Outcomes for pediatric acute lymphoblastic leukemia patients with intestinal perforation.

OBJECTIVES: Intestinal perforation during acute lymphoblastic leukemia (ALL) treatment in children is rare, but represents a severe complication with possible long-term consequences. In this study, we aim to provide an overview of the epidemiology and clinical characteristics of these patients; analyze surgical pathology findings for possible causes; and determine its impact on patients' therapy, nutritional status, and outcome. STUDY DESIGN: Historical chart review from January 2000 to October 2020 of children with ALL and intestinal perforation during therapy diagnosed at a single institution. Data collected included patient demographics, anthropometric measurements, ALL characteristics, diagnosis and surgery of intestinal perforation, pathology, adjustments to treatment plan, and outcome. RESULTS: Of 1840 ALL patients, 13 (0.7%) presented with intestinal perforation during treatment. Perforation occurred during induction phase in 91% of cases. Most patients underwent laparotomy with ostomy creation, and no patient died from the intervention or developed malnutrition. Pathology mainly revealed inflammation at the perforation site. Two samples showed leukemic infiltration and presence of microorganisms. Patients were able to resume ALL therapy in all cases. A total of eight patients (73%) were in first remission at last follow-up, with a median follow-up time of 42 months (interquartile range = 42). CONCLUSION: Early surgical intervention is a successful treatment approach for intestinal perforation in ALL patients. There is a clear predilection for induction phase in the occurrence of intestinal perforation in ALL patients. No specific cause was identified. Patients can receive bridging chemotherapy during surgical recovery and proceed with their treatment without apparent impact on outcome.

Precision cut intestinal slices, a novel model of acute food allergic reactions.

BACKGROUND: Food allergy affects up to 10% of the pediatric population. Despite ongoing efforts, treatment options remain limited. Novel models of food allergy are needed to study response patterns downstream of IgE-crosslinking and evaluate drugs modifying acute events. Here, we report a novel human ex vivo model that displays acute, allergen-specific, IgE-mediated smooth muscle contractions using precision cut intestinal slices (PCIS). METHODS: PCIS were generated using gut tissue samples from children who underwent clinically indicated surgery. Viability and metabolic activity were assessed from 0 to 24 h. Distribution of relevant cell subsets was confirmed using single nucleus RNA sequencing. PCIS were passively sensitized using plasma from peanut allergic donors or peanut-sensitized non-allergic donors, and exposed to various stimuli including serotonin, histamine, FcɛRI-crosslinker, and food allergens. Smooth muscle contractions and mediator release functioned as readouts. A novel program designed to measure contractions was developed to quantify responses. The ability to demonstrate the impact of antihistamines and immunomodulation from peanut oral immunotherapy (OIT) was assessed. RESULTS: PCIS viability was maintained for 24 h. Cellular distribution confirmed the presence of key cell subsets including mast cells. The video analysis tool reliably quantified responses to different stimulatory conditions. Smooth muscle contractions were allergen-specific and reflected the clinical phenotype of the plasma donor. Tryptase measurement confirmed IgE-dependent mast cell-derived mediator release. Antihistamines suppressed histamine-induced contraction and plasma from successful peanut OIT suppressed peanut-specific PCIS contraction. CONCLUSION: PCIS represent a novel human tissue-based model to study acute, IgE-mediated food allergy and pharmaceutical impacts on allergic responses in the gut.

Survival in very preterm infants with congenital diaphragmatic hernia and association with prenatal imaging markers: A retrospective cohort study.

