Background Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo‐obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. Methods Children referred with suspected PIPO between April 2012‐December 2019 who underwent both ADM and full‐thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. Results Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non‐PIPO diagnoses. Twenty‐three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro‐myopathy, and 10 non‐specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (ϰ = 0.068; p = 0.197), whereas the latter significantly correlated with enhanced ADM analysis (ϰ = 0.191; p = 0.003). The enhanced ADM score was significantly higher in PIPO versus non‐PIPO (16.0 vs. 8.0; p < 0.001). Conclusions As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non‐PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations.

From 1994 to 2012, the age at onset of thelarche and menarche of girls in Hat-Yai municipality declined by 0.2 and 0.3 years, respectively. The earlier age at onset of puberty had no effect on final adult height.

Objectives: In Wilson disease (WD), 24-hour urinary copper excretion (UCE) is recommended to be used for diagnosis. It may be a useful tool to assess the efficacy of treatment during follow-up; however, there are limited data regarding the cutoff value of 24-hour UCE during follow-up in children. Therefore, we aim to evaluate the clinical use of 24-hour UCE during follow-up in children with WD. Patients and Methods: Medical records of children diagnosed with WD at Kings’ College Hospital from 2005 to 2018 were retrospectively reviewed. The UCE, serum copper, and ceruloplasmin levels, tested during follow-up, were statistically analyzed. Results: Over the median duration of 7 years (range 1.4–14.4), 28 patients (age ranged 3.8–17.3 years) had UCE tests during follow-up. Of those, 21 patients had at least one 24-hour UCE test and 7 children had only spot UCE tests. In comparison with the level of 24-hour UCE collected at the first visit after penicillamine challenge test, the median excretion rate was significantly reduced over the follow-up period (P < 0.001), from 26.2 to 8.9 μmol/day following 1–2 years of therapy (P = 0.15), then reduced significantly to 2.2 μmol/day after 3–4 years (P = 0.009), and 5.6 μmol/day at >5 years of follow-up (P = 0.003). Conclusions: Our study suggests that within 1 year of treatment, the level of nonceruloplasmin-bound copper concentration (NCC) drops to <0.8 μmol/L. In the absence of progressive liver disease or signs of copper deficiency, 24-hour UCE decreases to ≤8 μmol/day and <6 μmol/day after 1 and 5 years of treatment, respectively.

Late allograft fibrosis in LT recipients can cause graft dysfunction and may result in re‐transplantation. TE is a non‐invasive tool for the assessment of liver fibrosis. We aimed to evaluate the prevalence of allograft fibrosis in pediatric LT recipients, identify factors associated with allograft fibrosis, and determine the diagnostic value of TE, compared to histology. All children who underwent LT for ≥3 years were included. TE was performed for LSM in all patients. LSM of ≥7.5 kPa was considered as abnormal and suggestive of allograft fibrosis. Percutaneous liver biopsy was performed when patients had abnormal LSM and/or abnormal LFTs. Histological fibrosis was diagnosed when METAVIR score ≥F1 or LAF scores ≥1. TE was performed in 43 patients and 14 (32.5%) had abnormal LSM suggestive of allograft fibrosis. Histological fibrosis was identified in 10 of the 15 patients (66.7%) who underwent percutaneous liver biopsy and associated findings included chronic active HBV infection (n = 3), and late acute rejection (n = 3). Multivariate analysis showed that graft age was significantly associated with allograft fibrosis (OR = 1.22, 95% CI: 1.05‐1.41, P = 0.01). In conclusion, late allograft fibrosis is common in children undergoing LT for ≥3 years and associated with graft age. HBV infection and late acute rejection are common associated findings. Abnormal TE and/or LFTs may guide physicians to consider liver biopsy for the detection of late allograft fibrosis in LT children.

The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal (GI) tract, is a vast, mesh-like network of neurons and glia embedded within the bowel wall. Through its complex circuitry and neuronal diversity, the ENS is capable of functioning autonomously but is modulated by inputs from the central nervous system (CNS). The communication between the ENS and CNS is bidirectional and, together with crosstalk of these systems with microbiota housed within the GI tract, underpins the so-called microbiota-gut-brain axis. The ENS functions as a master regulator and coordinates many of the essential functions of the body, including GI motility, sensation and secretion. It is also capable of interacting with other cells, including intestinal epithelial, neuroendocrine and immune cells, to regulate their development as well as structural and functional integrity. Disruption of these ENS interactions, especially during early life, is likely to contribute to the aetiopathogenesis of disorders of the GI tract as well as elsewhere in the body, including neurodegenerative diseases. In this article, we highlight recent advances in our understanding of the roles of the ENS, especially in its complex and reciprocal interactions that influence GI motility, sensation, intestinal epithelial integrity, immunity and neuroendocrine function, particularly focusing on the influence of the ENS in early life and early life programming.

Neuronal nitric oxide synthase (nNOS) neurons play a fundamental role in inhibitory neurotransmission, within the enteric nervous system (ENS), and in the establishment of gut motility patterns. Clinically, loss or disruption of nNOS neurons has been shown in a range of enteric neuropathies. However, the effects of nNOS loss on the composition and structure of the ENS remain poorly understood. The aim of this study was to assess the structural and transcriptional consequences of loss of nNOS neurons within the murine ENS. Expression analysis demonstrated compensatory transcriptional upregulation of pan neuronal and inhibitory neuronal subtype targets within the Nos1−/− colon, compared to control C57BL/6J mice. Conventional confocal imaging; combined with novel machine learning approaches, and automated computational analysis, revealed increased interconnectivity within the Nos1−/− ENS, compared to age-matched control mice, with increases in network density, neural projections and neuronal branching. These findings provide the first direct evidence of structural and molecular remodelling of the ENS, upon loss of nNOS signalling. Further, we demonstrate the utility of machine learning approaches, and automated computational image analysis, in revealing previously undetected; yet potentially clinically relevant, changes in ENS structure which could provide improved understanding of pathological mechanisms across a host of enteric neuropathies.

PurposeFunctional constipation (FC) is a common gastrointestinal (GI) problem affecting children's well-being and quality of life. Although polyethylene glycol (PEG) is recommended as the first line therapy, it is not always applicable in lower socioeconomic populations. Hence, this study aimed to compare clinical courses of FC in children treated with different medications in order to identify prognostic factors related to treatment outcomes.MethodsWe reviewed the medical records of patients aged ≤15 years diagnosed with FC according to the Rome IV criteria from 2007 to 2015 at the GI clinic, Songklanagarind Hospital. Baseline characteristic, medical history, and treatment outcomes were collected at first and subsequent visits.ResultsExactly 104 patients (median age at diagnosis, 2.8 years) were diagnosed with FC. The number of follow-up visits per patient ranged from 1 to 35. The median duration of follow-up was 18.0 months (range, 6.0–84.2 months). PEG was given to 21% of patients. During the follow up period, 76% of patients experienced first recovery with a median time to recovery of 9.8 months. There were no significant differences in time until first recovery and relapse between patients who received and those who did not receive PEG (p=0.99 and 0.06, respectively). Age >6 years, normal defecation frequency, no history of cow's milk protein allergy, and use of laxatives were associated with successful outcomes.ConclusionTreatment outcomes between patients who had and never had PEG demonstrated no significant difference in our study. Hence, current practices in laxative prescriptive patterns may be effective.

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