New-onset diabetes after pediatric heart transplantation: A review of the Pediatric Heart Transplant Study.

NDT is a well-defined complication after solid organ transplantation. Little has been published describing the incidence, risk factors, and effect on outcome after pediatric heart transplantation. We performed a retrospective evaluation of pediatric patients from the PHTS registry from 2004 to 2014. Group comparison, associated factors, incidence using Kaplan-Meier method, and risk factor and outcome analysis for NDT at 1 year post-transplant. Of the 2185 recipients, 1756 were alive and followed at 1 year. Overall freedom from NDT was 98.9%, 94.7%, and 92.6% at 1, 5, and 10 years, respectively. Patients with NDT were more likely to be black (non-Hispanic; P = 0.002), older at time of transplant (P < 0.0001), and have a higher BMI percentile at time of transplant (P < 0.0001). Adjusted risk factors for NDT at 1 year were older age at transplant (years; >12 years, OR: 8.8 and 5-12 years, HR: 8.0), obese BMI percentile at time of transplant (OR: 3.8), and steroid use at 30 days after transplant (OR: 4.7). Though uncommon, NDT occurs with a constant hazard after pediatric heart transplant; it occurs more often in older patients at transplant, those who are of black race, those who are obese, and those who use steroids. Therefore, targeted weight reduction and selective steroid use in at-risk populations could reduce the incidence of early NDT. Further data are needed to determine the risk imparted by transplantation, factors that predict late-onset NDT, and whether NDT alters the outcome after transplant.

Improved Survival While Waiting and Risk Factors for Death in Pediatric Patients Listed for Cardiac Transplantation.

Our aim is to determine (a) the effect of changes in pre-transplant management and era of listing on survival of children listed for HTx and (b) risk factors for death while waiting. This retrospective study included all children listed between 1/1993 and 12/2009 at our center. Survival was determined using survival analysis and competing outcomes modeling. There were 254 listed patients of whom 144 (57%) had congenital heart disease, 208 (82%) were status 1, 52 used ECMO (20%), and 28 used ventricular assist device support (VAD) (11%) beginning in 2005. Overall mortality while waiting was 17% at 6 months, and 69% underwent transplant. Seven of 95 patients (7%) died waiting after 2004 compared to 36 of 159 (23%) before. ECMO and earlier year of listing were significant risk factors (p < 0.001) for wait-list mortality, whereas mortality was significantly lower (p = 0.002) after availability of VADs. Race, gender, blood type, and congenital diagnosis were not significant risk factors for death. Survival in pediatric patients listed for HTx has improved significantly in the current era at our institution. The availability of pediatric VADs has had a significant impact on survival while waiting in children listed for transplantation.

Comparison of in-hospital and longer-term outcomes of hybrid and Norwood stage 1 palliation of hypoplastic left heart syndrome.

OBJECTIVES: The hybrid approach for the initial management of hypoplastic left heart syndrome shifts the risks of major open surgery from the vulnerable neonatal period to an older age. This study determined differences between the hybrid and the standard Norwood procedures in postoperative in-hospital mortality, renal failure, and survival to at least 2 years of age. METHODS: Data from the Pediatric Health Information System, a detailed hospital discharge database of 43 freestanding children's hospitals, were analyzed. The Pediatric Health Information System includes demographic information, diagnosis, and procedure and clinical service data. Instrumental variable regression techniques were used to estimate the predicted probability of in-hospital mortality, renal failure, and survival to 24 months of age for infants with hypoplastic left heart syndrome who received a hybrid or Norwood procedure. The statistical models controlled for demographics and comorbid chromosomal anomalies. RESULTS: A total of 3654 infants with hypoplastic left heart syndrome underwent intervention from 1998 to 2012. Of these, 242 underwent the hybrid approach and the remainder underwent the Norwood procedure. Instrumental variable models showed significantly reduced odds of patients who underwent the hybrid approach being diagnosed with renal failure (adjusted risk ratio [ARR], 0.48; 95% confidence interval [CI], 0.26-0.89); increased odds of surviving initial hospitalization (ARR, 1.28; 95% CI, 1.06-1.55); increased odds of survival, indicated by readmissions more than 6 months after initial hospitalization (ARR, 1.53; 95% CI, 1.05-2.22); and a decrease in length of stay by 20 days for the initial surgical hospitalization (95% CI, -27.4 to -13.9). CONCLUSIONS: The short term hospital-based outcomes and longer-term survival outcomes of the hybrid approach for hypoplastic left heart syndrome may be better than those of the Norwood procedure.

