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.

Comparative analysis of traumatic esophageal injury in pediatric and adult populations.

PURPOSE: Distribution and outcomes of traumatic injury of the esophagus (TIE) in pediatric versus adult populations are unknown. Our study sought to perform a descriptive analysis of TIE in children and adults. METHODS: We reviewed the National Trauma Data Bank (NTDB) for the years 2010-2015. Demographics, characteristics, and outcomes of pediatric (age < 16 years) and adult TIE patients were described and compared. RESULTS: Among 526,850 pediatric and 3,838,895 adult trauma patients, 90 pediatric (0.02%) and 1,411 (0.04%) adult TIE patients were identified. Demographics and esophageal injury severity did not differ. Children were more likely to sustain blunt trauma (63% versus 37%), with the most common mechanism being transportation-related accidents, were less-severely injured (median ISS 14 versus 22), and had fewer associated injuries (79% versus 95%) and complications (30% versus 51%) (all p < 0.001). Children had shorter hospitalizations (median 5 versus 10 days) and were more likely to be discharged home (84% versus 64%) (both p = 0.01). In-hospital mortality did not differ significantly between children and adults (10% versus 19%, p = 0.09). CONCLUSION: TIE in the pediatric population has unique characteristics compared to adults: it is more likely to be a result of blunt trauma, has lower injury burden, and has more favorable clinical outcomes.

Esophageal duplication cysts and closure of the muscle layer.

BACKGROUND: Foregut duplication cysts are rare congenital anomalies that require surgical intervention with approximately 10%-15% of all gastrointestinal duplication cysts originating from the esophagus. Consensus is lacking among surgeons regarding closure of the esophageal muscle layer after resection of an esophageal duplication cyst and long-term outcomes are poorly documented. Therefore, we conducted the first study comparing complication rates in patients undergoing closure versus nonclosure of the esophageal muscle layer after esophageal duplication cyst resection. MATERIALS AND METHODS: A retrospective cohort study at Boston Children's Hospital, Massachusetts General Hospital, Brigham and Women's Hospital, and the Floating Hospital for Children at Tufts Medical Center was conducted. Patients undergoing resection of esophageal duplication cysts between 1990 and 2012 were classified according to whether the esophageal muscle layer was closed or left open. Demographic data, surgical technique, preoperative symptoms, and both short-term (<30 d) and long-term (≥30 d) complication rates were abstracted from patient medical records. RESULTS: Twenty-five patients were identified with a median age of 15-y old (range, 2 mo to 68-y old) and an average follow-up of 1 y. Eleven patients had the esophageal muscle layer closed after surgical resection (44%). Of those 11 patients, one developed a short-term complication, dysphagia (9%, 95% CI: 2%, 38%). Only one patient returned to the operating room, after 30 d, for an upper endoscopy after developing symptoms of gastroesophageal reflux disease. Of the 14 patients who had their muscle layer left open, three patients (21%, 95% CI: 8%, 48%) developed short-term complications, two of whom required surgical intervention within 30 d. Furthermore, two additional patients required surgical intervention after 30 d for a long-term complication (diverticulum and cyst recurrence). CONCLUSIONS: Surgical complications occurred more frequently in patients who had the muscle layer left open after resection of an esophageal duplication cyst. In addition, most patients requiring reoperation for both short-term and long-term complications occurred in this group. Though small, this study is the first to evaluate the complications after resecting esophageal duplication cysts. Our results suggest that closing the esophageal muscle layer after removal of an esophageal duplication cyst may be indicated to prevent both complications and the need for reoperations.

Safety and Efficacy of Ceftolozane/Tazobactam Plus Metronidazole Versus Meropenem From a Phase 2, Randomized Clinical Trial in Pediatric Participants With Complicated Intra-abdominal Infection.

