Laura D. Cassidy

Initiation and Use of Propranolol for Infantile Hemangioma: Report of a Consensus Conference

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children

OBJECTIVE:To determine whether moderate hypothermia (HYPO) (32–33°C) begun in the early period after severe traumatic brain injury (TBI) and maintained for 48 hours is safe compared with normothermia (NORM) (36.5–37.5°C). METHODS:After severe (Glasgow Coma Scale score ≤8) nonpenetrating TBI, 48 children less than 13 years of age admitted within 6 hours of injury were randomized after stratification by age to moderate HYPO (32–33°C) treatment in conjunction with standardized head injury management versus NORM in a multicenter trial. An additional 27 patients were entered into a parallel single-institution trial of excluded patients because of late transfer or consent (delayed in transfer >6 h but within 24 h of admission), unknown time of injury (e.g., child abuse), and adolescence (e.g., aged 13–18 yr). Assessments of safety included mortality, infection, coagulopathy, arrhythmias, and hemorrhage as well as ability to maintain target temperature, mean intracranial pressure (ICP), and percent time of ICP less than 20 mm Hg during the cooling and subsequent rewarming phases. Additionally, assessments of neurocognitive outcomes were obtained at 3 and 6 months of follow-up. RESULTS:Moderate HYPO after severe TBI in children was found to be safe relative to standard management and NORM in children of all ages and in children with delay of initiation of treatment up to 24 hours. Although there was decreased mortality in HYPO in both studies, there was an increased potential for arrhythmias with HYPO, although they were manageable with fluid administration or rewarming. Additionally, there was a reduction in mean ICP during the first 72 hours after injury in both studies, although rebound ICP elevations in HYPO compared with those in NORM were noted for up to 10 to 12 hours after rewarming. Although functional outcome at 3 or 6 months did not differ between treatment groups, functional outcome tended to improve from the 3- to 6-month cognitive assessment in HYPO compared with NORM, although the sample size was too small for any definitive conclusions. CONCLUSION:HYPO is likely a safe therapeutic intervention for children after severe TBI up to 24 hours after injury. Further studies are necessary and warranted to determine its effect on functional outcome and intracranial hypertension.

Untreated surgical conditions in Sierra Leone: a cluster randomised, cross-sectional, countrywide survey

BACKGROUND Surgical care is increasingly recognised as an important part of global health yet data for the burden of surgical disease are scarce. The Surgeons OverSeas Assessment of Surgical Need (SOSAS) was developed to measure the prevalence of surgical conditions and surgically treatable deaths in low-income and middle-income countries. We administered this survey countrywide in Sierra Leone, which ranks 180 of the 187 nations on the UN Development Index. METHODS The study was done between Jan 9 and Feb 3, 2012. 75 of 9671 enumeration areas, the smallest administrative units in Sierra Leone, were randomly selected for the study clusters, with a probability proportional to the population size. In each cluster 25 households were randomly selected to take part in the survey. Data were collected via handheld tablets by trained local medical and nursing students. A household representative was interviewed to establish the number of household members (defined as those who ate from the same pot and slept in the same structure the night before the interview), identify deaths in the household during the previous year, and establish whether any of the deceased household members had a condition needing surgery in the week before death. Two randomly selected household members underwent a head-to-toe verbal examination and need for surgical care was recorded on the basis of the response to whether they had a condition that they believed needed surgical assessment or care. FINDINGS Of the 1875 targeted households, data were analysed for 1843 (98%). 896 of 3645 (25%; 95% CI 22·9-26·2) respondents reported a surgical condition needing attention and 179 of 709 (25%; 95% CI 22·5-27·9) deaths of household members in the previous year might have been averted by timely surgical care. INTERPRETATION Our results show a large unmet need for surgical consultations in Sierra Leone and provide a baseline against which future surgical programmes can be measured. Additional surveys in other low-income and middle-income countries are needed to document and confirm what seems to be a neglected component of global health. FUNDING Surgeons OverSeas, Thompson Family Foundation.

Treatment of necrotizing enterocolitis: an American Pediatric Surgical Association Outcomes and Clinical Trials Committee systematic review

