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Background Risk for infection and potential malignant degeneration are the most common arguments for resecting asymptomatic Congenital Pulmonary Airway Malformations (CPAM). We aimed to investigate if CT- imaging characteristics can be used to predict histopathological features, by using an objective quantitative CT scoring method. Methods Archival CPAM tissue samples were histologically re-assessed and patients who had a pre-operative volumetric CT-scan were included. Lung disease was quantified using the newly-developed congenital lung abnormality quantification(CLAQ) scoring method and obtained percentages were used to predict histopathological signs of inflammation and presence of mucinous proliferation (MP). Because MP is presumed a precursor for mucinous adenocarcinoma in situ (AIS) this method was also used to compare CT-scans of patients with AIS to those with only CPAM. Results Thirty-three CPAM patients were included of which 13(39%) had histological signs of inflammation and 8(24%) had a MP. Patients with inflammation had a significantly smaller lesion (14% vs 38%) while those with MP had more extensive disease (54%vs17%). Patients with AIS had a significantly smaller lesion compared to CPAM patients (5%vs29%). Significant predictors for inflammation were smaller lesion size and percentage hypodensity within lesions while a larger lesion size and percentage parenchymal hyperdensity (solid lung tissue components) were predictors for MP as well as AIS. Conclusions Smaller CPAM lesions may be more susceptible to inflammation while larger lesions may be associated with the presence of MP. Parenchymal hyperdensity is found as a predictor for MP as well as AIS and should therefore elicit more extensive gross sampling. Level of evidence Level III.

BACKGROUND: The effect of peri-operative management on the neonatal brain is largely unknown. Triggers for perioperative brain injury might be revealed by studying changes in neonatal physiology peri-operatively. OBJECTIVE: To study neonatal pathophysiology and cerebral blood flow regulation peri-operatively using the neuro-cardiovascular graph. DESIGN: Observational, prospective cohort study on perioperative neuromonitoring. Neonates were included between July 2018 and April 2020. SETTING: Multicentre study in two high-volume tertiary university hospitals. PATIENTS: Neonates with congenital diaphragmatic hernia were eligible if they received surgical treatment within the first 28 days of life. Exclusion criteria were major cardiac or chromosomal anomalies, or syndromes associated with altered cerebral perfusion or major neurodevelopmental impairment. The neonates were stratified into different groups by type of peri-operative management. INTERVENTION: Each patient was monitored using near-infrared spectroscopy and EEG in addition to the routine peri-operative monitoring. Neurocardiovascular graphs were computed off-line. MAIN OUTCOME MEASURES: The primary endpoint was the difference in neurocardiovascular graph connectivity in the groups over time. RESULTS: Thirty-six patients were included. The intraoperative graph connectivity decreased in all patients operated upon in the operation room (OR) with sevoflurane-based anaesthesia ( P

Purpose: Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual’s limb. In the early stage of experimental NEC, RIC decreased intestinal injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy. Methods: RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention. Results: We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility. Conclusions: The newly established NEC consortium has generated novel data on NEC diagnosis and defined the feasibility parameters for the introduction of a novel treatment in NEC. This phase II RCT will inform a future phase III RCT to evaluate the efficacy and safety of RIC in early-stage NEC.

IntroductionConsensus is lacking on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM). For future studies, the CONNECT consortium (the COllaborative Neonatal Network for the first European CPAM Trial)—an international collaboration of specialised caregivers—has established consensus on a core outcome set of outcome parameters concerning respiratory insufficiency, surgical complications, mass effect and multifocal disease. These outcome parameters have been incorporated in the CONNECT trial, a randomised controlled trial which, in order to develop evidence-based practice, aims to compare conservative and surgical management of patients with an asymptomatic CPAM.Methods and analysisChildren are eligible for inclusion after the CPAM diagnosis has been confirmed on postnatal chest CT scan and they remain asymptomatic. On inclusion, children are randomised to receive either conservative or surgical management. Subsequently, children in both groups are enrolled into a standardised, 5-year follow-up programme with three visits, including a repeat chest CT scan at 2.5 years and a standardised exercise tolerance test at 5 years.The primary outcome is exercise tolerance at age 5 years, measured according to the Bruce treadmill protocol. Secondary outcome measures are molecular genetic diagnostics, validated questionnaires—on parental anxiety, quality of life and healthcare consumption—, repeated imaging and pulmonary morbidity during follow-up, as well as surgical complications and histopathology. This trial aims to end the continuous debate surrounding the optimal management of asymptomatic CPAM.Ethics and disseminationThis study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Centre Rotterdam, The Netherlands, has approved this protocol (MEC-2022–0441). Results will be disseminated through peer-reviewed scientific journals and conference presentations.Trial registration numberNCT05701514.

Background Pectus excavatum (PE) could be part of a genetic disorder, which then has implications regarding comorbidity, the surgical correction of PE, and reproductive choices. However, referral of a patient presenting with PE for genetic analysis is often delayed because additional crucial clinical signs may be subtle or even missed in syndromic patients. We reviewed the literature to inventory known genetic disorders associated with PE and create a standardized protocol for clinical evaluation. Methods A systematic literature search was performed in electronic databases. Genetic disorders were considered associated with PE if studies reported at least five cases with PE. Characteristics of each genetic disorder were extracted from the literature and the OMIM database in order to create a practical guide for the clinician. Results After removal of duplicates from the initial search, 1632 citations remained. Eventually, we included 119 full text articles, representing 20 different genetic disorders. Relevant characteristics and important clinical signs of each genetic disorder were summarized providing a standardized protocol in the form of a scoring list. The most important clinical sign was a positive family history for PE and/or congenital heart defect. Conclusions Twenty unique genetic disorders have been found associated with PE. We have created a scoring list for the clinician that systematically evaluates crucial clinical signs, thereby facilitating decision making for referral to a clinical geneticist.

