A case series of successfully managing exomphalos major with awake graduated compression dressing and early enteral feeding.

INTRODUCTION: Exomphalos anomaly is defined as the herniation of abdominal viscera into the base of the umbilical cord, with only a membranous sac covering these contents. It has an incidence of approximately 1 in 4000-6000 births. Management of exomphalos major (EM) remains controversial and limited, with very few studies to guide decision-making. METHOD: This is a case series of four neonates with EM treated at a tertiary paediatric referral centre between 2018 and 2021 with a gradual compression dressing technique. RESULTS: Four neonates were diagnosed with EM. The average gestational age was 38 + 5 (range 38 + 2 - 39 + 2), and the average birth weight was 3.1 kg (range 2.56 - 3.49 kg). The defect size ranged between 5 and 7 cm. All patients were commenced on gradual compression dressing between days 1 and 3 of life. Dressings were applied at the bedside in the general neonatal ward. The average time taken to reach full feeds was 1 week; only one patient required parenteral nutrition. Three underwent surgical repair at two and 16 weeks of age; one had delayed repair at the age of 1 year because of the COVID-19 pandemic. None required patch repair. None required prolonged ventilation after repair. CONCLUSION: This case series describes a successful compression dressing technique that reduces sac content without the need for general anaesthetic or respiratory compromise, whereby simultaneous enteral feeding is tolerated.

Port removal in patients receiving emicizumab prophylaxis: A single centre experience and review of the literature.

INTRODUCTION: Treatment of patients with Haemophilia A has improved significantly in recent years since the advent of novel therapeutic agents such as emicizumab. The low annualised bleeding rates associated with emicizumab have liberated many patients from the need for central venous access devices (CVAD). Optimal peri-operative management of CVAD removal is not currently known and there are no specific formal recommendations available. AIM: We reviewed outcomes in a paediatric cohort in our centre undergoing CVAD removal without pre-operative factor or bypassing agent and reviewed the literature regarding port removal in patients on Emicizumab. METHODS: Ten male patients with severe Haemophilia A underwent CVAD removal without planned administration of factor concentrate or bypassing agent. Patients were monitored in hospital for 24 h with routine laboratory testing pre- and post-operatively. RESULTS: No significant bleeding episodes occurred in any patient, no patient required factor concentrate or bypassing agent and no patients were readmitted due to bleeding within 7 days of surgery. CONCLUSION: We propose that, in the era of emicizumab, prophylactic factor administration pre-operatively for elective CVAD removal is not required in the majority of cases.

Nucleic acid cytokine responses in obese children and infants of obese mothers.

Almost a third of Irish children are now overweight and the country ranks 58th out of 200 countries for its proportion of overweight youths. With the rising obesity epidemic, and the impaired immune responses of this population, it is vital to understand the effects that obesity has on the immune system and to design future therapeutics, adjuvants and vaccines with overweight and obese populations in mind. Many current vaccines use adjuvants that have been found to be less effective at stimulating the immune response in children compared with adults and there is now substantial effort to design paediatric-focused adjuvants. Additionally, vaccine responses have been shown to be less effective in obese populations indicating that this is a particularly vulnerable population. We have recently identified cytosolic nucleic acids (CNAs), as novel candidate adjuvants for childhood vaccines. Here we investigated whether immune responses to these candidate adjuvants were adversely affected in infants born to overweight or obese mothers, and in overweight and obese children. Type I Interferon (IFN) and proinflammatory cytokines such as Tumor Necrosis Factor α (TNFα) are vital for driving innate and adaptive immune responses. We found that childhood obesity conferred no significant adverse effect on CNA-induced Type I IFN responses when compared with lean children. Similarly, Type I IFN responses were intact in the cord blood of babies delivered from overweight and obese mothers, when compared with lean mothers. There was also no significant impact of obesity on CNA-induced TNFα responses in children or from cord blood of infants born to overweight/obese mothers. In all cases, there was a tendency towards decreased production of innate cytokine Type I Interferon and TNFα, however there was no significant negative correlation. Interestingly, high maternal BMI showed weak and moderate positive correlation with IL-12p70 and IFNγ, respectively, in response to CNA stimulation. This study demonstrates that future adjuvants can be tailored for these populations through the use of activators of CNA sensors.

Correlation of enteric NADPH-d positive cell counts with the duration of incubation period in NADPH-d histochemistry.

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining can be used in the enteric nervous system to determine nitrergic neuronal counts, critical in motility disorders such as intestinal neuronal dysplasia and hypoganglionosis. The reported incubation periods of specimens with NADPH-d staining solution has varied from 2 to 24 h. The aim of this study is to investigate the impact of the incubation period on the overall NADPH-d positive cell counts in porcine rectal submucosal plexus. The submucosal plexus of rectal specimens from 12-week-old pigs (n = 5) were studied. Conventional frozen sections were used to identify nitrergic neurons while whole-mount preparations were used to quantify the effect of prolonged duration of incubation on positively identified ganglion cells with NADPH-d histochemistry. The same submucosal ganglia on the conventional sections, and a minimum of 12 ganglia per whole-mount preparation specimen were photographed sequentially at 2, 6, and 24 h and used to count the number of nitrergic cells per ganglion. The same staining solution was used throughout the experiment. Results were analysed using a one-way ANOVA test. Prolonged incubation with the staining solution revealed new NADPH-d positive cells in the ganglia on the conventional sections. The total number of neurons counted in the 12 adjacent ganglia in the whole-mount specimens was 180 +/- 55, the mean neuronal cell per ganglion was 15 +/- 8 after 2 h of incubation. This increased to 357 +/- 17, and to 29 +/- 12 after 6 h (p < 0.05). A further increase was observed of 515 +/- 19 and 43 +/- 17 after 24 h (p < 0.05). When the photomicrographs were retrospectively analysed, not even the outline of the neuronal cells that stained with prolonged incubation was evident at the earlier time points. NADPH-d positive cell counts increase in proportion to the duration of incubation in NADPH-d histochemistry. Comparative studies attempting to quantify nitrergic cell counts in dysmotility disorders must take into account the variability in NADPH-d positive cell count associated with prolonged incubation in NADPH-d histochemistry.

