Development of a core outcome set for congenital pulmonary airway malformations: study protocol of an international Delphi survey.

IntroductionA worldwide lack of consensus exists on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) even though the incidence is increasing. Either a surgical resection is performed or a wait-and-see policy is employed, depending on the treating physician. Management is largely based on expert opinion and scientific evidence is scarce. Wide variations in outcome measures are seen between studies making comparison difficult thus highlighting the lack of universal consensus in outcome measures as well. We aim to define a core outcome set which will include the most important core outcome parameters for paediatric patients with an asymptomatic CPAM.Methods and analysisThis study will include a critical appraisal of the current literature followed by a three-stage Delphi process with two stakeholder groups. One surgical group including paediatric as well as thoracic surgeons, and a non-surgeon group including paediatric pulmonologists, intensive care and neonatal specialists. All participants will score outcome parameters according to their level of importance and the most important parameters will be determined by consensus.Ethics and disseminationElectronic informed consent will be obtained from all participants. Ethical approval is not required. After the core outcome set has been defined, we intend to design an international randomised controlled trial: the COllaborative Neonatal NEtwork for the first CPAM Trial, which will be aimed at determining the optimal management of patients with asymptomatic CPAM

Primary repair of esophageal atresia is followed by multiple diagnostic and surgical procedures.

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

Intralesional steroid injections to prevent refractory strictures in patients with oesophageal atresia: study protocol for an international, multicentre randomised controlled trial (STEPS-EA trial)

INTRODUCTION: Anastomotic stricture formation is the most common postoperative complication after oesophageal atresia (OA) repair. The standard of care is endoscopic dilatation. A possible adjuvant treatment is intralesional steroid injection, which is thought to inhibit scar tissue formation and thereby to prevent stricture recurrence. We hypothesise that this intervention could prevent refractory strictures and reduce the total number of dilatations needed in these children. METHODS AND ANALYSIS: This is an international multicentre randomised controlled trial. Children with OA type C (n=110) will be randomised into intralesional steroid injection followed by balloon dilatation or dilatation only. Randomisation and intervention will take place when a third dilatation is performed. The indication for dilatation will be confirmed with an oesophagram. One radiologist-blinded for randomisation-will review all oesophagrams. The primary outcome parameter is the total number of dilatations needed with <28 days' interval, which will be analysed with a linear-by-linear χ2 association test. Secondary outcome parameters include the level of dysphagia, the luminal oesophageal diameter and stricture length (measured on the oesophagrams), the influence of comedication on stricture formation, systemic effects of intralesional steroids (cortisol levels, length and weight) and the cost-effectiveness. Patients will undergo a second oesophagram; length and weight will be measured repeatedly; a scalp hair sample will be collected; and three questionnaires will be administered. The follow-up period will be 6 months, with evaluation at 2-3 weeks, 3 and 6 months after the intervention. ETHICS AND DISSEMINATION: Patients will be included after written parental informed consent. The risks and burden associated with this trial are minimal. The institutional review board of the Erasmus Medical Centre approved this protocol (MEC-2018-1586/NL65364.078.18). The results of the trial will be published in a peer-reviewed scientific journal and will be presented at international conferences. TRIAL REGISTRATION NUMBERS: 2018-002863-24 and NTR7726/NL7484.status: publishe

COllaborative Neonatal Network for the first European CPAM Trial (CONNECT): a study protocol for a randomised controlled trial.

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

Remote ischemic conditioning in necrotizing enterocolitis: study protocol of a multi-center phase II feasibility randomized controlled trial

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