Antireflux Surgery at National Surgical Quality Improvement Program-Pediatric Hospitals.

PURPOSE: This study aims to examine contemporary practice patterns and compare short-term outcomes for vesicoureteral reflux procedures (ureteral reimplant/endoscopic injection) using National Surgical Quality Improvement Program-Pediatric data. MATERIALS AND METHODS: Procedure-specific variables for antireflux surgery were developed to capture data not typically collected in National Surgical Quality Improvement Program-Pediatric (eg vesicoureteral reflux grade, urine cultures, 31-60-day followup). Descriptive statistics were performed, and logistic regression assessed associations between patient/procedural factors and outcomes (urinary tract infection, readmissions, unplanned procedures). RESULTS: In total, 2,842 patients (median age 4 years; 76% female; 68% open reimplant, 6% minimally invasive reimplant, 25% endoscopic injection) had procedure-specific variables collected from July 2016 through June 2018. Among 88 hospitals, a median of 24.5 procedures/study period were performed (range 1-148); 95% performed ≥1 open reimplant, 30% ≥1 minimally invasive reimplant, and 70% ≥1 endoscopic injection, with variability by hospital. Two-thirds of patients had urine cultures sent preoperatively, and 76% were discharged on antibiotics. Outcomes at 30 days included emergency department visits (10%), readmissions (4%), urinary tract infections (3%), and unplanned procedures (2%). Over half of patients (55%) had optional 31-60-day followup, with additional outcomes (particularly urinary tract infections) noted. Patients undergoing reimplant were younger, had higher reflux grades, and more postoperative occurrences than patients undergoing endoscopic injections. CONCLUSIONS: Contemporary data indicate that open reimplant is still the most common antireflux procedure, but procedure distribution varies by hospital. Emergency department visits are common, but unplanned procedures are rare, particularly for endoscopic injection. These data provide basis for comparing short-term complications and developing standardized perioperative pathways for antireflux surgery.

Development and Implications of an Evidence-based and Public Health-relevant Definition of Complicated Appendicitis in Children.

OBJECTIVE: To characterize the influence of intraoperative findings on complications and resource utilization as a means to establish an evidence-based and public health-relevant definition for complicated appendicitis. SUMMARY OF BACKGROUND DATA: Consensus is lacking surrounding the definition of complicated appendicitis in children. Establishment of a consensus definition may have implications for standardizing the reporting of clinical research data and for refining reimbursement guidelines. METHODS: This was a retrospective cohort study of patients ages 3 to 18 years who underwent appendectomy from January 1, 2013 to December 31, 2014 across 22 children's hospitals (n = 5002). Intraoperative findings and clinical data from the National Surgical Quality Improvement Program-Pediatric Appendectomy Pilot Database were merged with cost data from the Pediatric Health Information System Database. Multivariable regression was used to examine the influence of 4 intraoperative findings [visible hole (VH), diffuse fibrinopurulent exudate (DFE) extending outside the right lower quadrant (RLQ)/pelvis, abscess, and extra-luminal fecalith] on complication rates and resource utilization after controlling for patient and hospital-level characteristics. RESULTS: At least 1 of the 4 intraoperative findings was reported in 26.6% (1333/5002) of all cases. Following adjustment, each of the 4 findings was independently associated with higher rates of adverse events compared with cases where the findings were absent (VH: OR 5.57 [95% CI 3.48-8.93], DFE: OR 4.65[95% CI 2.91-7.42], abscess: OR 8.96[95% CI 5.33-15.08], P < 0.0001, fecalith: OR 5.01[95% CI 2.02-12.43], P = 0.001), and higher rates of revisits (VH: OR 2.02 [95% CI 1.34-3.04], P = 0.001, DFE: OR 1.59[95% CI 1.07-2.37], P = 0.02, abscess: OR 2.04[95% CI 1.2-3.49], P = 0.01, fecalith: OR 2.31[95% CI 1.06-5.02], P = 0.04). Each of the 4 findings was also independently associated with increased resource utilization, including longer cumulative length of stay (VH: Rate ratio [RR] 3.15[95% CI 2.86-3.46], DFE: RR 3.06 [95% CI 2.83-3.13], abscess: RR 3.94 [95% CI 3.55-4.37], fecalith: RR 2.35 [95% CI 1.87-2.96], P =  < 0.0001) and higher cumulative hospital cost (VH: RR 1.97[95% CI 1.64-2.37], P < 0.0001, DFE: RR 1.8[95% CI 1.55-2.08], P =  < 0.0001, abscess: RR 2.02[95% CI 1.61-2.53], P < 0.0001, fecalith: RR 1.49[95% CI 0.98-2.28], P = 0.06) compared with cases where the findings were absent. CONCLUSION AND RELEVANCE: The presence of a visible hole, diffuse fibrinopurulent exudate, intra-abdominal abscess, and extraluminal fecalith were independently associated with markedly worse outcomes and higher cost in children with appendicitis. The results of this study provide an evidence-based and public health-relevant framework for defining complicated appendicitis in children.

