Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial. Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia. Design, Setting, and Participants: A multicenter randomized clinical trial including preterm infants with inguinal hernia diagnosed during initial hospitalization was conducted between September 2013 and April 2021 at 39 US hospitals. Follow-up was completed on January 3, 2023. Interventions: In the early repair strategy, infants underwent inguinal hernia repair before neonatal intensive care unit discharge. In the late repair strategy, hernia repair was planned after discharge from the neonatal intensive care unit and when the infants were older than 55 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was occurrence of any prespecified serious adverse event during the 10-month observation period (determined by a blinded adjudication committee). The secondary outcomes included the total number of days in the hospital during the 10-month observation period. Results: Among the 338 randomized infants (172 in the early repair group and 166 in the late repair group), 320 underwent operative repair (86% were male; 2% were Asian, 30% were Black, 16% were Hispanic, 59% were White, and race and ethnicity were unknown in 9% and 4%, respectively; the mean gestational age at birth was 26.6 weeks [SD, 2.8 weeks]; the mean postnatal age at enrollment was 12 weeks [SD, 5 weeks]). Among 308 infants (91%) with complete data (159 in the early repair group and 149 in the late repair group), 44 (28%) in the early repair group vs 27 (18%) in the late repair group had at least 1 serious adverse event (risk difference, -7.9% [95% credible interval, -16.9% to 0%]; 97% bayesian posterior probability of benefit with late repair). The median number of days in the hospital during the 10-month observation period was 19.0 days (IQR, 9.8 to 35.0 days) in the early repair group vs 16.0 days (IQR, 7.0 to 38.0 days) in the late repair group (82% posterior probability of benefit with late repair). In the prespecified subgroup analyses, the probability that late repair reduced the number of infants with at least 1 serious adverse event was higher in infants with a gestational age younger than 28 weeks and in those with bronchopulmonary dysplasia (99% probability of benefit in each subgroup). Conclusions and Relevance: Among preterm infants with inguinal hernia, the late repair strategy resulted in fewer infants having at least 1 serious adverse event. These findings support delaying inguinal hernia repair until after initial discharge from the neonatal intensive care unit. Trial Registration: ClinicalTrials.gov Identifier: NCT01678638.

Pectus Carinatum: Factors That Contribute to Success and Failure of Nonoperative Treatment.

BACKGROUND: Pectus carinatum is a congenital chest wall deformity characterized by protrusion ofthe sternum and ribs. External bracing has been the gold standard treatment for this condition for the past 20 years. PURPOSE: The primary purpose of the study was to identify factors that contribute to treatment success of bracing for patients with pectus carinatum. The secondary aim was to identify the optimal age to recommend bracing for pectus carinatum. METHODS: 176 patients who were evaluated for a brace for pectus carinatum were contacted to participate in an online survey about their experience. A retrospective chart review was conducted on patients who participated in the survey. RESULTS: Subjects rated themselves as more confident afterbracing(P=.002). Patients who hadfamily sup- port, and no documented complaints (P = .024) and (P = .009) respectively, were more likely to say they had made the right choice to wear the brace. CONCLUSIONS: This study demonstrated that family support and fewer complaints are predictors of success for the brace.

Bilateral lung transplant for hereditary hemorrhagic telangiectasia in a pediatric patient.

HHT is an autosomal dominant vascular dysplasia, in which abnormalities of endothelial cells cause patients to develop mucocutaneous telangiectasias, and AVMs of the pulmonary, hepatic, and cerebral circulations. Pulmonary AVMs occur in more than 20% of patients with HHT, and presentation varies from simple diffuse telangiectasias to large complex structures. Surgical management is usually indicated for large pulmonary AVMs. Treatment options for pulmonary AVMs include therapeutic embolization, segmental or lobar resection of the affected lung, and less commonly lung transplantation. Here we report the first successful case of a bilateral lung transplant for a four-yr-old girl with HHT.

Pepducin-based intervention of thrombin-receptor signaling and systemic platelet activation.

Transmembrane signaling through G protein-coupled receptors (GPCRs) controls a diverse array of cellular processes including metabolism, growth, motility, adhesion, neuronal signaling and blood coagulation. The numerous GPCRs and their key roles in both normal physiology and disease have made them the target for more than 50% of all prescribed drugs. GPCR agonists and antagonists act on the extracellular side of the receptors, whereas the intracellular surface has not yet been exploited for development of new therapeutic agents. Here, we demonstrate the utility of novel cell-penetrating peptides, termed 'pepducins', that act as intracellular inhibitors of signal transference from receptors to G proteins. Attachment of a palmitate lipid to peptides based on the third intracellular loop of protease-activated receptor 1 (PAR1) or PAR4 (refs. 3-5) yielded potent inhibitors of thrombin-mediated aggregation of human platelets. Infusion of the anti-PAR4 pepducin into mice extended bleeding time and protected against systemic platelet activation, consistent with the phenotype of PAR4-deficient mice. We show that pepducins might be used to ascertain the physiological roles of GPCRs and rapidly determine the potential therapeutic value of blockade of a particular signaling pathway.

Combined en bloc liver-double kidney transplantation in an infant with IVC thrombosis.

We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver-kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney transplant from a size matched donor. In order to provide adequate venous outflow from the kidneys in the absence of a recipient infrarenal IVC, the donor liver and kidneys were procured en bloc with a common arterial inflow via the infrarenal aorta and common outflow via the suprahepatic IVC. Kidney transplantation in the absence of adequate recipient venous drainage may require unusual vascular reconstruction techniques. This case demonstrates a novel approach in patients who may require combined liver-kidney transplantation.

A comparison of laparoscopic gastrostomy tubes and percutaneous endoscopic gastrostomy in infants: results from a single institution.

