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Objectives: The purpose of the present study was to evaluate the association of open and closed Fontan fenestration status with event-free survival. Methods: All patients who underwent a fenestrated Fontan procedure at our institution from January 1994 through June 2007 were reviewed. Patient information was obtained from the medical records. The patients were assigned to 1 of 2 study groups, open or closed, according to their most recent fenestration status. Clinically relevant morbid events were tabulated, and Kaplan-Meier event analysis was used to create event-free probability curves with log-rank comparisons. Results: A total of 161 patients were classified as open and 51 as closed. The median interval to an event was 1.1 years (interquartile range, 0.1-3.3 years) after the Fontan procedure. The median interval to closure was 1.2 years (interquartile range, 0.7-3.3 years). The median interval to an event was 1.5 years (interquartile range, 0.1-4.6 years) in the closed group and 1.1 years (interquartile range, 0.1-3.3 years) in the open group. Event-free probability analysis revealed no significant difference between the 2 groups (P = .15). The median follow-up arterial oxygen saturation was greater in the closed group (96.0%; interquartile range, 94.0%-97.0%) than in the open group (91.0%; interquartile range, 86.0%-95.0%; P < .0001). Conclusions: Fenestration closure was associated with greater arterial oxygen saturation but not greater event-free survival. The interval to an event was slightly less than the interval to fenestration closure, suggesting potential merit in the evaluation of earlier fenestration closure. Adoption of specific fenestration management guidelines might help improve the overall outcomes and enhance the quality of future studies. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine if intestinal alkaline phosphatase (IAP) decreases intestinal injury resulting from experimentally induced necrotizing enterocolitis (NEC). We hypothesized that IAP administration prevents the initial development of NEC related intestinal inflammation. Methods: Pre- and full-term newborn Sprague–Dawley rat pups were sacrificed on day 1 of life. Pre-term pups were exposed to intermittent hypoxia and formula containing LPS to induce NEC. Select NEC pups were given 40, 4 or 0.4units/kg of bovine IAP (NEC+IAP40u, IAP4u or IAP0.4u) enterally, once daily. Ileal sections were evaluated by real-time PCR (qRT-PCR) for IAP, iNOS, IL-1β, IL-6, and TNF-α mRNA and immunofluorescence for 3-nitrotyrosine (3-NT). Results: Experimentally induced NEC decreased IAP mRNA expression by 66% (p ≤0.001). IAP supplementation increased IAP mRNA expression to control. Supplemental enteral IAP decreased nitrosative stress as measured by iNOS mRNA expression and 3-NT staining in the NEC stressed pups (p ≤0.01), as well as decreased intestinal TNF-α mRNA expression. In addition, IAP decreased LSP translocation into the serum in the treated pups. Conclusions: We conclude that enterally administered IAP prevents NEC-related intestinal injury and inflammation. Enteral IAP may prove a useful strategy in the prevention of NEC in preterm neonates. [Copyright &y& Elsevier]

Attitudes and beliefs reflecting cultural values can have a positive or negative influence on eating behaviors. Eating out may negatively affect diet quality through increased fat intake and larger portion sizes. In a representative sample of the Lower Mississippi Delta (LMD) consisting of 1601 African Americans (AA) and Caucasian (C) adults, the aim was to show that the frequency of eating out was lower among residents having a better attitude toward diet in addition to ethnic and socioeconomic differences. A comparison of those who thought it was important to (1) restrict salt (2) eat fruits and vegetables, (3) consume adequate fiber, (4) eat a variety of foods, (5) eat 2 servings of dairy daily (6) maintain a healthy weight, and (7) exercise regularly to those who did not. Those who thought it was important to eat plenty of fruits and vegetables (P< 0.001) ate out less often. Those who also thought that it was important to consume adequate fiber (P<0.005) also ate out less often, in addition to those who thought it was important to eat 2 servings of dairy daily (P <0.05) and have fruit for dessert (P<0.007). Using regression modeling with frequency of eating out as the outcome, religiosity, income, education, ethnicity, gender, food security, knowledge, and age as independent variables, the data showed that all but religiosity, food security and education were significant. Being younger, Caucasian or male or having a lower income or better healthy eating attitude resulted in eating out more. Previous research found diet to be poorer in those with lower income and education, and those residing in food insecure households. This suggests that income, age, ethnicity, and healthy eating perspective are important predictors of how often people eat out. Sensitivity to the beliefs and attitudes is important when planning effective nutrition interventions. [ABSTRACT FROM AUTHOR]