Clinical Outcome and Biological Predictors of Relapse After Nephrectomy Only for Very Low-risk Wilms Tumor: A Report From Children's Oncology Group AREN0532.

OBJECTIVE: To determine if observation alone after nephrectomy in very low-risk Wilms tumor (defined as stage I favorable histology Wilms tumors with nephrectomy weight <550g and age at diagnosis <2 years) results in satisfactory event-free survival and overall survival, and to correlate relapse with biomarkers. PATIENTS AND METHODS: The AREN0532 study enrolled patients with very low-risk Wilms tumor confirmed by central review of pathology, diagnostic imaging, and surgical reports. After nephrectomy, patients were followed without adjuvant chemotherapy. Evaluable tumors were analyzed for WT1mutation, 1p and 16q copy loss, 1q copy gain, and 11p15 imprinting. The study was powered to detect a reduction in 4-year EFS from 87% to 75% and overall survival from 95% to 88%. RESULTS: A total of 116 eligible patients enrolled with a median follow up of 80 months (range: 5-97 months). Twelve patients relapsed. Estimated 4-year event-free survival was 89.7% (95% confidence interval 84.1-95.2%) and overall survival was 100%. First sites of relapse were lung (n = 5), tumor bed (n = 4), and abdomen (n = 2), with one metachronous tumor in the contralateral kidney (n = 1) at a median time of 4.3 months for those who relapsed (range 2.3-44 months). The presence of intralobar (P = 0.46) or perilobar rests (P = 1.0) were not associated with relapse (P = 0.16). 1q gain, 1p and 16q loss, and WT1 mutation status were not associated with relapse. 11p15 methylation status was associated relapse (20% relapse with loss of heterozygosity, 25% with loss of imprinting, and 3.3% relapse with retention of the normal imprinting (P = 0.011)). CONCLUSIONS: Most patients meeting very low-risk criteria can be safely managed by nephrectomy alone with resultant reduced exposure to chemotherapy. Expansion of an observation alone strategy for low-risk Wilms tumor incorporating both clinical features and biomarkers should be considered.

Charge Awareness Affects Treatment Choice: Prospective Randomized Trial in Pediatric Appendectomy.

OBJECTIVE: To determine whether charge awareness affects patient decisions. BACKGROUND: Pediatric uncomplicated appendicitis can be treated with open or laparoscopic techniques. These 2 operations are considered to have clinical equipoise. METHODS: In a prospective, randomized clinical trial, nonobese children admitted to a children's hospital with uncomplicated appendicitis were randomized to view 1 of 2 videos discussing open and laparoscopic appendectomy. Videos were identical except that only one presented the difference in surgical materials charges. Patients and parents then choose which operation they desired. Videos were available in English and Spanish. A postoperative survey was conducted to examine factors that influenced choice. The trial was registered at ClinicalTrials.gov (NCT 01738750). RESULTS: Of 275 consecutive cases, 100 met enrollment criteria. In the group exposed to charge data (n = 49), 63% chose open technique versus 35% not presented charge data (P = 0.005). Patients were 1.8 times more likely to choose the less expensive option when charge estimate was given (95% confidence interval, 1.17-2.75). The median total hospital charges were $1554 less for those who had open technique (P < 0.001) and $528 less for the group exposed to charge information (P = 0.033). Survey found that 90% of families valued having input in this decision and 31% of patients exposed to charge listed it as their primary reason for their choice in technique. CONCLUSIONS: Patients and parents tended to choose the less expensive but equally effective technique when given the opportunity. A discussion of treatment options, which includes charge information, may represent an unrealized opportunity to affect change in health care spending.

