Yumei Cao

Bacteriocin production augments niche competition by enterococci in the mammalian gastrointestinal tract.

Enterococcus faecalis is both a common commensal of the human gastrointestinal tract and a leading cause of hospital-acquired infections. Systemic infections with multidrug-resistant enterococci occur subsequent to gastrointestinal colonization. Preventing colonization by multidrug-resistant E. faecalis could therefore be a valuable approach towards limiting infection. However, little is known about the mechanisms E. faecalis uses to colonize and compete for stable gastrointestinal niches. Pheromone-responsive conjugative plasmids encoding bacteriocins are common among enterococcal strains and could modulate niche competition among enterococci or between enterococci and the intestinal microbiota. We developed a model of colonization of the mouse gut with E. faecalis, without disrupting the microbiota, to evaluate the role of the conjugative plasmid pPD1 expressing bacteriocin 21 (ref. 4) in enterococcal colonization. Here we show that E. faecalis harbouring pPD1 replaces indigenous enterococci and outcompetes E. faecalis lacking pPD1. Furthermore, in the intestine, pPD1 is transferred to other E. faecalis strains by conjugation, enhancing their survival. Colonization with an E. faecalis strain carrying a conjugation-defective pPD1 mutant subsequently resulted in clearance of vancomycin-resistant enterococci, without plasmid transfer. Therefore, bacteriocin expression by commensal bacteria can influence niche competition in the gastrointestinal tract, and bacteriocins, delivered by commensals that occupy a precise intestinal bacterial niche, may be an effective therapeutic approach to specifically eliminate intestinal colonization by multidrug-resistant bacteria, without profound disruption of the indigenous microbiota.

Risk and Prevalence of Developmental Delay in Young Children With Congenital Heart Disease

BACKGROUND AND OBJECTIVE: Children with congenital heart disease (CHD) are at risk for developmental delay (DD). Changes in cognitive, language, and motor skills in early childhood have not been described. We report the results of a structured approach using longitudinal testing to identify problems and ensure early intervention in accordance with published guidelines. METHODS: Bayley Scales of Infant Development, Third Edition, were used to assess cognitive, language, and motor skills in 99 children with CHD. Subjects were evaluated 3 to 6 times in the first 3 years of life. DD was defined as scores >1 SD below the population mean. RESULTS: Cardiac anatomy was single ventricle (1V) in 34 subjects and 2 ventricles (2V) in 65. Medical comorbidities were present in 21% and genetic syndromes in 19%. Most subjects (75%) had DD in ≥1 area at ≥1 assessments. Subjects with 1V anatomy had equivalent outcomes to those with 2V. Cognitive and language scores declined in subjects with genetic syndromes but were stable and within the average range for subjects with 1V and 2V. Motor scores improved for subjects with 1V and 2V but remained low for those with genetic syndromes. In addition to age, need for supplemental tube feeding, longer cardiopulmonary bypass time, and shorter time since last hospitalization were significant predictors of developmental outcomes. CONCLUSIONS: DDs in young children with CHD are both common and dynamic. Providers should encourage longitudinal surveillance for children with CHD because exposure to risk and prevalence of DD change over time.

Outcomes of systemic to pulmonary artery shunts in patients weighing less than 3 kg: analysis of shunt type, size, and surgical approach.

OBJECTIVE To evaluate outcomes of systemic to pulmonary artery shunts (SPS) in patients weighing less than 3 kg with regard to shunt type, shunt size, and surgical approach. METHODS Patients weighing less than 3 kg who underwent modified Blalock-Taussig or central shunts with polytetrafluoroethylene grafts at our institution from January 1, 2000, to May 31, 2011, were reviewed. Patients who had undergone other major concomitant procedures were excluded from the analysis. Primary outcomes included mortality (discharge mortality and mortality before next planned palliative procedure or definitive repair), cardiac arrest and/or extracorporeal membrane oxygenation (ECMO), and shunt reintervention. RESULTS In this cohort of 80 patients, discharge survival was 96% (77/80). Postoperative cardiac arrest or ECMO occurred in 6/80 (7.5%), and shunt reintervention was required in 14/80 (17%). On univariate analysis, shunt reintervention was more common in patients with 3-mm shunts (11/30, 37%) compared with 3.5-mm (2/36, 6%) or 4-mm shunts (1/14, 7%) (P < .003). There were no statistically significant associations between shunt type, shunt size, or surgical approach and cardiac arrest/ECMO or mortality. Multiple logistic regression demonstrated that a shunt size of 3 mm (P = .019) and extracardiac anomaly (P = .047) were associated with shunt reintervention, whereas no variable was associated with cardiac arrest/ECMO or mortality. CONCLUSIONS In this high-risk group of neonates weighing less than 3 kg at the time of SPS, survival to discharge and the next planned surgical procedure was high. Outcomes were good with the 3.5- and 4-mm shunts; however, shunt reintervention was common with 3-mm shunts.