OBJECTIVE The optimal treatment of necrotizing enterocolitis (NEC) is a common challenge for pediatric surgeons. Although many studies have evaluated prevention and medical therapy for NEC, few guidelines for surgical care exist. The aim of this systematic review is to review and evaluate the currently available evidence for the surgical care of patients with NEC. METHODS Data were compiled from a search of PubMed, OVID, the Cochrane Library database, and Web of Science from January 1985 until December 2011. Publications were screened, and their references were hand-searched to identify additional studies. Clinicaltrials.gov was also searched to identify ongoing or unpublished trials. The American Pediatric Surgical Association Outcomes and Clinical Trials Committee proposed six questions deemed pertinent to the surgical treatment of NEC. Recent Cochrane Reviews examined three of these topics; a literature review was performed to address the additional three specific questions. RESULTS The Cochrane Reviews support the use of prophylactic probiotics in preterm infants less than 2500 grams to reduce the incidence of NEC, as well as the use of human breast milk rather than formula when possible. There is no clear evidence to support delayed initiation or slow advancement of feeds. For surgical treatment of NEC with perforation, there is no clear support of peritoneal drainage versus laparotomy. Similarly, there is a lack of evidence comparing enterostomy versus primary anastomosis after resection at laparotomy. There are little data to determine the length of treatment with antibiotics to prevent recurrence of NEC. CONCLUSION Based on available evidence, probiotics are advised to decrease the incidence of NEC, and human milk should be used when possible. The other reviewed questions are clinically relevant, but there is a lack of evidence-based data to support definitive recommendations. These areas of NEC treatment would benefit from future investigation.

The diagnosis and management of empyema in children: a comprehensive review from the APSA Outcomes and Clinical Trials Committee.

The aim of this study is to review the current evidence on the diagnosis and management of empyema. The American Pediatric Surgical Association Outcomes and Clinical Trials Committee compiled 8 questions to address. A comprehensive review was performed on each topic. Topics included the distinction between parapneumonic effusion and empyema, the optimal imaging modality in evaluating pleural space disease, when and how pleural fluid should be managed, the first treatment option and optimal timing in the management of empyema, the optimal chemical debridement agent for empyema, therapeutic options if chemical debridement fails, therapy for parenchymal abscess or necrotizing pneumonia and duration of antibiotic therapy after an intervention. The evidence was graded for each topic to provide grade of recommendation where appropriate.

Beyond feasibility: a comparison of newborns undergoing thoracoscopic and open repair of congenital diaphragmatic hernias

BACKGROUND Although both laparoscopic and thoracoscopic repair of congenital diaphragmatic hernia (CDH) have been described in the literature, neither appropriate selection criteria nor improved outcomes for minimally invasive repair over open repair have been clearly delineated. METHODS We reviewed our experience with neonatal CDH repair between 2004 and 2007 to determine clinical parameters that are associated with successful thoracoscopic CDH repair. We compared these patients to a similarly matched cohort of patients who had undergone an open neonatal CDH repair between 1999 and 2003. RESULTS From 2004 to 2007, 20 (61%) of 33 patients underwent successful neonatal thoracoscopic CDH repair. Characteristics common to all patients who underwent successful thoracoscopic repair included absence of congenital heart defects, no need for extracorporeal membrane oxygenation, ventilatory peak inspiratory pressure of less than 26 cmH(2)O, and oxygenation index less than 5 on the day of planned surgery. From 1999 to 2003, 40 patients underwent an open neonatal CDH repair, of which 18 (45%) patients would have matched our selection criteria for thoracoscopic repair. These 2 cohorts were similar in age, estimated gestational age, weight, APGAR scores, and oxygenation index at the time of surgery. The thoracoscopic cohort had statistically and clinically significant quicker return to full enteral feeds, had shorter duration on the ventilator postoperatively, and required less narcotic/sedation postoperatively. Less severe complications occurred in the thoracoscopic cohort. Adjusted total hospital charges were less for the thoracoscopic repair. CONCLUSIONS Successful thoracoscopic CDH repair can be expected in newborns, which has limited respiratory compromise. Thoracoscopic CDH repair is associated with lower morbidity and quicker recovery than traditional open repair and without increased risk of recurrence or complications.

All-terrain vehicle rules and regulations: impact on pediatric mortality

BACKGROUND/PURPOSE All-terrain vehicles (ATV) use by children leads to severe injury and death. Since the US Consumer Product Safety Commission consent decree expired in 1998, there has been little movement in regulating ATV use for children (<16 yr). The authors hypothesized that states with laws and regulations restricting pediatric ATV use may abrogate excess death compared with states without such restrictions. METHODS Pediatric mortality data reported to the consumer product safety commission from 1982 to 1998 were analyzed as well as state all-terrain vehicle requirements compiled by the Specialty Vehicle Institute of America in August 2001. The authors calculated ATV mortality rate by dividing ATV mortality frequency by 1980-2000 pediatric census results. They compared the top 26 states with the highest ATV mortality rates (TOP) with those of all other states (OTH) in terms of age, ATV type, ATV occupancy, and ATV laws. Chi-square analysis was performed. RESULTS There were 1,342 ATV pediatric deaths during the 16-year period. The TOP states averaged approximately a 2-fold increase in adjusted ATV mortality rate compared with the national ATV pediatric mortality rate. Ninety-two percent of TOP states have no licensing laws compared with 73% of the OTH states (P <.07). There is no difference between groups with regard to minimum age requirements and safety certification. CONCLUSIONS Current legal and regulatory standards have low probability of decreasing ATV-related pediatric mortality. States should adopt laws that restrict the use of ATVs for children less than 16 years of age and potentially prevent excess ATV-related pediatric mortality.

