Robert A Cusick

Indocyanine green (ICG) fluorescence imaging has emerged as a potential tool in evaluating biliary atresia, offering real-time visualisation of hepatobiliary excretion. Following intravenous administration, ICG is taken up by hepatocytes and excreted into bile, allowing assessment of biliary patency. In biliary atresia, absent or delayed fluorescence in the intestine may suggest obstruction. However, its diagnostic utility should be used with caution. We present a case highlighting a potential flaw in using ICG to diagnose biliary atresia.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly often accompanied by other structural anomalies and/or neurobehavioral manifestations. Rare de novo protein-coding variants and copy-number variations contribute to CDH in the population. However, most individuals with CDH remain genetically undiagnosed. Here, we perform integrated de novo and common-variant analyses using 1,469 CDH individuals, including 1,064 child-parent trios and 6,133 ancestry-matched, unaffected controls for the genome-wide association study. We identify candidate CDH variants in 15 genes, including eight novel genes, through deleterious de novo variants. We further identify two genomic loci contributing to CDH risk through common variants with similar effect sizes among Europeans and Latinx. Both loci are in putative transcriptional regulatory regions of developmental patterning genes. Estimated heritability in common variants is ∼19%. Strikingly, there is no significant difference in estimated polygenic risk scores between isolated and complex CDH or between individuals harboring deleterious de novo variants and individuals without these variants. The data support a polygenic model as part of the CDH genetic architecture. Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly. Genetic diagnoses are made in ∼30% of people with CDH, but the rest of the cases remain unexplained. We identified rare variants in novel genes and common variants in two loci that support a polygenic model for CDH genetic architecture.

Unintended perioperative hypothermia is associated with surgical site infection (SSI) in adults, prompting exhaustive efforts to maintain perioperative normothermia. Although these efforts are also made for pediatric patients, the association between hypothermia and SSI has not been demonstrated in children. We sought to determine whether perioperative hypothermia and other risk factors and clinical outcomes are associated with SSI in the pediatric population. This case-control study took place from January 2014 through December 2016 and included patients at a National Surgical Quality Improvement Program-participant academic children's hospital. All surgical patients were included in this retrospective analysis. SSI rates were determined. A univariate analysis was performed to determine clinical factors associated with SSI. A multivariate regression analysis was then performed to determine the predictive effect of minimum perioperative temperature for SSI. This study included 3541 patients, of which 92 (2.6%) developed SSI. A univariate analysis showed associations among SSI and higher perioperative temperatures, surgical specialty of otolaryngology and general surgery, and wound classification (American Society of Anesthesiologists [ASA] classification III and IV). A multivariate analysis determined the odds of SSI increased by a factor of 1.6 for every 1°C increase in minimum perioperative temperature. Unintended perioperative hypothermia in our pediatric patients was inversely associated with SSI. This finding suggests that pediatric SSI prevention may not require the efforts made for adult patients to maintain normothermia.

Objective Postpartum depression (PPD) affects 10–15% of mothers in the general population, and studies show increased incidence for mothers of infants with serious health conditions. This study investigates incidence of PPD in mothers of surgical patients in the neonatal intensive care unit (NICU) and characterizes these patients’ clinical and neurodevelopmental outcomes. Methods This retrospective cohort study analyzed Nebraska’s Tracking Infant Progress Statewide (TIPS) database and referring hospital medical records from February 2013 to June 2018. Upon NICU discharge, children were referred to the TIPS program, with scheduled follow-up appointments at approximately 6 months corrected age. All patients seen in NICU follow-up clinic with recorded scores for maternal Edinburgh postnatal depression screen (EPDS) were eligible except infants with congenital heart disease as this cohort was previously studied. Patients were stratified into groups based on presence or absence of a general surgical procedure within the first 6 months of life and positive (≥ 10) or negative (< 10) EPDS score. Statistical analyses assessed for significant differences between groups regarding gestational age, birth weight, maternal age, length of NICU stay (LOS), number of days on a ventilator, payment method, ethnicity, developmental testing, and rate of referral for early intervention services. Results Of 436 patients, 83 were surgical patients (16 with positive EPDS; 19.3% incidence), and 353 were non-surgical patients (44 with positive EPDS; 12.5% incidence). Statistical analysis showed no significant relationship between neonatal surgery and positive EPDS (χ 2  = 2.6, p = 0.1). While the surgical cohort had longer LOS and days on ventilator, maternal EPDS did not predict these factors. In the surgical cohort, mothers of children not independent on oral feeding at discharge were more likely to screen positive for depression (7/14, 50% vs. 7/61, 11%; p < 0.05). Conclusion Mothers of surgical patients are not significantly more likely to screen positive for post-partum depression compared to other NICU mothers. This underscores the importance of routine screening for PPD in mothers of both surgical and non-surgical NICU patients in order to identify parents and children at risk.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Purpose: The identification of urachal remnants is occurring more in infancy. Despite evidence that nonoperative management is effective, operative management remains common and has a high complication rate. We sought to determine if the complication rate after urachal resection is associated with age. Methods: Patients undergoing urachal remnant resection were identified from ACS NSQIP Pediatric from 2013 to 2017. Exclusion criteria included emergent operations, contaminated wounds, and any additional procedures. Patients were compared based on complication rates, need for reoperation or readmission, and length of stay. Results: A complication occurred in 16 of 476 patients (3.3%), 6 (1.3%) had reoperation, and 11 (2.3%) were readmitted. The median age for patients requiring reoperation was lower (0.1 years) than those not (1.3 years; p = 0.004). The median age of those readmitted was lower (0.4 years) than those not (1.4 years, p = 0.03), and a weak trend of longer length of stay in younger patients was identified (. = -0.16, p < 0.001). Conclusions: Operative management of younger patients resulted in greater risk of reoperation, readmission, and longer length of stay. Given that nonoperative management is effective, it may be of benefit to delay resection of urachal remnants to after 1 year of age. Study type: Treatment study. (c) 2020 Elsevier Inc. All rights reserved.

