Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes.

Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein-SFTPB (pulmonary surfactant protein B)-predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12-4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker-and perhaps mediator-of CVD risk in patients with T1DM.

Innate Immune Function and Organ Failure Recovery in Adults With Sepsis.

PURPOSE: Sepsis stimulates pro- and anti-inflammatory immune responses. The innate immune response is critical to organ injury repair. We tested for an association between innate immune function and organ function recovery in a prospective cohort of immune-competent adults with sepsis. METHODS: We conducted a prospective observational cohort study enrolling immune-competent adults with sepsis. We tested innate immune function by quantification of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production capacity in whole blood samples on hospital days 1, 4, and 6. The primary outcome was organ function recovery on day 4 defined as a 4-point decrease in the composite cardiovascular and respiratory Sequential Organ Failure Assessment (SOFA) score components or a SOFA score ≤2. RESULTS: Patients with sepsis who recovered organ function by day 4 (n = 11) had similar baseline characteristics when compared to those with ongoing organ failure (n = 13). Tumor necrosis factor α production capacity was similar between the 2 groups on hospital days 1 and 4 but significantly different on day 6. Patients who regained organ function recovery had significantly higher TNF-α production capacity on day 6 ( P = .01), which persisted after adjustment for age, Acute Physiology and Chronic Health Evaluation III score, and steroid administration ( P = .03). There was no difference in TNF-α production capacity over time in those who survived to hospital discharge versus nonsurvivors. CONCLUSION: Increasing TNF-α production capacity is associated with improved organ failure recovery. Further studies are needed to evaluate a causal association between innate immune suppression and organ failure recovery as well as predictive accuracy for hospital survival. Impaired TNF-α production as a marker of sepsis-associated innate immune dysfunction may be a feasible target for immune stimulation to decrease time to organ failure recovery.

Ambulatory glucose profile analysis of the juvenile diabetes research foundation continuous glucose monitoring dataset-Applications to the pediatric diabetes population.

BACKGROUND: Increased continuous glucose monitor (CGM) use presents both the benefit and burden of increased data for clinicians to rapidly analyze. The ambulatory glucose profile (AGP) is an evolving a universal software report for CGM data analysis. OBJECTIVES/HYPOTHESES: We utilized the Juvenile Diabetes Research Foundation-CGM dataset to evaluate the AGP across a broad spectrum of patients to show how AGP can be used clinically to assist with CGM-related decision making. We hypothesized that AGP metrics would be different across age and HbA1c strata. SUBJECTS: AGPs were generated from the JDRF-CGM trial dataset for all periods during which there were ≥10 days of CGM coverage in the 2 weeks adjacent to an HbA1c measurement yielding 1101 AGPs for 393 unique subjects. METHODS: AGPs were stratified by age group (8-14, 15-24, and ≥25 years) and HbA1c (within or above target for age) and compared for between group differences in AGP metrics via two-factor ANOVA. Glycemic differences between time periods were analyzed via segmented regression analysis. RESULTS: Glucose exposure (average and estimated A1c) and variability (standard deviation and interquartile range) were different between the low and high HbA1c levels. Within a given HbA1c level all age groups were significantly different from each other with older patients having lower averages with less variability than younger patients. CONCLUSIONS: AGP analysis of the JDRF-CGM data highlights significant differences in glycemic profiles between pediatric and adult age groups and between well and less well-controlled patient populations.

Factors associated with peritoneal dialysis catheter complications in children.

BACKGROUND/PURPOSE: Peritoneal dialysis (PD) is a common method of renal replacement therapy for children. However, placement of PD catheters has risk, and some are never used. METHODS: We conducted a retrospective chart review of children with a PD catheter placed between 2000 and 2014. Logistic regression analyses were used to identify covariates associated with complications. RESULTS: We identified 175 children with PD catheters. 110 complications developed in 80 children (45.7%). Complications including unexpected return to the operating room and peritonitis increased as the length of time a catheter was in place increased. Children who weighed <12.4 kg had 3.2 times greater odds of developing a leak (95% CI 1.21-8.63, p=0.02). Twelve children never used their PD catheters, 9 with acute kidney injury (AKI) who recovered from their disease more quickly than expected. No covariate was associated with nonuse. CONCLUSIONS: Complications with PD catheters are common and increase the longer catheters are in place. Lower weight children are at greater risk of PD catheter leak. Decreased initial volumes of dialysate in smaller children may mitigate this risk. Nonuse may be reduced if dialysis is permitted the day of placement for children with AKI.