Background : Children born with esophageal atresia (EA) face comorbidities and complications often requiring surgery and anesthesia. We aimed to assess all procedures performed under general anesthesia during their first 12 years of life. Methods : We performed a retrospective cohort study about subsequent surgeries and procedures requiring general anesthesia in children born with type C EA between January 2007 and December 2017, with follow-up to March 2019. Results : Of 102 eligible patients, 63 were diagnosed with comorbidities, of whom 18 had VACTERL association. Follow-up time for all patients varied between 14 months and 12 years (median 7 years). The patients underwent total 637 procedures, median 4 [IQR2-7] per patient. In the first year of life, 464 procedures were performed, in the second year 69 and in the third year 29. Thirteen patients underwent no other procedures than primary EA repair. In 57 patients, 228 dilatations were performed. Other frequently performed procedures were esophagoscopy (n=52), urologic procedures (n=44) and abdominal procedures (n=33). Conclusions : Patients with EA frequently require multiple anesthetics for a variety of procedures related to the EA, complications and comorbidities. This study can help care providers when counselling parents of a patient with an EA by giving them more insight into possible procedures they can be confronted with during childhood.

Most drugs are administered to children orally. An information gap remains on the protein abundance of small intestinal drug-metabolizing enzymes (DMEs) and drug transporters (DTs) across the pediatric age range, which hinders precision dosing in children. To explore age-related differences in DMEs and DTs, surgical leftover intestinal tissues from pediatric and adult jejunum and ileum were collected and analyzed by targeted quantitative proteomics for apical sodium–bile acid transporter, breast cancer resistance protein (BCRP), monocarboxylate transporter 1 (MCT1), multidrug resistance protein 1 (MDR1), multidrug resistance–associated protein (MRP) 2, MRP3, organic anion–transporting polypeptide 2B1, organic cation transporter 1, peptide transporter 1 (PEPT1), CYP2C19, CYP3A4, CYP3A5, UDP glucuronosyltransferase (UGT) 1A1, UGT1A10, and UGT2B7. Samples from 58 children (48 ileums, 10 jejunums, age range: 8 weeks to 17 years) and 16 adults (8 ileums, 8 jejunums) were analyzed. When comparing age groups, BCRP, MDR1, PEPT1, and UGT1A1 abundance was significantly higher in adult ileum as compared with the pediatric ileum. Jejunal BCRP, MRP2, UGT1A1, and CYP3A4 abundance was higher in the adults compared with children 0–2 years of age. Examining the data on a continuous age scale showed that PEPT1 and UGT1A1 abundance was significantly higher, whereas MCT1 and UGT2B7 abundance was lower in adult ileum as compared with the pediatric ileum. Our data contribute to the deeper understanding of the ontogeny of small intestinal drug-metabolizing enzymes and drug transporters and shows DME-, DT-, and intestinal location–specific, age-related changes. SIGNIFICANCE STATEMENT This is the first study that describes the ontogeny of small intestinal DTs and DMEs in human using liquid chromatography with tandem mass spectrometry–based targeted quantitative proteomics. The current analysis provides a detailed picture about the maturation of DT and DME abundances in the human jejunum and ileum. The presented results supply age-related DT and DME abundance data for building more accurate PBPK models that serve to support safer and more efficient drug dosing regimens for the pediatric population.

BACKGROUND: Adults with esophageal atresia (EA) require a multidisciplinary follow-up approach, taking into account gastroesophageal problems, respiratory problems and psychosocial wellbeing. Too little is known about the full scope of these individuals' healthcare needs. We aimed to map all medical and psychosocial needs of adults with EA and their family members, and to formulate healthcare recommendations for daily practice.METHODS: A qualitative study was performed, using data from recorded semi-structured interviews with two focus groups, one consisting of adult patients with EA (n = 15) and one of their family members (n = 13). After verbatim transcription and computerized thematic analysis, results were organized according to the International Classification of Functioning, Disability and Health. Ethical approval had been obtained.RESULTS: Healthcare needs were described through 74 codes, classified into 20 themes. Most important findings for patients included the impact of gastrointestinal and pulmonary problems on daily life, long-term emotional distress of patients and parents and the need of a standardized multidisciplinary follow-up program during both child- and adulthood.CONCLUSION: The focus groups revealed numerous physical and mental health problems, as well as social difficulties, that require attention from different healthcare providers. We have formulated several healthcare recommendations that physicians may use in long-term follow-up.

Background: This study characterized the gut microbiota and its diet‐related metabolic activity in children with intestinal failure (IF) on parenteral nutrition (PN) compared with healthy controls and in relation to disease characteristics. Methods: Serial fecal samples were collected from 15 IF patients (n = 68) and from 25 healthy children (n = 25). The fecal microbiota, and short chain fatty acids (SCFA) were measured. Results: The microbiota of patients with IF had a lower bacterial load (p = 0.003), Shannon diversity index (p

The lung is composed of a highly branched airway structure, which humidifies and warms the inhaled air before entering the alveolar compartment. In the alveoli, a thin layer of epithelium is in close proximity with the capillary endothelium, allowing for an efficient exchange of oxygen and carbon dioxide. During development proliferation and differentiation of progenitor cells generates the lung architecture, and in the adult lung a proper function of progenitor cells is needed to regenerate after injury. Malfunctioning of progenitors during development results in various congenital lung disorders, such as Congenital Diaphragmatic Hernia (CDH) and Congenital Pulmonary Adenomatoid Malformation (CPAM). In addition, many premature neonates experience continuous insults on the lung caused by artificial ventilation and supplemental oxygen, which requires a highly controlled mechanism of airway repair. Malfunctioning of airway progenitors during regeneration can result in reduction of respiratory function or (chronic) airway diseases. Pathways that are active during development are frequently re-activated upon damage. Understanding the basic mechanisms of lung development and the behavior of progenitor cell in the ontogeny and regeneration of the lung may help to better understand the underlying cause of lung diseases, especially those occurring in prenatal development or in the immediate postnatal period of life. This review provides an overview of lung development and the cell types involved in repair of lung damage with a focus on the airway.

