Trends in use of prostacyclin analogs for management of CDH-associated pulmonary hypertension.

PURPOSE: Off-label use of prostacyclins to manage congenital diaphragmatic hernia-associated pulmonary hypertension (CDH-PHTN) has been described over recent years, but use is not standardized across institutions. This study aims to describe trends in use of these medications in the CDH Study Group (CDHSG) patients. METHODS: The CDHSG was queried for all patients born from 2007 to 2019. Records were reviewed to describe the number of patients receiving prostacyclins, the day of life on which the agent was started, start time relative to ECLS, the duration of medication use, and continuation of the medication at the time of discharge. Finally, trends in use by year of birth were evaluated to assess for changes in use over time. RESULTS: There were 6439 patients identified from the registry who were born during the study period. 4372 (68%) patients received medications to treat pulmonary hypertension. Of these, 604 (14%) received a prostacyclin at some point during their care. The median start time for prostacyclins was 7.5 days of life (mean 16.9 days, SD 32.5 days), and the median duration was 12.5 days (mean 25.1 days, SD 49.1 days). Among patients who received prostacyclins, 340 patients required ECLS during care, 53 (15.5%) of whom started the prostacyclin prior to ECLS, and 159 (46.8%) of whom started prostacyclin therapy during their ECLS run. Only a small cohort (26/604, 4.3%) required continuation of the prostacyclin at the time of discharge. The proportion of patients receiving a prostacyclin remained relatively stable over the study period. CONCLUSIONS: While the proportion of patients receiving a prostacyclin for management of CDH-PHTN has remained relatively stable over the last 13 years, there is significant variation in timing of initiation and duration of use especially in the pre-ECLS period that warrants further investigation to describe optimal use in these patients.

Epidemiology of Hirschsprung disease in California from 1995 to 2013.

PURPOSE: This study seeks to update current epidemiology of Hirschsprung disease (HD) in California. METHODS: Using data from the California Office of Statewide Health Planning and Development Linked Birth (1995-2012) and Patient Discharge Databases (1995-2013), patients from either dataset with an ICD-9 diagnosis code of HD (751.3) or procedure code of Soave (48.41), Duhamel (48.65), or Swenson/other pull-through (48.49) were included. Patients > age 18 during their first admission were excluded. RESULTS: Of 9.3 million births, 2,464 patients were identified. Incidence was 2.2 cases/10,000 live births, with rates peaking at 2.9/10,000 births in 2002. Incidence was highest among African American (4.1/10,000) and Asian/Pacific Islander (2.5/10,000) births. Most were male (n = 1652, 67.1%). Sixty patients (2.4%) had Down syndrome. The median gestational age at birth was 38 weeks 6 days (interquartile range [IQR] 37 weeks 1 day-40 weeks 1 day). Mortality during the first year of life was 1.7%. Median age at death was 14.5 days (IQR 0-113 days). CONCLUSION: This is one of the largest population-based studies of HD. In California, the incidence of HD is stable, risk is highest among African American children, and the mortality rate is < 2%.

Association Between Early Prostacyclin Therapy and Extracorporeal Life Support Use in Patients With Congenital Diaphragmatic Hernia.

Importance: Prostacyclin (PGI2) is a therapeutic option to treat congenital diaphragmatic hernia (CDH)-associated pulmonary hypertension in neonates. Its use may decrease the need for extracorporeal life support (ECLS). Objective: To evaluate the association of early PGI2 therapy with ECLS use and outcomes among patients with CDH. Design, Setting, and Participants: This was a cohort study from the CDH Study Group (CDHSG) registry of patients born from January 2007 to December 2019. Patients were from 88 different tertiary pediatric referral centers worldwide that contributed data to the CDHSG. Patients were included in the study if they were admitted within the first week of life. Propensity score matching was performed using estimated gestational age, birth weight, transfer status, 1-minute and 5-minute Apgar scores, highest and lowest partial pressure of arterial carbon dioxide in the first 24 hours of life, and degree of pulmonary hypertension as covariates to generate a matched cohort of exposed and unexposed patients. Data were analyzed from January 2021 to December 2022. Exposures: Early PGI2 therapy was defined as initiation of PGI2 within the first week of life. Patients who received ECLS were included in the early PGI2 group if PGI2 was started prior to ECLS. Main Outcomes and Measures: The primary outcome of the study was the proportion of patients receiving ECLS in the exposed and unexposed groups. Results: Of 6227 patients who met inclusion criteria (mean [SD] gestational age, 37.4 [2.36] weeks; 2618 [42%] female), 206 (3.3%) received early PGI2 therapy. ECLS was used in 46 of 206 patients who received PGI2 (22.2%) and 1682 of 6021 who did not (27.9%). After propensity score matching, there were 147 patients in the treatment and control groups. Thirty-four patients who received PGI2 (23.3%) and 63 who did not (42.9%) received ECLS. Those who received PGI2 were less likely to receive ECLS (adjusted odds ratio, 0.39; 95% CI, 0.22-0.68) and had shorter mean (SD) duration of ECLS (8.6 [3.73] days vs 12.6 [6.61] days; P < .001), although there was no significant difference in in-hospital mortality. Conclusions and Relevance: In this study, there was decreased use of ECLS and decreased ECLS duration among patients with CDH who started PGI2 therapy during the first week of life. These results identify a potential advantage of early prostacyclin therapy in this population.