OBJECTIVES: To describe the outcomes of preterm born infants with congenital diaphragmatic hernia (CDH; ≤32.0 weeks of gestation) and the associations between prenatal imaging markers and survival. DESIGN: Retrospective cohort study. SETTING: Multicentre study in large referral centres. POPULATION: Infants with an isolated unilateral CDH, live born at 32.0 weeks or less of gestation, between January 2009 and January 2020. METHODS: Neonatal outcomes were evaluated for infants that were expectantly managed during pregnancy and infants that underwent fetoscopic endoluminal tracheal occlusion (FETO) therapy, separately. We evaluated the association between prenatal imaging markers and survival to discharge. Prenatal imaging markers included observed to expected lung-to-head ratio (o/e LHR), side of the defect, liver position, stomach position grade, and observed to expected total fetal lung volume (o/e TFLV). MAIN OUTCOME MEASURE: Survival to discharge. RESULTS: We included 53 infants born at 30+4 (interquartile range 29+1 -31+2 ) weeks. Survival in fetuses expectantly managed during pregnancy was 48% (13/27) in left-sided CDH and 33% (2/6) in right-sided CDH. Survival in fetuses that underwent FETO therapy was 50% (6/12) in left-sided CDH and 25% (2/8) in right-sided CDH. The o/e LHR at baseline was positively associated with survival in cases expectantly managed during pregnancy (odds ratio [OR] 1.20, 95% CI 1.07-1.42, p < 0.01), but not in cases that received FETO therapy (OR 1.01, 95% CI 0.88-1.15, p = 0.87). Stomach position grade (p = 0.03) and o/e TFLV were associated with survival (p = 0.02); liver position was not (p = 0.13). CONCLUSIONS: In infants with CDH born at or before 32 weeks of gestation, prenatal imaging markers of disease severity were associated with postnatal survival.

Fetal Sclerotherapy for Hydropic Congenital Cystic Adenomatoid Malformations of the Lung Refractory to Steroids: A Case Report and Review of the Literature.

Microcystic congenital cystic adenomatoid malformations (CCAM), when associated with hydrops, carry a dismal prognosis. Options for treatment are limited and experimental, including antenatal corticosteroids, open fetal surgery, laser ablation and, more recently, sclerotherapy. We describe a case of a large, predominantly microcystic CCAM in a hydropic fetus treated successfully with direct interstitial injection of a sclerosant agent (3% sodium tetradecyl sulfate) at 23+3 weeks gestation, after multiple failed courses of steroids. Elective thoracoscopic right lower lobectomy was performed at 1 year of life and there have been no respiratory or other medical morbidities since. A literature review of fetal lung masses treated with sclerosants antenatally reveals that sclerotherapy may represent a novel treatment option for large hydropic microcystic CCAMs, which are unresponsive to corticosteroids. Further studies are required to evaluate the utility and safety of fetal sclerotherapy, as this may represent an alternative minimally invasive treatment option to fetal lobectomy.

Key Residues at Third CDR3ß Position Impact Structure and Antigen Recognition of Human Invariant NK TCRs.

The human invariant NK (iNK) TCR is largely composed of the invariant TCR Vα24-Jα18 chain and semivariant TCR Vß11 chains with variable CDR3ß sequences. The direct role of CDR3ß in Ag recognition has been studied extensively. Although it was noted that CDR3ß can interact with CDR3α, how this interaction might indirectly influence Ag recognition is not fully elucidated. We observed that the third position of Vß11 CDR3 can encode an Arg or Ser residue as a result of somatic rearrangement. Clonotypic analysis of the two iNK TCR types with a single amino acid substitution revealed that the staining intensity by anti-Vα24 Abs depends on whether Ser or Arg is encoded. When stained with an anti-Vα24-Jα18 Ab, human primary invariant NKT cells could be divided into Vα24 low- and high-intensity subsets, and Arg-encoding TCR Vß11 chains were more frequently isolated from the Vα24 low-intensity subpopulation compared with the Vα24 high-intensity subpopulation. The Arg/Ser substitution also influenced Ag recognition as determined by CD1d multimer staining and CD1d-restricted functional responses. Importantly, in silico modeling validated that this Ser-to-Arg mutation could alter the structure of the CDR3ß loop, as well as the CDR3α loop. Collectively, these results indicate that the Arg/Ser encoded at the third CDR3ß residue can effectively modulate the overall structure of, and Ag recognition by, human iNK TCRs.

Duodeno-duodenostomy or duodeno-jejunostomy for duodenal atresia: is one repair better than the other?