In-feed use of heavy metal micronutrients in U.S. swine production systems and its role in persistence of multidrug-resistant salmonellae.

The study aimed to characterize the role of heavy metal micronutrients in swine feed in emergence of heavy-metal-tolerant and multidrug-resistant Salmonella organisms. We conducted a longitudinal study in 36 swine barns over a 2-year period. The feed and fecal levels of Cu(2+) and Zn(2+) were measured. Salmonella was isolated at early and late finishing. MICs of copper sulfate and zinc chloride were measured using agar dilution. Antimicrobial susceptibility was tested using the Kirby-Bauer method, and 283 isolates were serotyped. We amplified pcoA and czcD genes that encode Cu(2+) and Zn(2+) tolerance, respectively. Of the 283 isolates, 113 (48%) showed Cu(2+) tolerance at 24 mM and 164 (58%) showed Zn(2+) tolerance at 8 mM. In multivariate analysis, serotype and source of isolates were significantly associated with Cu(2+) tolerance (P < 0.001). Fecal isolates were more likely to be Cu(2+) tolerant than those of feed origin (odds ratio [OR], 27.0; 95% confidence interval [CI], 2.8 to 250; P = 0.0042) or environmental origin (OR, 5.8), implying the significance of gastrointestinal selective pressure. Salmonella enterica serotypes Typhimurium and Heidelberg, highly significant for public health, had higher odds of having >20 mM MICs of Cu(2+) than did "other" serotypes. More than 60% of Salmonella isolates with resistance type (R-type) AmStTeKm (32 of 53) carried pcoA; only 5% with R-type AmClStSuTe carried this gene. czcD gene carriage was significantly associated with a higher Zn(2+) MIC (P < 0.05). The odds of having a high Zn(2+) MIC (≥8 mM) were 14.66 times higher in isolates with R-type AmClStSuTe than in those with R-type AmStTeKm (P < 0.05). The findings demonstrate strong association between heavy metal tolerance and antimicrobial resistance, particularly among Salmonella serotypes important in public health.

A multicenter study of primary graft failure after infant heart transplantation: impact of extracorporeal membrane oxygenation on outcomes.

Primary graft failure is the major cause of mortality in infant HTx. The aim of this study was to characterize the indication and outcomes of infants requiring ECMO support due to primary graft failure after HTx. We performed a retrospective review of all infants (<1 yr) who underwent Htx from three institutions. From 1999 to 2008, 92 infants (<1 yr) received Htx. Sixteen children (17%) required ECMO after Htx due to low cardiac output syndrome. Eleven (69%) infants were successfully weaned off ECMO, and 9 (56%) infants were discharged with a mean follow-up of 2.3 ± 2.5 yr. Mean duration of ECMO in survivors was 5.4 days (2-7 days) compared with eight days (2-10 days) in non-survivors (p = NS). The five-yr survival rate for all patients was 75%; however, the five-yr survival rate was 40% in the ECMO cohort vs. 80% in the non-ECMO cohort (p = 0.0001). Graft function within one month post-Htx was similar and normal between ECMO and non-ECMO groups (shortening fraction = 42 ± 3 vs. 40 ± 2, p = NS). For infants, ECMO support for primary graft failure had a lower short-term and long-term survival rate vs. non-ECMO patients. Duration of ECMO did not adversely impact graft function and is an acceptable therapy for infants after HTx for low cardiac output syndrome.

Effects of quaternary benzo(c)phenanthridine alkaloids on growth performance, shedding of organisms, and gastrointestinal tract integrity in pigs inoculated with multidrug-resistant Salmonella spp.

OBJECTIVE: To evaluate effects of quaternary benzo(c)phenanthridine alkaloids (QBAs) against Salmonella spp and determine effects on growth performance, organism shedding, and gastrointestinal tract integrity in pigs inoculated with Salmonella enterica serovar Typhimurium. SAMPLE: 36 Salmonella isolates and twenty 5-week-old pigs. PROCEDURES: Minimum inhibitory concentration of QBAs against the Salmonella isolates was determined. Pigs were allocated to 4 groups and inoculated with Salmonella organisms. Pigs received diets supplemented with 1.5 g of QBAs/1,000 kg of feed, 0.75 g of QBAs/1,000 kg of feed, or 59.4 g of chlortetracycline/1,000 kg of feed or a nonsupplemented (control) diet. Pigs were weighed on day 0 and then weekly for 40 days. Fecal samples were collected to quantify Salmonella organisms. Gastrointestinal tract integrity was evaluated by measuring transepithelial resistance. RESULTS: In vitro, 9 of 36 (25%) Salmonella isolates were inhibited at 90 µg of QBAs/mL; all 36 were inhibited at 179 µg of QBAs/mL. Diets containing QBAs significantly decreased Salmonella spp shedding; shedding was lower 40 days after inoculation for pigs fed diets containing QBAs or chlortetracycline than for pigs fed the control diet. Growth performance was similar for pigs fed diets containing QBA or chlortetracycline. Gastrointestinal tract integrity was improved in pigs fed the diet containing 1.5 g of QBAs/1,000 kg of feed. CONCLUSIONS AND CLINICAL RELEVANCE: QBAs and chlortetracycline decreased Salmonella spp shedding but did not differ with regard to growth performance. Gastrointestinal tract integrity was better, albeit not significantly, in pigs fed diets containing QBAs. Further investigation into the role of QBAs and their mechanism as an immunomodulator is necessary.

Implementing recommended screening for critical congenital heart disease.

BACKGROUND AND OBJECTIVE: Critical congenital heart disease (CCHD) is endorsed by the US Secretary of Health and Human Services as part of the recommended uniform screening panel for newborns. Although initial recommendations for implementation exist, as states and hospitals have moved forward with implementation of screening, new challenges and areas for additional focus have been identified. The objective of this study was to develop recommendations to address current challenges and areas of focus surrounding CCHD newborn screening. METHODS: A workgroup of experts and stakeholders was convened in Washington, District of Columbia, for a 1-day meeting in February 2012. At the beginning of the meeting, the stakeholders held a brainstorming session to identify areas of main priority based on their experience. After this, stakeholders broke into small groups to refine recommendations, which were then finalized by consensus. RESULTS: Recommendations to address selection of screening equipment, standards for reporting of screening outcomes to stakeholders, training of health care providers and educating families, future research priorities, payment for screening, follow-up diagnostic testing, and public health oversight, and advocacy to facilitate effective and comprehensive screening were proposed. Suggestions for future work were developed. CONCLUSIONS: Screening for CCHD presents novel challenges and opportunities; however, addressing these will strengthen newborn screening and newborn care networks, and ultimately improve health outcomes.

Quantification, identification, and relevance of anti-human leukocyte antigen antibodies formed in association with the berlin heart ventricular assist device in children.

