The Perfect Storm: A Case of Rapid-Onset Obesity With Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor (ROHHADNET) With Heart Failure, Narcolepsy, and a Rare Location of a Pelvic Neuroendocrine Tumor.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease of concurrent respiratory dysfunction and autonomic dysregulation with endocrine abnormalities. ROHHADNET includes ROHHAD plus coexisting neuroendocrine tumors (NETs). We describe an eight-year-old boy, who originally presented at four years of age with rapid weight gain and hyperhidrosis and who developed mild obstructive sleep apnea (OSA). His clinical course was eventually complicated by hypoxic respiratory failure requiring admission to the pediatric intensive care unit (PICU). Echocardiogram at that time demonstrated dilated cardiomyopathy left ventricular ejection fraction (LVEF) of 28% at time of admission. His respiratory failure persisted despite average volume-assured pressure support (AVAPS) around the clock leading to tracheostomy placement for cardiopulmonary support. He also demonstrated autonomic instability with multiple pituitary hormone deficiencies. Computed tomography (CT) imaging of the abdomen and pelvis demonstrated a presacral soft tissue mass consistent with a tumor of neural crest origin. Daytime somnolence and confusion progressed and a low cerebrospinal fluid hypocretin level revealed a diagnosis of narcolepsy type 1.

Maternal preeclampsia as a risk factor for developing bronchopulmonary dysplasia in neonates.

OBJECTIVE: To determine the effect of preeclampsia on the development of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Retrospective cohort study of infants' ≤32 weeks' gestation admitted to a level-IV single center neonatal intensive care unit from 2014 to 2016. Infants with major congenital anomalies, death or transfer before 28 days were excluded. Infants were stratified by maternal preeclampsia status. Demographic, clinical, and laboratory data were reviewed. Logistic regression was used to examine predictors for BPD. MAIN OUTCOME MEASURE: The primary outcome was BPD incidence. RESULTS: 432 infants met inclusion criteria; 22% developed BPD, of which, 16% had severe BPD. Thirty-eight percent of infants were born to preeclamptic mothers, with 23% of those infants developing BPD. Infants born to preeclamptic mothers were delivered by cesarean section (88% vs. 60%; p<0.0001) more often and had lower birthweight (Median=1265g, IQR 910-1555 vs. Median=1388g, IQR 959-1752; p=0.008) compared to infants born to non-preeclamptic mothers. Higher incidence of intrauterine growth restriction was noted in pre-eclampsia group,24% vs 8%, p=0.0001). Gestational age, length of stay and days on ventilator were all associated with the development of BPD. In multivariable logistic regression, preeclampsia was not a risk factor for development of BPD (OR 1.12 [0.68, 1.83]). CONCLUSIONS: Preeclampsia was not a significant risk factor for development of BPD nor the severity of BPD in infants' ≤32 weeks' gestation. IUGR infants with or without preeclampsia mothers were at higher risk for BPD.

Current Utility of Sequential Organ Failure Assessment Score: A Literature Review and Future Directions.

The Sequential Organ Failure Assessment (SOFA) score is commonly used in the Intensive Care Unit (ICU) to evaluate, prognosticate and assess patients. Since its validation, the SOFA score has served in various settings, including medical, trauma, surgical, cardiac, and neurological ICUs. It has been a strong mortality predictor and literature over the years has documented the ability of the SOFA score to accurately distinguish survivors from non-survivors on admission. Over the years, multiple variations have been proposed to the SOFA score, which have led to the evolution of alternate validated scoring models replacing one or more components of the SOFA scoring system. Various SOFA based models have been used to evaluate specific clinical populations, such as patients with cardiac dysfunction, hepatic failure, renal failure, different races and public health illnesses, etc. This study is aimed to conduct a review of modifications in SOFA score in the past several years. We review the literature evaluating various modifications to the SOFA score such as modified SOFA, Modified SOFA, modified Cardiovascular SOFA, Extra-renal SOFA, Chronic Liver Failure SOFA, Mexican SOFA, quick SOFA, Lactic acid quick SOFA (LqSOFA), SOFA in hematological malignancies, SOFA with Richmond Agitation-Sedation scale and Pediatric SOFA. Various organ systems, their relevant scoring and the proposed modifications in each of these systems are presented in detail. There is a need to incorporate the most recent literature into the SOFA scoring system to make it more relevant and accurate in this rapidly evolving critical care environment. For future directions, we plan to put together most if not all updates in SOFA score and probably validate it in a large database a single institution and validate it in multisite data base.

Mycobacterium Avium Complex Presenting as Pulmonary Nodules in a Child With Sickle Cell Disease.

The case of a 10-year-old child with sickle cell disease with pulmonary nodules and prolonged fevers is reported here. The child was first diagnosed with sarcoidosis based on lung biopsy, but unresponsiveness to therapy led to a second lung biopsy, which revealed the true diagnosis of mycobacterium avium complex disease. Multiple possible explanations for why the patient became infected exist. The patient was baseline immunocompromised due to her sickle cell disease, was exposed to invasive procedures, was taking medications that may predispose to this type of infection, and was found to have a congenital immunodeficiency.

Antibiotic Exposure and Risk for Death or Bronchopulmonary Dysplasia in Very Low Birth Weight Infants.

We assessed the association between antibiotic exposure in the first 2 weeks of life and development of bronchopulmonary dysplasia in a cohort of very low birth weight infants. After controlling for the severity of illness, each additional day of antibiotic therapy was associated with both an increased risk for and severity of bronchopulmonary dysplasia.

HER receptor signaling confers resistance to the insulin-like growth factor-I receptor inhibitor, BMS-536924.

We have reported previously the activity of the insulin-like growth factor-I (IGF-IR)/insulin receptor (InsR) inhibitor, BMS-554417, in breast and ovarian cancer cell lines. Further studies indicated treatment of OV202 ovarian cancer cells with BMS-554417 increased phosphorylation of HER-2. In addition, treatment with the pan-HER inhibitor, BMS-599626, resulted in increased phosphorylation of IGF-IR, suggesting a reciprocal cross-talk mechanism. In a panel of five ovarian cancer cell lines, simultaneous treatment with the IGF-IR/InsR inhibitor, BMS-536924 and BMS-599626, resulted in a synergistic antiproliferative effect. Furthermore, combination therapy decreased AKT and extracellular signal-regulated kinase activation and increased biochemical and nuclear morphologic changes consistent with apoptosis compared with either agent alone. In response to treatment with BMS-536924, increased expression and activation of various members of the HER family of receptors were seen in all five ovarian cancer cell lines, suggesting that inhibition of IGF-IR/InsR results in adaptive up-regulation of the HER pathway. Using MCF-7 breast cancer cell variants that overexpressed HER-1 or HER-2, we then tested the hypothesis that HER receptor expression is sufficient to confer resistance to IGF-IR-targeted therapy. In the presence of activating ligands epidermal growth factor or heregulin, respectively, MCF-7 cells expressing HER-1 or HER-2 were resistant to BMS-536924 as determined in a proliferation and clonogenic assay. These data suggested that simultaneous treatment with inhibitors of the IGF-I and HER family of receptors may be an effective strategy for clinical investigations of IGF-IR inhibitors in breast and ovarian cancer and that targeting HER-1 and HER-2 may overcome clinical resistance to IGF-IR inhibitors.