Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn’s disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a ...whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier.
We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestlé) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n = 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n = 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12.
Four patients withdrew from the study because of intolerance by 48 hours, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P = .002; odds ratio for tolerance of CDED and PEN, 13.92; 95% confidence interval CI 1.68–115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission vs 20 (59%) of 34 children given EEN (P = .38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given EEN and then PEN (P = .01; odds ratio for remission in children given CDED and PEN, 3.77; CI 1.34–10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria.
CDED plus PEN was better tolerated than EEN in children with mild to moderate CD. Both diets were effective in inducing remission by week 6. The combination CDED plus PEN induced sustained remission in a significantly higher proportion of patients than EEN, and produced changes in the fecal microbiome associated with remission. These data support use of CDED plus PEN to induce remission in children with CD. Clinicaltrials.gov no: NCT01728870.
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Cell cell communication, which enables cells to coordinate their activity and is essential for growth, development and function, is usually ascribed a chemical or electrical origin. However, cells ...can exert forces and respond to environment elasticity and to mechanical deformations created by their neighbours113. The extent to which this mechanosensing ability facilitates intercellular communication remains unclear. Here we demonstrate mechanical communication between cells directly for the rst time, providing evidence for a long-range interaction that induces long-lasting alterations in interacting cells. We show that an isolated cardiac cell can be trained to beat at a given frequency by mechanically stimulating the underlying substrate. Deformations are induced using an oscillatory mechanical probe that mimics the deformations generated by a beating neighbouring cardiac cell. Unlike electrical eld stimulation, the probe-induced beating rate is maintained by the cell for an hour after the stimulation stops, implying that long-term modications occur within the cell. These long-term alterations provide a mechanism for cells that communicate mechanically to be less variable in their electromechanical delay. Mechanical coupling between cells therefore ensures that the final outcome of action potential pacing is synchronized beating. We further show that the contractile machinery is essential for mechanical communication.
Objective
To investigate the effectiveness of low‐dose aspirin (LDA) in the prevention of pre‐eclampsia (PE) among otherwise low‐risk twin gestations.
Methods
A historical cohort study consisting of ...all pregnant individuals with dichorionic diamniotic (DCDA) twin pregnancy who delivered between 2014 and 2020. Patients treated with LDA were matched by a 1:4 ratio to individuals who were not treated with LDA by age, body mass index and parity.
Results
During the study period, 2271 individuals carrying DCDA pregnancies delivered at our center. Of these, 404 were excluded for one or more additional major risk factors. The remaining cohort consisted of 1867 individuals of whom 142 (7.6%) were treated with LDA and were compared with a 1:4 matched group of 568 individuals who were not treated. The rate of preterm PE did not differ significantly between the two groups (18 12.7% in the LDA group vs. 55 9.7% in the no‐LDA group; P = 0.294, adjusted odds ratio 1.36, 95% confidence interval 0.77–2.40). There were no other significant between‐group differences.
Conclusions
Low‐dose aspirin treatment in pregnant individuals with DCDA twin gestations without additional major risk factors was not associated with a reduction in the rate of preterm PE.
Synopsis
Low‐dose aspirin treatment in twin gestations without additional major risk factors was not associated with a reduction in the rate of preterm pre‐eclampsia.
Neutrophil extracellular traps (NETs) are fibers composed of chromatin and neutrophil proteins released by activated neutrophils. NETs trap and kill microbes, activate dendritic and T cells, and are ...implicated in autoimmune and vascular diseases. The pathogenesis of inflammatory bowel disease (IBD) is multifactorial and characterized by chronic active mucosal inflammation with controversial contribution of neutrophils. Our aim is to describe the involvement of NETs in pediatric IBD. We retrospectively examined biopsies from the small bowel and colon of children at diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). The biopsies were labeled for neutrophil elastase, myeloperoxidase, DNA, chromatin and histones in order to identify NETs. Samples of two children with normal colonoscopy served as controls. Twelve patients (5 boys) were included, 6 with CD and 6 with UC. Their average age was 12.2 years (range 5–16). NETs were found in all samples from patients and not in the samples from the two controls. This is the first demonstration of the presence of NETs in biopsies taken from the small bowel and colon of pediatric patients with IBD. More studies are needed in order to identify the role of NETs in CD/UC pathogenesis.
Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on ...hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD.
Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months.
Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index BMI 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis (P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis (P = 0.001).
Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population.
TRN NCT04561804 (9/17/2020).