BACKGROUND: Ventricular assist devices (VADs) are increasingly being used in pediatric patients to provide long-term cardiac support. One potential complication of VAD therapy is the development of antibodies directed against human leukocyte antigens (HLA). This phenomenon has not been well described with the Berlin Heart EXCOR VAD, the most commonly used VAD in pediatric patients. METHODS: The records of all pediatric patients undergoing VAD support using the Berlin Heart device at our institution between April 2005 and August 2011 were reviewed retrospectively. Demographic and clinical data regarding the VAD course were collected. Assessment of anti-HLA antibodies was performed using Luminex, and antibodies were quantified using mean fluorescence intensity (MFI). Assessment for anti-HLA antibodies was performed before VAD implantation and in serial fashion after VAD implantation. Clinically significant anti-HLA antibodies (sensitization) were defined by an MFI of more than 1000. RESULTS: Thirty-six patients were supported with the Berlin Heart VAD; 13 met inclusion criteria. The majority (85%) carried the diagnosis of dilated cardiomyopathy. Evidence of sensitization pre-VAD was found in 69%; new-onset sensitization (the development of new antibodies on VAD) occurred in 69%. All patients survived to transplantation. In two patients, the retrospective crossmatch was positive, but only in one patient was the crossmatch positive for antibodies formed while on VAD. CONCLUSIONS: Using Luminex and MFI quantification, anti-HLA antibodies are common before VAD implantation in pediatric patients. While on VAD support, new anti-HLA antibodies formed in a majority, but the immediate impact of these antibodies appears to be limited.

Yersinia enterocolitica of porcine origin: carriage of virulence genes and genotypic diversity.

Yersinia enterocolitica is an important foodborne pathogen, and pigs are recognized as a major reservoir and potential source of pathogenic strains to humans. A total of 172 Y. enterocolitica recovered from conventional and antimicrobial-free pig production systems from different geographic regions (North Carolina, Ohio, Michigan, Wisconsin, and Iowa) were investigated to determine their pathogenic significance to humans. Phenotypic and genotypic diversity of the isolates was assessed using antibiogram, serogrouping, and amplified fragment length polymorphism (AFLP). Carriage of chromosomal and plasmid-borne virulence genes were investigated using polymerase chain reaction. A total of 12 antimicrobial resistance patterns were identified. More than two-thirds (67.4%) of Y. enterocolitica were pan-susceptible, and 27.9% were resistant against ß-lactams. The most predominant serogroup was O:3 (43%), followed by O:5 (25.6%) and O:9 (4.1%). Twenty-two of 172 (12.8%) isolates were found to carry Yersinia adhesion A (yadA), a virulence gene encoded on the Yersinia virulence plasmid. Sixty-nine (40.1%) isolates were found to carry ail gene. The ystA and ystB genes were detected in 77% and 26.2% of the strains, respectively. AFLP genotyping of isolates showed wide genotypic diversity and were grouped into nine clades with an overall genotypic similarity of 66.8-99.3%. AFLP analysis revealed that isolates from the same production system showed clonal relatedness, while more than one genotype of Y. enterocolitica circulates within a farm.

Conal septal morphometrics can identify higher risk neonates with tetralogy of Fallot.

BACKGROUND: Some neonates with tetralogy of Fallot (TOF) have rapid progression of right ventricular outflow tract obstruction, requiring early repair irrespective of Doppler gradient as measured in the neonatal period. The aim of this study was to test the hypothesis that infundibular morphology in neonates with TOF is associated with the occurrence of hypercyanotic spells and need for neonatal surgery. METHODS: Fifty patients with TOF undergoing surgical repair from 2003 to 2009 were studied. Neonatal echocardiograms were retrospectively analyzed to measure conal septal angle (the angle between the conal septum and the horizontal plane passing through the center of the aortic valve in the parasternal short-axis view, with a larger angle denoting more anterocephalad deviation of conal septum), conal septal thickness and length, the degree of aortic dextroposition, and sizes and Z scores of the pulmonary annulus and the main and branch pulmonary arteries. Outcomes included the occurrence of hypercyanotic spells and the need for neonatal surgery. RESULTS: The median age at first echocardiogram was 2 days (range, 0-12 days). The median age at surgery was 94 days (range, 5-282 days); hypercyanotic spells occurred in 17 patients (34%), and nine (18%) underwent neonatal repair. The presence of a wider conal septal angle was significantly associated with the occurrence of hypercyanotic spells (59 ± 21° vs 48 ± 13°, P = .023) and the need for neonatal surgery (67 ± 13° vs 48 ± 16°, P = .004). The positive and negative predictive values of hypercyanotic spells for conal septal angles ≥60° were 64% and 78%, respectively. Importantly, Doppler right ventricular outflow tract gradient at initial echocardiography, degree of aortic dextroposition, and pulmonary or aortic valve size were not associated with these outcomes. CONCLUSIONS: A wider conal septal angle is associated with the occurrence of hypercyanotic spells and the need for neonatal surgery.