Effect of gastrojejunal feedings on visits and costs in children with neurologic impairment.

OBJECTIVE: The objective of the present study was to determine the effect of gastrojejunal tube (GJT) feedings in children with neurologic impairment (NI) on gastroesophageal reflux disease (GERD)- and/or dysfunctional swallowing-related visits and their associated costs. METHODS: The present study is a retrospective cohort study of children with NI and GERD who underwent GJT placement at the study hospital from December 1999 to October 2006. Visits (emergency department, radiology, and hospitalizations) were reviewed from the time of birth until 1 year following GJT placement and classified as either not GERD and/or dysfunctional swallowing related or GERD and/or dysfunctional swallowing related (eg, pneumonias). Incident rate ratios (IRRs) were calculated by dividing the post-GJT visit rate by the pre-GJT visit rate. Other outcomes included associated costs, fundoplications, and deaths. RESULTS: Thirty-three patients met inclusion criteria. The IRR for total visits was 1.78 (95% confidence interval [CI] 1.12-2.81) and for GERD- and/or dysfunctional swallowing-related visits 2.88 (95% CI 1.68-4.94). Feeding tube-related visits (IRR 5.36, 95% CI 2.73-10.51) accounted for the majority. GERD- and/or dysfunctional swallowing-related costs per child per year were low overall, with no difference from pre-GJT versus post-GJT placement ($1851 vs $4601, P = 0.89). Seven (21%) children underwent Nissen fundoplication and 4 (12%) died within 1 year of GJT placement. Two deaths involved jejunal perforation. CONCLUSIONS: Children with NI and GERD who are treated with GJT feedings have significantly more GERD- and/or dysfunctional swallowing-related visits in the following year. The majority of these visits are because of the procedural complications, which are inexpensive. There is, however, mortality associated with the GJT and some children proceed to a fundoplication.

Pediatric liver lacerations and intensive care: evaluation of ICU triage strategies.

OBJECTIVE: To compare PICU admission criteria following blunt traumatic liver laceration based on CT grade and/or physiologic instability with actual practice to improve efficiency of ICU admission. DESIGN: Retrospective cohort study. SETTING: Patients with grade 3-6 liver lacerations, 2002-2010. PATIENTS: Hundred seventy-one infants and children, ages 1 month to 17 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preadmission signs of physiologic instability (i.e., coma and cardiac arrest), liver CT grading, and outcomes including length of stay and packed RBC transfusion after admission to ICU were collected. Multiple body region severe trauma was defined as more than or equal to 1 extra-abdominal body area abbreviated injury score more than or equal to 4. Actual ICU admissions were compared with predicted. Two patients died before ICU admission and five (3%) died afterward. Of 169 patients, 52 (31%) were initially admitted to the inpatient ward. Five percent received surgical care for liver injury. Twenty percent received packed RBCs emergently for shock, whereas 5% received their first packed RBCs after admission. Compared with ICU admissions, ward patients were significantly older, had lower Injury Severity Scores, and less operative care. Among ICU patients, transfusion for hemorrhagic shock was significantly associated with more severe injury scores. Sixty percent of ICU patients were not transfused. ICU triage determined by signs of physiologic instability predicted 53 admissions (31%) including seven of nine patients (78%) treated with transfusions after admission. Predicted ICU admission for nontransfused patients was lower-9%. Adding CT laceration grade more than or equal to 4 increased ICU admissions to 129 (76%). Among surviving ICU patients, 37 of 62 patients (60%) with isolated severe abdominal trauma and no systemic instability had ICU length of stay less than 1 day. CONCLUSIONS: Children with isolated abdominal injury and no physiologic instability can generally be treated without ICU admission. Adding grade more than or equal to 4 to usual ICU admission criteria resulted in excessive admission of stable patients.

Cessation of Antibiotics for Complicated Appendicitis at Discharge Does Not Increase Risk of Post-operative Infection.