Cardiopulmonary exercise testing (CPET) is limited to children able to tolerate the equipment. Modification of instrumentation to reduce invasiveness will open CPET to a wider population. Near Infrared Spectroscopy (NIRS) devices measure regional oxyhemoglobin saturation (rSO2). We aim to predict anaerobic threshold (AT) during CPET using multiorgan NIRS monitoring. Nineteen subjects were recruited. NIRS probes were placed on the forehead, para vertebral space, vastus lateralis, and deltoid muscle (rSO2 C, rSO2 R, rSO2 L and rSO2 A). rSO2 was recorded at six second intervals at rest, exercise, and through a five minute recovery period. The AT was computed using the v-slope method. AT was also predicted using NIRS data by identifying the inflection point of the rSO2 trends for all the four sites. AT can be estimated by the point of slope change of rSO2 R, rSO2 C and the four-site composite measure. Multisite NIRS monitoring of visceral organs is a potential predictor of AT. This allows for monitoring in all forms of exercise over a wide age range. [ABSTRACT FROM AUTHOR]

Dupont-Versteegden EE, Nagarajan R, Beggs ML, Bearden ED, Simpson PM, Peterson CA. Identification of cold-shock protein RBM3 as a possible regulator of skeletal muscle size through expression profiling. Am J Physiol Regul Integr Comp Physiol 295: R1263-R1273, 2008. First published August 27, 2008; doi:l0.l l52lajpregu.90455.2008.Changes in gene expression associated with skeletal muscle atrophy due to aging are distinct from those due to disuse, suggesting that the response of old muscle to inactivity may be altered. The goal of this study was to identify changes in muscle gene expression that may contribute to loss of adaptability of old muscle. Muscle atrophy was induced in young adult (6-mo) and old (32-mo) male Brown Norway! F344 rats by 2 wk of hindlimb suspension (HS), and soleus muscles were analyzed by cDNA microarrays. Overall, similar changes in gene expression with HS were observed in young and old muscles for genes encoding proteins involved in protein folding (heat shock proteins), muscle structure, and contraction, extracellular matrix, and nucleic acid binding. More genes encoding transport and receptor proteins were differentially expressed in the soleus muscle from young rats, while in soleus muscle from old rats more genes that encoded ribosomal proteins were upregulated. The gene encoding the cold-shock protein RNA-binding motif protein-3 (RBM3) was induced most highly with HS in muscle from old rats, verified by real-time RT-PCR, while no difference with age was observed. The cold-inducible RNA-binding protein (Cirp) gene was also overexpressed with HS, whereas cold-shock protein Y-box-binding protein-I was not. A time course analysis of RBM3 mRNA abundance during HS showed that upregulation occurred after apoptotic nuclei and markers of protein degradation increased. We conclude that a coldshock response may be part of a compensatory mechanism in muscles undergoing atrophy to preserve remaining muscle mass and that RBM3 may be a therapeutic target to prevent muscle loss. [ABSTRACT FROM AUTHOR]

