Prediction of Acquired Morbidity Using Illness Severity Indices in Pediatric Intensive Care Patients.

OBJECTIVES: To assess the ability of two illness severity scores, Pediatric Logistic Organ Dysfunction Score 2 and Pediatric Index of Mortality 3, in predicting PICU-acquired morbidity. DESIGN: Retrospective chart review conducted from April 2015 to March 2016. SETTING: Single-center study in a multidisciplinary PICU in a tertiary pediatric hospital in Singapore. PATIENTS: The study included all index admissions of patients 0-18 years old to the PICU during the study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three outcomes were assessed at hospital discharge: mortality, survival with new morbidity defined as an increase in the Functional Status Scale score of greater than or equal to 3 points from baseline, and survival without morbidity. Of 577 consecutive admissions, 95 were excluded: 82 readmissions, 10 patients greater than or equal to 18 years old, two patients with missing baseline data, and one transferred to another PICU. Of 482 patients, there were 37 hospital deaths (7.7%) and 39 (8.1%) with acquired new morbidity. Median admission Pediatric Logistic Organ Dysfunction Score 2 and Pediatric Index of Mortality 3 scores differed among the three outcome groups. In addition, differences were found in emergency admission and neurologic diagnosis rates, PICU mechanical ventilation usage rates, and PICU length of stay. The highest proportion of neurologic diagnoses was observed in the new morbidity group. The final model simultaneously predicted risks of mortality, survival with new morbidity and survival without morbidity using admission Pediatric Logistic Organ Dysfunction Score 2 score, admission type, neurologic diagnosis, and preexisting chronic disease. Pediatric Logistic Organ Dysfunction Score 2 was superior to Pediatric Index of Mortality 3 in predicting risks of mortality and new morbidity, as indicated by volume under surface values of 0.483 and 0.362, respectively. CONCLUSIONS: Risk of mortality, survival with new morbidity, and survival without morbidity can be predicted simultaneously using admission Pediatric Logistic Organ Dysfunction Score 2, admission type, admission diagnosis, and preexisting chronic disease. Future independent studies will be required to validate the proposed model before clinical implementation.

Body Composition and Acquired Functional Impairment in Survivors of Pediatric Critical Illness.

OBJECTIVES: To identify whether body mass and composition is associated with acquired functional impairment in PICU survivors. DESIGN: Retrospective dual-cohort study. SETTING: Single multidisciplinary PICU. PATIENTS: Two distinct PICU survivor cohorts: 432 unselected admissions from April 2015 to March 2016, and separately 92 patients with abdominal CT imaging at admission from January 2010 to December 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Admission body mass index and Functional Status Scale scores at admission, PICU discharge, and hospital discharge were obtained for all patients. Acquired functional impairment was defined as increase greater than or equal to 3 in Functional Status Scale from baseline. Patients were classified as having: "temporary acquired impairment" (acquired impairment at PICU discharge recovering by hospital discharge), "persistent acquired impairment" (acquired impairment at PICU discharge persisting to hospital discharge), and "no acquired impairment." CT scans were analyzed for skeletal muscle and fat area using National Institute of Health ImageJ software (Bethesda, MD). Multinomial logistic regression analyses were conducted to identify associations between body mass index, muscle and fat indices, and acquired functional impairment. High baseline body mass index was consistently predictive of persistent acquired impairment in both cohorts. In the second cohort, when body mass index was replaced with radiologic anthropometric measurements, greater skeletal muscle, and visceral adipose tissue indices were independently associated with persistent acquired impairment at hospital discharge (adjusted odds ratio, 1.29; 95% CI, 1.03-1.61; p = 0.024 and adjusted odds ratio, 1.13; 95% CI, 1.01-1.28; p = 0.042, respectively). However, this relationship was no longer significant in children with PICU stay greater than 2 days. CONCLUSIONS: In PICU survivors, baseline body mass and composition may play a role in the persistence of acquired functional impairment at hospital discharge. Characterization and quantification of skeletal muscle and fat deserves further study in larger cohorts of PICU children.

Long-Term Morbidities in Children with Critical Illness: Gaps and Opportunities.

INTRODUCTION: Improved mortality rates in paediatric critical care may come with the cost of increased morbidity. Goals of modern paediatric intensive care unit (PICU) management should focus on restoring long-term function of paediatric critical illness survivors. This review outlines our current knowledge on trajectories and risk factors of long-term morbidities in PICU survivors. Specifically, we aimed to identify current limitations and gaps in this area so as to identify opportunities for future investigations to reduce the burden of morbidities in these children. MATERIALS AND METHODS: A review of primary studies published in PubMed, EMBASE, and Cochrane databases in the last decade (2008-2017) describing long-term morbidities in PICU survivors was conducted. RESULTS: Children surviving critical illness continue to experience morbidities after discharge. A set of risk factors modify their long-term trajectories of recovery, with some children achieving their premorbid level of function, while some others deteriorate or die. Limitations in current methodologies of morbidity research impair our understanding on the causes of these morbidities. Opportunities for future endeavours to reduce the burden of these morbidities include identifying patients who are more likely to develop morbidities, evaluating the efficacy of early rehabilitation, identifying patients who might benefit from tight glycaemic control, characterising the optimal nutritional intervention, and improving management of increased intracranial pressure. CONCLUSION: Survivors of paediatric critical illness experience differing trajectories of recovery from morbidities. Future research is needed to expand our repertoire on management strategies to improve long-term function in these children.

Nuclear factor I/B is an oncogene in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive cancer often diagnosed after it has metastasized. Despite the need to better understand this disease, SCLC remains poorly characterized at the molecular and genomic levels. Using a genetically engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung, we identified several frequent, high-magnitude focal DNA copy number alterations in SCLC. We uncovered amplification of a novel, oncogenic transcription factor, Nuclear factor I/B (Nfib), in the mouse SCLC model and in human SCLC. Functional studies indicate that NFIB regulates cell viability and proliferation during transformation.