PURPOSE: The utilization of home antibiotic therapy following surgery for complicated pediatric appendicitis is highly variable. In 2019, we stopped home antibiotic therapy in this cohort at our institution. We sought to evaluate our outcomes following this protocol change. METHODS: We queried our institutional NSQIP Pediatrics data for all children undergoing appendectomy for complicated appendicitis between January 2015 and May 2022. We identified two cohorts: those discharged with home antibiotics (1/1/15-4/30/19) and those discharged with no home antibiotics (5/1/19-4/30/22). Both groups were treated with response based parenteral antibiotics while hospitalized and discharged when clinically well. Our primary outcome was postoperative deep organ space infection requiring intervention (drainage, aspiration, reoperation, or antibiotics). Secondary outcomes included length of stay, superficial site infection, Clostridium difficile colitis, ER visits, post-operative CT imaging, and readmission. RESULTS: There were 185 patients in the home antibiotic group (83% discharged with antibiotics) and 121 patients in the no home antibiotic group (8.3% discharged with antibiotics). There were no significant differences in deep organ space infection requiring intervention (7% vs. 7.4%, p = 1.0). Our length of stay was not different (4.5 days vs. 3.95 days, p = 0.32), nor were other secondary outcomes or patient characteristics. All patients had documented follow-up. CONCLUSIONS: We did not identify differences in deep organ space infections, length of stay or other events after eliminating home antibiotic therapy in our complicated appendicitis cohort. The use of home antibiotics following surgery for complicated appendicitis should be reconsidered. LEVEL OF EVIDENCE: III.

Evolution of the American College of Surgeons Children's Surgery Verification Program: Implications for optimizing multidisciplinary surgical care of the pediatric patient.

The Children's Surgery Verification Program of the American College of Surgeons began in 2016 based on the standards created by the Task Force for Children's Surgery. This program seeks to improve the surgical care of children by assuring the appropriate resources and robust performance improvement programs at participating centers. Three levels of centers with defined scopes of practice and matching resources are defined. Since its inception more than 50 center have been verified. A specialty hospital program was launched in 2019. The standards for all hospitals were revised in 2021 based on lessons learned. In this article the leaders of the program discuss the development, areas of greatest impact and future directions of the program.

The past, present and future of ACS NSQIP-Pediatric: Evolution from a quality registry to a comparative quality performance platform.

Quality and process improvement (QI/PI) in children's surgical care require reliable data across the care continuum. Since 2012, the American College of Surgeons' (ACS) National Surgical Quality Improvement Program-Pediatric (NSQIP-Pediatric) has supported QI/PI by providing participating hospitals with risk-adjusted, comparative data regarding postoperative outcomes for multiple surgical specialties. To advance this goal over the past decade, iterative changes have been introduced to case inclusion and data collection, analysis and reporting. New datasets for specific procedures, such as appendectomy, spinal fusion for scoliosis, vesicoureteral reflux procedures, and tracheostomy in children less than 2 years old, have incorporated additional risk factors and outcomes to enhance the clinical relevance of data, and resource utilization to consider healthcare value. Recently, process measures for urgent surgical diagnoses and surgical antibiotic prophylaxis variables have been developed to promote timely and appropriate care. While a mature program, NSQIP-Pediatric remains dynamic and responsive to meet the needs of the surgical community. Future directions include introduction of variables and analyses to address patient-centered care and healthcare equity.

Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation.