Pulse oximetry screening for critical congenital heart disease: a review.

Evidence demonstrates that screening newborns for critical CHD via SpO2 is practicable, efficacious, and has excellent sensitivity and specificity. SpO2 does not detect all forms of CHD, but does detect those presenting with hypoxemia. Although SpO2 screening has been recommended at the federal government level, states are ultimately responsible for the initiation and management of neonatal SpO2 screening programs. Issues of logistics, training and education, quality control, and reimbursement remain incompletely addressed but are anticipated to be resolved in the near future.

Noninvasive estimation of diastolic pulmonary artery pressure by Doppler analysis of tricuspid regurgitation velocity in pediatric patients.

PURPOSE: Diastolic pulmonary artery pressure (dPAP) is equal to right ventricular pressure at the time of pulmonary valve opening. We studied the accuracy of dPAP estimated from Doppler profile of tricuspid regurgitation (TR) jet in pediatric patients. METHODS: Echocardiograms were prospectively performed on consecutive pediatric heart transplant recipients undergoing right-heart catheterization and endomyocardial biopsy. An estimate of dPAP was obtained by superimposing the pulmonary valve opening time, indexed to the electrocardiogram, onto the TR Doppler tracing. Echocardiographic estimates of dPAP from end-diastolic pulmonary regurgitation (PR) were obtained for comparison. Catheter-derived right atrial pressure was added to the Doppler gradient in both groups. Doppler estimates and catheter-derived measurements of dPAP were compared using Lin correlation and Bland-Altman analysis. RESULTS: Sixty-five catheterization studies were performed on 35 patients (20 males): median age at enrollment: 12.1 years (4 months to 18 years); median time: since transplant of 1.2 years (21 days to 16.1 years). Adequate TR signal was obtained in a significantly higher proportion of patients than an adequate PR signal (65% vs. 43%, respectively, P = .007). Median catheter-derived dPAP was 12 mm Hg (6-30 mm Hg) and right atrial pressure was 6 mm Hg (1-17 mm Hg). Median estimated dPAP from TR was 15 mm Hg (range: 7-29 mm Hg), with the Lin correlation coefficient of 0.74 (95% confidence interval [CI]: 0.6-0.87). Median estimate for dPAP from PR was 10 mm Hg (range: 2-25 mm Hg), with the Lin correlation coefficient of 0.74 (95% CI: 0.58-0.9). There was excellent interobserver agreement for dPAP from TR with the Lin correlation coefficient of 0.946 (95% CI: 0.803-0.986). CONCLUSION: Doppler estimation of dPAP from TR is a novel, reliable, noninvasive method and compares favorably with estimation from PR. Adequate TR signal for estimation of dPAP can be obtained more frequently in children than adequate PR signal, thereby increasing the proportion of patients in whom dPAP can be estimated noninvasively.

Endorsement of Health and Human Services recommendation for pulse oximetry screening for critical congenital heart disease.

Incorporation of pulse oximetry to the assessment of the newborn infant can enhance detection of critical congenital heart disease (CCHD). Recently, the Secretary of Health and Human Services (HHS) recommended that screening for CCHD be added to the uniform screening panel. The American Academy of Pediatrics (AAP) has been a strong advocate of early detection of CCHD and fully supports the decision of the Secretary of HHS. The AAP has published strategies for the implementation of pulse oximetry screening, which addressed critical issues such as necessary equipment, personnel, and training, and also provided specific recommendations for assessment of saturation by using pulse oximetry as well as appropriate management of a positive screening result. The AAP is committed to the safe and effective implementation of pulse oximetry screening and is working with other advocacy groups and governmental agencies to promote pulse oximetry and to support widespread surveillance for CCHD. Going forward, AAP chapters will partner with state health departments to implement the new screening strategy for CCHD and will work to ensure that there is an adequate system for referral for echocardiographic/pediatric cardiac evaluation after a positive screening result. It is imperative that AAP members engage their respective policy makers in adopting and funding the recommendations made by the Secretary of HHS.