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-ß-lactamase inhibitor combination, is approved for the treatment of complicated urinary tract infections and complicated intra-abdominal infections (cIAI). The safety and efficacy of ceftolozane/tazobactam in pediatric participants with cIAI were assessed. METHODS: This phase 2 study (NCT03217136) randomized participants to either ceftolozane/tazobactam+metronidazole or meropenem for treatment of cIAI in pediatric participants (<18 years). The primary objective was to assess the safety and tolerability of intravenous ceftolozane/tazobactam+metronidazole. Clinical cure at end of treatment (EOT) and test of cure (TOC) visits were secondary end points. RESULTS: The modified intent-to-treat (MITT) population included 91 participants (ceftolozane/tazobactam+metronidazole, n = 70; meropenem, n = 21). Complicated appendicitis was the most common diagnosis (93.4%); Escherichia coli was the most common pathogen (65.9%). Adverse events (AEs) occurred in 80.0% and 61.9% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, drug-related AEs occurred in 18.6% and 14.3% and serious AEs occurred in 11.4% and 0% of participants receiving ceftolozane/tazobactam+metronidazole and meropenem, respectively. No drug-related serious AEs or discontinuations due to drug-related AEs occurred. Rates of the clinical cure for ceftolozane/tazobactam+metronidazole and meropenem at EOT were 80.0% and 95.2% (difference: -14.3; 95% confidence interval: -26.67 to 4.93) and at TOC were 80.0% and 100.0% (difference: -19.1; 95% confidence interval: -30.18 to -2.89), respectively; 6 of the 14 clinical failures for ceftolozane/tazobactam+metronidazole at TOC were indeterminate responses imputed as failures per protocol. CONCLUSION: Ceftolozane/tazobactam+metronidazole was well tolerated in pediatric participants with cIAI and had a safety profile similar to the established safety profile in adults. In this descriptive efficacy analysis, ceftolozane/tazobactam+metronidazole appeared efficacious.

Unintentional Window Falls in Children and Adolescents.

OBJECTIVE: Unintentional window falls represent a preventable source of injury and death in children. Despite major campaigns in some larger cities, there continue to be unintentional falls from windows throughout the United States. We aimed to identify risk factors and trends in unintentional window falls in the pediatric population in a national and regional sample. METHODS: A retrospective analysis of annual emergency department (ED) visits from the National Electronic Injury Surveillance System using product codes specific to windows, as well as patient encounters for unintentional window falls from January 2007 to August 2017 using site-specific trauma registries from 10 tertiary care children's hospitals in New England. National and state-specific census population estimates were used to compute rates per 100,000 population. RESULTS: There were 38,840 ED visits and 496 regional patients who unintentionally fell from a window across the study period between 0 and 17 years old. The majority of falls occurred in children under the age of 6 and were related to falls from a second story or below. A decreased trend in national ED visits was seen, but no change in rates over time for regional trauma center encounters. A high number of falls was found to occur in smaller cities surrounding metropolitan areas and from single family residences. CONCLUSIONS: Falls from windows represent a low proportion of overall types of unintentional sources of injury in children but are a high risk for severe disability. These results provide updated epidemiologic data for targeted intervention programs, as well as raise awareness for continued education and advocacy.

Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2.

A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum.

Thoracoscopic treatment of a neonatal traumatic pneumatocele.

Traumatic pneumatoceles appear rarely after pulmonary parenchymal or bronchial disruption. Treatment is usually expectant with intervention reserved for complications, such as infection, expansion, or cardiopulmonary deterioration. A 17-day-old female was transferred to our NICU with a left-sided pneumatocele resulting from an intraparenchymal chest tube insertion. She was born at 30 weeks gestation and required a chest tube insertion for severe hydrops fetalis with respiratory failure and associated chylothoraces. An acute deterioration following several weeks of clinical improvement was unsuccessfully treated with radiologically guided drainage. In this paper, we describe the thoracoscopic management of this case.

Laparoscopic-assisted colostomy in children.

INTRODUCTION: Colostomy morbidity has been reported to be as high as 50%. Laparoscopic-assisted colostomy (LAC) is associated with decreased colostomy complication. LAC is recommended for stoma formation in adults but has not been previously reported in children. In this paper, we report on our initial experience with LAC in children. MATERIALS AND METHODS: Using a two- to four-port (3.5-mm) technique, LAC was performed in a female with an imperforate anus and 2 male patients with complicated Hirschsprung's disease (HD), respectively. Data collected included operative time, time to recover bowel function, and morbidity. Close follow-up was done until stoma closure. RESULTS: The operative time was 144 minutes in the HD patients (including concomitant laparoscopic biopsies and a leveling colostomy) and 40 minutes in the imperforate anus patient. Median time to passage of both flatus and stool was 40 hours (range, 24-48). Time to commence feeds postop was 40 hours (range, 24-48). The median time of follow-up was 3 months (range, 2-9) until the stoma was taken down. No complications have occurred to date. CONCLUSIONS: LAC is safe and easily performed in neonates and infants. It facilitates accurate stoma placement and orientation. It allows additional bowel mobilization, especially in HD. In accordance with the adult experience, LAC seems to obviate stoma-related complications. Encouraged by our initial low morbidity rate, a prospective evaluation of this technique is planned.