Context. Studies examining the association between food insecurity and obesity in adults have produced conflicting results, and information is limited on the relationship between food insecurity and adult chronic health conditions, particularly in a high-risk population. Objective. To examine the association between household food insecurity and self-reported weight status and chronic disease in the Lower Mississippi Delta. Design. A two-stage stratified cluster sample representative of the population in 36 counties in the Lower Delta. Data were collected in a cross-sectional telephone survey using list assisted random digit dialing telephone methodology. Setting and Participants. A randomly selected sample of 1,457 adults from a free-living population. Main Outcome Measures. US Food Security Survey Module, self-reported height and weight status (obesity = body mass index > 30 kg/m²), and self-reported hypertension, high cholesterol, diabetes, heart disease, stroke, and a marker for metabolic syndrome. Results. In food-insecure adults, 42.3% were obese, a significantly higher rate than food secure adults (33.2%). After controlling for demographic variables, food insecurity was not independently associated with obesity. Income and the interaction between race and gender were significant predictors of obesity. Food insecure adults were significantly more likely to report hypertension (45.1% vs. 29.5%) diabetes (15.0% vs. 9.3%), heart disease (13.5% vs. 6.8%) and metabolic syndrome (10.1% vs. 4.4%). After controlling for demographic variables, food insecurity was associated with high cholesterol (Odds Ratio [OR] 1.65; 95% Confidence Interval [CI], 1.0 to 2.7), heart disease (OR 2.7: 95% CI, 1.5 to 4.8), and metabolic syndrome (OR 2.8; 95% CI, 1.4 to 5.5). Conclusions. The relationship between food insecurity and obesity in a high-risk population, may be due to income and demographic variables. Individuals in a rural high-risk population with high cholesterol, heart disease, and metabolic syndrome have a high likelihood of being food-insecure. Nutritional interventions targeting high-risk populations should address food insecurity. [ABSTRACT FROM AUTHOR]

Granulomatous and lymphocytic interstitial lung disease (GLILD) is a life-threatening complication in patients with common variable immunodeficiency (CVID), but the optimal treatment is unknown. Our aim was to determine whether rituximab with azathioprine or mycophenolate mofetil improves the high-resolution computed tomography (HRCT) chest scans and/or pulmonary function test results in patients with CVID and GLILD. A retrospective chart review of clinical and laboratory data on 39 patients with CVID and GLILD who completed immunosuppressive therapy was performed. Chest HRCT scans, performed before therapy and after the conclusion of therapy, were blinded, randomized, and scored independently by 2 radiologists. Differences between pretreatment and posttreatment HRCT scan scores, pulmonary function test results, and lymphocyte subsets were analyzed. Whole exome sequencing was performed on all patients. Immunosuppressive therapy improved patients' HRCT scan scores (P <.0001), forced vital capacity (P =.0017), FEV 1 (P =.037), and total lung capacity (P =.013) but not their lung carbon monoxide diffusion capacity (P =.12). Nine patients relapsed and 6 completed retreatment, with 5 of 6 of these patients (83%) having improved HRCT scan scores (P =.063). Relapse was associated with an increased number of B cells (P =.016) and activated CD4 T cells (P =.016). Four patients (10%) had pneumonia while undergoing active treatment, and 2 patients (5%) died after completion of therapy. Eight patients (21%) had a damaging mutation in a gene known to predispose (TNFRSF13B [n = 3]) or cause a CVID-like primary immunodeficiency (CTLA4 [n = 2], KMT2D [n = 2], or BIRC4 [n = 1]). Immunosuppression improved the HRCT scan scores in patients with (P =.0078) and without (P <.0001) a damaging mutation. Immunosuppressive therapy improved the radiographic abnormalities and pulmonary function of patients with GLILD. A majority of patients had sustained remissions. [ABSTRACT FROM AUTHOR]

Background: The aims of the study were to assess the performance of a clinically available cell‐free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. Methods: Observational, non‐interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy‐associated plasma samples were used for cfDNA measurements. Pre‐determined cut points were tested for analytic performance. Results: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df‐cfDNA values between rejection [0.21% (IQR 0.12–0.69)] and healthy samples [0.05% (IQR 0.01–0.14), p <.0001]. The pediatric rejection group had a median df‐cfDNA value of 0.93% (IQR 0.28–2.84) compared to 0.09% (IQR 0.04–0.23) for healthy samples, p =.005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. Conclusion: The study suggests that pediatric patients with rejection show higher levels of circulating df‐cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance. [ABSTRACT FROM AUTHOR]

