Pediatric asthma severity scores distinguish suitable inpatient level of care for children admitted for status asthmaticus.

Objective: To determine if the Pediatric Asthma Severity Score (PASS) can distinguish "late-rescues" (transfer to the pediatric intensive care unit [PICU] within 24-hours of general pediatric floor admission), "PICU readmissions" (readmission within 24-h after transfer to a lower inpatient level of care), and unplanned 30-day hospital readmission in children admitted with status asthmaticus.Methods: We performed a single center, retrospective cohort study in 328 children admitted for asthma exacerbation aged 5-18 years from May 2015 to October 2017. We sought to determine if PASS values preceding admission from the emergency department or transfer to the general pediatric unit will be greater in children with late rescues and PICU readmissions and if a cutoff PASS values exist to discriminate these events prior to intrafacility transfer.Results: Nine (5%) late-rescues and 5 (3%) PICU readmissions accounted for 14/328 (4%) composite outcomes. PASS values were greater in children with these events (8 [IQR:5-8] vs. 5 [IQR:3-6], p < .01). Logistic regression of PASS on composite outcome yielded an odds ratio of 1.4 (1.1-1.8, p < .01) and ROC curve of PASS on a composite outcome yielded an AUC of 0.74 (0.61-0.87) with a threshold of ≥ 9. Nine (3%) children experienced unplanned 30-day hospital readmissions but PASS preceding hospital discharge was neither discriminative nor associated with hospital readmission.Conclusions: PASS values ≥ 9 identify children at increased risk for late-rescue and PICU readmission. Applied with traditionally criteria for selection of inpatient level of care, PASS may assist providers in reducing acute inpatient disposition errors.

Pediatric Cannabinoid Hyperemesis: A Single Institution 10-Year Case Series.

PURPOSE: Cannabis hyperemesis (CH) is an under-recognized condition in patients with chronic or cyclic vomiting and who regularly use cannabis. Once thought to be rare, it is now increasingly recognized in both adults and children. We report a case series of adolescent patients with CH who presented at a single institution over 10 years. METHODS: Patients were included if they had a diagnosis code of cannabis-related or cyclic vomiting, experienced the onset of regular vomiting after starting to regularly use cannabis, and if no other diagnosis was found to better explain the presentation. Thirty-four patients aged 13-20 years (median 17 years) met the inclusion criteria. RESULTS: The presenting clinical features were broadly similar to adult CH: cyclic nausea and emesis after at least 3 months of regular cannabis use, abdominal pain, change in bowel habit, and symptomatic relief from hot showers or baths. No antiemetic was found to be of particular benefit. Follow-up was recorded in under half of the patients; documentation of drug history was also frequently incomplete. Clinicians should consider CH when assessing any adolescent with cyclic or chronic vomiting. CONCLUSIONS: A detailed drug history, preferably taken in the absence of parents or other involved adults and corroborated by urine drug screening, is helpful in substantiating the diagnosis. Further prospective studies are needed to confirm the incidence, prevalence, presenting features, and the effectiveness of treatments, including drug counseling and cessation. Based on our findings, we propose pragmatic criteria to aid in the diagnosis of pediatric CH.

Stress ulcer prophylaxis in children with status asthmaticus receiving systemic corticosteroids: a descriptive study assessing frequency of clinically important bleeding.

Objective: To determine the frequency of clinically important bleeding (CIB) among children hospitalized for status asthmaticus with and without exposure to stress ulcer prophylaxis (SUP).Methods: We performed a single-center, retrospective cohort in 217 children admitted for asthma exacerbation aged 5-18 years from May 2015 to May 2017. We assessed cohorts with and without exposure to SUP to determine if differences in frequency of CIB exist. Study outcomes included frequency of CIB, gastrointestinal complications (occult bleeding, macroscopic bleeding, gastric perforation, and acquired gastritis), and SUP-related adverse events (ventilator associated pneumonia, C. difficile colitis, necrotizing enterocolitis, and acute thrombocytopenia).Results: Ninety-two (42%) children received SUP of which 82 were admitted to the pediatric intensive care unit (PICU). There were no differences in asthma severity or known risk factors for CIB in children with and without SUP in the PICU subcohort. We observed no CIB or SUP-related adverse events. Two subjects acquired gastritis in the no-SUP cohort and one additional subject experienced occult gastrointestinal bleeding with spontaneous symptom resolution.Conclusion: Children admitted for status asthmaticus with and without SUP had no observed incidence of CIB. In this specific population, we propose a prerequisite assessment for the presence of known stress ulcer related gastrointestinal bleeding risk factors prior to the blanket administration of SUP.