Surgical therapy for Barrett's esophagus.

Given the anatomic and functional defects almost universally present in patients who have BE, antireflux surgery is the most reliable means of stopping acid and nonacid (alkaline) reflux. Because patients who have BE have end-stage GERD, they require durable and reliable control of reflux, and the Hill procedure and partial fundoplication are associated with unacceptably high failure rates. In addition, there is mounting evidence that the success rates for Nissen fundoplication are lower in patients who have BE than in patients who have less severe GERD. Given that the most common mode of failure of a laparoscopic Nissen fundoplication is herniation of the fundoplication into the chest, patients who have BE must be considered at risk for having a short esophagus. The failure rate may be reduced by the liberal addition of a Collis gastroplasty, but the long-term consequences of acid-secreting mucosa left above the fundoplication in patients who have BE remain unclear. Patients suspected of having a short esophagus on the basis of a large hiatal hernia, stricture, or long-segment BE should be considered for a transthoracic approach to their fundoplication, as this affords good esophageal mobilization and may obviate the need for a gastroplasty. Surgeons must pay particular attention to their own and published results and continue to refine the operation to maximize the likelihood of a good outcome in this difficult group of patients. It is only with excellent control of reflux that any differences in the risk of progression to dysplasia and cancer become apparent, and significant, between medically and surgically treated patients.

Early Closure of Gastroschisis After Silo Placement Correlates with Earlier Enteral Feeding.

OBJECTIVES: Gastroschisis is a congenital anomaly affecting 2.3-4.4/10,000 births. Previous studies show initiation of early enteral feeds predicts improved outcomes. We hypothesize that earlier definitive closure after silo placement; can lead to earlier enteral feed initiation. Design/ Setting/ Duration: Retrospective review of patients with gastroschisis from 2005 and 2014 at a single institution. MATERIAL AND METHODS: The data, including ethnicity, gestational age, birth weight, time to definitive closure, and time of first and full feeds, were analyzed using both Spearman's rho and the Kruskal-Wallis rank sum test where appropriate; a p value less than 0.05 was considered significant. RESULTS: Forty-three patients (24 males, 19 females) born with gastroschisis were identified. Overall survival rate was 88% (38/43). Forty of the 43 patients had a silo placed prior to definitive closure. Median days to closure were 6 (0 to 85) days. First feeds on average began on day of life (DOL) 17, and full feeds on DOL 25. Earlier closure of gastroschisis correlated with early initiation of feeds (p=0.0001) and shorter time to full feeds (p=0.018), closure by DOL4 showed a trend toward earlier feeding (p=0.13). CONCLUSION: Earlier closure of gastroschisis after silo placement was associated with earlier feed initiation and shorter time to full feeds.

Bile decompression in children with histopathological evidence of pre-existing liver cirrhosis.

Although it is agreed upon by most that adequate and timely bile decompression can preserve or even improve existing liver function much debate centers on whether pre-existing liver cirrhosis can also be reversed. To help answer this question we analyzed data on 47 children with choledochal cyst disease (CD) who underwent simultaneous liver biopsy during bile decompression surgery. We collected data on two groups of children with CD spanning two different time periods: January 1985 through November 1994 (Group A) and June 1995 through November 1999 (Group B). In Group A 37 children (16 boys and 21 girls ages 5 days to 10 years) underwent simultaneous liver biopsy during elective definitive surgery for CD. In Group B ten children (five boys and five girls age one month to 7 years) underwent liver biopsy twice: first during initial cyst decompression for acute obstruction and second during elective definitive surgery after resolution of acute disease. Degree of liver cirrhosis was based on a modified World Health Organization classification system (0-IV). In Group A 15/37 (40.5%) had significant liver cirrhosis at time of biopsy (III or IV) with altered liver function in all cases; eight of nine had normal liver function on follow-up, six were lost to follow-up. In Group B seven of ten (70%) had less liver cirrhosis on pathology at second operation with three unchanged; nine of ten (90%) regained normal liver function. We conclude that bile duct obstruction is the main cause of liver cirrhosis in children with CD. Adequate and timely bile decompression can restore normal liver function and even reverse severe cirrhosis.

