Minimally invasive repair of asymmetric pectus excavatum: An alternative technique to treating asymmetric morphology.

Minimally invasive repair of pectus excavatum or the Nuss procedure has become the standard operation for pectus excavatum repair. Pectus excavatum can be broadly divided into two categories: symmetric or asymmetric morphology. To optimize surgical outcomes of asymmetric pectus excavatum repair, previous work has proposed morphology-tailored bar shaping technique; the bar to be inserted is shaped asymmetrically to counter-balance the outer contour of the chest prior to the passage of the introducer across the chest. We describe an alternate approach that emphasizes precise introducer chest insertion and extraction and that highlights the direction of the introducer passage is from the higher asymmetric side to the lower contralateral side. The shape of the bar is determined after the introducer has been placed into the chest. This technique allows simultaneous compression of the higher asymmetric chest and elevation of the contralateral depressed side by the metal bar achieving excellent symmetric chest appearance. LEVEL OF EVIDENCE: Level V, Operative Technique.

A Novel Thoracic Ultrasound Measurement After Congenital Diaphragmatic Hernia Repair Identifies Decreased Diaphragmatic Excursion Associated With Adverse Respiratory and Surgical Outcomes.

Background and Aim: Congenital diaphragmatic hernia (CDH) is a rare defect often associated with pulmonary hypoplasia and abnormal pulmonary vascular development. Even after successful hernia repair, pulmonary disease may persist into adulthood. Impaired diaphragmatic motility may lead to compromised respiratory function long after index repair. This study investigates whether a novel ultrasound measurement, the diaphragmatic excursion ratio, can be a simple and non-invasive method to evaluate routine diaphragmatic motion after CDH repair, and whether it correlates with adverse surgical and respiratory outcomes. Materials and Methods: A cross-sectional study was conducted in consecutive patients who presented at medium-term follow-up visit between December 2017 and December 2018 after CDH repair at single pediatric hospital. Transthoracic ultrasound was performed with craniocaudal diaphragmatic excursion measured bilaterally during routine breathing. Diaphragmatic excursion ratios (diaphragmatic excursion of repaired vs. unrepaired side) were calculated and retrospectively compared with clinical data including demographics, length of stay, respiratory adjuncts, oral feeding, and need for gastrostomy. Results: Thirty-eight patients (median age at ultrasound, 24 months, interquartile range 11-60) were evaluated. Nine patients underwent primary repair, 29 had non-primary repair (internal oblique muscle flap or mesh patch). Patients with a diaphragmatic excursion ratio below the median (0.54) had longer hospital stays (median 77 vs. 28 days, p = 0.0007) more ventilator days (median 16 vs. 9 days, p =0.004), and were more likely to have been discharged on oxygen (68 vs. 16%, p = 0.001). They were also less likely to be exclusively taking oral feeds at 1-year post-surgery (37 vs. 74%, p = 0.02) and more likely to require a gastrostomy tube in the first year of life (74 vs. 21%, p = 0.003). Conclusions: Transthoracic ultrasound after CDH repair is practical method to assess diaphragm motion, and decreased diaphragm excursion ratio is associated with worse respiratory outcomes, a longer length of stay, and dependence on gastrostomy tube feeding within 1 year. Further prospective studies may help validate this novel ultrasound measurement and offer prognostic value.

NH2-terminal deletion of specific phosphorylation sites on PHOX2B disrupts the formation of enteric neurons in vivo.

Mutations in the paired-like homeobox 2 b (PHOX2B) gene are associated with congenital central hypoventilation syndrome (CCHS), which is a rare condition in which both autonomic dysregulation with hypoventilation and an enteric neuropathy may occur. The majority of patients with CCHS have a polyalanine repeat mutation (PARM) in PHOX2B, but a minority of patients have nonpolyalanine repeat mutations (NPARMs), some of which have been localized to exon 1. A PHOX2B-Y14X nonsense mutation previously generated in a human pluripotent stem cell (hPSC) line results in an NH2-terminus truncated product missing the first 17 or 20 amino acids, possibly due to translational reinitiation at an alternate ATG start site. This NH2-terminal truncation in the PHOX2B protein results in the loss of two key phosphorylation residues. Though the deletion does not affect the potential for PHOX2BY14X/Y14X mutant hPSC to differentiate into enteric neural crest cells (ENCCs) in culture, it impedes in vivo development of neurons in an in vivo model of human aganglionic small intestine.NEW & NOTEWORTHY A mutation that affects only 17-20 NH2-terminal amino acids in the paired-like homeobox 2 b (PHOX2B) gene hinders the subsequent in vivo establishment of intestinal neuronal cells, but not the in vitro differentiation of these cells.

