in the Fulton Index (p < 0.01). After PAB, mice spent significantly more time in NREM sleep compared to the control group over a 24 hour period (53.5 ± 1.5% vs. 46.6 ± 1.4%; p < 0.01) and exhibited an inability to both cycle into REM sleep and decrease delta density across the light/sleep period. Our results support a phenotype of impaired sleep cycling and increased 'sleepiness' in a mouse model of RV dysfunction.