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.

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.

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.

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.

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.

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.

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.

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.

Recent advances in our understanding of NEC diagnosis, prognosis and surgical approach.

Necrotising enterocolitis (NEC) remains a devasting condition that has seen limited improvement in outcomes in recent years. The incidence of the disease is increasing as more extremely premature infants survive. NEC is responsible for 1 in 10 neonatal deaths and up to 61% of survivors have significant neurodevelopmental delay. The aim of this review is to highlight recent advances in diagnosis, prognosis and surgical approach in this condition. Many recent studies have reported novel methods of diagnosis of NEC with the aim of earlier and more accurate identification. These include imaging and machine learning techniques. Prognostication of NEC is particularly important to allow earlier escalation of therapy. Around 25% of infants with NEC will require surgery and recent data has shown that time from disease onset to surgery is greater in infants whose indication for surgery is failed medical management, rather than pneumoperitoneum. This indication was also associated with worse outcomes compared to pneumoperitoneum. Ongoing research has highlighted several new methods of disease prognostication which includes differentiating surgical from medical NEC. Finally, recent randomised controlled trials in surgical technique are discussed along with the implications of these for practice. Further, high quality research utilising multi-centre collaborations and high fidelity data from electronic patient records is needed to address the issues discussed and ultimately improve outcomes in NEC.

Tunnelled external versus implanted port central venous catheters in paediatric oncology: a systematic review and meta-analysis.

OBJECTIVE: To evaluate and compare the complications associated with tunnelled external and implanted port (PORT) central venous catheters (CVCs) in children with cancer. DESIGN: A systematic review in accordance with PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines was performed (pre-registered on PROSPERO: CRD42022300869). MEDLINE, Web of Science and the Cochrane Library databases were searched. PATIENTS: Patients ≤18 years of age with haematological or solid malignancies. INTERVENTIONS: Studies comparing tunnelled external and PORT CVCs. MAIN OUTCOMES MEASURES: Infection, mechanical failure, thrombosis, bleeding, acceptability, quality of life (QoL), cost, premature removal, and days from insertion to removal for any reason. RESULTS: Twenty-three observational studies met the inclusion criteria, representing 6644 devices and 6032 patients. Tunnelled external CVCs were associated with an increased risk for systemic infection (OR 2.10, 95% CI 1.59 to 2.77, p<0.001, 16 studies, 3425 devices). There was no significant difference in the risk of localised infection (OR 1.15, 95% CI 0.66 to 2.01, p=0.62, 5 studies, 979 devices). Tunnelled external CVCs were also associated with a significantly increased risk of mechanical complications (OR 2.47, 95% CI 1.21 to 5.05, p=0.01, 11 studies, 2187 devices) and premature device removal (OR 3.24, 95% CI 1.28 to 8.22, p=0.01, 6 studies, 1514 devices). CONCLUSION: This study shows that PORTs associate with a reduced risk of infectious and mechanical complications, and a lower overall risk of removal, compared with tunnelled external CVCs in children with cancer. Further work is required to confirm these findings in a prospective randomised trial and to compare cost implications and acceptability to patients and caregivers.

Assessing micro- vs macro-costing approaches for treating appendicitis in children with appendicectomy or non-operatively.

OBJECTIVES: We conducted a health economic sub-study within a feasibility RCT comparing a non-operative treatment pathway as an alternative to appendicectomy for the treatment of uncomplicated acute appendicitis in children. The objectives were to understand and assess data collection tools and methods and to determine indicative costs and benefits assessing the feasibility of conducting a full economic evaluation within the definitive trial. METHODS: We compared different methods of estimating treatment costs including micro-costing, hospital administrative data (PLICS) and health system (NHS) reference costs. We compared two different HRQoL instruments (CHU-9D and EQ-5D-5L) in terms of data completeness and sensitivity to change over time, including potential ceiling effects. We also explored how the timing of data collection and duration of the analysis could affect QALYs (Quality Adjusted Life Years) and the results of the cost-utility analysis (CUA) within the future RCT. RESULTS: Using a micro-costing approach, the total per treatment costs were in alignment with hospital administrative data (PLICS). Average health system reference cost data (macro-costing using NHS costs) could potentially underestimate these treatment costs, particularly for non-operative treatment. Costs incurred following hospital discharge in the primary care setting were minimal, and limited family borne costs were reported by parents/carers. While both HRQoL instruments performed relatively well, our results highlight the problem of ceiling effect and the importance of the timing of data collection and the duration of the analysis in any future assessment using QALYs and CUA. CONCLUSIONS: We highlighted the importance of obtaining accurate individual-patient cost data when conducting economic evaluations. Our results suggest that timing of data collection and duration of the assessment are important considerations when evaluating cost-effectiveness and reporting cost per QALY. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435.

Outcomes 1 year after non-operative management of uncomplicated appendicitis in children: Children with AppendicitiS during the CoronAvirus panDEmic (CASCADE) study.

BACKGROUND: A major shift in treatment of appendicitis occurred early in the SARS-CoV-2 pandemic with non-operative management used commonly outside research protocols and in units with limited previous experience. This study aims to compare real-world outcomes of surgery versus non-operative management of uncomplicated appendicitis in children with 1-year follow-up. METHOD: A prospective multicentre observational study of children treated for uncomplicated appendicitis at 74 hospitals in the UK and Ireland from 1 April to 31 July 2020 was performed. Propensity-score matched analysis was conducted using age, sex, C-reactive protein at diagnosis and duration of symptoms as covariates. Primary outcomes were success of non-operative management defined as achieving 1-year follow-up without undergoing appendicectomy due to recurrent appendicitis or ongoing symptoms, and occurrence of any predefined complication (intra-abdominal collection, wound infection, bowel obstruction or reintervention). RESULTS: Of 1464 children with presumed uncomplicated appendicitis, 1027 (70.2 per cent) underwent surgery and 437 (29.9 per cent) underwent non-operative management. Ninety-four children (21.5 per cent) treated by initial non-operative management required appendicectomy during the index hospital admission while recurrent appendicitis after discharge occurred in 25 (10.4 per cent) children within 1 year. The overall success rate of non-operative management at 1 year was 63.1 per cent (95 per cent c.i. 58.0 to 68.3 per cent). For propensity-score matched analyses, 688 children undergoing surgery and 307 undergoing non-operative management were included. Any predefined complication occurred in 50 (7.3 per cent) children undergoing surgery and in four (1.3 per cent) children undergoing non-operative management (OR 5.9 (95 per cent c.i. 2.1 to 16.6)) in the propensity-score matched cohort. There was no mortality or stoma formation. CONCLUSION: Non-operative management is a safe and valid alternative to appendicectomy in children with uncomplicated appendicitis.

Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis.

Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis.