Predicting and Surviving Prolonged Critical Illness After Congenital Heart Surgery.

OBJECTIVES: Prolonged critical illness after congenital heart surgery disproportionately harms patients and the healthcare system, yet much remains unknown. We aimed to define prolonged critical illness, delineate between nonmodifiable and potentially preventable predictors of prolonged critical illness and prolonged critical illness mortality, and understand the interhospital variation in prolonged critical illness. DESIGN: Observational analysis. SETTING: Pediatric Cardiac Critical Care Consortium clinical registry. PATIENTS: All patients, stratified into neonates (≤28 d) and nonneonates (29 d to 18 yr), admitted to the pediatric cardiac ICU after congenital heart surgery at Pediatric Cardiac Critical Care Consortium hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 2,419 neonates and 10,687 nonneonates from 22 hospitals. The prolonged critical illness cutoff (90th percentile length of stay) was greater than or equal to 35 and greater than or equal to 10 days for neonates and nonneonates, respectively. Cardiac ICU prolonged critical illness mortality was 24% in neonates and 8% in nonneonates (vs 5% and 0.4%, respectively, in nonprolonged critical illness patients). Multivariable logistic regression identified 10 neonatal and 19 nonneonatal prolonged critical illness predictors within strata and eight predictors of mortality. Only mechanical ventilation days and acute renal failure requiring renal replacement therapy predicted prolonged critical illness and prolonged critical illness mortality in both strata. Approximately 40% of the prolonged critical illness predictors were nonmodifiable (preoperative/patient and operative factors), whereas only one of eight prolonged critical illness mortality predictors was nonmodifiable. The remainders were potentially preventable (postoperative critical care delivery variables and complications). Case-mix-adjusted prolonged critical illness rates were compared across hospitals; six hospitals each had lower- and higher-than-expected prolonged critical illness frequency. CONCLUSIONS: Although many prolonged critical illness predictors are nonmodifiable, we identified several predictors to target for improvement. Furthermore, we observed that complications and prolonged critical care therapy drive prolonged critical illness mortality. Wide variation of prolonged critical illness frequency suggests that identifying practices at hospitals with lower-than-expected prolonged critical illness could lead to broader quality improvement initiatives.

Characteristics, Risk Factors, and Outcomes of Extracorporeal Membrane Oxygenation Use in Pediatric Cardiac ICUs: A Report From the Pediatric Cardiac Critical Care Consortium Registry.

OBJECTIVES: Cardiopulmonary failure in children with cardiac disease differs from the general pediatric critical care population, yet the epidemiology of extracorporeal membrane oxygenation support in cardiac ICUs has not been described. We aimed to characterize extracorporeal membrane oxygenation utilization and outcomes across surgical and medical patients in pediatric cardiac ICUs. DESIGN: Retrospective analysis of the Pediatric Cardiac Critical Care Consortium registry to describe extracorporeal membrane oxygenation frequency and outcomes. Within strata of medical and surgical hospitalizations, we identified risk factors associated with extracorporeal membrane oxygenation use through multivariate logistic regression. SETTING: Tertiary-care children's hospitals. PATIENTS: Neonates through adults with cardiac disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 14,526 eligible hospitalizations from August 1, 2014, to June 30, 2016; 449 (3.1%) included at least one extracorporeal membrane oxygenation run. Extracorporeal membrane oxygenation was used in 329 surgical (3.5%) and 120 medical (2.4%) hospitalizations. Systemic circulatory failure and extracorporeal cardiopulmonary resuscitation were the most common extracorporeal membrane oxygenation indications. In the surgical group, risk factors associated with postoperative extracorporeal membrane oxygenation use included younger age, extracardiac anomalies, preoperative comorbidity, higher Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery category, bypass time, postoperative mechanical ventilation, and arrhythmias (all p < 0.05). Bleeding requiring reoperation (25%) was the most common extracorporeal membrane oxygenation complication in the surgical group. In the medical group, risk factors associated with extracorporeal membrane oxygenation use included acute heart failure and higher Vasoactive Inotropic Score at cardiac ICU admission (both p < 0.0001). Stroke (15%) and renal failure (15%) were the most common extracorporeal membrane oxygenation complications in the medical group. Hospital mortality was 49% in the surgical group and 63% in the medical group; mortality rates for hospitalizations including extracorporeal cardiopulmonary resuscitation were 50% and 83%, respectively. CONCLUSIONS: This is the first multicenter study describing extracorporeal membrane oxygenation use and outcomes specific to the cardiac ICU and inclusive of surgical and medical cardiac disease. Mortality remains high, highlighting the importance of identifying levers to improve care. These data provide benchmarks for hospitals to assess their outcomes in extracorporeal membrane oxygenation patients and identify unique high-risk subgroups to target for quality initiatives.

Family food talk, child eating behavior, and maternal feeding practices.