The purpose of this study was to evaluate trends in management of urachal anomalies at our institution and the safety of nonoperative care. Based on our experience managing urachal remnants from 2000 to 2010 (reported in 2012), we adopted a more conservative approach, including preoperative antibiotic use, refraining from using voiding cystourethrograms (VCUG), postponing surgery until at least six months of age, and considering nonoperative management. A retrospective analysis of urachal anomaly cases was conducted (2011–2016) to assess trends in practice. Charts indicating anomalies of the urachus were pulled and trends in management (nonoperative versus surgical treatment), VCUG and antibiotic use, and outcomes were reviewed. Data from 2000–2010 and 2013–2016 were compared. Our findings indicate care has shifted towards nonoperative management. A smaller proportion of patients from 2013–2016 was treated surgically compared to 2000–2010. Patients receiving nonoperative treatment exhibited lower rates of complication relative to surgically managed cases. VCUGs were eliminated as a diagnostic tool for evaluating urachal anomalies. Prophylactic preoperative antibiotic use was standardized. No patients with a known urachal remnant presented later with an abscess or sepsis. We find that a shift towards nonoperative treatment of urachal anomalies did not adversely affect overall outcomes. We recommend observing minimally symptomatic patients, especially those under six months old. Performance improvement. Level IV.

Ventilation practices have changed significantly since the initial reports in the mid 1980 of successful use of permissive hypercapnia and spontaneous ventilation [often called gentle ventilation (GV)] in infants with congenital diaphragmatic hernia (CDH). However, there has been little standardization of these practices or of the physiologic limits that define GV. We sought to ascertain among Diaphragmatic Hernia Research and Exploration; Advancing Molecular Science (DHREAMS) centers’ GV practices in the neonatal management of CDH. Pediatric surgeons and neonatologists from DHREAMS centers completed an online survey on GV practices in infants with CDH. The survey gathered data on how individuals defined GV including ventilator settings, blood gas parameters and other factors of respiratory management. A total of 87 respondents, from 12 DHREAMS centers completed the survey for an individual response rate of 53% and a 92% center response rate. Approximately 99% of the respondents defined GV as accepting higher carbon dioxide (PCO ) and 60% of the respondents also defined GV as accepting a lower pH. There was less consensus about the use of sedation and neuromuscular blocking agents in GV, both within and across the centers. Acceptable pH and PCO levels are broader than the goal ranges. Despite a lack of formal standardization, the results suggest that GV practice is consistently defined as the use of permissive hypercapnia with mild respiratory acidosis and less consistently with the use of sedation and neuromuscular blocking agents. GV is the reported practice of surveyed neonatologists and pediatric surgeons in the respiratory management of infants with CDH.

Purpose: Humanitarianism is by definition a moral of kindness, benevolence and sympathy extended to all human beings. In our view as surgeons working in underserved countries, humanitarianism means performing the best operation in the best possible circumstances with high income country (HIC) results and training in-country surgeons to do the same. Hernia Repair for the Underserved (HRFU), a not for profit organization, is developing a long term public health initiative for hernia surgery in Western Hemisphere countries. We report the progress of HRFUs methods to render humanitarian care. Methods: In a collaborative effort, Creighton University and the Institute for Latin American Concern developed an outpatient surgery site for hernia surgery in Santiago, Dominican Republic. Based on this experience, we developed a sustainable care model by recruiting American and European Hernia Society expert surgeons, staff members they recommended, building relationships with local and industry partners, and selecting local surgeons to be trained in mesh hernioplasty. HRFU then extended the care model to other Western Hemisphere countries. Results: Between 2004 and 2015, the HRFU elective hernia morbidity and mortality rates for 2052 hernia operations were 0.7 and 0%, respectively. This is consistent with outcomes from HICs and confirms the feasibility of a public health initiative based on the principles of the Preferential Option for the Poor. Conclusions: HRFU has recorded HIC morbidity and mortality rates for hernia surgery in low and middle income countries and has initiated a new surgical training model for sustainability of effect.

Congenital diaphragmatic hernia (CDH) is a prevalent major congenital anomaly with significant morbidity and mortality. Thirty to 40% mortality in CDH is largely attributed to pulmonary hypoplasia and pulmonary hypertension (PH). We hypothesized that the underlying genetic risk factors for hereditary PH are shared with CDH associated PH. Participants were recruited as part of the Diaphragmatic Hernia Research & Exploration; Advancing Molecular Science (DHREAMS) study, a prospective cohort of neonates with a diaphragmatic defect enrolled from 2005 to 2012. PH affected patients with available DNA for sequencing had one of the following: moderate or severe PH on echocardiography at 3months of age; moderate of severe PH at 1month of age with death occurring prior to the 3month echocardiogram; or on PH medications at 1month of age. We sequenced the coding regions of the hereditary PH genes bone morphogenetic protein receptor type II (BMPR2), caveolin 1 (CAV1) and potassium channel subfamily K, member 3 (KCNK3) to screen for mutations. There were 29 CDH patients with PH including 16 males and 13 females. Sequencing of BMPR2, CAV1, and KCNK3 coding regions did not identify any pathogenic variants in these genes. Prognosis study Level IV