Gastroschisis associated changes in the placental transcriptome.

The congenital condition gastroschisis is associated with delayed villous development and placental malperfusion, suggesting placental involvement. This study uses RNA sequencing to compare the placental transcriptome in pregnancies with and without gastroschisis. 180 coding genes were differentially expressed, mapping to multiple gene ontology pathways. Altered placental gene expression may represent fetal signalling to the placenta, and these changes could contribute to the pathogenesis of gastroschisis and associated morbidities, including fetal growth restriction.

UK neonatal stoma practice: a population study.

OBJECTIVE: The optimal time for neonatal stoma closure is unclear and there have been calls for a trial to compare early and late surgery. The feasibility of such a trial will depend on the population of eligible infants and acceptability to families and health professionals. In this study, we aimed to determine current UK practice and characteristics of those undergoing stoma surgery. DESIGN: A retrospective cohort study of neonates who had undergone stoma surgery (excluding anorectal malformations and Hirschsprung's disease) using three national databases: the National Neonatal Research Database (NNRD, 2012-2019), British Association of Paediatric Surgeons Congenital Anomalies Surveillance System (BAPS-CASS, 2013-2014) and Hospital Episode Statistics-Admitted Patient Care (HES-APC, 2011-2018). RESULTS: 1830 eligible neonates were identified from NNRD, 163 from BAPS-CASS, 2477 from HES-APC. Median (IQR) duration of stoma in days was 57 (36-80) in NNRD, 63 (41-130) in BAPS-CASS and 78 (55-122) for neonates identified from HES-APC. At the time of closure, there were low rates of invasive ventilation (13%), inotrope use (5%) and recent steroids use (4%). Infants who underwent earlier closure (<9 weeks) were less preterm (median 28 weeks vs 25 weeks), have higher birth weight (median 986 g vs 764 g) and more likely to have stoma complications (29% vs 5%). CONCLUSION: There are sufficient UK neonates undergoing stoma formation for a trial. Stoma closure is performed at around 2 months, with clinical stability, gestation, weight and stoma complications appearing to influence timing. The variation in practice we document indicates there is opportunity to optimise practice through a trial.

Methods of identifying surgical Necrotizing Enterocolitis-a systematic review and meta-analysis.

BACKGROUND: Current data suggests potential benefit of earlier surgery for necrotizing enterocolitis (NEC) however this requires accurate prognostication early in the disease course. This study aims to identify and determine the effectiveness of previously reported methods or tests for the identification of surgical NEC. METHODS: Systematic review and meta-analysis with registration on PROSPERO including articles describing a method of identifying surgical NEC. Outcomes of interest were effectiveness and repeatability of index test. RESULTS: Of the 190 full-text articles screened, 90 studies were included which contained 114 methods of identifying surgical NEC in 9546 infants. Of these methods, 44 were a scoring system, 37 a single biomarker, 24 an imaging method, and 9 an invasive method. Sensitivity and specificity ranged from 12.8-100% to 13-100%, respectively. Some methods (9.6%) provided insufficient methods for repeatability within clinical practice or research. Meta-analyses were possible for only 2 methods, the metabolic derangement 7 score and abdominal ultrasound. CONCLUSIONS: A range of methods for identifying surgical NEC have been identified with varying overall performance and uncertainties about reproducibility and superiority of any method. External validation in large multicentre datasets should allow direct comparison of accuracy and prospective study should evaluate impact on clinical outcomes. IMPACT: Earlier identification of need for surgery in necrotizing enterocolitis (NEC) has the potential to improve the unfavourable outcomes in this condition. As such, many methods have been developed and reported to allow earlier identification of surgical NEC. This study is the first synthesis of the literature which identifies previously reported methods and the effectiveness of these. Many methods, including scoring systems and biomarkers, appear effective for prognostication in NEC and external validation is now required in multicentre datasets prior to clinical utility.

Investigations, management and outcome of neonates presenting with distal intestinal obstruction: challenging the need for contrast enemas.