PURPOSE: The surgical management of neonates with duodenal atresia (DA) involves re-establishment of intestinal continuity, either by duodeno-duodenostomy (DD) or by duodeno-jejunostomy (DJ). Although the majority of pediatric surgeons perform DD repair preferentially, we aimed to analyze the outcome of DA neonates treated with either surgical technique. METHODS: Following ethical approval (REB:1000047737), we retrospectively reviewed the charts of all patients who underwent DA repair between 2004 and 2014. Patients with associated esophageal/intestinal atresias and/or anorectal malformations were excluded. Outcome measures included demographics (gender, gestational age, and birth weight), length of mechanical ventilation, time to first and full feed, length of hospital admission, weight at discharge (z-scores), and postoperative complications (anastomotic stricture/leak, adhesive obstruction, and need for re-laparotomy). Both DD and DJ groups were compared using parametric or non-parametric tests, with data presented as mean ± SD or median (interquartile range). RESULTS: During the study period, 92 neonates met the inclusion criteria. Of these, 47 (51%) had DD and 45 (49%) DJ repair. All procedures were performed open, apart from one laparoscopic DJ. Overall, DD and DJ groups had similar demographics. Likewise, we found no differences between the two groups for length of ventilation (p = 0.6), time to first feed (p = 0.5), time to full feed (p = 0.4), length of admission (p = 0.6), prokinetic use (p = 0.5), nor weight at discharge (p = 0.1). When the 30/92 (33%) patients with trisomy-21 (DD = 16, DJ = 14) were excluded from analysis, the groups still had similar weight at discharge (p = 0.2). Postoperative complication rate was not different between the two groups. One patient per group died, due to respiratory failure (DD) and sepsis (DJ). CONCLUSIONS: This study demonstrates that in neonates with duodenal atresia, duodeno-duodenostomy and duodeno-jejunostomy have similar outcomes. These findings are relevant for surgeons who repair duodenal atresia laparoscopically, as duodeno-jejunostomy had equal clinical outcomes and may be easier to perform.

Long-term outcomes following H-type tracheoesophageal fistula repair in infants.

PURPOSE: To evaluate outcomes following repair of H-type tracheoesophageal fistula (TEF). METHODS: Retrospective chart review of infants with H-type TEF treated at our institution between 2000 and 2014. Patient demographics, surgical management, and postoperative function were evaluated. RESULTS: Of the 268 patients with esophageal atresia/TEF treated at our center, 16 (6%) had an H-type TEF (10 males). Thirteen (81%) had associated anomalies. All patients were symptomatic: choking and sputtering were the most common presentation (n = 10, 63%). Diagnosis Age at diagnosis was 8 days (1 day-34 months). All patients were diagnosed based on a single esophagogram. Prior to surgery, 12 (75%) patients underwent bronchoscopy and 11 underwent cannulation of the TEF tract. Surgery All patients underwent open repair. One was started thoracoscopically but converted to open due to esophageal sero-muscular injury. Repair was achieved in all patients via a transcervical approach (right-sided incision in 15). One patient had an unsuccessful prior attempt at repair using tissue glue. Following TEF division, 11 patients had tissue interposition grafts placed (9 muscle, 2 fat). Postoperative course Eight (50%) patients had postoperative vocal cord paresis (6 right-sided, 2 bilateral). A patient developed recurrent TEF 78 days postoperatively that was subsequently repaired. Follow-up At 41 months (8-143), there were no mortalities, all patients with vocal cord paresis were asymptomatic despite the fact that only 3 of 8 (38%) regained function, and nine (56%) patients had gastro-esophageal reflux requiring treatment. CONCLUSIONS: This large, single-center series demonstrates that H-type TEF can be diagnosed with esophagogram at an early age. Postoperative recurrent laryngeal nerve paresis and gastro-esophageal reflux disease are common following repair. Although most patients with vocal cord paresis eventually become asymptomatic, two-thirds do not regain vocal cord function. This reinforces the importance of routine examination of vocal cord movement following H-type TEF repair.

Nutritional Intake, Energy Expenditure, and Growth of Infants Following Congenital Diaphragmatic Hernia Repair.

