Conservative Management of Pneumatosis Intestinalis and Portal Venous Gas After Pediatric Liver Transplantation.

BACKGROUND: Pneumatosis intestinalis (PI) is a rare pathologic finding in pediatric liver transplant (PLT) recipients. The presentation and course of PI can range from asymptomatic and clinically benign to life threatening, with no consensus regarding management of PI in children. We aim to review the clinical presentation and radiologic features of PLT recipients with PI and to report the results of conservative management. METHODS: A retrospective medical chart review was conducted on PLT recipients between November 1995 and May 2016. Parameters evaluated at PI diagnosis included pneumatosis location, presence of free air or portal venous gas (PVG), symptoms, laboratory findings, and medication regimen. RESULTS: PI developed in 10 of 130 PLT patients (7.7%) between 8 days and 7 years (median: 113 days) posttransplant. Five of the patients were male, and the median age was 2 years (range, 1-17 years). PI was located in 1 to 2 abdominal quadrants in 6 patients, and 3 patients had PVG. At diagnosis, all patients were on steroids and immunosuppressant medication and 6 patients had a concurrent infection. Laboratory findings were unremarkable. Symptoms were present in 7 patients. Nine patients were managed conservatively, and 1 patient received observation only. All patients had resolution of PI at a median of 7 days (range, 2-14 days). CONCLUSIONS: PI can occur at any time after PLT and appears to be associated with steroid use and infectious agents. If PI/PVG is identified and the patient is clinically stable, initiation of a standard management algorithm may help treat these patients conservatively, thus avoiding surgical intervention.

Right trisegmentectomy after portal vein embolization in a high-risk toddler with hepatoblastoma.

Portal vein embolization (PVE) is a pre-operative treatment modality in adults undergoing hepatectomy with concerns of post-operative liver failure from insufficient future liver remnant (FLR). PVE induces growth in the FLR. The success of this technique is well described in adults, but not in young children with hepatoblastoma.

Organ allocation and utilization in pediatric transplantation.

Pediatric transplant candidates include heart, lung, liver, pancreas, small intestine, and kidney. The purpose of this article is to review the history and current methods for determining priority of the above-mentioned transplantable organs. The methods used by the authors involved the review of historical and current manuscripts and UNOS policy documents. We summarized the findings in order to create a concise review of the current policies and wait times for transplantation in pediatric transplant patients.

Microcystin-LR induced liver injury in mice and in primary human hepatocytes is caused by oncotic necrosis.

Microcystins are a group of toxins produced by freshwater cyanobacteria. Uptake of microcystin-leucine arginine (MC-LR) by organic anion transporting polypeptide 1B2 in hepatocytes results in inhibition of protein phosphatase 1A and 2A, and subsequent cell death. Studies performed in primary rat hepatocytes demonstrate prototypical apoptosis after MC-LR exposure; however, no study has directly tested whether apoptosis is critically involved in vivo in the mouse, or in human hepatocytes. MC-LR (120 µg/kg) was administered to C57BL/6J mice and cell death was evaluated by alanine aminotransferase (ALT) release, caspase-3 activity in the liver, and histology. Mice exposed to MC-LR had increases in plasma ALT values, and hemorrhage in the liver, but no increase in capase-3 activity in the liver. Pre-treatment with the pan-caspase inhibitor z-VAD-fmk failed to protect against cell death measured by ALT, glutathione depletion, or hemorrhage. Administration of MC-LR to primary human hepatocytes resulted in significant toxicity at concentrations between 5 nM and 1 µM. There were no elevated caspase-3 activities and pretreatment with z-VAD-fmk failed to protect against cell death in human hepatocytes. MC-LR treated human hepatocytes stained positive for propidium iodide, indicating membrane instability, a marker of necrosis. Of note, both increases in PI positive cells, and increases in lactate dehydrogenase release, occurred before the onset of complete actin filament collapse. In conclusion, apoptosis does not contribute to MC-LR-induced cell death in the in vivo mouse model or in primary human hepatocytes in vitro. Thus, targeting necrotic cell death mechanisms will be critical for preventing microcystin-induced liver injury.

Comparative effectiveness of catheter salvage strategies for pediatric catheter-related bloodstream infections.