Background Viral respiratory tract infections increase the risk of development and exacerbation of atopic disease. Previously, we demonstrated the requirement for a neutrophil (PMN) subset expressing CD49d to drive development of postviral atopic airway disease in mice. Objective We sought to determine whether human CD49d+ PMNs are present in the nasal mucosa during acute viral respiratory tract infections and further characterize this PMN subset in human subjects and mice. Methods Sixty subjects (5-50 years old) were enrolled within 4 days of acute onset of upper respiratory symptoms. Nasal lavage for flow cytometry and nasal swabs for viral PCR were performed at enrollment and during convalescence. The Sendai virus mouse model was used to investigate the phenotype and functional relevance of CD49d+ PMNs. Results CD49d+ PMN frequency was significantly higher in nasal lavage fluid during acute respiratory symptoms in all subjects (2.9% vs 1.0%, n = 42, P <.001). In mice CD49d+ PMNs represented a "proatopic" neutrophil subset that expressed cysteinyl leukotriene receptor 1 (CysLTR1) and produced TNF, CCL2, and CCL5. Inhibition of CysLTR1 signaling in the first days of a viral respiratory tract infection was sufficient to reduce accumulation of CD49d+ PMNs in the lungs and development of postviral atopic airway disease. Similar to the mouse, human CD49d+ PMNs isolated from nasal lavage fluid during a viral respiratory tract infection expressed CysLTR1. Conclusion CD49d and CysLTR1–coexpressing PMNs are present during symptoms of an acute viral respiratory tract infection in human subjects. Further study is needed to examine selective targeting of proatopic neutrophils as a potential therapeutic strategy to prevent development of postviral atopic airway disease. Graphical abstract [ABSTRACT FROM AUTHOR]

Objective To derive and validate an objective definition of postoperative bleeding in neonates and infants undergoing cardiac surgery with cardiopulmonary bypass. Methods Using a retrospective cohort of 124 infants and neonates, we included published bleeding definitions and cumulative chest tube output over different postoperative periods (eg, 2, 12, or 24 hours after intensive care unit admission) in a classification and regression tree model to determine chest tube output volumes that were associated with red blood cell transfusions and surgical re-exploration for bleeding in the first 24 hours after intensive care unit admission. After the definition of excessive bleeding was determined, it was validated via a prospective cohort of 77 infants and neonates. Results Excessive bleeding was defined as ≥7 mL/kg/h for ≥2 consecutive hours in the first 12 postoperative hours and/or ≥84 mL/kg total for the first 24 postoperative hours and/or surgical re-exploration for bleeding or cardiac tamponade physiology in the first 24 postoperative hours. Excessive bleeding was associated with longer length of hospital stay, increased 30-day readmission rate, and increased transfusions in the postoperative period. Conclusions The proposed standard definition of excessive bleeding is based on readily obtained objective data and relates to important early clinical outcomes. Application and validation by other institutions will help determine the extent to which our specialty should consider this definition for both clinical investigation and quality improvement initiatives. [ABSTRACT FROM AUTHOR]

Objectives: Central venous access devices, including peripherally inserted central catheters and central venous catheters, are often needed in critically ill patients, but also are associated with complications, including central-line associated bloodstream infections and venous thromboembolism. We compared different central venous access device types and these complications in the PICU.Design: Multicenter, cohort study.Setting: One hundred forty-eight participating Virtual PICU Systems, LLC, hospital PICU sites.Patients: Pediatric patients with central venous access placed from January 1, 2010, to December 31, 2015.Interventions: None.Measurements and Main Results: Patient and central venous access device variables postulated to be associated with central-line associated bloodstream infection and venous thromboembolism were included. Data were analyzed using Pearson chi-square test or Fisher exact test for categorical variables, Mann-Whitney U test for continuous variables, and logistic regression and classification trees for multivariable analysis that examined significant predictors of venous thromboembolism or central-line associated bloodstream infection. Analysis included 74,196 first lines including 4,493 peripherally inserted central catheters and 66,194 central venous catheters. An increased rate of venous thromboembolism (peripherally inserted central catheter: 0.93%, central venous catheter: 0.52%; p = 0.001) (peripherally inserted central catheter: 8.65/1,000 line days, central venous catheter: 6.29/1,000 line days) and central-line associated bloodstream infection (peripherally inserted central catheter: 0.73%, central venous catheter: 0.24%; p = 0.001) (peripherally inserted central catheter: 10.82/1,000 line days, central venous catheter: 4.97/1,000 line days) occurred in peripherally inserted central catheters. In multivariable analysis, central venous catheters had decreased association with central-line associated bloodstream infection (odds ratio, 0.505; 95% CI, 0.336-0.759; p = 0.001) and venous thromboembolism (odds ratio, 0.569; 95% CI, 0.330-0.982; p = 0.043) compared with peripherally inserted central catheters.Conclusions: Peripherally inserted central catheters are associated with higher rates of central-line associated bloodstream infection and venous thromboembolism than central venous catheters in children admitted to the PICU. [ABSTRACT FROM AUTHOR]