The US Multi-Society Task Force on Colorectal Cancer, with invited experts, developed a consensus statement and recommendations to assist health care providers with appropriate management of patients ...with biallelic mismatch repair deficiency (BMMRD) syndrome, also called constitutional mismatch repair deficiency syndrome. This position paper outlines what is known about BMMRD, the unique genetic and clinical aspects of the disease, and reviews the current management approaches to this disorder. This article represents a starting point from which diagnostic and management decisions can undergo rigorous testing for efficacy. There is a lack of strong evidence and a requirement for further research. Nevertheless, providers need direction on how to recognize and care for BMMRD patients today. In addition to identifying areas of research, this article provides guidance for surveillance and management. The major challenge is that BMMRD is rare, limiting the ability to accumulate unbiased data and develop controlled prospective trials. The formation of effective international consortia that collaborate and share data is proposed to accelerate our understanding of this disease.
Knowledge and understanding of risk mechanisms associated with pediatric feeding disorder (PFD) remain limited. We aimed to investigate factors associated with PFD and their relation to specific PFD ...types according to the recent consensus WHO-based definition. We retrospectively reviewed the medical records of children with PFD and retrieved their demographic and clinical characteristics. Healthy age- and sex-matched children served as controls. Included were 254 children with PFD median (interquartile range) age 16.4 (9.5-33) months at diagnosis and 108 children in the control group median age 24.85 (14.5-28.5) months. According to the WHO-based definition, disturbances in oral intake were predominantly related to nutritional dysfunction in 118 (46.6%), feeding skill dysfunction in 83 (32.3%), medical conditions in 42 (16.7%) and psychosocial dysfunction in 11 (4.4%). In multivariate analysis, children with PFD had a higher risk for lower socioeconomic background (P < 0.01) and low birth weight (26.8% compared to 7.4%, P < 0.001). Moreover, significantly fewer children in the PFD group were breastfed (75% versus 89%, P = 0.003). There were no significant differences in any of those variables between PFD types. In conclusion, low socioeconomic status, lack of breastfeeding, and low birth weight were significantly more frequent in children with PFD. PDF manifest as multiple dysfunctions, thus highlighting the need to offer these children and their families multidisciplinary care.
The effect of biologic therapy on the incidence of inflammatory bowel disease (IBD)-related hospitalizations is controversial. The high efficacy of biologic agents is weighted against potential ...therapy-related adverse events, however, there are no data on the effect of biologic therapy on the indications for hospitalization in IBD. We aimed to evaluate the impact of biologic therapy on the indications and rate of hospitalization in pediatric IBD.
This retrospective cohort study included all children (< 18 years of age) with IBD who were hospitalized in our medical center from January 2004 to December 2019. Data on demographics, disease characteristics and course, and therapy were collected, as were the indications for and course of hospitalizations. We evaluated the relationship between therapy with biologic agents, indications and rates of hospitalization.
Included were 218 hospitalizations of 100 children, of whom 65 (65%) had Crohn's disease and 35 (35%) had ulcerative colitis. The indications for hospitalization were IBD exacerbations or complications in 194 (89%) and therapy-related adverse events in 24 (11%). The patients of 56 (25.7%) hospitalizations were receiving biologic therapy. In a multivariate analysis, no correlation between therapy and indication for hospitalization was found (p = 0.829). Among children under biologic therapy, a decrease in the rate of hospitalizations from 1.09 (0.11-3.33) to 0.27 (0-0.47) per year was observed for patients that were hospitalized during 2016-2019 (p = 0.043).
Biologic therapy did not influence the indication for hospitalization, but were associated with a decrease in the rate of hospitalization during 2016-2019 in pediatric IBD.
Aim
Understanding the association between pediatric feeding disorder (PFD) and age of presentation is limited. We aimed to investigate factors associated with PFD among different age groups.
Methods
...Retrospective analysis of medical records of infants and toddlers diagnosed with PFD, according to the World Health Organization‐based definition. We compared children aged 1–12 months to those aged 13–72 months.
Results
Included were 253 children with PFD (median interquartile range age 16.4 9.5–33 months at diagnosis, 56% boys). Significantly more children in the younger age group were girls (52.6% vs. 34.4%, respectively, p = .03) and preterm (25% vs. 14%, p = .03). They had more hospitalizations (34% vs. 23%, p = .03) and needed more prescription medications (36% vs. 17%, p < .01). Additionally, disturbances in oral intake were primarily linked to feeding skills dysfunction in the younger group and nutritional dysfunction in the older group (39.6% vs. 23.7% and 55% vs. 38%, respectively, p = .02).
Conclusions
Infants under 1 year old with PFD represent a distinct patient group with unique characteristics and outcomes. The age of presentation plays a significant role in children with PFD, necessitating tailored treatment strategies.
This is a retrospective analysis of medical records of infants and toddlers diagnosed with pediatric feeding disorder (PFD), according to the World Health Organization‐based definition. Significantly more children in the younger age group (1–12 months) were born preterm. They had more hospitalizations and needed more prescription medications. Additionally, disturbances in oral intake were primarily linked to feeding skills dysfunction in the younger group and nutritional dysfunction in the older group (13–72 months). Further longitudinal studies are needed in order to better assess the outcome of specific therapeutic modalities among children of different ages who are diagnosed with PFD.
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