OBJECTIVE: To examine the association between prenatal stomach position (SP) grade and stomach volume (SV) and the need for pulmonary hypertension (PH) treatment after birth in prenatally diagnosed left-sided congenital diaphragmatic hernia (CDH), live born >34 weeks.METHODS: In retrospect, SP grade and SV were determined in fetuses with isolated left-sided CDH from 19 weeks gestational age (GA) onwards at three different time periods (≤24 weeks' GA: US1, 24-30 weeks' GA: US2; ≥30 weeks' GA: US3). Primary outcome was need for treatment of PH after birth. Secondary analyses included the predictive value of SP and SV for other respiratory outcomes and postnatal defect size.RESULTS: A total of 101 fetuses were included. SP grade was significantly associated with need for treatment of PH (US1, US2, and US3: p < 0.02). Also, prenatal SP grade was positively associated with defect size and development of chronic lung disease (CLD) in survivors. No association was found between SV and respiratory morbidities or postnatal defect size.CONCLUSION: SP grade in left-sided CDH fetuses is associated with an increased need for PH treatment, a larger postnatal defect size and CLD in survivors. We consider SP determination a valuable contribution to the prenatal assessment of left-sided CDH.

Objectives To develop a clinical guideline for structured assessment and uniform reporting of congenital lung abnormalities (CLA) on Computed Tomography (CT)-scans. Materials and Methods A systematic literature search was conducted for articles describing CT-scan abnormalities of congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration (BPS), congenital lobar emphysema (CLE) and bronchogenic cyst (BC). A structured report using objective features of CLA was developed after consensus between a pediatric pulmonologist, radiologist and surgeon. Results Of 1581 articles identified, 158 remained after title-abstract screening by two independent reviewers. After assessing full-texts, we included 28 retrospective cohort-studies. Air-containing cysts and soft tissue masses are described in both CPAM and BPS while anomalous arterial blood supply is only found in BPS. Perilesional low-attenuation areas, atelectasis and mediastinal shift may be found in all aforementioned abnormalities and can also be seen in CLE as a cause of a hyperinflated lobe. We have developed a structured report, subdivided into five sections: Location & Extent, Airway, Lesion, Vascularization and Surrounding tissue. Conclusions CT-imaging findings in CLA are broad and nomenclature is variable. Overlap is seen between and within abnormalities, possibly due to definitions often being based on pathological findings, which is an unsuitable approach for CT imaging. We propose a structured assessment of CLA using objective radiological features and uniform nomenclature to improve reporting.

IntroductionPulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in these infants might contribute to the development of pulmonary hypertension after birth—in particular umbilical cord clamping before lung aeration. An ovine model of diaphragmatic hernia demonstrated that cord clamping after lung aeration, called physiological-based cord clamping (PBCC), avoided the initial high pressures in the lung vasculature while maintaining adequate blood flow, thereby avoiding vascular remodelling and aggravation of pulmonary hypertension. We aim to investigate if the implementation of PBCC in the perinatal stabilisation period of infants born with a CDH could reduce the incidence of pulmonary hypertension in the first 24 hours after birth.Methods and analysisWe will perform a multicentre, randomised controlled trial in infants with an isolated left-sided CDH, born at ≥35.0 weeks. Before birth, infants will be randomised to either PBCC or immediate cord clamping, stratified by treatment centre and severity of pulmonary hypoplasia on antenatal ultrasound. PBCC will be performed using a purpose-built resuscitation trolley. Cord clamping will be performed when the infant is considered respiratory stable, defined as a heart rate >100 bpm, preductal oxygen saturation >85%, while using a fraction of inspired oxygen of Ethics and disseminationCentral ethical approval was obtained from the Medical Ethical Committee of the Erasmus MC, Rotterdam, The Netherlands (METC 2019-0414). Local ethical approval will be obtained by submitting the protocol to the regulatory bodies and local institutional review boards.Trial registration numberNCT04373902.

Background Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor’s experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. Methods An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. Results Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5–300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. Conclusions We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions.

Contains fulltext : 220734.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. METHODS: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. RESULTS: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter >/= 97.7(th) percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02-2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). CONCLUSIONS: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited. (c) 2019 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

In children, intense levels of anxiety during anesthetic induction are associated with a higher risk of pain, poor recovery, and emergence delirium. Therefore, it is important to identify these high-risk children at hospital arrival. The current study examined internalizing behavior (Child Behavior Checklist, CBCL) and state anxiety measures (modified Yale Preoperative Anxiety Scale, mYPAS, and State Trait Anxiety Inventory for Children, STAIC) at hospital arrival as predictors of anxiety during induction of anesthesia. One hundred children (aged 4 to 12 years) undergoing elective daycare surgery were included. The STAIC and mYPAS at hospital arrival were significant predictors of anxiety during induction, whereas CBCL was not. The STAIC state form at hospital arrival was the strongest predictor and could be used to identify children who will experience intense levels of anxiety during anesthetic induction, with sufficient to good diagnostic accuracy. Using the STAIC at hospital arrival allows targeted interventions to reduce anxiety in children.

__Background:__ Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations. __Methods:__ We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP arraybased genotyping, and compared the results to mouse transcriptome data of the developing foregut. __Results:__ We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time-points. Two pathways were significantly enriched (p < 1 × 10−5): proliferation and differentiation of smooth muscle cells and self-renewal of satellite cells. __Conclusions:__ None of our findings could fully explain the combination of abnormalities on its own, which makes complex inheritance the most plausible genetic explanation, most likely in combination with mechanical and/or environmental factors. As we did not find one defining monogenetic cause for the EA/IHPS phenotype, the impact of the corrective surgery could should be further investigated.