BACKGROUND: Intravascular catheter salvage may be attempted in clinically suitable cases in pediatric patients with catheter-related bloodstream infections. The purpose of this study was to assess the effectiveness of ethanol and hydrochloric acid (HCl) locks in achieving catheter salvage through decision-analysis modeling. METHODS: A Markov decision model was created to simulate catheter salvage using three management strategies: systemic antibiotics alone, antibiotics plus HCl lock, and antibiotics plus ethanol lock. One-way and two-way sensitivity analyses were performed for all model variables. Infection control rates and recurrence rates for each strategy were derived from prospective institutional data and existing pediatric literature. Costs were derived from institutional charges. RESULTS: With antibiotics alone, 73% of patients would require line replacement within 100days, compared to only 31% and 19% of patients treated with HCl and ethanol lock, respectively. Incremental cost per additional catheter salvaged is $89 for HCl lock and $456 for ethanol lock. Superior efficacy of adjunct lock therapy is insensitive to changes in the anticipated duration of central access requirement and to clinically relevant variations in all model input variables. CONCLUSION: HCl or ethanol locks are cost-effective adjuncts to systemic antibiotics for attempted catheter salvage in the setting of catheter-related bloodstream infections.

Adaptive simulation training using cumulative sum: a randomized prospective trial.

BACKGROUND: Cumulative sum (Cusum) is a novel tool that can facilitate adaptive, individualized training curricula. The purpose of this study was to use Cusum to streamline simulation-based training. METHODS: Preclinical medical students were randomized to Cusum or control arms and practiced suturing, intubation, and central venous catheterization in simulation. Control participants practiced between 8 and 9 hours each. Cusum participants practiced until Cusum proficient in all tasks. Group comparisons of blinded post-test evaluations were performed using Wilcoxon rank sum. RESULTS: Forty-eight participants completed the study. Average post-test composite score was 92.1% for Cusum and 93.5% for control (P = .71). Cusum participants practiced 19% fewer hours than control group participants (7.12 vs 8.75 hours, P < .001). Cusum detected proficiency relapses during practice among 7 (29%) participants for suturing and 10 (40%) for intubation. CONCLUSIONS: In this comparison between adaptive and volume-based curricula in surgical training, Cusum promoted more efficient time utilization while maintaining excellent results.

Chest radiography does not alter the treatment course for children after rigid bronchoscopy.

The purpose of this study was to evaluate the usefulness of chest radiography in the direction of postbronchoscopy clinical therapy. From 2001 to 2011, 368 rigid bronchoscopies were performed at a single institution in 221 children. Indications for bronchoscopy, concomitant bronchoscopic procedures, and results of postoperative chest radiography were evaluated. Rigid bronchoscopy was performed in children at a median age of 2.21 years (range, two days to 20 years). Chest radiography was performed at the discretion of the primary surgeon after 275 (74.7%) procedures. Malpositioning of the endotracheal or tracheostomy tube occurred in 1.5 per cent (n = three of 203) of ventilated patients postbronchoscopy. Pneumothorax occurred in 0.5 per cent (n = two of 368) of children and followed laser degranulation (n = one of 117 [0.9%]) and removal of an aspirated foreign body (n = one of 80 [1.3%]). Neither child required tube thoracostomy. Three children necessitated intraoperative tube thoracostomy placement for symptomatic pneumothoraces before radiographic assessment. No children sustained postprocedural complications in the absence of postbronchoscopy radiography. Postbronchoscopy chest radiography in the absence of defined symptomatology is not associated with a change in the postprocedural treatment course, suggesting selective application may be appropriate after at-risk bronchoscopic interventions. Such practice will limit the future cost and radiation exposure associated with this common procedure.

The effect of race and gender on pediatric surgical outcomes within the United States.

PURPOSE: The purpose of this study was to examine risk-adjusted associations between race and gender on postoperative morbidity, mortality, and resource utilization in pediatric surgical patients within the United States. METHODS: 101,083 pediatric surgical patients were evaluated using the U.S. national KID Inpatient Database (2003 and 2006): appendectomy (81.2%), pyloromyotomy (9.8%), intussusception (6.2%), decortication (1.9%), congenital diaphragmatic hernia repair (0.7%), and colonic resection for Hirschsprung's disease (0.2%). Patients were stratified according to gender (male: 63.1%, n=63,783) and race: white (n=58,711), Hispanic (n=26,118), black (n=9,103), Asian (n=1,582), Native American (n=474), and other (n=5,096). Multivariable logistic regression modeling was utilized to evaluate risk-adjusted associations between race, gender, and outcomes. RESULTS: After risk adjustment, race was independently associated with in-hospital death (p=0.02), with an increased risk for black children. Gender was not associated with mortality (p=0.77). Postoperative morbidity was significantly associated with gender (p<0.001) and race (p=0.01). Gender (p=0.003) and race (p<0.001) were further associated with increased hospital length of stay. Importantly, these results were dependent on operation type. CONCLUSION: Race and gender significantly affect postoperative outcomes following pediatric surgery. Black patients are at disproportionate risk for postoperative mortality, while black and Hispanic patients have increased morbidity and hospital resource utilization. While gender does not affect mortality, gender is a determinant of both postoperative morbidity and increased resource utilization.

