Rachel Harwood

Background: Achalasia is rare disease in children and young people (CYP) that causes significant symptoms and often requires invasive interventions. There is currently no consensus on the optimal management strategy. This study investigated the current management and outcomes of CYP with achalasia in the UK. Methods: A retrospective study was conducted of CYP (aged ≤ 16 years) diagnosed with achalasia between 2011 and 2021 in the UK. The study was co-designed with the patient group Achalasia Action. Data were collected from patient records. The primary outcome was treatment success. Results: In all, 126 patients were included from 13 UK centres; 64 of the patients (50.8%) were male and the median age at diagnosis was 12 (interquartile range (i.q.r.) 9–14) years. The most frequent presenting features were dysphagia (73.8%), vomiting (53.2%), and weight loss (38.9%). The median time from symptom onset to diagnosis was 11 (i.q.r. 6–24) months. Treatment success was achieved in 55 of 120 patients (45.8%) after first-line intervention. Heller’s cardiomyotomy (HCM) as the first-line intervention had a higher success rate than endoscopic balloon dilatation (EBD; (52 of 72 (72%) versus 3 of 48 (6%), respectively; P < 0.001). However, overall HCM had a higher frequency of complications than EBD (17 of 98 (17%) versus 3 of 57 (5%), respectively; P = 0.045). In the entire cohort, 53% of patients reported symptoms at the 1-year follow-up. Conclusions: Variation exists in the management of CYP with achalasia in the UK. The highest rates of treatment success were associated with HCM. Many CYP remain symptomatic after treatment and require multiple interventions. The present data can be used to inform management decisions in CYP with achalasia.

Plasma indoxyl sulfate (IS) and its clearance correlate better with tubular injury markers (Kim-1, NGAL) than filtration markers (GFR, creatinine) in chronic nephrectomy rats and chronic/acute ischemic injury (IRI) in mice. Mass spectrometry imaging showed higher cortical but lower medullary IS accumulation in mice, in which proximal tubular transporters were downregulated. In vitro organic anion transporter 1-mediated IS transport decreased post-IRI. Together, plasma IS and its clearance may be used as kidney tubular function markers.

Objective To investigate SARS-CoV-2 vaccine uptake and effectiveness in children and young people (CYP) with life-limiting neurodisability. Design We undertook a retrospective cohort study using national hospital data in England from 21 December 2020 to 2 September 2022 to describe SARS-CoV-2 vaccination uptake, and then examined COVID-19 hospitalisation, paediatric intensive care unit (PICU) admission and death following SARS-CoV-2 infection by vaccination status using Cox regression models. Patients CYP aged 5–17 with life-limiting neurodisability. Results We identified 38 067 CYP with life-limiting neurodisability; 13 311 (35.0%) received at least one SARS-CoV-2 vaccine, with uptake higher among older, white CYP, from less deprived neighbourhoods. Of 8134 CYP followed up after a positive SARS-CoV-2 test, 1547 (19%) were vaccinated. Within 28 days of infection, 309 (4.7%) unvaccinated CYP were hospitalised with COVID-19 compared with 75 (4.8%) vaccinated CYP. Of 46 (0.7%) unvaccinated CYP were admitted to PICU compared with 10 (0.6%) vaccinated CYP. Of 20 CYP died within 28 days of SARS-CoV-2 infection, of which 13 were unvaccinated. Overall, adjusted hazard of hospitalisation for COVID-19 or admission to PICU did not vary by vaccination status. When the Alpha-Delta SARS-CoV-2 variants were dominant, hazard of hospitalisation with COVID-19 was significantly lower among vaccinated CYP (HR 0.26 (0.09 to 0.74)), with no difference seen during Omicron (HR 1.16 (0.74 to 1.81)). Conclusions SARS-CoV-2 vaccination was protective of COVID-19 hospitalisation among CYP with life-limiting neurodisability during Alpha-Delta, but not for other SARS-CoV-2 variants. Vaccine uptake was low and varied by ethnicity and deprivation.