BACKGROUND/PURPOSE: Laparoscopic gastrostomy (LG) and percutaneous endoscopic gastrostomy (PEG) are two common methods for gastrostomy feeding tube placement in children. There have been limited studies evaluating these surgical interventions in infants under 12 months of age. METHODS: This study is a retrospective review of 186 patients who underwent either LG or PEG placement over a 5-year period at a single institution. The primary outcome for this study was the complication rate between the two groups. RESULTS: Of 186 patients who underwent gastrostomy tube placements, n = 130 patients comprised the PEG cohort, and n = 56 made up the LG cohort. The demographics of the two cohorts were comparable in weight, age, and co-morbidities. The overall complication rate was 29.6% The breakdown of 31.5% complications in the PEG group vs. 25% in the laparoscopic group was not statistically different. However, the PEG group did have significantly more patients who required general anesthetic for additional procedures related to G tube placement. CONCLUSION: Laparoscopy and endoscopy are both acceptable options for gastrostomy tube placements in infants. However, this study identifies that PEG placements are associated with significantly increased risk for the need of additional procedures requiring general anesthesia in this patient population.

Pain Management in Pectus Excavatum Surgery: A Comparison of Subcutaneous Catheters Versus Epidurals in a Pediatric Population.

BACKGROUND: Pectus excavatum is a common chest wall anomaly. Achieving optimal pain control is a priority for adolescents undergoing surgical correction of this condition. Options for pain control include the use of subcutaneous catheters (On-Q® pumps) and epidurals. The objective of this study is to demonstrate the feasibility of using subcutaneous catheters for pain control and to compare them with the use of epidurals during surgical correction of pectus excavatum. MATERIALS AND METHODS: We identified patients who underwent pectus excavatum repair at our institution between January 2010 and August 2016. Patients were divided into two cohorts (epidural or On-Q pump). Patient charts were reviewed for length of stay, pain scores, pain medications, and complications. RESULTS: A total of 124 patients were included. Forty percent of patients used an epidural (n = 50), and 60% had the On-Q pump (n = 74). The average patient age was 15.6 years. The average Haller index was 4.3. The On-Q pump population had a significant decrease in postoperative length of stay (mean [M] = 4.86, standard deviation [SD] = 0.85) compared with the epidural population (M = 5.60, SD = 0.97); P ≤ .001. There was a significant difference observed in pain scores for patients on the epidural (M = 2.91, SD = 1.13) and On-Q pump (M = 3.81, SD = 1.19; P ≤ .001). There was n = 1 wound infection in each group. CONCLUSION: The use of bilateral subcutaneous infusion catheters is a safe and effective method for pain control in patients undergoing surgical correction of pectus excavatum. Even though the degree of pain control is not necessarily superior to epidurals, in this study, the catheters were associated with a shorter postoperative length of stay in this patient population and did not increase the incidence of complications.

A murine model of graft-vs-host disease after in utero hematopoietic cell transplantation.

PURPOSE: Graft-vs-host disease (GvHD) is a known complication of in utero bone marrow transplantation. However, GvHD has been difficult to study owing to frequent fetal demise. We describe the first consistent murine model of GvHD with postnatal survival after in utero hematopoietic cell transplantation. METHODS: A 50/50 mixture of bone marrow and splenocytes (10(6)) from 6-week-old C57/BL6 (H2-b) mice was injected intraperitoneally into Balb/c (H2-d) fetuses at e14 to 16. Live born pups were followed for clinical GvHD. Peripheral blood and hematopoietic organ chimerism was confirmed by flow cytometry and polymerase chain reaction. Organ samples were isolated for histology. RESULTS: Twenty-seven (75%) of 36 surviving pups displayed clinical GvHD by 2 weeks compared with 9 developmentally normal pups. Mean difference in weight between the 2 groups was 2.9 g at 7 days and 5.2 g at 14 days of life (P < .0001). All 27 pups with clinical GvHD and 1 normal-appearing pup had blood chimerism ranging from 1.5% to 65%. Eight of the 9 normal-appearing pups had 0% chimerism. Histologic analysis revealed findings of GvHD in liver, spleen, small intestine, and skin specimens of only chimeric pups. CONCLUSIONS: A consistent murine model of GvHD can be achieved after in utero transplantation of major histocompatibility complex-mismatched bone marrow and splenocytes. Future studies will use this model to examine approaches to prevent GvHD after in utero stem cell transplantation.

Safety of minimal immunosuppression in liver transplantation for hepatoblastoma.

BACKGROUND: Despite aggressive chemotherapy, recurrence of disease remains the leading cause of death after liver transplantation (LTx) for hepatoblastoma (HB). Unfortunately, little is known about the effects of immunosuppression on recurrence and posttransplant outcomes. We hypothesized that minimal immunosuppression can be safely used in these recipients. METHODS: In 2004, we adopted a minimal immunosuppression regimen using daclizumab induction and tacrolimus monotherapy. Kaplan-Meier survival curves were generated. RESULTS: From 2004 to 2006, 6 children underwent primary LTx for HB with neoadjuvant and adjuvant chemotherapy. Patient survival was 100% at 12 months and at 24 months, without graft loss. One patient died 28 months after transplantation. Recurrence-free survival was 83% at 12 months and at 24 months. Despite minimal immunosuppression (IS), 4 of 6 HB recipients remained rejection-free. When compared to other LTx recipients receiving minimal IS, HB recipients trended to have better rejection-free survival (HB, 83% at 12 months and 62.5% at 24 months vs all others, 36% and 36%, respectively; P = .19). CONCLUSION: Our short-term patient and graft survival rates are comparable to those reported for all HB recipients in the United Network for Organ Sharing database. Although not statistically significant, our rejection-free survival data suggest that HB recipients may be less likely to reject than other recipients.