PURPOSE: To characterise the investigations, management and ultimate diagnosis of neonates with distal intestinal obstruction. METHODS: Retrospective review of term (> 37 weeks) neonates with admission diagnosis of distal intestinal obstruction over 10 years (2012-2022). Patient pathways were identified and associations between presentations, response to treatments and outcome investigated. RESULTS: A total of 124 neonates were identified and all included. Initial management was colonic irrigation in 108, contrast enema in 4, and laparotomy in 12. Of those responding to irrigations none underwent contrast enema. Ultimately, 22 neonates proceeded to laparotomy. Overall, 106 had a suction rectal biopsy and 41 had genetic testing for cystic fibrosis. Final diagnosis was Hirschsprung disease (HD) in 67, meconium ileus with cystic fibrosis (CF) in 9, meconium plug syndrome in 19 (including 3 with CF), intestinal atresia in 10 and no formal diagnosis in 17. Median length of neonatal unit stay was 11 days (7-19). CONCLUSIONS: Initial management of neonates with distal bowel obstruction should be colonic irrigation since this is therapeutic in the majority and significantly reduces the need for contrast enema. These infants should all have suction rectal biopsy to investigate for HD unless another diagnosis is evident. If a meconium plug is passed, testing for CF is recommended. Evaluation and therapy are multimodal and time consuming, placing burden on resources and families.

The Insertion and Management of Gastrostomies in Children in the United Kingdom - A Survey of Practice.

BACKGROUND: Gastrostomy insertion is one of the most frequently performed procedures by specialist paediatric surgeons. We aimed to determine practice across the United Kingdom (UK) and in particular to identify areas where there was consistency or variation in practice between practitioners and centres. METHODS: A structured survey was distributed to all consultant practitioners who insert gastrostomies in the UK. Practice surrounding a range of aspects of gastrostomy care including insertion technique, device use, post-operative management and subsequent care were determined. RESULTS: Of total 135 practitioners who insert gastrostomies, responses were received from 103 (76%) with responses received from all UK centres. There was variation between centres in the provision of pre-operative information, and between practitioners in preferred device, insertion techniques, post-operative feeding practice and change/removal procedures. The most frequently preferred device for primary gastrostomy insertion was a Freka® PEG (36%) button device (30%), CorFlo™ PEG (21%), or G-tube (10%). Laparoscopy was always used when inserting either PEG or button device by over 50% of respondents and selectively used by the majority of the remainder. Feeds were started between 1 and 24 h post-insertion, most practitioners (64%) plan a minimum one night hospital stay but a third plan for more than one night. CONCLUSION: There is considerable variation in practice for most stages of the pathway for children having a gastrostomy. Further work is warranted to understand the relationship between different practices and patient outcomes, resource use and cost and subsequently to develop best practice guidelines.

Transcriptomic analysis of the effect of remote ischaemic conditioning in an animal model of necrotising enterocolitis.

Necrotising enterocolitis (NEC) has a complex pathophysiology but the common end-point is ischaemia reperfusion injury (IRI) and intestinal necrosis. We have previously reported that RIC significantly reduces the intestinal injury in a rat model of NEC. Here we describe the changes in intestinal mRNA occurring in the intestine of animals exposed to IRI, both with and without RIC. Related rat-pups were randomly assigned to four groups: SHAM, IRI only, RIC only and RIC + IRI. IRI animals, underwent 40 min of intestinal ischaemia, and 90 min of reperfusion. Animals that underwent RIC had three cycles of 5 min of alternating ischaemia/reperfusion by means of a ligature applied to the hind limb. Samples from the terminal ileum were immediately stored in RNA-preserving media for later next generation sequencing and transciptome analysis using R v 3.6.1. Differential expression testing showed that 868 genes differentially expressed in animals exposed to RIC alone compared to SHAM and 135 in the IRI and RIC group compared to IRI alone. Comparison between these two sets showed that 25 genes were differentially expressed in both groups. Pro-inflammatory molecules: NF-ĸß2, Cxcl1, SOD2 and Map3k8 all show reduced expression in response to RIC. Targeted gene analysis revealed increased expression in PI3K which is part of the so-called RISK-pathway which is a key part of the protective mechanisms of RIC in the heart. Overall, this transcriptomic analysis shows that RIC provides a protective effect to the intestine via anti-inflammatory pathways. This could be particularly relevant to treating and preventing NEC.

European Pediatric Surgeons' Association Survey on Timing of Inguinal Hernia Repair in Premature Infants.

AIM: This article evaluates the practice patterns of European Pediatric Surgeons' Association (EUPSA) members regarding the timing of inguinal hernia (IH) repair in premature infants. METHODS: Online survey containing 29 questions distributed to EUPSA members during January 2023. RESULTS: A total of 180 responds were received. Overall, IH repair prior to discharge was favored by 60% of respondents when there was a history of incarceration and 56% when there was not. In the case of very/extremely premature infants (< 32 weeks) with no history of incarceration, fewer (43%) respondents postpone the surgery until after discharge. The majority of respondents cited the risk of incarceration as the reason for advocating surgery prior to discharge, whereas a reduced risk of apnea was the most cited reason for respondents who prefer delayed surgery. Open approach under general anesthesia was favored by 54% of respondents, with 27% of them preferring open approach with spinal anesthesia. Laparoscopic surgery for premature infants is used in 11% while 7% of them preferred in all premature infants including extremely/very premature ones. Contralateral side evaluation was never done by 40% of respondents and 29% only performed it only during laparoscopic repair. The majority of respondents (77%) indicated that they have an overnight stay policy for premature infants < 45 weeks of gestation. CONCLUSION: There is variation in the practice patterns of pediatric surgeons in the treatment of IH in premature infants. Due to the concern for the high risk of incarceration, IH repair before discharge was the most prevalent practice. Lower risk of postoperative apnea was cited as the most common reason for delaying surgery. Randomized studies are required to establish the optimal timing for IH repair in premature infants.