Thoracoscopic thymectomy in children with myasthenia gravis.

Although conservative medical management is the mainstay in the treatment of myasthenia gravis (MG), severest forms of the disease often require surgical thymectomy. Thoracoscopic thymectomy (TT) represents a minimally invasive alternative to traditional thymectomy via sternotomy. We present our preliminary experience with TT as definitive treatment for severe forms of MG. The charts of 5 children (4 girls and 1 boy; age range, 11-17 years) who underwent TT for MG were retrospectively reviewed. TT was typically performed via left thoracoscopy using 4- or 5-mm ports with 1 of the ports enlarged at the end of the procedure for specimen retrieval. Thymic veins were identified and ligated with surgical clips in all cases. Surgical parameters assessed were the following: operating time, intra- and postoperative complications, length of postoperative stay, and resolution of symptoms. Follow-up ranged from 6 months to 2 years. All 5 TTs were successfully completed. In 1 case, right-sided thoracoscopy was added to ensure complete gland excision. Surgical pathology in all cases demonstrated complete excision. Mean operating time was 121 minutes (range 88 minutes to 188 minutes). There were no intra- or postoperative complications. Length of postoperative stay averaged 1.6 days (range, 1 to 3 days). Four of 5 (80%) had clear resolution of symptoms with 1 showing minimal resolution at 6 months. Thoracoscopic thymectomy is a safe and potentially attractive alternative to traditional thymectomy via median sternotomy in severe forms of myasthenia gravis. Complete thymectomy, the goal of traditional surgical treatment for myasthenia gravis, can effectively by achieved via this minimally invasive technique.

Minimally invasive surgery for pediatric solid neoplasms.

The role of minimally invasive surgery (MIS) in children with solid neoplasms is slowly evolving. MIS appears to be an ideal way to obtain diagnostic information (i.e., tissue biopsy) in children with solid neoplasms, but its role as an ablative/curative technique is controversial. We examined the safety, reliability, and outcome of decisions made on the basis of MIS performed in children with solid neoplasms. A total of 28 children (19 boys and nine girls; age range, 14 months to 17 years) with solid neoplasms underwent 29 MIS procedures between July 1, 2000 and June 30, 2002. Complications, biopsy results, and outcomes were reviewed. Successful ablation via MIS was defined as clear microscopic margins on permanent pathology and no evidence of remnant disease on follow-up diagnostic radiological examination. There were 20 thoracoscopic and nine laparoscopic procedures. Laparoscopy included purely diagnostic without tissue biopsy or simply determination of resectability (two), incisional biopsy (two), and excisional biopsy (five; two adrenalectomy and three oophorectomy). Thoracoscopy included 15 lung biopsies and five biopsies of mediastinal masses. Diagnostic accuracy was 100 per cent in all cases. MIS as an ablative technique was successful in 10 of 10 cases. No children were found retrospectively to have been inadequately treated via MIS. We conclude that MIS can be used safely and successfully to diagnose children with suspicious solid neoplasms. Furthermore MIS may have a role as an ablative/curative technique in carefully selected circumstances.

Management of patients with combined tracheoesophageal fistula, esophageal atresia, and duodenal atresia.

INTRODUCTION: Patients with combined esophageal atresia (EA), tracheoesophageal fistula (TEF), and duodenal atresia (DA) pose a rare management challenge. PRESENTATION OF CASE: Three patients with combined esophageal atresia (EA), tracheoesophageal fistula (TEF), and duodenal atresia safely underwent a staged approach inserting a gastrostomy tube and repairing the EA/TEF first followed by a duodenoduodenostomy within one week. None of the patients suffered significant pre- or post-operative complications and our follow-up data (between 12 and 24 months) suggest that all patients eventually outgrow their reflux and respiratory symptoms. DISCUSSION: While some authors support repair of all defects in one surgery, we recommend a staged approach. A gastrostomy tube is placed first for gastric decompression before TEF ligation and EA repair can be safely undertaken. The repair of the DA can then be performed within 3-7 days under controlled circumstances. CONCLUSION: A staged approach of inserting a gastrostomy tube and repairing the EA/TEF first followed by a duodenoduodenostomy within one week resulted in excellent outcomes.