Laparoscopic Treatment of Slipping Rib Syndrome in Pediatric Patients.

Background: Slipping rib syndrome (SRS) is an often unrecognized cause of lower chest and upper abdominal pain in children and adolescents. Surgical resection of the cartilaginous portions of the slipping rib often provides permanent pain relief, with the standard surgical approach being an open resection. A minimally invasive approach has not been reported previously; we report a novel laparoscopic technique for the treatment of SRS with satisfactory results. Materials and Methods: A retrospective review of all consecutive pediatric patients who underwent laparoscopic cartilage resection during the year 2019 and open cartilage resection during the year 2018 was included. Following data were recorded: age of patients, length of symptoms, length of procedure, length of cartilage resection, length of stay, resolution of pain, cosmetic acceptability, and postoperative complications. Results: Four patients underwent laparoscopic slipping rib resection without complication during the year 2019. The mean age of symptom onset was 15 (range 14-16) years old, mean length of symptoms was 1.4 (0.5-2.0) years, and mean age at operation was 16.5 (16-18) years old. The average length of the procedure was 72.8 (55-102) minutes, and mean length of cartilage removed was 2.3 (1.9-3.0) cm. Three patients underwent standard open operation during the year 2018. All patients reported complete resolution of their chronic pain at their 6-month follow-up visit. Conclusions: Laparoscopic technique can be used to treat SRS. All patients reported high satisfaction from resolution of chronic pain and the cosmetic appearance of their surgical scars.

A Giant Childhood Mesenteric Lipoblastoma With Extensive Maturation.

Abdominal lipoblastomas are uncommon soft tissue tumors in children and rarely arise from the mesentery. Due to intraabdominal location and slow growth, these masses can go unnoticed for long periods of time and often found on surgical exploration. We present a case of a 12-year-old male with years of abdominal distension accompanied by new onset early satiety that was found to have an intra-abdominal mass. He underwent an exploratory laparotomy revealing a large 33 x 27 x 15 cm rubbery mesenteric mass displacing the entire intra-abdominal contents, connected by a single vascular pedicle and encasing a loop of small intestine. The mass was resected and the patient did well without signs of recurrence. Histology confirmed the presence of mature adipocytes but on further cytogenetic analysis, a translocation between chromosomes 2 and 8 at the 12q arm was detected, which is often associated with lipoblastomas. This case represents the one of the largest mesenteric lipoblastomas that matured extensively to lipoma-like histology at the time of surgical resection.

Postoperative Opioid Analgesia Impacts Resource Utilization in Infants Undergoing Pyloromyotomy.

BACKGROUND: Opioid analgesia is often avoided in infants undergoing pyloromyotomy. Previous studies highlight an association between opioid use and prolonged hospitalization after pyloromyotomy. However, the impact of opioid use on healthcare resource utilization and cost is unknown. We hypothesized that use of opioids after pyloromyotomy is associated with increased resource utilization and costs. METHODS: A retrospective cohort study was conducted identifying healthy infants aged <6 mo with a diagnosis of pyloric stenosis who underwent pyloromyotomy from 2005 to 2015 among 47 children's hospitals using the Pediatric Health Information System database. Time of opioid exposure was categorized as day of surgery (DOS) alone, postoperative use alone, or combined DOS and postoperative use. Primary outcomes were the standardized unit cost, a proxy for resource utilization, billed charges to the patient/insurer, and hospital costs. A multivariable log-linear mixed-effects model was used to adjust for patient and hospital level factors. RESULTS: Overall, 11,008 infants underwent pyloromyotomy with 2842 (26%) receiving perioperative opioids. Most opioid use was confined to the DOS alone (n = 2,158, 19.6%). Infants who received opioids on DOS and postoperatively exhibited 13% (95% confidence interval [CI]: 7%-20%, P-value <0.001) higher total resource utilization compared with infants who did not receive any opioids. Billed charges were 3% higher (95% CI: 0%-5%, P-value = 0.034) for infants receiving opioids isolated to the postoperative period alone and 6% higher (95% CI: 2%-11%, P-value = 0.004) for infants receiving opioids on the DOS and postoperatively. CONCLUSIONS: Postoperative opioid use among infants who underwent pyloromyotomy was associated with increased resource utilization and costs.