OBJECTIVE: To determine the independent impact of acute kidney injury (AKI) and renal replacement therapy (RRT) in infants and children who receive extracorporeal membrane oxygenation. Despite continued expertise/technological advancement, patients who receive extracorporeal membrane oxygenation have high mortality. AKI and RRT portend poor outcomes independent of comorbidities and illness severity in several critically ill populations. DESIGN: Retrospective cohort study. The primary variables explored are AKI (categorical complication code for serum creatinine > 1.5 mg/dL or International Statistical Classification of Diseases and Related Health Problems, Revision 9 for acute renal failure), and RRT (complication/Current Procedural Terminology code for dialysis or hemofiltration). Multiple variables previously associated with mortality in this population were controlled, using logistic stepwise regression. Decision tree modeling was performed to determine optimal variables and cut points to predict mortality. PATIENTS: Critically ill neonates (0-30 days old) and children (> 30 days but < 18 yrs old) in the Extracorporeal Life Support Organization registry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Neonatal mortality was 2175 (27.4%) of 7941. Nonsurvivors experienced more AKI (413 [19%] of 2175 vs. 225 [3.9%] of 5766, p < .0001), and more received RRT (863 [39.7%] of 2175 vs. 923 [16.0%] of 5766, p < .0001) than survivors. Pediatric mortality was 816 (41.6%) of 1962. Pediatric nonsurvivors similarly experienced more AKI (264 [32.3%] of 816 vs. 138 [12.0%] of 1146, p < .0001) and RRT (487 [58.9%] of 816 vs. 353 [30.8%] of 1146, p < .0001) than survivors. After adjusting for confounding variables, the adjusted odds ratio for neonatal group was 3.2 (p < .0001) post AKI and 1.9 (p < .0001) given RRT. Similarly, the pediatric adjusted odds ratio for mortality was 1.7 (p < .001) post AKI and 2.5 (p < .0001) given RRT. AKI and RRT were essential in the neonatal and pediatric mortality decision trees. CONCLUSIONS: After adjusting for known predictors of mortality, AKI and RRT independently predict mortality in neonates and children, who receive extracorporeal membrane oxygenation. Ascertainment of AKI risk factors, testing novel therapies, and optimizing the timing/delivery of RRT may positively impact survival.

Impact of consolidation of cases on post-operative outcomes for index pediatric surgery cases.

BACKGROUND: The effect of the consolidation of neonatal pediatric surgical cases to limited surgeons within a hospital is unknown. We elected to model the distribution of complex neonatal procedures using an economic measure of market concentration, the Herfindahl-Hirschmann Index (HHI), and study its effect on outcomes of index pediatric surgical operations. METHODS: We used data from 49 US children's hospitals between 2007 and 2017 for the following procedures: congenital diaphragmatic hernia repair (CDH), esophageal atresia and tracheoesophageal fistula repair (EA/TEF), and pull-through for Hirschsprung disease (HD). Mixed effects logistic regression modeling was used to adjust for salient patient characteristics to determine the effect of HHI on in-hospital mortality, condition-specific one-year re-operation, and one-year unplanned readmissions. RESULTS: A total of 2270 infants were identified who underwent surgery for the three conditions of interest. On multivariable analysis, increasing HHI was not associated with differences in mortality or condition-specific re-operation within the first year. A decrease in the number of unplanned readmissions at highly concentrated centers was seen for HD (RR 0.8 CI (0.69-0.97), p = 0.02) and CDH (RR 0.4 CI (0.28-0.71), p < 0.001). CONCLUSIONS: Pediatric surgical specialization did not affect mortality or condition-specific re-operation. However, it did decrease the number of unplanned readmissions following CDH repairs and pull-throughs for HD. STUDY DESIGN: Retrospective Cohort Study. LEVEL OF EVIDENCE: Level II.

Laparotomy versus peritoneal drainage for necrotizing enterocolitis and perforation.

BACKGROUND: Perforated necrotizing enterocolitis is a major cause of morbidity and mortality in premature infants, and the optimal treatment is uncertain. We designed this multicenter randomized trial to compare outcomes of primary peritoneal drainage with laparotomy and bowel resection in preterm infants with perforated necrotizing enterocolitis. METHODS: We randomly assigned 117 preterm infants (delivered before 34 weeks of gestation) with birth weights less than 1500 g and perforated necrotizing enterocolitis at 15 pediatric centers to undergo primary peritoneal drainage or laparotomy with bowel resection. Postoperative care was standardized. The primary outcome was survival at 90 days postoperatively. Secondary outcomes included dependence on parenteral nutrition 90 days postoperatively and length of hospital stay. RESULTS: At 90 days postoperatively, 19 of 55 infants assigned to primary peritoneal drainage had died (34.5 percent), as compared with 22 of 62 infants assigned to laparotomy (35.5 percent, P=0.92). The percentages of infants who depended on total parenteral nutrition were 17 of 36 (47.2 percent) in the peritoneal-drainage group and 16 of 40 (40.0 percent) in the laparotomy group (P=0.53). The mean (+/-SD) length of hospitalization for the 76 infants who were alive 90 days after operation was similar in the primary peritoneal-drainage and laparotomy groups (126+/-58 days and 116+/-56 days, respectively; P=0.43). Subgroup analyses stratified according to the presence or absence of radiographic evidence of extensive necrotizing enterocolitis (pneumatosis intestinalis), gestational age of less than 25 weeks, and serum pH less than 7.30 at presentation showed no significant advantage of either treatment in any group. CONCLUSIONS: The type of operation performed for perforated necrotizing enterocolitis does not influence survival or other clinically important early outcomes in preterm infants. (ClinicalTrials.gov number, NCT00252681.).