Families discuss food and eating in many ways that may shape child eating habits. Researchers studying how families talk about food have examined this process during meals. Little work has examined parent-child food-related interactions outside of mealtime. We assessed family food talk at home outside of mealtime and tested whether food talk was associated with obesogenic child eating behaviors, maternal feeding practices, or child weight. Preschool and school-aged mother-child dyads (n = 61) participated in naturalistic voice recording using a LENA (Language ENvironment Analysis) recorder. A coding scheme was developed to reliably characterize different types of food talk from LENA transcripts. Mothers completed the Children's Eating Behavior Questionnaire (CEBQ) and Child Feeding Questionnaire (CFQ) to assess child eating behaviors and maternal feeding practices. Child weight and height were measured and body mass index z-score (BMIz) calculated. Bivariate associations among food talk types, as a proportion of total speech, were examined and multivariate regression models used to test associations between food talk and child eating behaviors, maternal feeding practices, and child BMIz. Proportion of child Overall Food Talk and Food Explanations were positively associated with CEBQ Food Responsiveness and Enjoyment of Food (p's < 0.05). Child food Desire/Need and child Prep/Planning talk were positively associated with CEBQ Enjoyment of Food (p < 0.05). Child Food Enjoyment talk and mother Overt Restriction talk were positively associated with CEBQ Emotional Over-Eating (p < 0.05). Mother Monitoring talk was positively associated with CFQ Restriction (p < 0.05). Mother Prep/Planning talk was negatively associated with child BMIz. Food talk outside of mealtimes related to child obesogenic eating behaviors and feeding practices in expected ways; examining food talk outside of meals is a novel way to consider feeding practices and child eating behavior.

Observed self-regulation is associated with weight in low-income toddlers.

Obesity emerges in early childhood and tracks across development. Self-regulation develops rapidly during the toddler years, yet few studies have examined toddlers' self-regulation in relation to concurrent child weight. Further, few studies compare child responses in food and non-food-related tasks. Our goal was to examine toddlers' observed behavioral and emotional self-regulation in food and non-food tasks in relation to their body mass index z-score (BMIz) and weight status (overweight/obese vs. not). Observational measures were used to assess self-regulation (SR) in four standardized tasks in 133 low-income children (M age = 33.1 months; SD = 0.6). Behavioral SR was measured by assessing how well the child could delay gratification for a snack (food-related task) and a gift (non-food-related task). Emotional SR was measured by assessing child intensity of negative affect in two tasks designed to elicit frustration: being shown, then denied a cookie (food-related) or a toy (non-food-related). Task order was counterbalanced. BMIz was measured. Bivariate correlations and regression analyses adjusting for child sex, child race/ethnicity, and maternal education were conducted to examine associations of SR with weight. Results were that better behavioral SR in the snack delay task associated with lower BMIz (ß = -0.27, p < 0.05) and lower odds of overweight/obesity (OR = 0.66, 95% CI 0.45, 0.96), but behavioral SR in the gift task did not associate with BMIz or weight status. Better emotional SR in the non-food task associated with lower BMIz (ß = -0.27, p < 0.05), and better emotional SR in food and non-food tasks associated with lower odds of overweight/obesity (OR = 0.65, 95% CI 0.45, 0.96 and OR = 0.56, 95% CI 0.37, 0.87, respectively). Results are discussed regarding how behavioral SR for food and overall emotional SR relate to weight during toddlerhood, and regarding early childhood obesity prevention implications.

Evaluation of [99mTc-(CO)3-X-Y-Bombesin(7-14)NH2] conjugates for targeting gastrin-releasing peptide receptors overexpressed on breast carcinoma.

BACKGROUND: Gastrin-releasing peptide (GRP) receptors are overexpressed on a variety of human carcinomas, including those of the breast. These receptors may be targeted with bombesin (BBN), which binds to GRP receptors with high affinity and specificity. The aim of this study was to develop a (99m)Tc(I)-BBN analog with favorable pharmacokinetic properties in order to improve the visualization of breast cancer tissue. MATERIALS AND METHODS: Solid-phase peptide synthesis was used to produce a series of X-Y-BBN-NH2 conjugates, where X is pyrazolyl (PZ1) or 2,3-diaminopropionic acid (DPR) and Y is a spacer sequence. Their metallated counterparts were prepared by reacting [(99m)Tc-(H(2)O)(3)(CO)(3)](+) with the corresponding ligand. RESULTS: While the PZ1 conjugates exhibited higher GRP receptor binding affinities in vitro, the DPR analogs demonstrated superior target tissue accumulation and pharmacokinetic properties in vivo. CONCLUSION: These results demonstrate the ability of the DPR derivatives (Y=glycylserylglycine, triserine) to clearly identify the T47-D tumor tissue in xenografted SCID mice.

Radiolabeled regulatory peptides for imaging and therapy.

PURPOSE OF REVIEW: The purpose of the present review is to describe new, innovative strategies of diagnosing and treating specific human cancers using a cadre of radiolabeled regulatory peptides. RECENT FINDINGS: Peptide receptor-targeted radionuclide therapy is a method of site-directed radiotherapy that specifically targets human cancers expressing a cognate receptor-subtype in very high numbers. Ideally, the procedure targets only the primary or metastatic disease and is minimally invasive, with little radiation damage to normal, collateral tissues. For treatment strategies of this type to be effective, it is critical to evaluate the toxicity of the treatment protocol, the radiation dosimetry of the therapeutic regimen, and the biological profile of the radiopharmaceutical, including biodistribution and pharmacokinetics of the drug. Site-directed molecular imaging procedures via gamma-scintigraphy can address many of the critical issues associated with peptide receptor-targeted radionuclide therapy and it is, therefore, necessary to describe the effective balance between the clinical benefits and risks of this treatment strategy. SUMMARY: Continued development in the design or chemical structure of radiolabeled, biologically active peptides could do much to improve the targeting ability of these drugs, thereby creating new and innovative strategies for diagnosis or treatment of human cancers.