Long-gap esophageal atresia: gastric transposition or esophageal lengthening with delayed primary anastomosis? A systematic review.

PURPOSE: This study aims to evaluate different surgical approaches to long-gap esophageal atresia (LGEA) with or without tracheoesophageal fistula (TEF) is unclear. METHODS: A systematic literature review was done comparing gastric transposition versus esophageal lengthening with delayed primary anastomosis in infants with LGEA+/-TEF. The primary outcome was time to full oral feeds. Secondary outcomes were time to full enteric feeds, need for further surgery, growth, mortality, and postoperative adverse events. RESULTS: No comparative studies were found. However, the literature was re-interrogated for non-comparative studies. Four hundred thirty-eight articles were identified and screened, and 18 met the inclusion criteria. All were case series. Forty-three infants underwent gastric transposition, and 106 had esophageal lengthening with delayed primary anastomosis. One study on gastric transposition reported time to full oral feeds, and one study in each group reported growth. Time to full enteric feeds was reported in one study in each group. 30% of infants had further surgery following gastric transposition, including hiatus hernia repair (5/43, 12%) and esophageal dilation (7/43, 16%). Following esophageal lengthening, 62/106 (58%) had anti-reflux surgery, 58/106 (55%) esophageal dilatation and 11/106 (10%) esophageal stricture resection. Anastomotic complications occurred in 13/43 (30%), gastrointestinal in 16/43 (37%), respiratory in 17/43 (40%), and nerve injury in 2/43 (5%) of the gastric transposition group. In the esophageal lengthening group, anastomotic complications occurred in 68/106 (64%), gastrointestinal in 62/106 (58%), respiratory in 6/106 (6%), and none sustained nerve injury. Each group had one death due to a cause not directly related to the surgical procedure. CONCLUSIONS: This systematic review highlights the morbidity associated with both surgical procedures and the variety in reporting outcomes.

A Study of Safety and Effectiveness of Evicel Fibrin Sealant as an Adjunctive Hemostat in Pediatric Surgery.

INTRODUCTION: Data on the use of fibrin sealants to control intraoperative bleeding in children are scarce. Evicel Fibrin Sealant (Ethicon Inc., Raritan, New Jersey, United States) was found safe and effective in clinical trials of adults undergoing various surgery types. We evaluated the safety and efficacy of Evicel versus Surgicel Absorbable Hemostat (Ethicon Inc.) as adjunctive topical hemostats for mild/moderate raw-surface bleeding in pediatric surgery. METHODS: A phase III randomized clinical trial was designed as required by the European Medicines Agency's Evicel Pediatric Investigation Plan: 40 pediatric subjects undergoing abdominal, retroperitoneal, pelvic, or thoracic surgery were randomized to Evicel or Surgicel, to treat intraoperative mild-to-moderate bleeding. Descriptive analyses included time-to-hemostasis and rates of treatment success (4, 7, 10 minutes), intraoperative treatment failure, rebleeding, and thromboembolic events. RESULTS: Forty of 130 screened subjects aged 0.9 to 17 years were randomized 1:1 to Evicel or Surgicel. Surgeries were predominantly open abdominal procedures. The median bleeding area was 4.0 cm2 for Evicel and 1.0 cm2 for Surgicel. The median time-to-hemostasis was 4.0 minutes for both groups. The 4-, 7-, and 10-minute treatment success rates were 80.0% versus 65.0%, 100.0% versus 80.0%, and 95.0% versus 90.0%, whereas treatment failure rates were 5.0% versus 25.0%, for Evicel and Surgicel, respectively. No deaths or thrombotic events occurred. Re-bleeding occurred in 5.0% of Evicel and 10.0% of Surgicel subjects. CONCLUSIONS: In accordance with adult clinical trials, this randomized study supports the safety and efficacy of Evicel for controlling mild-to-moderate surgical bleeding in a broad range of pediatric surgical procedures.