Management of pediatric patients with refractory constipation who fail cecostomy.

BACKGROUND: Antegrade continence enema (ACE) is a recognized therapeutic option in the management of pediatric refractory constipation. Data on the long-term outcome of patients who fail to improve after an ACE-procedure are lacking. PURPOSE: To describe the rate of ACE bowel management failure in pediatric refractory constipation, and the management and long term outcome of these patients. METHODS: Retrospective analysis of a cohort of patients that underwent ACE-procedure and had at least 3-year-follow-up. Detailed analysis of subsequent treatment and outcome of those patients with a poor functional outcome was performed. RESULTS: 76 patients were included. 12 (16%) failed successful bowel management after ACE requiring additional intervention. Mean follow-up was 66.3 (range 35-95 months) after ACE-procedure. Colonic motility studies demonstrated colonic neuropathy in 7 patients (58%); abnormal motility in 4 patients (33%), and abnormal left-sided colonic motility in 1 patient (9%). All 12 patients were ultimately treated surgically. Nine patients (75%) had marked clinical improvement, whereas 3 patients (25%) continued to have poor function issues at long term follow-up. CONCLUSIONS: Colonic resection, either segmental or total, led to improvement or resolution of symptoms in the majority of patients who failed cecostomy. However, this is a complex and heterogeneous group and some patients will have continued issues.

Spontaneous hemothorax in multiple exostoses: a case report and review of literature.

Abstract Multiple hereditary exostoses is a rare autosomal dominant disorder characterized by the growth of multiple osteochondromas. We describe the thoracoscopic remodeling of a spiculated costal exostotic lesion responsible for spontaneous recurrent hemothoraces in a 17-year-old male patient with multiple hereditary exostoses.

Feingold syndome: a rare but important cause of syndromic tracheoesophageal fistula.

Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are common congenital malformations and are associated with additional anomalies in approximately half of cases. Feingold syndrome is an important genetic cause of syndromic EA-TEF to consider in patients with associated microcephaly and digital anomalies. We present a case report of a male infant with EA-TEF, microcephaly, subtle facial dysmorphism, dysplastic kidney, short fifth fingers, second finger clinodactyly, and increased spacing between the first and second toes bilaterally. His clinical presentation was suggestive of Feingold syndrome, and genetic testing of the MYCN gene confirmed the diagnosis. Feingold syndrome is an autosomal dominant condition, and therefore, the diagnosis has important implications for genetic counseling.

CD40 ligation restores cytolytic T lymphocyte response and eliminates fibrosarcoma in the peritoneum of mice lacking CD4+ T cells.

Absence of CD4(+) T cell help has been suggested as a mechanism for failed anti-tumor cytotoxic T lymphocytes (CTL) response. We examined the requirement for CD4(+) T cells to eliminate an immunogenic murine fibrosarcoma (6132A) inoculated into the peritoneal cavity. Immunocompetent C3H mice eliminated both single and repeat intraperitoneal (IP) inoculums, and developed high frequency of 6132A-specific interferon-gamma (IFNgamma)-producing CTL in the peritoneal cavity. Adoptive transfer of peritoneal exudate cells (PEC) isolated from control mice, protected SCID mice from challenge with 6132A. In contrast, CD4 depleted mice had diminished ability to eliminate tumor and succumbed to repeat IP challenges. Mice depleted of CD4(+) T cells lacked tumor-specific IFNgamma producing CTL in the peritoneal cavity. Adoptive transfer of PEC from CD4 depleted mice failed to protect SCID mice from 6132A. However, splenocytes isolated from same CD4 depleted mice prevented tumor growth in SCID mice, suggesting that 6132A-specific CTL response was generated, but was not sustained in the peritoneum. Treating CD4 depleted mice with agonist anti-CD40 antibody, starting on days 3 or 8 after initiating tumor challenge, led to persistence of 6132A-specific IFNgamma producing CTL in the peritoneum, and eliminated 6132A tumor. The findings suggest that CTL can be activated in the absence of CD4(+) T cells, but CD4(+) T cells are required for a persistent CTL response at the tumor site. Exogenous stimulation through CD40 can restore tumor-specific CTL activity to the peritoneum and promote tumor clearance in the absence of CD4(+) T cells.