Characteristics of pediatric non-cardiac eCPR programs in United States and Canadian hospitals: A cross-sectional survey.

OBJECTIVE: To characterize practices surrounding pediatric eCPR in the U.S. and Canada. METHODS: Cross-sectional survey of U.S. and Canadian hospitals with non-cardiac eCPR programs. Variables included hospital and surgical group demographics, eCPR inclusion/exclusion criteria, cannulation approaches, and outcomes (survival to decannulation and survival to discharge). RESULTS: Surveys were completed by 40 hospitals in the United States (37) and Canada (3) among an estimated 49 programs (82% response rate). Respondents tended to work in >200 bed free-standing children's hospitals (27, 68%). Pediatric general surgeons respond to activations in 32 (80%) cases, with a median group size of 7 (IQR 5,9.5); 8 (20%) responding institutions take in-house call and 63% have a formal back-up system for eCPR. Dedicated simulation programs were reported by 22 (55%) respondents. Annual eCPR activations average approximately 6/year; approximately 39% of patients survived to decannulation, with 35% surviving to discharge. Cannulations occurred in a variety of settings and were mostly done through the neck at the purview of cannulating surgeon/proceduralist. Exclusion criteria used by hospitals included pre-hospital arrest (21, 53%), COVID+ (5, 13%), prolonged CPR (18, 45%), lethal chromosomal anomalies (15, 38%) and terminal underlying disease (14, 35%). CONCLUSIONS: While there are some similarities regarding inclusion/exclusion criteria, cannulation location and modality and follow-up in pediatric eCPR, these are not standard across multiple institutions. Survival to discharge after eCPR is modest but data on cost and long-term neurologic sequela are lacking. Codification of indications and surgical approaches may help clarify the utility and success of eCPR.

Epidemiology of swallow dysfunction in CDH patients.

PURPOSE: There is a growing body of literature regarding long-term pulmonary outcomes in children with congenital diaphragmatic hernia (CDH). Oral feeding skills in these children are often delayed. Chronic descending aspiration due to uncoordinated swallowing can further insult the already compromised lung parenchyma in these children. This study describes patterns of swallowing dysfunction and aspiration in patients with CDH. METHODS: Records of all children treated for CDH at our institution from January 2014 to December 2019 were reviewed. Concern for swallowing dysfunction was marked by performance of a video-fluoroscopic swallow study (VFSS). We determined the frequency of aspiration on VFSS and how frequently that finding changed patient management. We also evaluated for association between clinical suspicion of swallow dysfunction and descriptors of CDH severity. RESULTS: Sixty-nine patients were treated during this 6-year time period. Of those, 10 (14%) had a VFSS as an inpatient, and 25 (36%) had one as an outpatient. Eight (80%) inpatient and 17 (68%) outpatient studies identified aspiration. VFSS results changed management in 80% of patients, often by altering the consistency of oral feeds. There were no associations between CDH side, defect size or need for a patch and need for a VFSS. CONCLUSIONS: The frequency of aspiration in the CDH population is high. Identification of aspiration on VFSS leads to changes in treatment aimed at protecting the lungs. Additionally, the severity of the CDH was not associated with aspiration on VFSS.

Epidemiology of gastroschisis: A population-based study in California from 1995 to 2012.