Comparison of Tolerance and Complication Rates Between Early and Delayed Feeding After Percutaneous Endoscopic Gastrostomy Placement in Children.

BACKGROUND: Enteral nutrition is commonly initiated 24 hours after percutaneous endoscopic gastrostomy (PEG) in children. Adult studies report safe refeeding within 1 to 6 hours of PEG, and these findings have been cautiously applied to children. Comparative studies assessing early versus next-day refeeding in children are currently lacking. This study evaluates feeding tolerance and complications following early versus next-day refeeding in children. METHODS: This is a single-center, pre-post study. In June 2015 our clinical practice changed to begin refeeding within 6 hours of PEG. Children receiving early refeeding from December 2015 to August 2017 were included. A retrospective cohort from February 2013 to April 2015 was used for comparison. RESULTS: Forty-six children received early refeeding after PEG and 37 received next-day refeeding. Gender distribution was similar in the 2 groups. Early refeeding patients were slightly older (3.5 vs 2.2 years) and heavier (15.5 vs 11.5 kg) at PEG placement compared to next-day refeeding patients. Early refeeding patients experienced greater postprocedural nausea and/or vomiting (19% vs 8%, P < 0.001) and leakage, irritation, and infection around the stoma (19% vs 0.0%, P < 0.001). Compared to early refeeders, next-day refeeding patients experienced higher occurrence of fever (35% vs 13%, P = 0.021), longer nutritional disruption (24.6 vs 3.7 hours, P < 0.001), and longer length of stay (51 vs 27 hours; P < 0.001). One next-day refeeding patient experienced peritonitis. One early refeeding patient experienced cellulitis requiring hospitalization and a second experienced gastrostomy tube migration into the peritoneal cavity requiring removal. CONCLUSION: Early refeeders experienced higher rates of postprocedural nausea or vomiting and irritation, leakage, or infection around the stoma; but experienced lower rates of postoperative fever. Early refeeding resulted in reduced nutritional interruption and hospital length of stay.

Percutaneous Endoscopic Gastrostomy After Cardiothoracic Surgery in Children Less Than 2 Months Old: An Assessment of Long-Term Malnutrition Status and Gastrostomy Outcomes.

OBJECTIVES: Infants with critical congenital heart disease undergoing cardiothoracic surgery commonly experience chronic malnutrition and growth failure. We sought to determine whether placement of a percutaneous endoscopic gastrostomy was associated with reduced moderate-severe malnutrition status and to describe percutaneous endoscopic gastrostomy-related clinical and safety outcomes in this population. DESIGN: Single-center, retrospective cohort study. SETTING: Two hundred fifty-nine-bed, tertiary care, pediatric referral center. PATIENTS: Children with congenital heart disease less than 2 months old undergoing cardiothoracic surgery from 2007 to 2013 with and without percutaneous endoscopic gastrostomy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were weight for age z scores during hospitalization, at 6 months, and 1 year after cardiothoracic surgery. Secondary outcomes were frequency of percutaneous endoscopic gastrostomy revision, percutaneous endoscopic gastrostomy complications, and mortality. Statistical analyses included Wilcoxon rank-sum, Fisher exact, and Student t tests. Two hundred twenty-two subjects met study criteria, and 77 (35%) had percutaneous endoscopic gastrostomy placed at a mean of 45 ± 31 days after cardiothoracic surgery. No differences were noted for demographics, comorbidities, and weight for age z score at birth and at the time of cardiothoracic surgery. The percutaneous endoscopic gastrostomy cohort had greater Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery risk category (4 [4-5] vs 4 [2-4]) and length of stay (71 d [49-101 d] vs 26 d [15-42 d]). Mean weight for age z score at the time of percutaneous endoscopic gastrostomy was -2.8 ± 1.3. Frequency of moderate-severe malnutrition (weight for age z score, ≤ -2) was greater in children with percutaneous endoscopic gastrostomy at discharge (78% vs 48%), 6 months (61% vs 16%), and 1 year (41% vs 2%). Index mortality was lower in children with percutaneous endoscopic gastrostomy at 30 days (8% vs 0%) and hospital discharge (19% vs 4%). However, no mortality differences were observed after discharge. Growth velocity after percutaneous endoscopic gastrostomy was greater (44 ± 19 vs 10 ± 9 g/d). Children tolerated percutaneous endoscopic gastrostomy without hemodynamic compromise, minor percutaneous endoscopic gastrostomy complications, and anticipated percutaneous endoscopic gastrostomy revisions. Children without mortality had percutaneous endoscopic gastrostomy removal at a median duration of 253 days (133-545 d). Children with univentricular physiology had improved in-hospital mean growth velocity (6.3 vs 24.4 g/d; p < 0.01) and reduced 1-year rate moderate-severe malnutrition (66.7% vs 36.9%; p < 0.01) after percutaneous endoscopic gastrostomy placement. CONCLUSIONS: Percutaneous endoscopic gastrostomy placement was well tolerated and associated with improved postoperative growth velocity in children with critical congenital heart disease undergoing cardiothoracic surgery less than 2 months old. These findings were also noted in our subanalysis of children with univentricular physiology. Persistent rates of moderate-severe malnutrition were noted at 1-year follow-up. Although potential index mortality benefit was observed, definitive data are still needed.