Accuracy of Suction Rectal Biopsy for Diagnosis of Hirschsprung's Disease in Neonates.

INTRODUCTION: Recent publications have questioned the sensitivity of suction rectal biopsy (SRB) for diagnosis of Hirschsprung's disease (HD) in newborns. A recent European survey reported that 39% of pediatric surgeons performed full-thickness transanal biopsies due to concerns about the accuracy of SRB. We sought to examine our contemporary SRB experience in infants. MATERIALS AND METHODS: A review was performed (2007-2016) of patients under 6 months of age who had a SRB at our children's hospital. The cohort was subdivided by postmenstrual age at time of SRB: preterm (< 40 weeks, A), term neonate (40-44 weeks, B), and infant (> 44 weeks, C). The pathology reports from endorectal pull-through were used as gold standard confirmation. One-year follow-up of patients with negative SRB was used to confirm accurate diagnosis. RESULTS: A total of 153 patients met the criteria and a total of 159 SRBs (< 2,500 g; n = 26) were performed (A = 60, B = 58, C = 35). Forty-three patients were diagnosed with HD (A = 25, B = 15, C = 3). A second SRB was performed in 6 (3.9%) patients due to inadequate tissue (A = 2, B = 2, C = 2) with HD diagnosed in 5. No complications occurred. Sensitivity and specificity of SRB was 100% in all age groups. Half of the patients with a negative SRB had at least 1 year follow-up, with none subsequently diagnosed with HD. CONCLUSION: SRB results in adequate tissue for evaluation of HD in nearly all patients less than 6 months of age on the first attempt and is highly accurate in the preterm and newborn infants. No complications occurred, even among infants less than 2,500 g.

Group A streptococcal infection of an intramuscular venous malformation: a case report and review of the literature.

Intramuscular venous malformations are uncommon benign masses of vascular origin that can occur anywhere in the body. They can be small and clinically insignificant or can be large and violate tissue planes and viscera. Presentation is as variable as the extent of the lesions. They can be diagnosed as a result of local pain and swelling or as incidental findings. Rarely, venous malformations can get infected and present with fever or other more severe systemic symptoms. The literature is sparse regarding infection of intramuscular venous malformations. This case describes the presentation, diagnosis, and management of a patient with group A streptococcal infection of a previously undiagnosed intramuscularvenous malformation in a patient who presented to our pediatric emergency department.

Single-stage repair of rectoperineal and rectovestibular fistulae can be safely delayed beyond the neonatal period.

PURPOSE: We sought to examine the short-term outcomes following single-stage repair of rectoperineal and rectovestibular fistulae in infants and identify risk factors for wound complication. METHODS: Patients with a rectoperineal or rectovestibular fistula treated with a single-stage repair beyond the neonatal period (>30days of age) at a pediatric colorectal center (2011-2016) were reviewed. RESULTS: 36 patients with a rectoperineal and 7 patients with a rectovestibular fistula were repaired using the Posterior Sagittal Anorectoplasty (PSARP) approach. Median follow-up was 31months. The median age and weight at the time of repair were 166days and 6.5kg. Four patients (11%) suffered a wound complication (3 rectoperineal, 1 rectovestibular). Two required a diverting colostomy to allow wound healing. Two patients suffered skin separation managed with local wound care. All 4 patients experienced satisfactory wound healing without anoplasty stricture. Two different patients developed a stricture of the neo-anus. Age and weight at time of repair, gender, and presence of a genitourinary anomaly were not associated with wound complications. CONCLUSION: Delayed single-stage repair of rectoperineal and rectovestibular fistulae can be performed safely in infants beyond the newborn period. With attentive treatment, satisfactory healing can be anticipated if a wound complication is encountered. LEVEL OF EVIDENCE: Retrospective Comparative Study, Level III.