BACKGROUND/OBJECTIVES: The pathophysiology of failure to thrive in congenital diaphragmatic hernia (CDH) has not been fully elucidated, and the nutritional care of these infants is hindered by paucity of data on the optimal calorie requirements for growth. The primary objective of this study was to investigate the energy intake required for infants with CDH to grow optimally at the time of first hospital discharge. The secondary objectives were to assess their measured resting energy expenditure in infancy, and their long-term growth outcomes. METHODS: Nutritional intake, anthropometrics, indirect calorimetry results, and respiratory status of infants with CDH from 2011 to 2014 were collected retrospectively. Data on confounders (gastroesophageal reflux disease and feeding intolerance, respiratory rate and pulmonary hypertension) were also collected. Analyses were performed using Stata (College Station, TX). RESULTS: Of the 72 infants diagnosed with CDH during that period of time, 43 met the inclusion criteria. A caloric intake of 125.0 ±â€Š20 kcal · kg · day was required to meet discharge weight gain criteria (25-35 g · kg · day). In a subset of 17 patients, measured resting energy expenditure was higher than predicted resting energy expenditure (58.0 ±â€Š18 vs 46.6 ±â€Š3 kcal · kg · day, P < 0.05), and 59% of infants were hypermetabolic (measured resting energy expenditure >110% of predicted resting energy expenditure) in early infancy. Failure to thrive prevalence at discharge was 16.2% compared to 3.6% and 4.2% at 12- and 24-months of age, respectively (P = 0.03; P = 0.005, respectively). CONCLUSIONS: Optimal weight gain can be achieved with higher than predicted calorie provision. Most infants with CDH are hypermetabolic. Despite this, failure to thrive prevalence can improve during the first year of life.

Outcome of esophageal atresia/tracheoesophageal fistula in extremely low birth weight neonates (<1000 grams).

PURPOSE: To review the outcomes of extremely low birth weight (ELBW, <1000 g) infants with esophageal atresia/tracheoesophageal fistula (EA/TEF). METHODS: Health records of ELBW EA/TEF infants treated at our institution from 2000 to 2014 were reviewed (REB1000046653). Demographics, operative approach and postoperative complications were analyzed. Data are reported as median (range). RESULTS: Of 268 EA/TEF infants, 8 (3 %, five females) were ELBW (930 g, 540-995). Gestational age was 28 weeks (23-32). Seven had type-C EA/TEF and one type B. OUTCOMES: One trisomy 18 infant received no treatment and died; one initially diagnosed as type A had primary repair at 126 days of life (DOL); six underwent TEF ligation (three trans-pleural) with primary repair in one and delayed anastomosis in two (DOL 120 and 178). The remaining three died (gastrostomy dehiscence and peritonitis, liver hemorrhage during peritoneal drain insertion, severe chronic lung disease and brain hemorrhages). At a median follow-up of 3 years (range 15 months-5 years), all survivors are thriving. CONCLUSION: ELBW infants with EA/TEF are rare and result in high morbidity and mortality. Mortality is mainly related to complications not associated with EA/TEF repair. Fistula ligation followed by delayed anastomosis seems to achieve a better outcome in ELBW infants.

Preservation of native esophagus in infants with pure esophageal atresia has good long-term outcomes despite significant postoperative morbidity.

PURPOSE: To evaluate long-term outcomes of pure esophageal atresia (EA) repair with preservation of native esophagus. METHODS: Infants with pure EA treated at our institution (2000-2010) and with minimum 5-year follow-up were reviewed (REB:1000046653). Data analysed included demographics, management and outcomes and are reported as mean ± SD/median (range). RESULTS: Of 185 infants with EA, 12 (7 %) had pure EA (gestational age: 36 ± 2.4 weeks, birth weight: 2353 ± 675 g). Ten had associated anomalies, including trisomy-21 (n = 2) and duodenal atresia (n = 1). SURGERY: 1 patient (short gap) underwent primary thoracoscopic anastomosis, 11 had gastrostomy (Stamm, n = 5; image-guided, n = 6) as initial procedure. At definitive repair (age: 128 ± 91 days; weight 5.5 ± 2.3 kg): ten had primary anastomosis and 1 had Collis gastroplasty. No patient had esophageal replacement surgery. OUTCOMES: three patients had gastrostomy dehiscence requiring re-operation. At post-operative esophagram, seven had anastomotic leak successfully treated conservatively. Seven patients developed strictures requiring balloon dilatations (median two dilatations, range 1-10), six received antireflux surgery. At 7-year follow-up (range 5-15 years), all patients had the gastrostomy closed and were on full oral feeds. CONCLUSIONS: The management of pure EA continues to be challenging. The preservation of native esophagus is possible with significant morbidity. The long-term outcomes are favourable.

Mortality of Pediatric Surgical Lung Biopsies in Ontario, Canada, 2000-2019.