BACKGROUND: Although the incidence of gastroschisis is increasing, risk factors are not clearly identified. METHODS: Using the Linked Birth Database from the California Office of Statewide Health Planning and Development from 1995 to 2012, patients with gastroschisis were identified by ICD-9 diagnosis/procedure code or birth certificate designation. Logistic regressions examined demographics, birth factors, and maternal exposures on risk of gastroschisis. RESULTS: The prevalence of gastroschisis was 2.7 cases per 10,000 live births. Patients with gastroschisis had no difference in fetal exposure to alcohol (p = 0.609), narcotics (p = 0.072), hallucinogenics (p = 0.239), or cocaine (p = 0.777), but had higher exposure to unspecified/other noxious substances (OR 3.27, p = 0.040; OR 2.02, p = 0.002). Gastroschisis was associated with low/very low birthweight (OR 5.08-16.21, p < 0.001) and preterm birth (OR 3.26-10.0, p < 0.001). Multivariable analysis showed lower risk in black (OR 0.44, p < 0.001), Asian/Pacific Islander (OR 0.76, p = 0.003), and Hispanic patients (OR 0.72, p < 0.001) compared to white patients. Risk was higher in rural areas (OR 1.24-1.76, p = 0.001). Compared to women age < 20, risk decreased with advancing maternal age (OR 0.49-OR 0.03, p < 0.001). Patients with gastroschisis had increased total charges ($336,270 vs. $9012, p < 0.001) and length of stay (38.1 vs. 2.9 days, p < 0.001). Mortality was 4.6%. CONCLUSIONS: This is the largest population-based study summarizing current epidemiology of gastroschisis in California. TYPE OF STUDY: Retrospective comparative cohort study. LEVEL OF EVIDENCE: III.

Subcutaneous local anesthetic infusion could eliminate use of epidural analgesia after the Nuss procedure.

AIM: To compare outcomes of continuous subcutaneous infusion of local anesthetic and epidural analgesia following the Nuss procedure. PATIENTS & METHODS: A retrospective chart review compared patients managed with subcutaneous local anesthetic infusion (n = 12) versus thoracic epidural (n = 19) following the Nuss procedure from March 2013 to June 2015. RESULTS: There was no difference in hospital length of stay or days on intravenous narcotics. Epidural catheter placement prolonged operating room time (146.58 ± 28.30 vs 121.42 ± 21.98 min, p = 0.01). Average pain scores were slightly higher in the subcutaneous infusion group (3.72 ± 1.62 vs 2.35 ± 0.95, p = 0.02), but of negligible clinical significance. CONCLUSION: Continuous subcutaneous infusion of local anesthetic could eliminate the need for thoracic epidural for pain management after the Nuss procedure.

Outcomes of bedside sutureless umbilical closure without endotracheal intubation for gastroschisis repair in surgical infants.

INTRODUCTION: Newborns with gastroschisis have historically undergone surgical repair under general anesthesia. Our institution recently transitioned to the sutureless umbilical closure for gastroschisis. We sought to evaluate the feasibility of bedside gastroschisis repair without endotracheal intubation. METHODS: A retrospective review was performed of neonates with gastroschisis who underwent sutureless umbilical closure from 2011 to 2015. Clinical characteristics and outcomes between groups were compared. RESULTS: In total, 53 infants underwent sutureless umbilical closure. Closure without endotracheal intubation was attempted in 23 (43%) babies and was successful in 15 (65%) infants. Two of the 8 patients who required intubation needed a temporary silo. Neonates successfully repaired without intubation were more premature (p < 0.01), smaller at birth (p = 0.01), and repaired nearly an hour sooner (p < 0.01). There were no differences in time to full enteral nutrition, length of stay, bowel ischemia, or sepsis. CONCLUSION: Bedside sutureless umbilical closure without intubation is feasible and effective in newborns with gastroschisis. The procedure decreases time to gastroschisis closure. Smaller and more premature neonates were more likely to be successfully closed without intubation.

Isolation of myogenic progenitor cell population from human placenta: A pilot study.