Germline but not somatic de novo mutations are common in human congenital diaphragmatic hernia.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that causes high newborn morbidity and mortality. CDH is considered to be a multifactorial disease, with strong evidence implicating genetic factors. Although recent studies suggest the biological role of deleterious germline de novo variants, the effect of gene variants specific to the diaphragm remains unclear, and few single genes have been definitively implicated in human disease. METHODS: We performed genome sequencing on 16 individuals with CDH and their unaffected parents, including 10 diaphragmatic samples. RESULTS: We did not detect damaging somatic mutations in diaphragms, but identified germline heterozygous de novo functional mutations of 14 genes in nine patients. Although the majority of these genes are not known to be associated with CDH, one patient with CDH and cardiac anomalies harbored a frameshift mutation in NR2F2 (aka COUP-TFII), generating a premature truncation of the protein. This patient also carried a missense variant predicted to be damaging in XIRP2 (aka Myomaxin), a transcriptional target of MEF2A. Both NR2F2 and MEF2A map to chromosome 15q26, where recurring de novo deletions and unbalanced translocations have been observed in CDH. CONCLUSIONS: Somatic variants are not common in CDH. To our knowledge, this is the second case of a germline de novo frameshift mutation in NR2F2 in CDH. Since NR2F2 null mice exhibit a diaphragmatic defect, and XIRP2 is implicated in cardiac development, our data suggest the role of these two variants in the etiology of CDH, and possibly cardiac anomalies.

Association of Intraoperative Findings With Outcomes and Resource Use in Children With Complicated Appendicitis.

Importance: The influence of disease severity on outcomes and use of health care resources in children with complicated appendicitis is poorly characterized. Adjustment for variation in disease severity may have implications for ensuring fair reimbursement and comparative performance reporting among hospitals. Objective: To examine the association of intraoperative findings as a measure of disease severity with complication rates and resource use in children with complicated appendicitis. Design: This retrospective cohort study used clinical data from the American College of Surgeons National Surgical Quality Improvement Program pediatric appendectomy pilot database (NSQIP-P database) and cost data from the Pediatric Health Information System database. Twenty-two children's hospitals participated in the NSQIP Pediatric Appendectomy Collaborative Pilot Project. Patients aged 3 to 18 years with complicated appendicitis who underwent an appendectomy from January 1, 2013, through December 31, 2014, were included in the study. Appendicitis was categorized in the NSQIP-P database as complicated if any of the following 4 intraoperative findings occurred in the operative report: visible hole, fibropurulent exudate in more than 2 quadrants, abscess, or extraluminal fecalith. Data were analyzed from January 1, 2013, through December 31, 2014. Main Outcomes and Measures: Thirty-day postoperative adverse event rate, revisit rate, hospital cost, and length of stay. Multivariable regression was used to estimate event rates and outcomes for all observed combinations of intraoperative findings, with adjusting for patient characteristics and clustering within hospitals. Results: A total of 1333 patients (58.7% boys; median age, 10 years; interquartile range, 7-12 years) were included; multiple intraoperative findings of complicated appendicitis were reported in 589 (44.2%). Compared with single findings, the presence of multiple findings was associated with higher rates of surgical site infection (odds ratio, 1.40; 95% CI, 0.95-2.06; P = .09), higher revisit rates (odds ratio, 1.60; 95% CI, 1.15-2.21; P = .005), longer length of stay (rate ratio, 1.45; 95% CI, 1.36-1.55; P < .001), and higher hospital cost (rate ratio, 1.35; 95% CI, 1.19-1.53; P < .001). Significant differences were found among different combinations of intraoperative findings for all outcomes, including a 3.6-fold difference in rates of surgical site infection (range, 7.5% for fecalith alone to 27.2% for all 4 findings; P = .002), a 2.6-fold difference in revisit rates (range, 8.9% for exudate alone to 22.9% for all 4 findings; P = .001), a 2.2-fold difference in length of stay (range, 4.0 days for exudate alone to 8.9 days for all 4 findings; P < .001), and a 2.4-fold difference in mean cumulative cost (range, $13 296 for exudate alone to $32 282 for all 4 findings; P < .001). Conclusions and Relevance: More severe presentations of complicated appendicitis are associated with worse outcomes and greater resource use. Severity adjustment may be needed to ensure fair reimbursement and comparative performance reporting, particularly at hospitals treating underserved populations where more severe presentations are common.