Providers' Perceptions Versus Practices Inform Pediatric Colorectal Enhanced Recovery After Surgery Implementation.

INTRODUCTION: There are many barriers to the implementation of an enhanced recovery after surgery (ERAS) pathway. The aim of this study was to compare surgeon and anesthesia perceptions with current practices prior to the initiation of an ERAS protocol in pediatric colorectal patients and to use that information to inform ERAS implementation. METHODS: This was a mixed method single institution study of barriers to implementation of an ERAS pathway at a free-standing children's hospital. Anesthesiologists and surgeons at a free-standing children's hospital were surveyed regarding current practices of ERAS components. A retrospective chart review was performed of 5- to 18-y-old patients undergoing colorectal procedures between 2013 and 2017, followed by the initiation of an ERAS pathway, and a prospective chart review for 18 mo postimplementation. RESULTS: The response rate was 100% (n = 7) for surgeons and 60% (n = 9) for anesthesiologists. Preoperative nonopioid analgesics and regional anesthesia were rarely used. Intraoperatively, 54.7% of patients had a fluid balance of <10 cc/kg/h and normothermia was achieved in only 38.7%. Mechanical bowel prep was frequently utilized (48%). Median nil per os time was significantly longer than required at 12 h. Postoperatively, 42.9% of surgeons reported that patients could have clears on postoperative day zero, 28.6% on postoperative day one, and 28.6% after flatus. In reality, 53.3% of patients were started on clears after flatus, with a median time of 2 d. Most surgeons (85.7%) expected patients to get out of bed once awake from anesthesia; however, median time that patients were out of bed was postoperative day one. While most surgeons reported frequent use of acetaminophen and/or ketorolac, only 69.3% received any nonopioid analgesic postoperatively, with only 41.3% receiving two or more nonopioid analgesics. Nonopioid analgesia showed the highest rates of improvement from retrospective to prospective: preoperative use of analgesics increased from 5.3% to 41.2% (P < 0.0001), postoperative use of acetaminophen increased by 27.4% (P = 0.5), Toradol by 45.5% (P = 0.11), and gabapentin by 86.7% (P < 0.0001). Postoperative nausea/vomiting prophylaxis with >1 class of antiemetic increased from 8% to 47.1% (P < 0.001). The length of stay was unchanged (5.7 versus 4.4 d, P = 0.14). CONCLUSIONS: For the successful implementation of an ERAS protocol, perceptions versus reality must be assessed to determine current practices and identify barriers to implementation.

Association of Surgeon Representation on NIH Study Sections With Receipt of Funding by Surgeon-scientists.

OBJECTIVE: Our goal was to evaluate the relationship between surgeon representation on NIH study sections and success in grant funding. SUMMARY OF BACKGROUND DATA: NIH funding for surgeon-scientists is declining. Prior work has called for increased surgeon participation in the grant review process as a strategy to increase receipt of funding by surgeon-scientists. METHODS: A retrospective review of surgeon (primary department: General, Urology, Orthopedic, Ophthalmology, Otolaryngology, Neurosurgery) representation on NIH study sections and receipt of funding was performed using NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) and 2019 Blue Ridge Institute for Medical Research data. NIH chartered study section panels and ad hoc reviewers for each 2019 review date were also obtained. RESULTS: In 2019, 9239 individuals reviewed in at least 1 of the 168 study sections [190 (2.1%) surgeons, 64 (0.7%) standing members, 126 (1.4%) ad-hoc]. Most surgeons on study sections were male (65%) professors (63%). Surgeons most commonly served on bioengineering, technology, and surgical sciences (29.6% surgeons), diseases and pathophysiology of the visual system (28.3%), and surgery, anesthesiology and trauma (21%). In 2019, 773 surgeons received 1235 NIH grants (>$580 M) out of a total of 55,012 awards (2.2%). Funded surgeons were predominantly male (79%), White (68%), non-Hispanic (97%), full professors (50%), and 43% had additional advanced degrees (MPH/PhD/MBA). surgery, anesthesiology and trauma, diseases and pathophysiology of the visual system, and bioengineering, technology, and surgical sciences were the most common study sections that reviewed funded grants to surgeon-scientists. Ninety-two surgeons both received grant funding and served on study section. Study sections with higher surgeon representation were more likely to fund surgeon-scientists (P < 0.001). CONCLUSIONS: Surgeon representation on NIH study sections is strongly associated with receipt of funding by surgeon-scientists. Increasing NIH study section representation by surgeons may help to preserve the surgeon-scientist phenotype.