Developing a core outcome set for the health outcomes for children and adults with congenital oesophageal atresia and/or tracheo-oesophageal fistula: OCELOT task group study protocol.

INTRODUCTION: Heterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions to standardise outcome reporting, facilitate meta-analysis and improve the relevance of research for patients and families. Our aim is to develop an internationally-agreed, comprehensive COS for OA-TOF, relevant from birth through to transition and adulthood. METHODS AND ANALYSIS: A long list of outcomes will be generated using (1) a systematic review of existing studies on OA-TOF and (2) qualitative research with children (patients), adults (patients) and families involving focus groups, semistructured interviews and self-reported outcome activity packs. A two-phase Delphi survey will then be completed by four key stakeholder groups: (1) patients (paediatric and adult); (2) families; (3) healthcare professionals; and (4) researchers. Phase I will include stakeholders individually rating the importance and relevance of each long-listed outcome using a 9-point Likert scale, with the option to suggest additional outcomes not already included. During phase II, stakeholders will review summarised results from phase I relative to their own initial score and then will be asked to rescore the outcome based on this information. Responses from phase II will be summarised using descriptive statistics and a predefined definition of consensus for inclusion or exclusion of outcomes. Following the Delphi process, stakeholder experts will be invited to review data at a consensus meeting and agree on a COS for OA-TOF. ETHICS AND DISSEMINATION: Ethical approval was sought through the Health Research Authority via the Integrated Research Application System, registration no. 297026. However, approval was deemed not to be required, so study sponsorship and oversight were provided by Alder Hey Children's NHS Foundation Trust. The study has been prospectively registered with the COMET Initiative. The study will be published in an open access forum.

Punctate inner choroidopathy: A review of the current diagnostic and therapeutic approaches.

Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females. Clinically, it manifests as small, yellowish-white lesions in the inner choroid and outer retina, often associated with inflammatory changes. Accurate diagnosis remains a challenge due to its resemblance to other posterior uveitic entities, necessitating an astute clinical eye and advanced imaging techniques for differentiation. Multimodal imaging plays a crucial role by offering valuable insights, as it enables the visualization of various abnormalities related to uveitis. The pathogenesis of PIC is still a subject of debate, with a complex interplay of genetic, immunological, and environmental factors proposed. Managing PIC presents multiple challenges for clinicians. Firstly, variable disease severity within and among patients requires diverse treatments, from observation to aggressive immunosuppression and/or anti-VEGF therapy. Secondly, treatment must distinguish between primary causes of vision loss. New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes. Thirdly, deciding on maintenance therapy is complex, balancing PIC prognosis variability against immunosuppression risks. Some patients have long periods of inactivity and remission, while others face sudden, vision-threatening episodes during quiescent phases. Through a systematic review of the literature, this paper sheds light on the current understanding of PIC, its challenges, and the prospects for future research. By synthesizing existing knowledge, it aims to aid clinicians in accurate diagnosis and guide treatment decisions for improved visual outcomes in individuals affected by PIC.

A Minimally Interventional Approach to Oesophageal Atresia Repair With Early Enteral Feeding is Safe, Optimises Neonatal Outcomes, and Reduces Resource use.

PURPOSE: Recent series of newborn Oesophageal Atresia (OA) repair continue to report widespread use of chest drains, gastrostomy, routine contrast studies and parenteral nutrition (PN) despite evidence suggesting these are superfluous. We report outcomes using a minimally interventional approach to post-operative recovery. METHODS: Ethically approved (15/WA/0153), single-centre, retrospective case-note review of consecutive infants with OA 2000-2022. Infants with OA and distal trache-oesophageal fistula undergoing primary oesophageal anastomosis at initial surgery were included (including those with comorbidities such as duodenal atresia, anorectal malformation and cardiac lesions). Our practice includes routine use of a trans-anastomotic tube (TAT), no routine chest drain nor gastrostomy, early enteral and oral feeding, no routine PN and no routine contrast study. Data are median (IQR). RESULTS: Of total 186 cases of OA treated during the time period, 157 met the inclusion criteria of which 2 were excluded as casenotes unavailable. TAT was used in 150 infants. A chest drain was required in 13 (8%) and two infants had a neonatal gastrostomy. Enteral feeds were started on postoperative day 2 (2-3), full enteral feeds established by day 4 (4-6) and oral feeds started on day 5 (4-8). PN was required in 15%. Median postoperative length of stay was 10 days (8-17). Progress was quicker in term infants than preterm. One infant died of cardiac disease prior to neonatal discharge. Two planned post-operative contrast studies were performed (surgeon preference) and a further 7 due to clinical suspicion of anastomotic leak. Contrast study was therefore avoided in 94%. There were 2 anastomotic leaks; both presented clinically at day 4 and day 8 after oral feeds had been started. CONCLUSION: Our minimally interventional approach is safe. It facilitates prompt recovery with lower resource use, reduced demand on nursing staff, reduced radiation burden, and early discharge home compared to published series without adversely affecting outcomes. LEVEL OF EVIDENCE: Level 4.