Same-Day versus Overnight Observation after Outpatient Pediatric Percutaneous Liver Biopsy: A Retrospective Cohort Study.

PURPOSE: Percutaneous liver biopsy (PLB), a diagnostic procedure to identify several hepatobiliary disorders, is considered safe with low incidence of associated complications. While postoperative monitoring guidelines are suggested for adults, selection of procedural recovery time for children remains at the discretion of individual operators. We aim to determine if differences exist in frequency of surgical complications, unplanned admissions, and healthcare cost for children undergoing outpatient PLB for cohorts with same-day vs. overnight observation. METHODS: We performed a retrospective cohort study in children 1 month to 17 years of age undergoing ultrasound-guided PLB from January 2009 to August 2017 at a tertiary care, pediatric referral center. Cohorts were defined by postprocedural observation duration: same-day (≤8 hours) vs. overnight observation. Outcomes included surgical complications, medical interventions, unscheduled hospitalization within 7 days, and total encounter costs. RESULTS: One hundred and twelve children met study criteria of which 18 (16.1%) were assigned to same-day observation. No differences were noted in demographics, anthropometrics, comorbidities, biopsy indications, or preoperative coagulation profiles. No major complications or acute hospitalizations after PLB were observed. Administration of analgesia and fluid boluses were isolated and given within 8 hours. Compared to overnight monitoring, same-day observation accrued less total costs (US $992 less per encounter). CONCLUSION: Same-day observation after PLB in children appears well-tolerated with only minor interventions and complications observed within 8 hours of procedure. We recommend a targeted risk assessment prior to selection of observation duration. Same-day observation appears an appropriate recovery strategy in otherwise low-risk children undergoing outpatient PLB.

PTPN11 Plays Oncogenic Roles and Is a Therapeutic Target for BRAF Wild-Type Melanomas.

Melanoma is one of the most highly mutated cancer types. To identify functional drivers of melanoma, we searched for cross-species conserved mutations utilizing a mouse melanoma model driven by loss of PTEN and CDKN2A, and identified mutations in Kras, Erbb3, and Ptpn11. PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the RAS/RAF/MAPK pathway. Although PTPN11 is an oncogene in leukemia, lung, and breast cancers, its roles in melanoma are not clear. In this study, we found that PTPN11 is frequently activated in human melanoma specimens and cell lines and is required for full RAS/RAF/MAPK signaling activation in BRAF wild-type (either NRAS mutant or wild-type) melanoma cells. PTPN11 played oncogenic roles in melanoma by driving anchorage-independent colony formation and tumor growth. In Pten- and Cdkn2a-null mice, tet-inducible and melanocyte-specific PTPN11E76K expression significantly enhanced melanoma tumorigenesis. Melanoma cells derived from this mouse model showed doxycycline-dependent tumor growth in nude mice. Silencing PTPN11E76K expression by doxycycline withdrawal caused regression of established tumors by induction of apoptosis and senescence, and suppression of proliferation. Moreover, the PTPN11 inhibitor (SHP099) also caused regression of NRASQ61K -mutant melanoma. Using a quantitative tyrosine phosphoproteomics approach, we identified GSK3α/ß as one of the key substrates that were differentially tyrosine-phosphorylated in these experiments modulating PTPN11. This study demonstrates that PTPN11 plays oncogenic roles in melanoma and regulates RAS and GSK3ß signaling pathways. IMPLICATIONS: This study identifies PTPN11 as an oncogenic driver and a novel and actionable therapeutic target for BRAF wild-type melanoma.