Variations of L- and D-amino acid levels in the brain of wild-type and mutant mice lacking D-amino acid oxidase activity.

D-amino acids are now recognized to be widely present in organisms and play essential roles in biological processes. Some D-amino acids are metabolized by D-amino acid oxidase (DAO), while D-Asp and D-Glu are metabolized by D-aspartate oxidase (DDO). In this study, levels of 22 amino acids and the enantiomeric compositions of the 19 chiral proteogenic entities have been determined in the whole brain of wild-type ddY mice (ddY/DAO+/+), mutant mice lacking DAO activity (ddY/DAO-/-), and the heterozygous mice (ddY/DAO+/-) using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No significant differences were observed for L-amino acid levels among the three strains except for L-Trp which was markedly elevated in the DAO+/- and DAO-/- mice. The question arises as to whether this is an unknown effect of DAO inactivity. The three highest levels of L-amino acids were L-Glu, L-Asp, and L-Gln in all the three strains. The lowest L-amino acid level was L-Cys in ddY/DAO+/- and ddY/DAO-/- mice, while L-Trp showed the lowest level in ddY/DAO+/+mice. The highest concentration of D-amino acid was found to be D-Ser, which also had the highest % D value (~ 25%). D-Glu had the lowest % D value (~ 0.01%) in all the three strains. Significant differences of D-Leu, D-Ala, D-Ser, D-Arg, and D-Ile were observed in ddY/DAO+/- and ddY/DAO-/- mice compared to ddY/DAO+/+ mice. This work provides the most complete baseline analysis of L- and D-amino acids in the brains of ddY/DAO+/+, ddY/DAO+/-, and ddY/DAO-/- mice yet reported. It also provides the most effective and efficient analytical approach for measuring these analytes in biological samples. This study provides fundamental information on the role of DAO in the brain and may be relevant for future development involving novel drugs for DAO regulation.

d-Leucine: Evaluation in an epilepsy model.

BACKGROUND: Current medicines do not provide sufficient seizure control for nearly one-third of patients with epilepsy. New options are needed to address this treatment gap. We recently found that the atypical amino acid d-leucine protected against acutely-induced seizures in mice, but its effect in chronic seizures has not been explored. We hypothesized that d-leucine would protect against spontaneous recurrent seizures. We also investigated whether mice lacking a previously-described d-leucine receptor (Tas1R2/R3) would be protected against acutely-induced seizures. METHODS: Male FVB/NJ mice were subjected to kainic acid-induced status epilepticus and monitored by video-electroencephalography (EEG) (surgically implanted electrodes) for 4weeks before, during, and after treatment with d-leucine. Tas1R2/R3 knockout mice and controls underwent the maximal electroshock threshold (MES-T) and 6-Hz tests. RESULTS: There was no difference in number of calendar days with seizures or seizure frequency with d-leucine treatment. In an exploratory analysis, mice treated with d-leucine had a lower number of dark cycles with seizures. Tas1R2/R3 knockout mice had elevated seizure thresholds in the MES-T test but not the 6-Hz test. CONCLUSIONS: d-Leucine treatment was ineffective against chronic seizures after kainic acid-induced status epilepticus, but there was some efficacy during the dark cycle. Because d-leucine is highly concentrated in the pineal gland, these data suggest that d-leucine may be useful as a tool for studying circadian patterns in epilepsy. Deletion of the Tas1R2/R3 receptor protected against seizures in the MES-T test and, therefore, may be a novel target for treating seizures.