The potential for malignant degeneration is the most common reason for some practitioners to resect asymptomatic congenital pulmonary airway malformations (CPAMs). We aimed to investigate the potential of various immunohistochemical (IHC) and genomic biomarkers to predict the presence of mucinous proliferations (MPs) in CPAM. Archival CPAM tissue samples were re-assessed and underwent IHC analysis using a panel of differentiating markers (TTF1/CDX2/CC10/MUC2/MUC5AC/p16/p53/DICER1). In each sample, intensity of IHC staining was assessed separately in normal lung tissue, CPAM, and MP tissue, using a semiquantitative approach. Likewise, next-generation targeted sequencing of known adult lung driver mutations, including KRAS/BRAF/EGFR/ERBB2, was performed in all samples with MP and in control samples of CPAM tissue without MP. We analyzed samples of 25 CPAM type 1 and 25 CPAM type 2 and found MPs in 11 samples. They were all characterized by strong MUC5AC expression, and all carried a KRAS mutation in the MP and adjacent nonmucinous CPAM tissue, whereas the surrounding normal lung tissue was negative. By contrast, in less than half (5 out of 12) control samples lacking MP, the CPAM tissue also carried a KRAS mutation. KRAS mutations in nonmucinous CPAM tissue may identify lesions with a potential for malignant degeneration and may guide histopathological assessment and patient follow-up.

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, the physiological changes occurring during the fetal-to-neonatal transition in CDH, novel delivery room strategies and early predictors of adverse outcomes. The combination of improvements in the perinatal stabilisation period and early prediction of adverse outcomes may mitigate the need for specific postnatal management strategies.

Introduction To date, no consensus has been reached on the optimal management of congenital lung abnormalities, and factors predicting postnatal outcome have not been identified. We developed an objective quantitative computed tomography (CT) scoring method, and assessed its value for clinical decision‐making. Methods Volumetric CT‐scans of all patients born with a congenital lung abnormality between January 1999 and 2018 were assessed. Lung disease was quantified using the newly‐developed congenital lung abnormality quantification (CLAQ) scoring method. In 20 equidistant axial slices, cells of a square grid were scored according to the abnormality within. The scored CT parameters were used to predict development of symptoms, and SD scores for spirometry and exercise tolerance (Bruce treadmill test) at 8 years of age. Results CT‐scans of 124 patients with a median age of 5 months were scored. Clinical diagnoses included congenital pulmonary airway malformation (49%), bronchopulmonary sequestration (27%), congenital lobar overinflation (22%), and bronchogenic cyst (1%). Forty‐four patients (35%) developed symptoms requiring surgery of whom 28 (22%) patients became symptomatic before a CT‐scan was scheduled. Lesional hyperdensity was found as an important predictor of symptom development and decreased exercise tolerance. Using receiver operating characteristic analysis, an optimal cut‐off value for developing symptoms was found at 18% total disease. Conclusion CT‐quantification of congenital lung abnormalities using the CLAQ method is an objective and reproducible system to describe congenital lung abnormalities on chest CT. The risk for developing symptoms may increase when more than a single lung lobe is affected.

Introduction: A congenital lung abnormality (CLA) is often found in conjunction with other abnormalities but screening guidelines for newborns with CLA have not yet been reported. We aimed to assess the incidence of associated anomalies in CLA patients born or followed up at our centre and the need for additional screening of newborns with a CLA. Methods: From a retrospective chart review of all patients born with a CLA between January 1999 and January 2019, we identified patients diagnosed with a congenital pulmonary airway malformation, bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst, or lung agenesis. Associated anomalies were noted and categorized according to the affected organ system. Results: Twenty-eight (14%) of 196 CLA patients had a major associated anomaly. This was most frequent in conjunction with a lung agenesis (100%) or bronchogenic cyst (29%). Congenital heart defects (32%) and gastrointestinal defects (18%) were the most frequently associated anomalies. Examination of newborns with a CLA should focus on the cardiovascular and gastrointestinal tract, and a chest and abdominal radiograph may be useful to assess signs of major associated anomalies, regardless of the clinical course.

Background The most frequent complication after esophageal atresia repair remains anastomotic stricture formation. The initial treatment is endoscopic dilatation. Intralesional steroid injection (ISI) might be an effective adjuvant treatment in case of recurrent strictures. In this series we present our initial experience with this intervention. Methods Data on primary surgery, stricture treatment, postoperative complications, outcome and growth were retrospectively collected from electronic patient records. Findings were analyzed by descriptive statistics and mixed model analysis. Results Between 2014 and 2017, ISI was performed for severe recurrent anastomotic strictures in six patients (median age at injection 12.4 (2.1–34.7) months) after a median of 6 (2–20) dilatations. In five patients ISI was successful and the stenosis was cleared. No postoperative complications were reported, especially none related to acute adrenal suppression. Comparing the year before with the year after ISI, a significant positive change for weight (r = 0.70, p = 0.003) was calculated versus a negative change for height (r = − 0.87, p = 0.003). Conclusions We found ISI to be an effective adjuvant treatment to recurrent anastomotic stricture dilatation after esophageal atresia repair, without postoperative complications or symptoms of adrenal suppression. It remains important, however, to monitor growth effects. Further evaluation is required in a large prospective study. Type of study Treatment study, Level IV (case series).

Contains fulltext : 219856.pdf (Publisher’s version ) (Closed access) Exercise capacity deteriorates in school-aged children born with major anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. The aim of the present study was to evaluate whether exercise capacity can be improved in the short term and long term in children born with anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. Therefore, we evaluated two different interventions in this single-blinded randomized controlled trial. Forty participants were randomly assigned to group A: standardized anaerobic high-intensity interval training plus online lifestyle coaching program, B: online lifestyle coaching program only, or C: standard of care. Inclusion criteria were as follows: score

Supplemental Digital Content is available in the text, Objectives: The aim of the study was to evaluate acid and nonacid gastroesophageal reflux in infants and school-aged children with esophageal atresia (EA) using pH-impedance (pH-MII) monitoring. Methods: Between 2012 and 2017, all 24-hour pH-MII studies performed in infants (≤18 months) and 8-year olds with EA were included. Antiacid therapy was discontinued before study. Exclusion criteria were: isolated tracheoesophageal fistula; esophageal replacement therapy; tube feeding; and monitoring