Pediatric Solid Organ Transplant Recipients: Transition to Home and Chronic Illness Care

Pediatric SOT recipients are medically fragile and present with complex care issues requiring high‐level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self‐managing their childs complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty‐one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post‐discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post‐discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post‐discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self‐manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post‐discharge care.

Risk Factors for Abnormal Developmental Trajectories in Young Children With Congenital Heart Disease

Background— Children with congenital heart disease are at risk for developmental delay. This study sought to identify early risk factors for abnormal developmental trajectories in children with congenital heart disease. Methods and Results— Children with congenital heart disease at high risk for developmental delay, without known genetic abnormality, and with ≥3 assessments by the use of the Bayley Scales of Infant and Toddler Development, Third Edition, were studied. Logistic regression was used to assess the impact of patient and clinical factors on cognitive, language, and motor score trajectories; classified as: average or improved if all scores were ≥85 (<1 standard deviation below the mean) or increased to ≥85 and never decreased; or abnormal if all scores were <85, fell to <85 and never improved, or fluctuated above and below 85. Data on 131 children with 527 Bayley Scales of Infant and Toddler Development, Third Edition assessments were analyzed. Subject age was 5.5 to 37.4 months. Overall, 56% had cognitive, language, and motor development in the average range. Delays occurred in single domains in 23%. Multiple domains were delayed in 21%. More cardiac surgeries, longer hospital stay, poorer linear growth, and tube feeding were associated with worse outcomes in all domains (P<0.05). In the multivariable model, the need for tube feeding was a risk factor for having an abnormal developmental trajectory (odds ratio, 5.1–7.9). Minority race and lack of private insurance had significant relationships with individual domains. Conclusions— Longitudinal developmental surveillance identified early factors that can help quantify the risk of developmental delay over time. Strategies to improve modifiable factors and early therapeutic intervention can be targeted to children at highest risk.

Comparison of WHO and CDC growth charts in predicting pulmonary outcomes in cystic fibrosis.

Objectives: The relation of weight-for-length (WFL) and weight-for-age (WFA) measurements with pulmonary function in patients with cystic fibrosis (CF) using the World Health Organization (WHO) growth standards has not been evaluated. The objective of the present study was to show that the relation of WFL and WFA measurements at 2 years with forced expiratory volume in 1 second (FEV1) at 6 to 8 years differs when using the WHO versus the Centers for Disease Control and Prevention (CDC) growth charts. Methods: We assessed 1155 patients in the CF Foundation Patient Registry born between 2001 and 2004. Comparisons were made between the CDC and WHO growth charts. Results: The WFL percentiles are significantly higher for the WHO growth standards compared with those for the CDC growth charts (median and interquartile range [IQR] WHO—64.8 [41.7–84.9], CDC—48.1 [23.7–75.7], P < 0.0001). WFL and WFA percentiles at 2 years on both charts are strongly associated with FEV1 at 6 to 8 years of age. The FEV1 at 6 to 8 years was statistically significantly lower for children who were classified as reaching a WFL ≥50th percentile at 2 years by WHO standards alone versus those who qualified by both growth charts (median and IQR 103 [94–115] vs 107 [96–117], P < 0.05). Continued weight gain between 2 and 6 years was associated with a higher lung function at age 6 to 8 years. Conclusions: Although children attaining the 50th WFL percentile on the WHO growth chart by age 2 years have a lower FEV1 at 6 years than children attaining the same percentile on the CDC chart, both groups of children attain clinically normal FEV1. Further studies are needed to determine whether this difference is clinically meaningful.

Changes in cerebral oxygen saturation correlate with S100B in infants undergoing cardiac surgery with cardiopulmonary bypass.