Congenital diaphragmatic hernia-associated pulmonary hypertension.

Congenital diaphragmatic hernia (CDH) is characterized by a developmental insult which compromises cardiopulmonary embryology and results in a diaphragmatic defect, allowing abdominal organs to herniate into the hemithorax. Among the significant pathophysiologic components of this condition is pulmonary hypertension (PH), alongside pulmonary hypoplasia and cardiac dysfunction. Fetal pulmonary vascular development coincides with lung development, with the pulmonary vasculature evolving alongside lung maturation. However, in CDH, this embryologic development is impaired which, in conjunction with external compression, stifle pulmonary vascular maturation, leading to reduced lung density, increased muscularization of the pulmonary vasculature, abnormal vascular responsiveness, and altered molecular signaling, all contributing to pulmonary arterial hypertension. Understanding CDH-associated PH (CDH-PH) is crucial for development of novel approaches and effective management due to its significant impact on morbidity and mortality. Antenatal and postnatal diagnostic methods aid in CDH risk stratification and, specifically, pulmonary hypertension, including fetal imaging and gas exchange assessments. Management strategies include lung protective ventilation, fluid optimization, pharmacotherapies including pulmonary vasodilators and hemodynamic support, and extracorporeal life support (ECLS) for refractory cases. Longitudinal re-evaluation is an important consideration due to the complexity and dynamic nature of CDH cardiopulmonary physiology. Emerging therapies such as fetal endoscopic tracheal occlusion and pharmacological interventions targeting key CDH pathophysiological mechanisms show promise but require further investigation. The complexity of CDH-PH underscores the importance of a multidisciplinary approach for optimal patient care and improved outcomes.

The CDH Study Group: Past, Present, and Future.

The Congenital Diaphragmatic Hernia Study Group (CDHSG) is an international consortium of medical centers actively collecting and voluntarily contributing data pertaining to live born congenital diaphragmatic hernia (CDH) patients born and/or managed at their institutions. These data are aggregated to construct a comprehensive registry that participating centers can access to address specific clinical inquiries and track patient outcomes. Since its establishment in 1995, 147 centers have taken part in this initiative, including 53 centers from 17 countries outside the United States, with 95 current active centers across the globe. The registry has amassed data on over 14,000 children, resulting in the creation of over 75 manuscripts based on registry data to date. International, multicenter consortia enable health care professionals managing uncommon, complex, and diverse diseases to formulate evidence-based hypotheses and draw meaningful and generalizable conclusions for clinical inquiries. This review will explore the formation and structure of the CDHSG and its registry, outlining their functions, center participation, and the evolution of data collection. Additionally, we will provide an overview of the evidence generated by the CDHSG, with a particular emphasis on contributions post-2014, and look ahead to the future directions the study group will take in addressing CDH.

Hydrops and congenital diaphragmatic hernia: reported incidence and postnatal outcomes. Analysis of the congenital diaphragmatic hernia study group registry.

OBJECTIVE: Congenital Diaphragmatic Hernia (CDH) associated with hydrops is rare. The aim of this study was to describe the incidence of this combination of anomalies and the postnatal outcomes from a large database for CDH. STUDY DESIGN: Data from the multicenter, multinational database on infants with prenatally diagnosed CDH (CDHSG Registry) born from 2015 to 2021 were analyzed. RESULTS: A total of 3985 patients were entered in the registry during the study period, 3156 were prenatally diagnosed and 88 were reported to have associated fluid in at least 1 compartment, representing 2.8% of all prenatally diagnosed CDH cases in the registry. The overall survival to discharge for CDH patients with hydrops was 43%. The hydropic CDH group had lower birth weight and gestational age at birth, and increased incidence of right-sided CDH (55%), and rate of non-repair (45%). However, the survival rate for hydropic infants with CDH undergoing surgical repair was 80%. Other associated anomalies were more common in hydropic CDH (50% vs 37%, p = 0.001). CONCLUSION: Hydropic CDH is rare, only 2.8% of all prenatally diagnosed cases, and more commonly occurring in right-sided CDH. Survival rates are low, with higher rates of non-repair. However, decision-making regarding goals of care and an aggressive surgical approach in selected cases may result in survival rates comparable to non-hydropic cases.