Surgical outcomes analysis of pediatric peritoneal dialysis catheter function in a rural region.

PURPOSE: The purpose of this study was to analyze the experience with peritoneal dialysis (PD) at a high-volume, single center institution that supports a rural population. METHODS: From 2000 to 2010, 88 children (median age: 1.98 years, [range: 2 days-20.2 years]) received 134 PD catheters for the management of acute and chronic renal failure. The primary outcome of interest was the incidence of primary PD catheter failure (replacement or revision within 60 days). Operative technique, longitudinal outcomes, and time intervals to transplantation were analyzed. RESULTS: Median time to transplant from the institution of dialysis was 1.4 years [range: 0.3-6.4 years]. Primary catheter failure occurred in 24.6% of cases. Infants less than 6 months of age demonstrated an increased incidence of primary catheter failure (p = 0.02). The operative technique for catheter placement was not associated with the incidence of primary failure. Postoperative complications included peritonitis (22.7%), omental plugging (11.9%), pericatheter drainage (9.0%), and exit site infection (3.0%). CONCLUSION: Peritoneal dialysis provides a safe and effective renal replacement therapy for regional pediatric centers that serve a rural population. However, primary catheter failure rates remain high at 24.6%. The surgical technique for placement had no effect on this failure rate in our patient population. Infants less than 6 months of age are at increased risk for primary catheter failure and warrant intensive surveillance.

Pediatric cervicomediastinal hibernoma: a case report.

Hibernoma is a rare lipomatous tumor of brown fat origin. Though uniformly benign in nature these tumors may cause symptoms secondary to extrinsic compression of neighboring structures. Hibernomas may be found anywhere that normal fetal brown fat may be located but are most commonly located in the thigh. We present a case of a hibernoma presenting as an unusual cervicomediastinal mass in a 6-year-old male. This mass was discovered during a diagnostic chest x-ray for pneumonia and treated by resection. Complete surgical resection is considered curative. Hibernoma should be considered in the differential diagnosis of any lipomatous tumor.

Primary payer status is significantly associated with postoperative mortality, morbidity, and hospital resource utilization in pediatric surgical patients within the United States.

PURPOSE: Current healthcare reform efforts have highlighted the potential impact of insurance status on patient outcomes. The influence of primary payer status (PPS) within the pediatric surgical patient population remains unknown. The purpose of this study was to examine risk-adjusted associations between PPS and postoperative mortality, morbidity, and resource utilization in pediatric surgical patients within the United States. METHODS: A weighted total of 153,333 pediatric surgical patients were evaluated using the national Kids' Inpatient Database (2003 and 2006): appendectomy, intussusception, decortication, pyloromyotomy, congenital diaphragmatic hernia repair, and colonic resection for Hirschsprung's disease. Patients were stratified according to PPS: Medicare (n=180), Medicaid (n=51,862), uninsured (n=12,539), and private insurance (n=88,753). Multivariable hierarchical regression modeling was utilized to evaluate risk-adjusted associations between PPS and outcomes. RESULTS: Overall median patient age was 12 years, operations were primarily non-elective (92.4%), and appendectomies accounted for the highest proportion of cases (81.3%). After adjustment for patient, hospital, and operation-related factors, PPS was independently associated with in-hospital death (p<0.0001) and postoperative complications (p<0.02), with increased risk for Medicaid and uninsured populations. Moreover, Medicaid PPS was also associated with greater adjusted lengths of stay and total hospital charges (p<0.0001). Importantly, these results were dependent on operation type. CONCLUSIONS: Primary payer status is associated with risk-adjusted postoperative mortality, morbidity, and resource utilization among pediatric surgical patients. Uninsured patients are at increased risk for postoperative mortality while Medicaid patients accrue greater morbidity, hospital lengths of stay, and total charges. These results highlight a complex interaction between socioeconomic and patient-related factors, and primary payer status should be considered in the preoperative risk stratification of pediatric patients.