Objectives: The relationship of cerebral saturation measured by near-infrared spectroscopy with serum biomarker of brain injury S100B was investigated in infants undergoing cardiac surgery with cardiopulmonary bypass. Design: Prospective cohort study. Setting: Single-center children’s hospital. Patients: Forty infants between 1 and 12 months old weighing greater than or equal to 4 kg with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass were enrolled. Interventions: None. Measurements and Main Results: Serum S100B was measured at eight time points over 72 hours using enzyme-linked immunosorbent assay. Physiologic data including arterial, cerebral, and somatic regional oxygen saturations measured by near-infrared spectroscopy were synchronously recorded at 1-minute intervals from anesthesia induction through 72 postoperative hours. The arterial-cerebral oxygen saturation difference was calculated as the difference between arterial saturation and cerebral regional saturation. Thirty-eight patients, 5.4 ± 2.5 months old, were included in the analysis; two were excluded due to the use of postoperative extracorporeal membrane oxygenation. Seventeen patients (44.7%) had preoperative cyanosis. S100B increased during cardiopulmonary bypass in all patients, from a median preoperative baseline of mean ± SE: 0.055 ± 0.038 to a peak of 0.610 ± 0.038 ng/mL, p less than 0.0001. Patients without preoperative cyanosis had a higher S100B peak at the end of cardiopulmonary bypass. Although the absolute cerebral regional saturation on cardiopulmonary bypass was not associated with S100B elevation, patients who had arterial-cerebral oxygen saturation difference greater than 50 at any time during cardiopulmonary bypass had a higher S100B peak (mean ± SE: 1.053 ± 0.080 vs 0.504 ± 0.039 ng/mL; p < 0.0001). Conclusions: A wide cerebral arteriovenous difference measured by near-infrared spectroscopy during cardiopulmonary bypass is associated with increased serum S100B in the perioperative period and may be a modifiable risk factor for neurological injury.

Paneth cell defects in Crohn’s disease patients promote dysbiosis

BACKGROUND Paneth cell dysfunction has been implicated in a subset of Crohns disease (CD) patients. We previously stratified clinical outcomes of CD patients by using Paneth cell phenotypes, which we defined by the intracellular distribution of antimicrobial proteins. Animal studies suggest that Paneth cells shape the intestinal microbiome. However, it is unclear whether Paneth cell phenotypes alter the microbiome complexity in CD subjects. Therefore, we analyzed the correlation of Paneth cell phenotypes with mucosal microbiome composition and ileal RNA expression in pediatric CD and noninflammatory bowel disease (non-IBD) patients. METHODS Pediatric CD (n = 44) and non-IBD (n = 62) patients aged 4 to 18 were recruited prior to routine endoscopic biopsy. Ileal mucosal samples were analyzed for Paneth cell phenotypes, mucosal microbiome composition, and RNA transcriptome. RESULTS The prevalence of abnormal Paneth cells was higher in pediatric versus adult CD cohorts. For pediatric CD patients, those with abnormal Paneth cells showed significant changes in their ileal mucosal microbiome, highlighted by reduced protective microbes and enriched proinflammatory microbes. Ileal transcriptome profiles showed reduced transcripts for genes that control oxidative phosphorylation in CD patients with abnormal Paneth cells. These transcriptional changes in turn were correlated with specific microbiome alterations. In non-IBD patients, a subset contained abnormal Paneth cells. However, this subset was not associated with alterations in the microbiome or host transcriptome. CONCLUSION Paneth cell abnormalities in human subjects are associated with mucosal dysbiosis in the context of CD, and these changes are associated with alterations in oxidative phosphorylation, potentially in a feedback loop. FUNDING The research was funded by Helmsley Charitable Trust (to T.S. Stappenbeck, R.J. Xavier, and D.P.B. McGovern), Crohns and Colitis Foundation of America (to N.H. Salzman, T.S. Stappenbeck, R.J. Xavier, and C. Huttenhower), and Doris Duke Charitable Foundation grant 2014103 (to T.C. Liu).

Transposition of the great arteries--outcomes and time interval of early neonatal repair.

Background: This study evaluates the relationship of morbidity and resource utilization with the timing of early neonatal repair of transposition of the great arteries and intact ventricular septum (d-TGA/IVS). Methods: All patients with d-TGA/IVS who underwent arterial switch in the first 14 days of life, between January 2000 and May 2011, were reviewed. Patients undergoing repair at ≤4 days of age were categorized as group I, 5 to 7 days as group II, and 8 to 14 days as group III. Outcomes included mortality, morbidity, and resource utilization. Results: Hospital survival was 69 (98.6%) of 70. The length of stay (LOS) and total charges were lowest in group I—15.5 days compared to group II—18.0 days and group III—23.5 days (P = .005); group I—US

Kinetics of phytosterol metabolism in neonates receiving parenteral nutrition

128,219 compared to group II—US