Rationale: Surgical lung biopsies are often required for the definitive diagnosis of nonmalignant pediatric diffuse lung diseases; however, the literature on mortality after surgical lung biopsy in pediatric patients is sparse. Objectives: To determine the 30-day postoperative mortality rate after surgical lung biopsies for nonmalignant lung disease in pediatric patients in Ontario, Canada, and to identify risk factors associated with mortality. Methods: We performed an observational cohort study using population-based health administrative data available from ICES in Ontario, Canada, from 2000 to 2019. Cases were identified using the Canadian Classification of Health Interventions. Inclusion criteria were first surgical lung biopsies between 2000 and 2019 and age <18 years. Individuals with lung cancer, lung transplant, or missing data were excluded. A multivariable logistic regression model with generalized estimating equation was used to estimate the 30-day odds of mortality after surgical lung biopsy and to identify patient characteristics associated with increased mortality while accounting for clustering by hospital. Results: We identified 1,474 pediatric patients who underwent surgical lung biopsy in Ontario between 2000 and 2019. The overall mortality rates decreased over the study duration from 6.6% (2000-2004) to 3.0% (2015-2019). The study cohort for multivariate analyses consisted of 1,342 patients who had complete data. The pediatric mortality 30 days after surgical lung biopsy was 5.1% but was <1% in elective cases. Risk factors for increased mortality included open surgical lung biopsy (vs. video-assisted) (odds ratio [OR], 13.13; 95% confidence interval [CI], 3.76, 45.87; P < 0.001), nonelective procedure (OR, 11.74; 95% CI, 3.51, 39.27; P < 0.001), younger age (<3 mo) (OR, 6.04; 95% CI, 2.40, 15.22; P < 0.001), and higher comorbidity score (OR, 1.15; 95% CI, 1.05, 1.26; P = 0.003). Conclusions: Pediatric mortality postsurgical lung biopsy is not insignificant, particularly in nonelective procedures. Other important risk factors to consider when pursuing pathologic diagnosis include surgical approach, younger age, and higher comorbidity.

The long-term outcomes of symptomatic congenital lobar emphysema patients.

INTRODUCTION: Surgical (OP) management for symptomatic congenital lobar emphysema (CLE) is the standard of care with nonoperative (NOP) approach applied for asymptomatic cases. The aim of this study is to report the outcomes for NOP approach to the care of symptomatic CLE infants. METHODS: A retrospective study of CLE patients treated 2000-2021 at a single institution. Patients with CLE and respiratory symptoms were included. RESULTS: Overall, 23 children had symptomatic CLE, and 12 had NOP management. The median age at diagnosis was 38.5 days (50) in the NOP group versus 25 days (20) in the OP group (p = 0.31). There was no significant difference in the location of the involved lobe, term birth, postnatal diagnosis and gender, and both groups required noninvasive support in 33% of the cases. There was a trend towards higher frequency of oxygen support in the OP group preoperatively (89% vs. 42%, p = 0.07). The median length of stay was 14 days in the NOP group compared to a median postsurgery stay of 7.5 days in the OP group. In follow-up, there was no significant difference in respiratory readmission in first year of life, growth delay, treatment with asthma medication or body mass index in the NOP versus OP group. None of the children in the NOP group required surgery during follow-up. CONCLUSIONS: A NOP approach for symptomatic CLE infants can have favorable long-term outcomes. Further studies will be required to identify markers to aid in clinical decision-making.

Surgical management of acute life-threatening events affecting esophageal atresia and/or tracheoesophageal fistula patients.