Permissive hypercapnia in the management of congenital diaphragmatic hernia: our institutional experience.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a potentially lethal anomaly associated with pulmonary hypoplasia and persistent pulmonary hypertension. Permissive hypercapnia is a strategy designed to reduce lung injury from mechanical ventilation in infants. It has been shown to be a potentially superior method of ventilator management for patients with CDH. In 2001, the Divisions of Neonatology and Pediatric Surgery at the University of Virginia Children's Hospital established permissive hypercapnia as the management strategy for treatment of CDH. We hypothesized that permissive hypercapnia would be associated with improved outcomes in this patient population. STUDY DESIGN: This retrospective review compares outcomes of infants treated for CDH in the extracorporeal membrane oxygenation (ECMO) era before and after initiation of permissive hypercapnia at a single institution. Outcomes were compared using univariate statistical analysis. RESULTS: Ninety-one patients were available for analysis and were divided into 2 groups: 42 (Group 1) treated before and 49 (Group 2) treated after implementation of permissive hypercapnia. Survival was higher in Group 2 (85.8% vs 54.8%; p = 0.001; relative risk [RR] 3.17). Morbidity was lower in Group 2 and approached statistical significance (65.3% vs 83.3%; p = 0.052). Patients in Group 2 were repaired later, had a lower rate of ECMO use, and were extubated earlier. There was no difference in hospital stay. CONCLUSIONS: The use of permissive hypercapnia for infants with CDH was associated with decreased mortality, a longer period of ventilation before repair with a shorter period of ventilation after repair, a lower rate of ECMO use, and no lengthening of hospital stay. Permissive hypercapnia remains the standard of care for ventilation of infants with CDH at our institution.

Controlled induction of distributed microdeformation in wounded tissue via a microchamber array dressing.

Mechanical stimuli are known to play an important role in determining the structure and function of living cells and tissues. Recent studies have highlighted the role of mechanical signals in mammalian dermal wound healing. However, the biological link between mechanical stimulation of wounded tissue and the subsequent cellular response has not been fully determined. The capacity for researchers to study this link is partially limited by the lack of instrumentation capable of applying controlled mechanical stimuli to wounded tissue. The studies outlined here tested the hypothesis that it was possible to control the magnitude of induced wound tissue deformation using a microfabricated dressing composed of an array of open-faced, hexagonally shaped microchambers rendered in a patch of silicone rubber. By connecting the dressing to a single vacuum source, the underlying wounded tissue was drawn up into each of the microchambers, thereby inducing tissue deformation. For these studies, the dressings were applied to full-thickness murine dermal wounds with 200 mmHg vacuum for 12 h. These studies demonstrated that the dressing was capable of inducing wound tissue deformation with values ranging from 11 to 29%. Through statistical analysis, the magnitude of the induced deformation was shown to be a function of both microchamber height and width. These results demonstrated that the dressing was capable of controlling the amount of deformation imparted in the underlying tissue. By allowing the application of mechanical stimulation with varying intensities, such a dressing will enable the performance of sophisticated mechanobiology studies in dermal wound healing.

Liver-specific functional studies in a microfluidic array of primary mammalian hepatocytes.

Nearly half a billion dollars in resources are lost each time a drug candidate is withdrawn from the market by the Food and Drug Administration (FDA) for reasons of liver toxicity. The number of late-phase drug developmental failures due to liver toxicity could potentially be reduced through the use of hepatocyte-based systems capable of modeling the response of in vivo liver tissue to toxic insults. With this article, we report progress toward the goal of realizing an array of primary hepatocytes for use in high-throughput liver toxicity studies. Described herein is the development of a 64 (8 x 8) element array of microfluidic wells capable of supporting micropatterned primary rat hepatocytes in coculture with 3T3-J2 fibroblasts. Each of the wells within the array was continuously perfused with medium and oxygen in a nonaddressable format. The key features of the system design and fabrication are described, including the use of two microfluidic perfusion networks to provide the coculture with an independent and continuous supply of cell culture medium and oxygen. Also described are the fabrication techniques used to selectively pattern hepatocytes and 3T3-J2 fibroblasts within the wells of the array. The functional studies used to demonstrate the synthetic and metabolic capacity of the array are outlined in this article. These studies demonstrate that the hepatocytes contained within the array are capable of continuous, steady-state albumin synthesis (78.4 microg/day, sigma = 3.98 microg/day, N = 8) and urea production (109.8 microg/day, sigma = 11.9 microg/day, N = 8). In the final section of the article, these results are discussed as they relate to the final goal of this research effort, the development of an array of primary hepatocytes for use in physiologically relevant toxicology studies.