Comparison of Growth Performance of Antibiotic-free Yorkshire Crossbreds Sired by Berkshire, Large Black, and Tamworth Breeds Raised in Hoop Structures.

The objective of this study was to compare body weight, ADG, and feed:gain ratio of antibiotic-free pigs from Yorkshire dams and sired by Yorkshire (YY), Berkshire (BY), Large Black (LBY) or Tamworth (TY) boars. All the crossbred pigs in each of three trials were raised as one group from weaning to finishing in the same deep-bedded hoop, providing a comfortable environment for the animals which allowed rooting and other natural behaviors. Birth, weaning and litter weights were measured and recorded. From approximately 50 kg to market weight (125 kg), feed intake and body weights were recorded manually (body weight) or using a FIRE (Feed Intake Recording Equipment, Osborne Industries Inc. Osborne, Kansas) system with eight individual feeding stations. Feed intake data for 106 finishing pigs between 140 and 210 d of age and the resulting weights and feed conversion ratios were analyzed by breed type. Least square means for body weights (birth, weaning and to 240 d) were estimated with Proc Mixed in SAS 9.2 for fixed effects such as crossbreed and days of age within the sire breed. The differences within fixed effects were compared using least significant differences with DIFF option. Individual birth weights and weaning weights were influenced by sire breed (p<0.05). For birth weight, BY pigs were the lightest, TY and YY pigs were the heaviest but similar to each other and LBY pigs were intermediate. For weaning weights, BY and LBY pigs were heavier than TY and YY pigs. However, litter birth and weaning weights were not influenced by sire breed, and average daily gain was also not significantly different among breed types. Tamworth sired pigs had lower overall body weight gain, and feed conversion was lower in TY and YY groups than BY and LBY groups (p<0.05), however, number of observations was somewhat limited for feed conversion and for Tamworth pigs. Overall, no convincing differences among breed types were noted for this study, but growth performance in the outdoor environment was satisfactory.

Comparison of pork quality and sensory characteristics for antibiotic free yorkshire crossbreds raised in hoop houses.

The objective of this study was to compare pork characteristics and to determine consumer acceptability of pork chops from antibiotic free Yorkshire crossbreds sired by Berkshire (BY), Large Black (LBY), Tamworth (TY) or Yorkshire (YY) boars and reared in hoop houses. The experiments were conducted at the North Carolina Agricultural and Technical State University (NCA&TSU) Farm in Greensboro, NC and the Cherry Research Station Center for Environmental Farming Systems (CEFS) Alternative Swine Unit in Goldsboro, NC (source of antibiotic free Yorkshire sows used at both places). Twenty-four sows were artificially inseminated at each location in each of three trials. Litters were weaned at 4 wks old, and reared within deep-bedded outdoor hoop houses. To compare pork characteristics, 104 randomly selected animals were harvested at a USDA-inspected abattoir at approximately 200 d of age. Variables measured included pH, color score, L*, a*, b*, marbling score, drip loss, hot carcass weight, backfat thickness (BF), loin muscle area (LMA), and slice shear force. Sensory panel tests were also conducted at two time periods. The data was analyzed with GLM in SAS 9.01 including location, trial, and sire breed as fixed effects. Backfat thickness, LMA, color score and a* were different among breeding groups (p<0.05). The LBY pigs had thicker backfat and smaller LMA than the other breed types. The TY and YY had less backfat than all other breed groups. Color score was lower for YY than BY and LBY but intermediate for TY. The a* was lower for TY than other breeds except LBY which was intermediate. For one sensory panel test, YY pork was more preferred overall as well as for juiciness and texture compared to BY and LBY (p<0.05), but no impact of breed type was noted for the other test, with values similar for BY, LBY, TY and YY pork. This information may help small farmers make decisions about breed types to use for outdoor production.