Partial splenectomy for hereditary spherocytosis: a multi-institutional review

BACKGROUND/PURPOSE Partial splenectomy has emerged as a surgical option for selected children with hereditary spherocytosis, with the goal of reducing anemia while preserving splenic function. This multi-institutional study is the largest series to date examining outcomes data for partial splenectomy in patients with hereditary spherocytosis. METHODS Data were collected retrospectively from 5 North American pediatric hospitals. Sixty-two children underwent partial splenectomy for hereditary spherocytosis between 1990 and 2008. RESULTS At 1 year following partial splenectomy, mean hemoglobin significantly increased by 3.0 ± 1.4 g/dL (n = 52), reticulocyte count decreased by 6.6% ± 6.6% (n = 41), and bilirubin level decreased by 1.3 ± 0.9 mg/dL (n = 25). Patients with poor or transient hematologic response were found to have significantly more splenic regeneration postoperatively compared with patients with a durable clinical response (maximal spleen dimension, 9.0 ± 3.4 vs 6.3 ± 2.2 cm). Clinically significant recurrence of anemia or abdominal pain led to completion splenectomy in 4.84% of patients. No patients developed postsplenectomy sepsis. CONCLUSIONS Our multi-institutional review indicates that partial splenectomy for hereditary spherocytosis leads to sustained and clinically significant improvement in hematologic profiles and clinical symptoms in most patients. Our data support partial splenectomy as an alternative for selected children with hereditary spherocytosis.

Traumatic Injuries in Developing Countries: Report From a Nationwide Cross-Sectional Survey of Sierra Leone

OBJECTIVE To use a nationwide household survey tool to provide an estimate of injury prevalence, mechanisms of traumatic injuries, and number of injury-related deaths in a low-income country. DESIGN A randomized, cross-sectional nationwide survey using the Surgeons OverSeas Assessment of Surgical Need tool was conducted in 2012. SETTING Sierra Leone, Africa. PARTICIPANTS Three thousand seven hundred fifty randomly selected participants throughout Sierra Leone. MAIN OUTCOME MEASURES Mechanisms of injury based on age, sex, anatomic location, cause, and sociodemographic factors as well as mechanisms of injury-related deaths in the previous year were the primary outcome measures. RESULTS Data were collected and analyzed from 1843 households and 3645 respondents (98% response rate). Four hundred fifty-two respondents (12%) reported at least 1 traumatic injury in the preceding year. Falls were the most common cause of nonfatal injuries (40%). The extremities were the most common injury site regardless of age or sex. Traffic injuries were the leading cause of injury-related deaths (32% of fatal injuries). CONCLUSIONS This study provides baseline data on the mechanisms of traumatic injuries as well as the sociodemographic factors affecting injury prevalence in one of the worlds poorest nations. It is anticipated that these data will provide an impetus for further studies to determine injury severity, associated disability, and barriers to accessing care in these resource-poor areas.

Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model

BACKGROUND Previously, we have shown that supplementation of intestinal alkaline phosphatase (IAP) decreased severity of necrotizing enterocolitis (NEC)-associated intestinal injury. We hypothesized that IAP administration is protective of intestinal epithelial barrier function in a dose-dependent manner. METHODS Control rat pups were vaginally delivered and breast-fed. Premature rats were divided into 4 groups: formula fed with lipopolysaccharide and hypoxia (NEC) or additional daily bovine IAP 40, 4, or 0.4 U/kg (NEC + IAP 40 U, IAP 4 U, or IAP 0.4 U). RESULTS Necrotizing enterocolitis is associated with decreased IAP protein expression and activity. Supplemental IAP increases IAP activity in intestinal homogenates and decreased NEC injury score in a dose-dependent manner. Intestinal injury as measured by fluorescein isothiocyanate-dextran flux from ileal loops showed increased permeability vs control, but supplemental IAP reversed this. Tight junction proteins claudin-1, claudin-3, occludin, and zonula occludin 1 were elevated in the NEC and IAP-treated groups with differences in expression patterns. No differences in messenger RNA levels were observed on postinjury day 3. Intestinal alkaline phosphatase administration decreases intestinal NEC injury in a dose-dependent manner. CONCLUSION Early enteral supplemental IAP may reduce NEC-related injury and may be useful for preserving the intestinal epithelial barrier function.