R-Spondin 1 (RSPO1) Increases Mouse Intestinal Organoid Unit Size and Survival in vitro and Improves Tissue-Engineered Small Intestine Formation in vivo.

Introduction: Cell therapy and tissue engineering has recently emerged as a new option for short bowel syndrome (SBS) treatment, generating tissue engineered small intestine (TESI) from organoid units (OU) and biodegradable scaffolds. The recombinant human R-Spondin 1 (rhRSPO1) protein may be a key player in this process due to its mitogenic activity in intestinal stem cells. Objective: Aiming at optimizing the TESI formation process and advancing this technology closer to the clinic, we evaluated the effects of rhRSPO1 protein on OU culture and TESI formation. Methods: Intestinal OU were isolated from C57BL/6 mice and cultured in Matrigel in the presence or absence of recombinant human rhRSPO1. Throughout the culture, OU growth and survival rates were evaluated, and cells were harvested on day 3. OU were seeded onto biodegradable scaffolds, in the presence or absence of 5 µg of rhRSPO1 and implanted into the omentum of NOD/SCID mice in order to generate TESI. The explants were harvested after 30 days, weighed, fixed in formalin and embedded in paraffin for histological analysis and immunofluorescence for different cell markers. Results: After 3 days, rhRSPO1-treated OU attained a larger size, when compared to the control group, becoming 5.7 times larger on day 6. Increased survival was observed from the second day in culture, with a 2-fold increase in OU survival between days 3 and 6. A 4.8-fold increase of non-phosphorylated ß-catenin and increased relative expression of Lgr5 mRNA in the rhRSPO1-treated group confirms activation of the canonical Wnt pathway and suggests maintenance of the OU stem cell niche and associated stemness. After 30 days of in vivo maturation, rhRSPO1-treated TESI presented a larger mass than constructs treated with saline, developing a more mature intestinal epithelium with well-formed villi and crypts. In addition, the efficiency of OU-loaded rhRSPO1-treated scaffolds significantly increased, forming TESI in 100% of the samples (N = 8), of which 40% presented maximum degree of development, as compared to 66.6% in the control group (N = 9). Conclusion: rhRSPO1 treatment improves the culture of mouse intestinal OU, increasing its size and survival in vitro, and TESI formation in vivo, increasing its mass, degree of development and engraftment.

Induced pluripotent stem cell-derived enteric neural crest cells repopulate human aganglionic tissue-engineered intestine to form key components of the enteric nervous system.

Models for enteric neuropathies, in which intestinal nerves are absent or injured, are required to evaluate possible cell therapies. However, existing options, including transgenic mice, are variable and fragile. Here immunocompromised mice were implanted with human pluripotent stem cell-derived tissue-engineered small intestine 10 weeks prior to a second survival surgery in which enteric nervous system precursor cells, or saline controls, were injected into the human intestinal organoid-derived tissue-engineered small intestine and analyzed 4 weeks later. Human intestinal organoid-derived tissue-engineered small intestine implants injected with saline as controls illustrated formation of intestinal epithelium and mesenchyme without an enteric nervous system. Second surgical introduction of human pluripotent stem cell-generated enteric nervous system precursors into developing human intestinal organoid-derived tissue-engineered small intestine implants resulted in proliferative migratory neuronal and glial cells, including multiple neuronal subtypes, and demonstrated function in contractility assays.

Spleen Organoid Units Generate Functional Human and Mouse Tissue-Engineered Spleen in a Murine Model.