OBJECTIVES: To longitudinally evaluate self-reported and proxy-reported health status (HS) and quality of life (QoL) of school-aged children born with esophageal atresia (EA). METHODS: We obtained Pediatric Quality of Life Inventory (HS) and DUX-25 (QoL) questionnaires from children born with EA between 1999 and 2011 at 8 and/or 12 years old. Children completed self-reports during neuropsychological assessments in a prospective longitudinal follow-up program. Parents filled out proxy-reports at home. Total and subscale scores were evaluated longitudinally and compared with sex-specific reference norms. RESULTS: In total, 110 participants (62% boys) were included. Self-reported HS improved significantly between 8 and 12 years for both boys (mean difference [md] 4.35, effect size [ES] 0.54, P = 0.009) and girls (md 3.26, ES 0.63, P = 0.004). Proxy-reported HS tended to improve over time, while self-reported and proxy-reported QoL tended to decline. Self-reported HS at 8 years was below normal for both boys (md -5.44, ES -0.35, P

Summary Background Although the survival rate of esophageal atresia (EA) has increased to over 90%, the risk of functional long-term neurodevelopmental deficits is uncertain. Studies on long-term outcomes of children with EA show conflicting results. Therefore, we provide an overview of the current knowledge on the long-term neurodevelopmental outcome of children with EA. Methods We performed a structured literature search in Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google scholar on November 8, 2020 with the keywords ‘esophageal atresia’, ‘long-term outcome’, ‘motor development’, ‘cognitive development’, and ‘neurodevelopment’. Results The initial search identified 945 studies, of which 15 were included. Five of these published outcomes of multiple tests or tested at multiple ages. Regarding infants, one of six studies found impaired neurodevelopment at 1 year of age. Regarding preschoolers, two of five studies found impaired neurodevelopment; the one study assessing cognitive development found normal cognitive outcome. Both studies on motor function reported impairment. Regarding school-agers, the one study on neurodevelopmental outcome reported impairment. Cognitive impairment was found in two out of four studies, and motor function was impaired in both studies studying motor function. Conclusions Long-term neurodevelopment of children born with EA has been assessed with various instruments, with contrasting results. Impairments were mostly found in motor function, but also in cognitive performance. Generally, the long-term outcome of these children is reason for concern. Structured, multidisciplinary long-term follow-up programs for children born with EA would allow to timely detect neurodevelopmental impairments and to intervene, if necessary.

Contains fulltext : 245512.pdf (Publisher’s version ) (Open Access) Patients with Hirschsprung disease (HSCR) do not always receive a genetic diagnosis after routine screening in clinical practice. One of the reasons for this could be that the causal mutation is not present in the cell types that are usually tested-whole blood, dermal fibroblasts or saliva-but is only in the affected tissue. Such mutations are called somatic, and can occur in a given cell at any stage of development after conception. They will then be present in all subsequent daughter cells. Here, we investigated the presence of somatic mutations in HSCR patients. For this, whole-exome sequencing and copy number analysis were performed in DNA isolated from purified enteric neural crest cells (ENCCs) and blood or fibroblasts of the same patient. Variants identified were subsequently validated by Sanger sequencing. Several somatic variants were identified in all patients, but causative mutations for HSCR were not specifically identified in the ENCCs of these patients. Larger copy number variants were also not found to be specific to ENCCs. Therefore, we believe that somatic mutations are unlikely to be identified, if causative for HSCR. Here, we postulate various modes of development following the occurrence of a somatic mutation, to describe the challenges in detecting such mutations, and hypothesize how somatic mutations may contribute to 'missing heritability' in developmental defects.

Congenital diaphragmatic hernia (CDH) is a congenital structural anomaly in which the diaphragm has not developed properly. It may occur either as an isolated anomaly or with additional anomalies. It is thought to be a multifactorial disease in which genetic factors could either substantially contribute to or directly result in the developmental defect. Patients with aneuploidies, pathogenic variants or de novo Copy Number Variations (CNVs) impacting specific genes and loci develop CDH typically in the form of a monogenetic syndrome. These patients often have other associated anatomical malformations. In patients without a known monogenetic syndrome, an increased genetic burden of de novo coding variants contributes to disease development. In early years, genetic evaluation was based on karyotyping and SNP-array. Today, genomes are commonly analyzed with next generation sequencing (NGS) based approaches. While more potential pathogenic variants are being detected, analysis of the data presents a bottleneck—largely due to the lack of full appreciation of the functional consequence and/or relevance of the detected variant. The exact heritability of CDH is still unknown. Damaging de novo alterations are associated with the more severe and complex phenotypes and worse clinical outcome. Phenotypic, genetic—and likely mechanistic—variability hampers individualpatient diagnosis, short and long-term morbidity prediction and subsequent care strategies. Detailed phenotyping, clinical follow-up at regular intervals and detailed registries are needed to find associations between long-term morbidity, genetic alterations, and clinical parameters. Since CDH is a relatively rare disorder with only a few recurrent changes large cohorts of patients are needed to identify genetic associations. Retrospective whole genome sequencing of historical patient cohorts using will yield valuable data from which today's patients and parents will profit Trio whole genome sequencing has an excellent potential for future re-analysis and data-sharing increasing the chance to provide a genetic diagnosis and predict clinical prognosis. In this review, we explore the pitfalls and challenges in the analysis and interpretation of genetic information, present what is currently known and what still needs further study, and propose strategies to reap the benefits of genetic screening.

Tracheoesophageal Fistula (TOF) is a congenital anomaly for which the cause is unknown in the majority of patients. OA/TOF is a variable feature in many (often mono-) genetic syndromes. Research using animal models targeting genes involved in candidate pathways often result in tracheoesophageal phenotypes. However, there is limited overlap in the genes implicated by animal models and those found in OA/TOF-related syndromic anomalies. Knowledge on affected pathways in animal models is accumulating, but our understanding on these pathways in patients lags behind. If an affected pathway is associated with both animals and patients, the mechanisms linking the genetic mutation, affected cell types or cellular defect, and the phenotype are often not well understood. The locus heterogeneity and the uncertainty of the exact heritability of OA/TOF results in a relative low diagnostic yield. OA/TOF is a sporadic finding with a low familial recurrence rate. As parents are usually unaffected, de novo dominant mutations seems to be a plausible explanation. The survival rates of patients born with OA/TOF have increased substantially and these patients start families; thus, the detection and a proper interpretation of these dominant inherited pathogenic variants are of great importance for these patients and for our understanding of OA/TOF aetiology.