Recent advances in the treatment of complex congenital diaphragmatic hernia-a narrative review.

Background and Objective: Congenital diaphragmatic hernia (CDH) is an anomaly of the cardiopulmonary system maturation process that results from both a global embryopathy and concomitant mechanical compression of the cardiopulmonary system from the abdominal contents during fetal maturation. This results in pulmonary hypertension, pulmonary hypoplasia, and cardiac dysfunction, requiring intense critical care management. The patients with highest risk CDH are the most challenging, resource-intensive, and bear most of the mortality. Advances at the basic, translational, and clinical research levels are leading to novel therapies and management strategies for complex, high-risk CDH. Our objective is to review novel approaches in thinking and management for the most complex and high-risk CDH patients. These include patients with prenatal and postnatal indicators of high-risk defects, those receiving extracorporeal life support (ECLS), and those with concomitant anomalies such as complex cardiac and/or chromosomal abnormalities. Methods: PubMed was searched in late 2022 and early 2023 to identify relevant evidence. Search terms included congenital diaphragmatic hernia (CDH)", "extracorporeal life support (ECLS)", "pulmonary hypertension", "dual-hit hypothesis", "risk reduction", "cardiac/chromosomal anomalies", and "novel therapies". We included trials, multicenter studies (prospective and retrospective), single-center reports, and review articles/expert opinion. Key Content and Findings: CDH is a congenital anomaly of the cardiopulmonary and diaphragmatic systems that represents a spectrum of disease. High-risk or complex patients are defined by prenatal/postnatal risk stratification, receipt of ECLS, and/or having concomitant anomalies, representing the severe end of that spectrum. Overall survival of high-risk CDH is about 50% and comprises the vast majority of mortality, mandating special emphasis. The development of risk-stratification processes, best practices or guidelines of management, and novel therapies is critical to optimize the care of these infants. Conclusions: CDH patients with high-risk disease remain a challenging subset of CDH patients. Increasing opportunities for survival are being realized with novel, investigational approaches.

Extracorporeal life support in congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is the most common indication for ECLS in neonatal respiratory failure. The ultimate purpose of ECLS is to grant cardiopulmonary support, allowing time for operative intervention and optimization of cardiopulmonary function as the pathophysiologic processes of pulmonary hypertension, pulmonary hypoplasia, and ventricular dysfunction either improve or resolve. In CDH, ECLS plays a crucial role in the management of the most challenging patients, facilitating postnatal stabilization, allowing a ventilation strategy which minimizes barotrauma and volutrauma, and permitting treatment of and recovery from pulmonary hypertension and/or cardiac dysfunction. Understanding the nuances of CDH patients, which differ from other forms of neonatal respiratory failure, and the benefits of ECLS for these infants, is crucial for effective management. CDH patients present distinct challenges. Every aspect of ECLS, from mode of support and anticoagulation medication to pump selection, ventilation strategy, pulmonary hypertension management, and the weaning process, requires meticulous consideration. ECLS for CDH serves as a bridge to making informed decisions, granting clinicians stability and time to manage / recover from specific pathophysiologic consequences, and it offers the potential for survival among even the most challenging and complex patients. As overall care and management for infants with CDH receiving ECLS continue to improve, the focus has shifted toward managing survivor morbidity. Given the multisystem nature of the disease, this requires significant experience, expertise, and multidisciplinary teamwork to optimize long-term outcomes for these patients.

Heterogeneous antibodies against SARS-CoV-2 spike receptor binding domain and nucleocapsid with implications for COVID-19 immunity.

Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR-confirmed, SARS-CoV-2-hospitalized patients, as well as 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD-binding antibodies exhibited neutralizing capacity, but only 74% of N-protein-positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.