Congenital duodenal obstruction repair with and without transanastomotic tube feeding: a systematic review and meta-analysis.

OBJECTIVE: To determine the impact of transanastomotic tube (TAT) feeding in congenital duodenal obstruction (CDO). DESIGN: Systematic review with meta-analysis. PATIENTS: Infants with CDO requiring surgical repair. INTERVENTIONS: TAT feeding following CDO repair versus no TAT feeding. MAIN OUTCOME MEASURES: The main outcome was time to full enteral feeds. Additional outcomes included use of parenteral nutrition (PN), cost and complications from either TAT or central venous catheter. Meta-analyses were undertaken using random-effects models (mean difference (MD) and risk difference (RD)), and risk of bias was assessed using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool. RESULTS: Twelve out of 373 articles screened met the inclusion criteria. All studies were observational and two were prospective. Nine studies, containing 469 infants, were available for meta-analysis; however, four were excluded due to serious or critical risk of bias. TAT feeding was associated with reduced time to full enteral feeds (-3.34; 95% CI -4.48 to -2.20 days), reduced duration of PN (-6.32; 95% CI -7.93 to -4.71 days) and reduction in nutrition cost of £867.36 (95% CI £304.72 to £1430.00). Other outcomes were similar between those with and without a TAT including inpatient length of stay (MD -0.97 (-5.03 to 3.09) days), mortality (RD -0.01 (-0.04 to 0.01)) and requirement for repeat surgery (RD 0.01 (-0.03 to 0.05)). CONCLUSION: TAT feeding following CDO repair appears beneficial, without increased risk of adverse events; however, certainty of available evidence is low. Earlier enteral feeding and reduced PN use are known to decrease central venous catheter-associated risks while significantly reducing cost of care. PROSPERO REGISTRATION NUMBER: CRD42022328381.

Development Methodology, Availability, and Implementation of Core Outcome Sets in Pediatric Surgery.

Core outcome sets (COSs) provide a mechanism to guide researchers and clinicians when deciding which outcomes to report in research related to a specific clinical condition or intervention. The intention behind creating a COS for a specific condition is to improve the reporting of important and meaningful outcomes, thus enhancing the relevance of research. Additionally, a COS helps facilitate comparison of outcomes between different clinical studies and reduces research waste. In this paper, we discuss the availability of COSs in the field of pediatric general surgery. We provide an overview of the methodologies used to develop a COS, including common pitfalls, and finally, we discuss COS uptake and implementation. An understanding of all these aspects is important for researchers considering developing a new COS and for those reading research where a COS has been developed or used within a study. Failure to adequately appreciate the nuances of COS development, in particular, risks fundamental flaws that may jeopardize COS validity and subsequently hinder COS uptake and implementation.

Research priorities for children's cancer: a James Lind Alliance Priority Setting Partnership in the UK.

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities. PARTICIPANTS: Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population. RESULTS: Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children's surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was 'can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?' CONCLUSIONS: We have identified research priorities for children's cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

Congenital lung malformations.

Congenital lung malformations (CLMs) are rare developmental anomalies of the lung, including congenital pulmonary airway malformations (CPAM), bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and isolated congenital bronchial atresia. CLMs occur in 4 out of 10,000 live births. Postnatal presentation ranges from an asymptomatic infant to respiratory failure. CLMs are typically diagnosed with antenatal ultrasonography and confirmed by chest CT angiography in the first few months of life. Although surgical treatment is the gold standard for symptomatic CLMs, a consensus on asymptomatic cases has not been reached. Resection, either thoracoscopically or through thoracotomy, minimizes the risk of local morbidity, including recurrent infections and pneumothorax, and avoids the risk of malignancies that have been associated with CPAM, bronchopulmonary sequestration and bronchogenic cyst. However, some surgeons suggest expectant management as the incidence of adverse outcomes, including malignancy, remains unknown. In either case, a planned follow-up and a proper transition to adult care are needed. The biological mechanisms through which some CLMs may trigger malignant transformation are under investigation. KRAS has already been confirmed to be somatically mutated in CPAM and other genetic susceptibilities linked to tumour development have been explored. By summarizing current progress in CLM diagnosis, management and molecular understanding we hope to highlight open questions that require urgent attention.