BACKGROUND: Following surgical correction, many patients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) present to the emergency department (ED) with acute airway complications. We sought to determine the incidence and risk factors for severe acute life-threatening events (ALTEs) in pediatric patients with repaired congenital EA/TEF and the outcomes of operative interventions. METHODS: A retrospective cohort chart review was performed on patients with EA/TEF with surgical repair and follow-up at a single centre from 2000 to 2018. Primary outcomes included 5-year ED visits and/or hospitalizations for ALTEs. Demographic, operative, and outcome data were collected. Chi-square tests and univariate analyses were performed. RESULTS: In total, 266 EA/TEF patients met inclusion criteria. Of these, 59 (22.2%) had experienced ALTEs. Patients with low birth weight, low gestational age, documented tracheomalacia, and clinically significant esophageal strictures were more likely to experience ALTEs (p < 0.05). ALTEs occurred prior to 1 year of age in 76.3% (45/59) of patients with a median age at presentation of 8 months (range 0-51 months). Recurrence of ALTEs after esophageal dilatation was 45.5% (10/22), mostly due to stricture recurrence. Patients experiencing ALTEs received anti-reflux procedures (8/59, 13.6%), airway pexy procedures (7/59, 11.9%), or both (5/59, 8.5%) within a median age of 6 months of life. The resolution and recurrence of ALTEs after operative interventions are described. CONCLUSION: Significant respiratory morbidity is common among patients with EA/TEF. Understanding the multifactorial etiology and operative management of ALTEs have an important role in their resolution. TYPE OF STUDY: Original Research, Clinical Research. LEVEL OF EVIDENCE: Level III Retrospective Comparative Study.

Leukemia-initiating cells in human T-lymphoblastic leukemia exhibit glucocorticoid resistance.

T-cell acute lymphoblastic leukemia (T-ALL) is associated with a significant risk of disease relapse, but the biological basis for relapse is poorly understood. Here, we identify leukemiainitiating cells (L-ICs) on the basis of functional assays and prospective isolation and report a role for L-ICs in T-ALL disease and relapse. Long-term proliferation in response to NOTCH1 activating signals in OP9-DL1 coculture system or capacity to initiate leukemia in xenografts by the CD7(+)CD1a(-) subset of primary T-ALL samples was superior to other subsets, refining the identity of T-ALL L-ICs. T-ALL engraftment was improved in nonobese diabetic/severe combined immunodeficiency (NOD/scid)IL2Rγ(null) (NSG) mice compared with NOD/scid with anti-CD122 treatment (NS122), but both showed changes in leukemia immunophenotype. Clonal analysis of xenografts using the TCRG locus revealed the presence of subclones of T-ALL L-ICs, some of which possess a selective growth advantage and correlated with the capacity of CD7(+)CD1a(+) xenograft cells to engraft secondary NSG mice. Treatment of high-risk T-ALL xenografts eliminated CD1a(+) T-ALL cells, but CD1a(-) cells were resistant and their number was increased. Our results establish that primary CD1a(-) T-ALL cells are functionally distinct from CD1a(+) cells and that the CD7(+)CD1a(-) subset is enriched for L-IC activity that may be involved in mediating disease relapse after therapy.

Risk factors for prolonged mechanical ventilation in neonates following gastrointestinal surgery.

Background: Prolonged mechanical ventilation (MV) should be avoided in neonates. Noninvasive ventilation (NIV) can facilitate weaning from MV but has risks for patients immediately following foregut surgery due to the potential risk of anastomotic leak. We evaluated the risk factors for prolonged MV following intestinal surgery in neonates. Methods: We retrospectively reviewed 253 neonates undergoing intestinal surgery in 2017-2018 to identify risk factors for prolonged MV, and determine the correlation between NIV and anastomotic leak in a tertiary neonatal intensive care unit that performs the greatest number of neonatal surgeries in Ontario. Results: The most common diagnoses were necrotizing enterocolitis/spontaneous intestinal perforation (NEC/SIP) 21%, intestinal atresia 16%, esophageal atresia/tracheoesophageal fistula 14%, ano-rectal malformation 13%, malrotation/volvulus 11%, gastroschisis 9% and omphalocele 4%. The median (IQR) duration of MV post-surgery was 3 (1-8) days with 25.7 % (n=65) of neonates on MV for >7 days. Compared to infants on MV post-surgery for ≤7 days, those with MV>7 days were of lower gestational age, birth weight and weight at surgery, but a higher proportion underwent stoma creation, had a longer duration of opioid administration and higher rates of moderate to severe bronchopulmonary dysplasia (BPD) and mortality (P<0.05). Generalized linear regression analysis showed lower gestational age (GA) and longer opioid administration were associated with longer duration of MV (P<0.001), but indication for surgery, weight at surgery and stoma creation didn't correlate with longer duration of MV (P>0.05). Of the 122 patients handled by one-stage resection with primary anastomosis, 22.1% (n=27) received NIV with 74.1% (n=20) commenced on NIV after 7 days post-surgery, anastomotic leak was detected in 2.5 % (3/122) patients and didn't correlate with NIV. Conclusions: Lower GA and longer opioid administration were risk factors for prolonged MV in neonates following intestinal surgery. Further research is needed to investigate modifiable practices around pain assessment/ventilation in these patients, and the correlation between NIV and anastomotic leak.

Congenital diaphragmatic hernia: lung-to-head ratio and lung volume for prediction of outcome.

OBJECTIVE: The purpose of this study was to evaluate observed/expected (O/E) lung-to-head ratio (LHR) by ultrasound (US) and total fetal lung volume (TFLV) by magnetic resonance imaging as neonatal outcome predictors in isolated fetal congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective study of 72 fetuses with isolated CDH, in whom O/E LHR and TFLV were evaluated as survival predictors. RESULTS: O/E LHR on US and O/E TFLV by magnetic resonance imaging were significantly lower in newborn infants with isolated CDH who died compared with survivors (30.3 ± 8.3 vs 44.2 ± 14.2; P < .0001 for O/E LHR; 21.9 ± 6.3 vs 41.5 ± 17.6; P = .001 for O/E TFLV). Area under receiver-operator characteristics curve for survival for O/E LHR was 0.80 (95% confidence interval, 0.70-0.90). On multivariate analysis, O/E LHR predicted survival, whereas hernia side and first neonatal pH did not. For each unit increase in O/E LHR, mortality odds decreased by 11% (95% confidence interval, 4-17%). CONCLUSION: In fetuses with isolated CDH, O/E LHR (US) independently predicts survival and may predict severity, allowing management to be optimized.

Airway Clearance in Tracheomalacia.

Airway clearance is an essential part of airway maintenance to ensure the airway lumen is protected against particulate and infectious insults. The mechanisms involved in airway clearance include intrinsic structural and cellular components that can be impaired or inhibited through developmental defects and surgical interventions. Tracheomalacia is a developmental defect of the airway that can contribute to the mechanical failure to clear the airway. This chapter will review the mechanisms of airway clearance and the processes that can impair this vital process.

Surgical conditions of the diaphragm: posterior diaphragmatic hernias in infants.

The care of the neonate with CDH has significantly evolved from an approach characterized by aggressive ventilation and emergency surgical repair, to the current use of permissive hypercapnea, physiologic stabilization, elective surgical repair, and multidisciplinary follow-up. Overall survival now approaches 80%, but this improvement has been associated with increased recognition of respiratory, cardiac, gastrointestinal, and neurodevelopmental morbidity. Topics of continuing controversy in the management of CDH include the value of fetal tracheal occlusion, the expanding role of ECMO, and the use of minimal access techniques for surgical repair.

Predictors of Long-Term Pulmonary Morbidity in Children with Congenital Diaphragmatic Hernia.

PURPOSE: The aim is to identify prognostic markers of long-term pulmonary morbidity among congenital diaphragmatic hernia (CDH) survivors. METHODS: A single-institution, retrospective review was performed on all CDH patients from 2000 and 2012 (REB#1000053383). Liver position, patch use, and pulmonary function tests (PFTs) (forced expiratory volume at 1 second [FEV1] and forced vital capacity [FVC] expressed as mean % predicted + SD) were recorded. Data were analyzed using analysis of variance. RESULTS: Patients with acceptable and reproducible PFT (n = 72 for 202 total PFT) with patch repair and liver up (n = 28) had significantly lower FEV1 (72.4 + 17.6) than those with no patch and liver down (n = 98, FEV1= 86.3 + 15.9, p = 0.002). Patients with patch repair and liver down (n = 40) also had significantly lower FEV1 (76.6 + 14.4) than those with liver down and no patch (p = 0.0463). Patients with liver up and patch repair had PFT results consistent with moderate reduction of lung function, while the remainder had mild to no decrease in lung function. All CDH patients older than 14 years had a reduction in FEV1/FVC consistent with obstructive phenotype, with a mean FEV1/FVC = 62.3 for patch repair group and FEV1/FVC = 76.1 in the no patch group. CONCLUSION: Decreased pulmonary function of CDH survivors correlated with the use of patch repair and liver position. CDH lung disease should be monitored in adulthood.