Background & Aims A rapid and reliable point-of-care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high-pressure liquid chromatography with electrochemical detection (HPLC-EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. Methods We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen-associated acute liver injury, and 33 patients with acetaminophen-associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC-EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal–Wallis test or rank-sum test for continuous variables. Results AcetaSTAT discriminated between patients with and without acetaminophen-associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen-associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without ( P < .001). AcetaSTAT identified patients with acetaminophen-associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non–acetaminophen-associated acute liver injury; HPLC-EC and biochemical profiles were consistent with acetaminophen-associated acute liver injury in 3 of these cases. Conclusions The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC-EC results in identifying patients with acetaminophen-associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is the leading cause of death and long-term disability among injured children. Early feeding has been shown to improve outcomes in adults, with some similar evidence in children with severe TBI. We aimed to examine the current practice of initiation of enteral nutrition in children with TBI and to evaluate the risk factors associated with delayed initiation of enteral nutrition.Methods: This retrospective, multicenter study used the Pediatric Trauma Assessment and Management Database including all children with head trauma discharged from five pediatric intensive care units (PICU) at pediatric trauma centers between January 1, 2013 and December 31, 2013. We compared demographics, injury and procedure data, time to initiation of nutrition, and injury and illness severity scores between patients who received enteral nutrition early (≤ 48 h) and late (> 48 h). Fisher's exact and Mann-Whitney U tests compared discrete and continuous variables. Univariate and multivariable analyses evaluated variables associated with delayed initiation of feeding. Outcomes of interest included mortality, complications, ventilator days, hospital and ICU length of stay, and functional status at ICU discharge.Results: In the 416 patients in the study, the overall mortality was 2.6%. The majority of patients (83%; range 69-88% between five sites, p = 0.0008) received enteral nutrition within 48 h of PICU admission. Lower Glasgow Coma Scale scores and higher Injury Severity Score (ISS) were independently associated with delayed initiation of enteral nutrition. Delayed enteral nutrition was independently associated with worse functional status at PICU discharge (p = 0.02) but was not associated with mortality or increased length of stay.Conclusions: Children with severe TBI and higher ISS were more likely to have delayed initiation of enteral nutrition. Delayed enteral nutrition was an independent risk factor for worse functional status at ICU discharge for the entire cohort, but not for the severe TBI group. [ABSTRACT FROM AUTHOR]

Background Premature and critically ill infants receiving total parenteral nutrition (TPN) are at risk for dyslipidemia, and altered cholesterol levels in early life may contribute to later cardiovascular risk. Data regarding plasma cholesterol response to TPN in young infants are lacking. Objective To determine the changes in plasma cholesterol levels during the first week of life in infants receiving TPN and a comparison group of infants who did not receive TPN during routine care. Methods In a prospective, pilot cohort study, 38 neonates (30 TPN vs. 8 No-TPN) underwent serial blood sampling during the first week of life. Gas chromatography–mass spectrometry was used to measure cholesterol in plasma and TPN administered to study participants. Results Baseline cholesterol level was similar between groups. In contrast to infants who did not receive TPN, cholesterol levels during the first week of life were significantly higher than baseline in infants receiving TPN (maximum cholesterol response 34% vs. 103% change from baseline, No-TPN vs. TPN, respectively, P = .036). After adjusting for cumulative cholesterol received by infants receiving TPN, maximum cholesterol response remained inversely related to gestational age and birth weight ( P < .05). Conclusion Plasma cholesterol significantly increases during the first week of life in neonates receiving TPN. A higher cholesterol response was induced by TPN in infants of lower gestational age and birth weight. [ABSTRACT FROM AUTHOR]