Magnetic resonance imaging (MRI) procedures often evoke anxiety in children. Further, anxious children may be less likely to participate in MRI research, leading to a possible selection bias, and may be more likely to move during image acquisition, resulting in lower image quality and possible information bias. Therefore, state anxiety is problematic for functional and structural MRI studies. Children with behavioral problems, such as internalizing and externalizing behaviors, may be more likely to experience state anxiety prior to and during MRI scanning. Therefore, our first aim was to investigate the relationship between internalizing/externalizing behavior and children’s MRI-related state anxiety. Our second aim was to investigate the relationship between internalizing and externalizing behavior and MRI research participation. Our final aim was to investigate the effect of internalizing and externalizing behavior as well as MRI-related anxiety on image quality in children. We included 1,241 six- to ten-year-old children who underwent a mock MRI. Afterwards, if not too anxious, these children were scanned using a 3-Tesla GE Discovery MRI system (n= 1,070). Internalizing and externalizing behaviors were assessed with the Child Behavior Checklist. State anxiety was assessed with a visual analogue scale. Internalizing behaviors were positively associated with child state anxiety, as reported by child, parent, and researcher. For state anxiety reported by the parent and researcher, this relationship was independent of externalizing behaviors. Externalizing behaviors were related to state anxiety reported by the researcher, but this difference was not independent of internalizing behaviors, pointing towards a relationship via the shared variance with internalizing behaviors. Further, children with more internalizing and externalizing behaviors were less likely to participate in the actual MRI scanning procedure. Lastly, internalizing and externalizing behaviors, as well as MRI-related state anxiety were associated with worse image quality. These results underscore the potential for biases and methodological issues caused by MRI-related state anxiety in children.

Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo. This study included three groups of patients, two groups without coding variants in disease associated genes: HSCR-AAM and HSCR patients without associated anomalies (HSCR-isolated). The third group consisted of all HSCR patients in which a confirmed pathogenic rare coding variant was identified. We compared these patient groups to unaffected controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients without RET coding variants. CNV profiling proved that specifically HSCR-AAM patients had larger Copy Number (CN) losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plausible candidate genes located within CN losses. Validation in zebrafish using CRISPR/Cas9 targeting confirmed the contribution of UFD1L, TBX2, SLC8A1, and MAPK8 to ENS development. In addition, we revealed epistasis between reduced Ret and Gnl1 expression and between reduced Ret and Tubb5 expression in vivo. Rare large CN losses—often de novo—contribute to HSCR in HSCR-AAM patients. We proved the involvement of six genes in enteric nervous system development and Hirschsprung disease., Author summary Hirschsprung disease is a congenital disorder characterized by the absence of intestinal neurons in the distal part of the intestine. It is a complex genetic disorder in which multiple variations in our genome combined, result in disease. One of these variations are Copy Number Variations (CNVs): large segments of our genome that are duplicated or deleted. Patients often have Hirschsprung disease without other symptoms. However, a proportion of patients has additional associated anatomical malformations and neurological symptoms. We found that CNVs, present in patients with associated anomalies, are more often larger compared to unaffected controls or Hirschsprung patients without other symptoms. Furthermore, Copy Number (CN) losses are enriched for constrained coding regions (CCR; genes usually not impacted by genomic alterations in unaffected controls) of which the expression is higher in the developing intestinal neurons compared to the intestine. We modelled loss of these candidate genes in zebrafish by disrupting the zebrafish orthologues by genome editing. For several genes this resulted in changes in intestinal neuron development, reminiscent of HSCR observed in patients. The results presented here highlight the importance of Copy Number profiling, zebrafish validation and evaluating all CCR expressed in developing intestinal neurons during diagnostic evaluation.

BACKGROUND: Children with intestinal failure (IF) receiving long-term parenteral nutrition (PN) have altered body composition (BC), but data on BC changes from start of PN onwards are lacking. OBJECTIVE: We aimed to assess growth and BC in infants after neonatal intestinal surgery necessitating PN and at risk for IF, and to explore associations with clinical parameters. DESIGN: Prospective cohort study in infants after intestinal surgery. IF was defined as PN-dependency for > 60 days. Standard deviation scores (SDS) for anthropometry were calculated until 6 months corrected age. In a subgroup, fat mass (FM) and fat-free mass (FFM) were measured with air-displacement plethysmography at 2- and 6-months corrected age. SDS for length-adjusted FM index and FFM index were calculated. Associations between cumulative amount of PN and BC parameters were analyzed with linear mixed-effect models. RESULTS: Ninety-five neonates were included (54% male, 35% born

Aim of Study: The use of extracorporeal membrane oxygenation (ECMO) has increased as a result of technological developments and the expansion of indications. Relatedly, the number of patients undergoing surgery during ECMO is also rising, at least in the adult population. Little is known on surgery in children during ECMO-therapy. We therefore aimed to assess the frequencies and types of surgical interventions in neonatal and pediatric patients on ECMO and to analyze surgery-related morbidity and mortality.Methods: We retrospectively collected information of all patients on ECMO over a 10-year period in a single tertiary and designated ECMO-center, excluding patients undergoing cardiac surgery, and correction of congenital diaphragmatic hernia. Chi-squared test and Mann-Whitney U test were used to analyze data.Main Results: Thirty-two of 221 patients (14%) required surgery when on ECMO. Common interventions were thoracotomy (32%), laparotomy (23%), fasciotomy (17%), and surgical revision of ECMO (15%). Complications occurred in 28 cases (88%), resulting in a 50% in-hospital mortality rate. Surgical patients had a longer ICU stay and longer total hospital stay compared to those not receiving surgery during ECMO. No significant difference in mortality was found when comparing surgical to non-surgical patients (50 vs. 41%).Conclusions: Approximately one in seven neonatal or pediatric patients required surgical intervention during ECMO, of whom almost 90% developed a complication, resulting in a 50% mortality rate. These results should be taken into account in counseling.