Introduction: Splenectomy is common after trauma or hematologic disease, and alters immune protection against pathogens, which may lead to fulminant infection with high mortality. Yet the spleen has demonstrable regenerative capacity and cells might be recovered and reimplanted at the time of injury or excision to avoid these risks. Methods: Tissue-engineered spleen (TESp) was generated from ActinGFP mice (mTESp) or human donor spleen (hTESp) through implantation of spleen organoid units (spleen OU), in NOD/SCID mice with concurrent splenectomy, on a biodegradable scaffold. Explants were evaluated and blood smears were obtained to investigate the presence of target cells or Howell-Jolly bodies, which are erythrocyte sequelae of asplenia. Results: TESp was generated from mouse (mTESp) and human (hTESp) donor cells with essential splenic components: red and white pulp with trabeculae. mTESp and hTESp demonstrated green fluorescent protein- or lamin-positive costaining with proliferating cell nuclear antigen, CD4, and CD11c, identifying proliferative donor cells and key immune components of the spleen of donor origin. Animals with hTESp and mTESP combined with splenectomy had significantly fewer Howell-Jolly bodies on blood smears than controls. Conclusion: TESp from mouse and human donor cells can be generated by 4 weeks and contains donor immune cells identified by CD4 and CD11c. TESp reduces postsplenectomy erythrocyte inclusions, indicating possible function. Impact Statement Overwhelming postsplenectomy infection is rare but highly mortal. Tissue-engineered spleen (TESp) was generated from murine (mTESp) and human (hTESp) donors and appeared histologically similar to native spleen. Both mTESp and hTESp demonstrated proliferative cells of donor spleen origin. Importantly, functional cells were demonstrated on imaging with a corresponding reduction in the number of erythrocyte inclusions in blood smears that are typically identified in patients with asplenia and indicate a lack of clearance by functional spleen tissue. Taken together, these findings indicate that this approach might be clinically relevant as a future human therapy.

The Association Between Opioid Use and Outcomes in Infants Undergoing Pyloromyotomy.

PURPOSE: The purpose of this study was to describe the frequency and variation of opioid use across hospitals in infants undergoing pyloromyotomy and to determine the impact of opioid use on postoperative outcomes. METHODS: A retrospective cohort study (2005-2015) was conducted by using the Pediatric Health Information System (PHIS) database, including infants (aged <6 months) with pyloric stenosis who underwent pyloromyotomy. Infants with significant comorbidities were excluded. Opioid use was classified as a patient receiving at least 1 opioid medication during his or her hospital stay and categorized as preoperative, day of surgery, or postoperative (≥1 day after surgery). Outcomes included prolonged hospital length of stay (LOS; ≥3 days) and readmission within 30 days. FINDINGS: Overall, 25,724 infants who underwent pyloromyotomy were analyzed. Opioids were administered to 6865 (26.7%) infants, with 1385 (5.4%) receiving opioids postoperatively. In 2015, there was significant variation in frequency of opioid use by hospital, with 0%-81% of infants within an individual hospital receiving opioids (P < 0.001). Infants only receiving opioids on the day of surgery exhibited decreased odds of prolonged hospital LOS (odds ratio [OR], 0.85; 95% CI, 0.78-0.92). Infants who received an opioid on both the day of surgery and postoperatively exhibited increased odds of a prolonged hospital LOS (OR, 1.71; 95% CI, 1.33-2.20). Thirty-day readmission was not associated with opioid use (OR, 1.03; 95% CI, 0.93-1.14). IMPLICATIONS: There is national variability in opioid use for infants undergoing pyloromyotomy, and postoperative opioid use is associated with prolonged hospital stay. Nonopioid analgesic protocols may warrant future investigation.

A 10-Month-Old Infant Presenting With Signs of Precocious Puberty Secondary to a Sclerosing Stromal Tumor of the Ovary in the Absence of Hormonal Elevation.

Precocious puberty in an infant is an alarming and infrequent finding, making the differential diagnosis difficult for practitioners. Precocious puberty secondary to a sclerosing stromal tumor (SST) of the ovary is rare. We present a case of a child that began precocious puberty at 3 months of age including development of breast buds, pubic hair, growth spurt, and menarche 5 days prior to presenting to pediatric endocrinology at 10 months. She underwent right salpingo-oophorectomy which demonstrated a soft tissue mass occupying almost the entire ovary with a tan-pink fleshy cut surface. Histological examination confirmed a variant of SST. This case represents an extremely young onset of precocious puberty secondary to a variant of SST without hormonal elevation.