PURPOSE: The purpose of this study was to demonstrate a method of isolating myogenic progenitor cells from human placenta chorionic villi and to confirm the myogenic characteristics of the isolated cells. METHODS: Cells were isolated from chorionic villi of a second trimester male placenta via a combined enzymatic digestion and explant culture. A morphologically distinct subpopulation of elongated and multinucleated cells was identified. This subpopulation was manually passaged from the explant culture, expanded, and analyzed by fluorescence in situ hybridization (FISH) assay, immunocytochemistry, and flow cytometry. Myogenic characteristics including alignment and fusion were tested by growing these cells on aligned polylactic acid microfibrous scaffold in a fusion media composed of 2% horse serum in Dulbecco's modified Eagle medium/high glucose. RESULTS: The expanded subpopulation was uniformly positive for integrin α-7. Presence of Y-chromosome by FISH analysis confirmed chorionic villus origin rather than maternal cell contamination. Isolated cells grew, aligned, and fused on the microfibrous scaffold, and they expressed myogenin, desmin, and MHC confirming their myogenic identity. CONCLUSION: Myogenic progenitor cells can be isolated from human chorionic villi. This opens the possibility for translational and clinical applications using autologous myogenic cells for possible engraftment in treatment of chest and abdominal wall defects.

Intercostal nerve cryoablation versus thoracic epidural catheters for postoperative analgesia following pectus excavatum repair: Preliminary outcomes in twenty-six cryoablation patients.

BACKGROUND: Multimodal pain management strategies are used for analgesia following pectus excavatum repair. However, the optimal regimen has not been identified. We describe our early experience with intercostal cryoablation for pain management in children undergoing the Nuss procedure and compare early cryoablation outcomes to our prior outcomes using thoracic epidural analgesia. METHODS: A multi-institutional, retrospective review of fifty-two patients undergoing Nuss bar placement with either intercostal cryoablation (n=26) or thoracic epidural analgesia (n=26) from March 2013 to January 2016 was conducted. The primary outcome was hospital length of stay. Secondary outcomes included telemetry unit monitoring time, total intravenous narcotic use, duration of intravenous narcotic use, and postoperative complications. RESULTS: Patients who underwent intercostal cryoablation had a significant reduction in the mean hospital length of stay, time in a monitored telemetry bed, total use of intravenous narcotics, and the duration of intravenous narcotic administration when compared to thoracic epidural patients. Cryoablation patients had a slightly higher rate of postoperative complications. CONCLUSION: Intercostal cryoablation is a promising technique for postoperative pain management in children undergoing repair of pectus excavatum. This therapy results in reduced time to hospital discharge, decreased intravenous narcotic utilization, and has eliminated epidurals from our practice. LEVEL OF EVIDENCE: Retrospective study - level III.

The influence of herbs, spices, and regular sausage and chicken consumption on liking of reduced fat breakfast and lunch items.

UNLABELLED: Adults often consume more fat than is recommended. We examined factors that may improve liking of reduced fat and reduced saturated fat foods, including the addition of herbs and spices and habitual consumption of different high-fat and low-fat food items. We randomized adults to taste 3 different conditions: full fat (FF), reduced fat with no added spice (RF), and reduced fat plus spice (RFS). Subjects rated their liking of French toast, sausage and the overall meal, or chicken, vegetables, pasta, and the overall meal on a 9-point hedonic Likert scale. Overall liking of the RF breakfast and lunch meals were lower than the FF and RFS versions (breakfast: 6.50 RF compared with 6.84 FF, P = 0.0061; 6.50 RF compared with 6.82 RFS, P = 0.0030; lunch: 6.35 RF compared with 6.94 FF, P < 0.0001; 6.35 RF compared with 6.71 RFS, P = 0.0061). RFS and FF breakfast and lunch meals, French toast, chicken, and vegetable likings were similar. FF and RFS conditions were liked more than RF for the breakfast and lunch meals, French toast, chicken entrée, and vegetables. Liking of all 3 sausage conditions was similar. FF pasta was liked more than RFS and RF (7.47 FF compared with 6.42 RFS, P < 0.0001; 7.47 FF compared with 6.47 RF, P < 0.0001). Habitual consumption of roasted chicken was associated with reduced liking of FF chicken (r = -0.23, P = 0.004) and FF pasta (r = -0.23, P = 0.005). Herbs and spices may be useful for improving the liking of lower fat foods and helping Americans maintain a diet consistent with the U.S. Dietary Guidelines. PRACTICAL APPLICATION: Americans consume more fat than is recommended in the Dietary Guidelines for Americans. This study shows that you can take foods like French toast, chicken, or a vegetable side and cut the fat and calories by up to 50% while restoring flavor with herbs and spices. People typically use butter, cheese, or fatty meat to enhance the flavor of their food. We found that even when we reduced the fat in our meals by using lower fat dairy and meat products but then added herbs and spices, we were able to deliver the flavor people desire for a fraction of the calories.