New insights into the neuromuscular anatomy of the ileocecal valve.

The neuroanatomy of the ileocecal valve (ICV) is poorly understood. A better understanding of this important functional component of the gastrointestinal tract would enable surgeons to reconstruct an effective valve following surgical resection of the ICV. ICVs were examined in young pigs (N = 5) using frontal and transverse paraffin embedded and frozen sections. Hematoxylin+Eosin (H+E) staining, acetylcholinesterase (AchE), and NADPH-diaphorase (NADPH-d) histochemistry and protein gene product 9.5 (PGP 9.5) and C-kit immunohistochemistry were performed. The H+E staining revealed that the ICV consists of three muscle layers: an external circular muscle layer continuous with that of the ileal circular muscle layer, an inner circular muscle layer continuous with that of the cecal circular muscle layer, and a single longitudinal muscle layer, which appears to be secondary to a fusion of the ileal and cecal longitudinal muscle layers. The AchE, NADPH-d, and PGP 9.5 staining revealed two distinct coaxial myenteric plexuses, together with superficial and deep submucosal plexuses. The C-kit immunostaining showed a continuous myenteric ICC network within the ICV. The structure of the neuromuscular components within the ICV suggests that the valve is a result of a simple intussusception of the terminal ileum into the cecum. This knowledge may help surgeons in their future attempts at reconstructing more anatomically and functionally suitable ICVs following surgical resection of native ICVs.

New hypothesis on the pathogenesis of ileocecal intussusception.

PURPOSE: Ileocecal intussusception is a relatively common surgical emergency in infants and young children. The etiology of intussusception is not clearly understood. Nitric oxide (NO) is a major inhibitory neurotransmitter in the enteric nervous system, which causes relaxation of the smooth muscles. In a lipopolysaccharide-induced experimental model of intussusception, altered intestinal motility is shown to be the result of increased NO released from various inflammatory mediators, which in turn leads to increased incidence of intussusception. The aim of this study was to examine the age-related changes in the nitrergic innervation of the ileocecal valve (ICV) to gain insights into the pathogenesis of intussusception. METHOD: Whole-mount preparations of the myenteric plexus from the ileum, ICV, and proximal colon were stained using NADPH diaphorase histochemistry in newborn piglets (n = 3), 4-week-old (n = 3), 12-week-old (n = 3), and adult pigs (n = 3). Using light microscopy, the number of ganglia per square centimeter, the number of cells per ganglion, and the number of ganglion cells per square centimeter were determined. RESULTS: There were striking regional and age-related differences in nitrergic innervation of myenteric plexus. Density of nitrergic neurons was significantly higher in the ICV than in the terminal ileum and proximal large bowel in the young animals (P < .001). CONCLUSION: These findings suggest that the inflammatory reactions that usually precede intussusception may cause overproduction of NO by the nitrergically hyperinnervated ICV causing relaxation of the ICV and thereby facilitating ileocecal intussusception.

The effect of age on colocalization of acetylcholinesterase and nicotinamide adenine dinucleotide phosphate diaphorase staining in enteric neurons in an experimental model.

PURPOSE: Cholinergic and nitrergic neurons form 2 main subpopulations of the myenteric neurons, and they have been the targets of detailed morphological investigations in bowel motility disorders. However, little is known regarding the colocalization of neurotransmitters within the same enteric neurons. The aim of this study was to determine the histochemical colocalization of cholinergic and nitrergic neurons in the porcine distal large bowel myenteric plexus from fetal to adulthood. METHODS: Distal large bowel specimens were taken from 6 randomly selected age groups (3 animals in each group) from midway of gestation to adulthood. The myenteric plexus was exposed using whole-mount technique. After nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) staining, cells per ganglion were counted. Then the specimens were stained with acetylcholinesterase (AChE), and the cells that were stained with individual enzymes and with both enzymes were counted. RESULTS: Colocalization of AChE and NADPH-d was seen in all age groups, and it was highest during the mid part of gestation (30%) and decreased steadily thereafter into adulthood (8%). The individual number of NADPH-d- and AChE-positive neurons per ganglion remained constant till 4 weeks of age and significantly increased thereafter into adulthood. CONCLUSION: The use of double-labeling histochemical technique shows for the first time the colocalization of cholinergic and nitrergic activity in a large population of enteric neurons in the late fetal and newborn period. Age-related loss of cholinergic and nitrergic colocalization in the myenteric plexus is most likely a maturational process.