Objective To describe the COVID-19 pandemic’s impact on acute appendicitis management on children and young people (CYP). Design Retrospective cohort study. Setting All English National Health Service hospitals. Patients Acute appendicitis admissions (all, simple, complex) by CYP (under-5s, 5–9s, 10–24s). Exposure Study pandemic period: February 2020–March 2021. Comparator pre-pandemic period: February 2015–January 2020. Main outcome measures Monthly appendicectomy and laparoscopic appendicectomy rate trends and absolute differences between pandemic month and the pre-pandemic average. Proportions of appendicitis admissions comprising complex appendicitis by hospital with or without specialist paediatric centres were compared. Results 101 462 acute appendicitis admissions were analysed. Appendicectomy rates fell most in April 2020 for the 5–9s (−18.4% (95% CI −26.8% to −10.0%)) and 10–24s (−28.4% (−38.9% to −18.0%)), driven by reductions in appendicectomies for simple appendicitis. This was equivalent to −54 procedures (−68.4 to −39.6) and −512 (−555.9 to −467.3) for the 5–9s and 10–24s, respectively. Laparoscopic appendicectomies fell in April 2020 for the 5–9s (−15.5% (−23.2% to −7.8%)) and 10–24s (−44.8% (−57.9% to −31.6%) across all types, which was equivalent to −43 (−56.1 to 30.3) and −643 (−692.5 to −593.1) procedures for the 5–9s and 10–24s, respectively. A larger proportion of complex appendicitis admissions were treated within trusts with specialist paediatric centres during the pandemic. Conclusions For CYP across English hospitals, a sharp recovery followed a steep reduction in appendicectomy rates in April 2020, due to concerns with COVID-19 transmission. This builds on smaller-sized studies reporting the immediate short-term impacts.

This study focuses on ischaemia-reperfusion injury (IRI) in kidneys, a cause of acute kidney injury (AKI) and end-stage kidney disease (ESKD). Traditional kidney damage assessment methods are semi-quantitative and subjective. This study aims to use a convolutional neural network (CNN) to segment murine kidney structures after IRI, quantify damage via CNN-generated pathological measurements, and compare this to conventional scoring. The CNN was able to accurately segment the different pathological classes, such as Intratubular casts and Tubular necrosis, with an F1 score of over 0.75. Some classes, such as Glomeruli and Proximal tubules, had even higher statistical values with F1 scores over 0.90. The scoring generated based on the segmentation approach statistically correlated with the semiquantitative assessment (Spearman’s rank correlation coefficient=0.94). The heatmap approach localised the intratubular necrosis mainly in the outer stripe of the outer medulla, while the tubular casts were also present in more superficial or deeper portions of the cortex and medullary areas. This study presents a CNN model capable of segmenting multiple classes of interest, including acute IRI-specific pathological changes, in a whole mouse kidney section and can provide insights into the distribution of pathological classes within the whole mouse kidney section.

Objective: A recent publication has suggested that expedited time to theater in gastroschisis results in higher rates of primary closure and decreases the length of stay (LOS). This study primarily aims to assess the impact of time to first management of neonates with gastroschisis on the LOS. Methods: Neonates admitted between August 2013 and August 2020 with gastroschisis were included. Data were collected retrospectively, and neonates with complex gastroschisis were excluded. Variables including gestation, birth weight, time of first management, primary/delayed closure and use of patch were evaluated as possible confounding variables. The outcome measures were time to full feeds, time on parenteral nutrition (PN) and LOS. Univariate and multivariate linear regression analyses were performed. P2=0.00, p=0.82) but did demonstrate a consistent positive association between time to first feed and LOS and delayed closure, resulting in a longer time to full feeds and a longer time on PN. Conclusions: The time to first management was not associated with a change in LOS in these data. Further prospective evaluation of the impact of reducing the time to first feed on the LOS is recommended. Level of evidence: IV.

Introduction: Feeding difficulties are common and multifactorial in children with Fibroblast Growth Factor Receptor-2 (FGFR-2) mutations. Intestinal rotation anomalies have been demonstrated to occur more frequently in animals with FGFR-2 mutations. This study aims to describe intestinal rotation anomalies, surgical management, and feeding assistance in children with FGFR-2 mutations who have undergone upper gastrointestinal (UGI) contrast studies. Methods: Retrospective data were collected of children born between 1988 and 2020 in a UK quaternary craniofacial unit with FGFR-2–associated craniosynostosis. A consultant survey of approach to malrotation was undertaken. Results: Thirty-four children were included, 17 (50%) female. Six (18%) had UGI symptoms, which included bilious vomiting (n=2), nonbilious vomiting (n=5), retching (n=1), feed intolerance (n=3), and failure to thrive (n=3). Nine had a gastrostomy in situ. Intestinal rotation anomalies occurred in 4 (12%) children, 3 of whom underwent a Ladd procedure and two third required gastrojejunal feeding postoperatively. Consultants agreed that all children with FGFR-2 mutation and UGI symptoms should undergo UGI contrast study, as should children requiring a gastrostomy. Discussion: Intestinal rotation anomalies in children with FGFR-2 mutations occur more frequently than the general population. Prompt consideration of UGI contrast in symptomatic children with FGFR-2 mutation is recommended to enable early surgical management of children with malrotation.