Objective To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach‐bladder distance, using three‐dimensional (3D) ultrasound. Methods This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis. We calculated stomach volumes (n = 223) using Sonography‐based Automated Volume Count. The shortest stomach‐bladder distance (n = 241) was determined using multiplanar visualization of the volume datasets. We used linear mixed modelling to evaluate the effect of gestational age and type of gastroschisis (simple or complex) on fetal stomach volume and stomach‐bladder distance. Results We included 79 affected fetuses. Sixty‐six (84%) had been assessed with 3D ultrasound at least once; 64 of these 66 were liveborn, nine (14%) had complex gastroschisis. With advancing gestational age, stomach volume significantly increased, and stomach‐bladder distance decreased (both P, What's already known about this topic? Infants with complex gastroschisis have a higher risk of morbidity than those with simple gastroschisis.Many attempts have been made to prenatally predict complex gastroschisis, using two‐dimensional ultrasound parameters. What does this study add? This longitudinal prospective multicenter study is the first to evaluate the possible benefit of the use of three‐dimensional ultrasound in fetuses with gastroschisis.Fetal stomach volume and stomach‐bladder distance, measured during pregnancy using three‐dimensional ultrasound, cannot predict complex gastroschisis.

Postoperatively, young infants are admitted overnight in view of the risk for respiratory complications such as desaturation and apnea. This risk seems much lower than previously reported. Until what age this risk persists, and which infants might actually qualify for day-care treatment, is unknown.We retrospectively reviewed medical charts from preterm infants45 weeks postconceptional age (PCA), 45-60 weeks PCA, and term infants3 months admitted overnight after inguinal hernia repair, from January 2011 to December 2015 in a large tertiary children's hospital. Postoperative complications (divided into respiratory, circulatory, neurologic, and other), recurrence, and reoperation were documented and compared between groups.Medical charts of 485 patients were reviewed. Postoperative respiratory complications (mainly desaturations or apnea) had been documented for 27 of 76 (35.5%) preterm infants45 weeks PCA, for 13 of 221 (5.9%) preterm infants 45-60 weeks PCA, and for 3 of 188 (1.6%) term infants (P.001). An analysis of the 221 preterm infants 45-60 weeks PCA showed statistically significantly more respiratory complications in 76 infants with a respiratory history (eg, bronchopulmonary dysplasia) compared with the others (respectively 13.2% vs 0.7%; P.001). In these infants, lower gestational age at the time of surgery was statistically significantly predictive for the development of respiratory complications (odds ratio [OR], 0.68 [95% confidence interval {CI}, 0.52-0.89]; P = .005), but respiratory history (OR, 3.50 [0.34-36.28]; P = .294) and American Society of Anesthesiologists (ASA) physical status (OR, 1.54 [95% CI, 0.31-7.65]; P = .598 for ASA physical status II and OR, 6.11 [95% CI, 0.76-49.05]; P = .089 for ASA physical status III) were not predictive.Incidence of postoperative respiratory complications is high in preterm infants45 weeks PCA requiring postoperative overnight saturation and heart rate monitoring. Incidence of postoperative complications in preterm born infants 45-60 weeks PCA varies. Gestational age and possibly presence of respiratory history can be used to estimate the need for overnight admission in these infants. Postoperative respiratory complications after inguinal hernia repair in ASA physical status I and II term born infants1 month of age are uncommon, which justifies day-care admission for this type of surgical procedure.

Objective Children with congenital diaphragmatic hernia (CDH) are at risk for pulmonary morbidity. Data on longitudinal evaluation of lung function in CDH are scarce. We hypothesized that CDH patients would have impaired lung function that worsens over time. We evaluated lung function and its determinants at ages 8 and 12 years. Methods Dynamic and static lung volumes, and diffusion capacity were measured. Extracorporeal membrane oxygenation (ECMO) treatment, the standardized European neonatal treatment protocol, patch repair, duration of ventilation, type of initial mechanical ventilation, and nitric oxide treatment were entered as covariates in linear mixed models with standard deviation score (SDS) lung function parameters (FEV1, FEF 25‐75, and K CO) as dependent variables. Results Seventy‐six children (27 ECMO‐treated) born between 1999 and 2009 performed 113 reliable lung function tests. Severity of airflow obstruction deteriorated significantly from age 8 to 12 years: estimated mean difference (95% confidence interval [CI]) SDS FEV1 was −0.57 (−0.79 to −0.36) and SDS FEF25‐75 was −0.63 (−0.89 to −0.37), both P

Introduction Multiple reports have questioned the feasibility of neonatal thoracoscopic repair of congenital diaphragmatic hernia (CDH) and esophageal atresia (EA). The aim of this study is to examine the effects of CO2 pneumothorax on cerebral and renal rSO2 and to assess the potential predictive value of these data on neurodevelopmental outcome after neonatal thoracoscopic surgery for CDH or EA. Materials and Methods A prospective observational pilot study. Cerebral and renal regional tissue oxyhemoglobine saturation (rSO2) rSO2 were assessed using near-infrared spectroscopy (NIRS) during thoracoscopic surgery in neonates with CDH and with EA, in addition to routine anesthesia monitoring. Cerebral and renal rSO2, linked to repeated arterial blood gas analyses, heart rate, blood pressure, and to structured longitudinal neurodevelopmental follow-up. Results Baseline estimated marginal means of cerebral rSO2 values (CDH: 82%, EA: 91%) did not change significantly during pneumothorax (CDH: 81%, EA 79% [n.s. versus baseline]) despite severe acidosis (lowest pH, CDH: 6.99, EA: 7.1). Neurodevelopmental outcomes at 24 months were normal in all 7 patients who were available for evaluation. Conclusion Neonatal thoracoscopic repair of CDH and EA using CO2-pneumothorax leads to severe acidosis. Cerebral rSO2 remained within clinical acceptable limits during intraoperative periods of acidosis. Neurodevelopmental outcome was favorable within the first 24 months. The potential of NIRS to further improve perioperative care and long-term outcome in this specific patient group deserves further investigation.

Background In 2011, we implemented a new video-based system for quality control of laparoscopic pyloromyotomy. More than 3 years later, we evaluated how the implementation had gone and assessed its usability in predicting postoperative outcomes. Materials and Methods Four key point images or short video-segments were to be recorded perioperatively: prepyloromyotomy, parallel-mobility testing, perforation testing, and postpyloromyotomy. Data of all 134 patients undergoing laparoscopic pyloromyotomy from September 2011 to December 2014 were analyzed retrospectively. Five pediatric surgeons independently assessed the anonymized operative images for predicting reoperation and time to full-enteral feeding. Results The percentage of operations during which images were recorded increased from 45% in 2012 to 75% in 2014. Over the study period, one or more images were recorded in 89 of the 134 (66%) patients. In only 17 of 89 patients (19%), all four images were documented. The key point images or videos were made for prepyloromyotomy in 49%, parallel-mobility testing in 85%, perforation testing in 42%, and postpyloromyotomy in 94% of 89 patients. Five patients (3.7%) were reoperated for incomplete pyloromyotomy (N = 4) or mucosal perforation (N = 1). Images were recorded during the first operation in four of the five reoperated patients. The need of reoperation was correctly predicted for two of the four patients. Full-enteral feeding within 24 hours was correctly predicted for 67% of the patients (range: 47–88%). Conclusion The increase in recorded images over the years is promising. The implementation of the quality control system did not contribute to a significant decrease in the complication rate, which was already very low. Still, reoperation or a protracted postoperative course could only be predicted with moderate accuracy from the operative images, therefore, for now the use of perioperative images in a medicolegal setting should be advised against. Improved compliance with image recording and better instructions for evaluating the images might improve the usefulness of perioperative images in, e.g., telementoring, education, and medicolegal practice.

Background Epidural analgesia (EDA) is used as postoperative pain treatment in children, but little is known about its efficacy after laparotomy in children. This retrospective study investigated the efficacy of postoperative EDA after laparotomy in children and the frequencies of adverse effects and complications. Materials and Methods Data of all children aged 0 to 18 years undergoing laparotomy and treated with EDA in our hospital from January 2014 to December 2015 were collected. EDA was classified as successful either if the catheter was removed when there was no further need, and the patient was comfortable with oral/rectal analgesics or when EDA was continued after intervention. Results Ninety children with a median age of 3.7 years were included in the study. In 65% (59/90), EDA was classified as successful. In 34% (20/59) of all successful cases, an additional intervention was needed. In 35% (31/90), the catheter was removed earlier than planned, in half of these cases after an intervention. The primary reason for earlier removal was inadequate analgesia and technical failure. Adverse effects occurred in 18% and complications in 1% of cases. The successful group was significantly younger than the unsuccessful (p = 0.003). Conclusion EDA after laparotomy positively contributed to postoperative pain treatment in two-thirds of children. Numbers of adverse effects and complications were low. It is important to optimize pain management after laparotomy in children; thus, further prospective studies should focus on optimizing EDA and comparing EDA with other techniques of analgesia.

More than one billion people worldwide suffer from congenital and chronic respiratory diseases, leading to high rates in mortality and morbidity. The unpredictability of disease progression and responsiveness towards treatment requires sophisticated experimental models to better mimic the patient-specific biology of the airways. Currently, the best reproducible in vitro airway system is the air-liquid interface (ALI) method, a static, air-exposed airway epithelial layer. However, this model lacks the cellular diversity and 3D structure of the in vivo microenvironment, the flow dynamics and the mechanical stretch of the human lung. To address these issues, we aim to stepwise develop a dynamic and reproducible three-dimensional model of the human airway by co-culturing human primary cells and/or induced pluripotent stem cell (iPSC)-derived lung epithelial cells. First, we optimized media culture conditions for the co-cultures of human primary lung endothelial cells (hLECs) with human primary bronchial epithelial cells (hPBECs) and human primary lung fibroblasts (hLFs). We will show the co-culture medium that best promotes survival, proliferation and differentiation of hPBECs to mucociliary cells. Next, we increased the complexity of the ALI culture system by seeding hPBECs on top of hydrogels containing hLFs, and seeding hLECs at the basal side of the insert membrane. Transdifferentiation of the different cell types will also be evaluated to prevent cells from losing their phenotype and being under stress in the co-culture model. These complex cultures will subsequently be subjected to dynamic flow to investigate the effect on the viability and differentiation potential of the various cell types.

Introduction Many aspects of the management of esophageal atresia (EA) and tracheoesophageal fistula (TEF) are controversial and the evidence for decision making is limited. Members of the European Reference Network for Rare Inherited Congenital Anomalies (ERNICA) conducted a consensus conference on the surgical management of EA/TEF based on expert opinions referring to the latest literature. Materials and Methods Nineteen ERNICA representatives from nine European countries participated in the conference. The conference was prepared by item generation, item prioritization by online survey, formulation of a final list containing the domains diagnostics, preoperative, operative, and postoperative management, and literature review. The 2-day conference was held in Berlin in October 2018. Anonymous voting was conducted via an internet-based system. Consensus was defined when 75% of the votes scored 6 to 9. Results Fifty-two items were generated with 116 relevant articles of which five studies (4.3%) were assigned as level-1evidence. Complete consensus (100%) was achieved on 20 items (38%), such as TEF closure by transfixing suture, esophageal anastomosis by interrupted sutures, and initiation of feeding 24 hours postoperatively. Consensus ≥75% was achieved on 37 items (71%), such as routine insertion of transanastomotic tube or maximum duration of thoracoscopy of 3 hours. Thirteen items (25%) were controversial (range of scores, 1–9). Eight of these (62%) did not reach consensus. Conclusion Participants of the conference reached significant consensus on the management of patients with EA/TEF. The consensus may facilitate standardization and development of generally accepted guidelines. The conference methodology may serve as a blueprint for further conferences on the management of congenital malformations in pediatric surgery.