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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Liver X receptor (LXR) agonists slow atherogenesis, but cause hepatic steatosis and dysfunction in part by increasing expression of sterol regulatory element binding protein 1-c (SREBP1-c), a ...transcription factor that upregulates fatty acid (FA) synthesis. n−3 FAs decrease hepatic FA synthesis by down-regulating SREBP1-c. To test the hypothesis that n−3 FAs decrease hepatic steatosis in mice given LXR agonist, C57BL/6 mice received daily gavage of an LXR agonist T0901317 (LXR
T) or vehicle for 4
weeks with concomitant intakes chow or high-fat diets enriched in saturated fat (SAT) or n−3 fat (n−3). Mice on LXR
T and SAT developed hepatomegaly with a large increase in size and number of hepatic lipid droplets; an n−3 diet reduced liver weight/body weight with decreased hepatic steatosis and triglyceride levels. Effects of n−3 diet on hepatic lipogenesis were linked to a blunting of LXR
T upregulation of hepatic SREBP1-c and FA synthase mRNA. n−3 diets also normalized LXR
T-mediated increases of plasma ALT and AST levels, whereas SAT diet increased these markers.
Conclusion: These studies suggest that n−3 FAs when given together with LXR agonists have the potential to improve both hepatic steatosis and hepatotoxicity in humans that might receive LXR agonists to decrease risk of atherosclerosis.
► LXR agonist and saturated fat ingestion lead to hepatic steatosis and dysfunction. ► n−3 fatty acids decrease LXR agonist-mediated hepatic steatosis. ► This is linked to decreasing hepatic SREBP-1c and fatty acid synthase mRNA. ► n−3 diet also normalizes LXR agonist-mediated increases of hepatotoxicity.
Objectives
Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption. Homozygous DGAT1 ...deficiency often presents with severe diarrhea and protein‐losing enteropathy (PLE) in the 1st weeks of life. Because severe restriction of fat intake controls diarrhea and decreases PLE, total parenteral nutrition (TPN) was the initial standard therapy in infants and children. We present tertiary center experience managing infants and children with DGAT1 deficiency resulting in the development of a nutritional approach that minimizes the use of TPN.
Methods
From 2014 to 2020, 12 infants with DGAT1 deficiency were treated. Stool output, growth, and development, as well as essential fatty acid status, were monitored. This retrospective experience formed the basis for treatment recommendations, which include an ultralow fat formula with intermittent peripheral intravenous lipid infusions during the 1st year of life.
Results
All patients with prolonged intestinal fat exposure had PLE, which resolved when treated with the nutrition protocol. Essential fatty acid status as measured by triene:tetraene ratios normalized in all treated patients. Over time, early genetic diagnosis and prompt initiation of an ultralow fat diet with peripheral intravenous lipid infusions replaced the need for TPN.
Conclusions
Children with DGAT1 deficiency respond to dietary restriction of lipids. Management with a novel nutritional approach provides effective treatment for infants with DGAT1 deficiency, treats diarrhea and PLE, promotes growth and development, avoids TPN dependency, and decreases the potential for essential fatty acid deficiency.
What is Known
Homozygous DGAT1 deficiency causes congenital diarrhea/intestinal failure associated with protein‐losing enteropathy.
Affected infants are often dependent on total parenteral nutrition (TPN) in early life.
What is New
DGAT1 deficient patients treated with ultra‐low‐fat formula and periodic peripheral intravenous lipid supplementation maintained normal growth and development.
Triene:tetraene ratios were consistent with essential fatty acid status.
In infants with DGAT1 deficiency, ultra‐low‐fat formula coupled with periodic peripheral intravenous lipid supplementation prevents the need for prolonged TPN, while maintaining adequate growth and essential fatty acid status as well as achieving enteral autonomy.
Celiac disease (CD), an immune-mediated enteropathy, has a clinical spectrum that is remarkably wide and includes neuropsychiatric manifestations. While studies of adults have shown sleep ...disturbances, there is limited data in children. Our objectives were to assess the association between sleep disturbances and CD in children, and the effect of a gluten-free diet.
Parents of children 3-12 years old referred for endoscopy completed the Sleep Disturbance Scale for Children and modified Epworth Sleepiness Scale. Children with CD were compared with healthy controls and children with abdominal pain but no definitive findings on investigation. Parents of children with CD and abdominal pain were contacted after 6 months for follow-up.
We enrolled 101 patients, mean age 6.5 (2.8), 51% female, 38 with CD, 18 abdominal pain, and 45 healthy. Sleep Disturbance Scale for Children scores were 37.4 (8.7), 41.3 (11.3), and 45.4 (13.7) in healthy controls, CD, and abdominal pain, respectively (
= .024). There was a significant difference in the disorders of arousal domain (
= .044). There were no significant differences on the modified Epworth Sleepiness Scale. A trend toward improvement in Sleep Disturbance Scale for Children scores was seen in children with CD presenting with abdominal pain after 6 months on a gluten-free diet (
= .07).
In this first prospective study of sleep disturbances in children with CD, we show high rates of disturbed sleep compared with healthy children. Sleep disturbances did not improve on a gluten-free diet and may be driven by abdominal pain.
Reiter J, Abuelhija H, Slae M, et al. Sleep disorders in children with celiac disease: a prospective study.
. 2023;19(3):591-594.
To examine whether patients with non-infectious uveitis (NIU) are at increased risk for celiac disease (CeD).
Celiac antibody testing was completed in 112 patients. The control group included ...patients who had undergone upper endoscopy for suspicion of CeD.
2/112 (1.79%) of patients with NIU had positive anti-tTG serology and CeD was confirmed in both patients. When compared to the expected risk of CeD in the general Israeli population of 0.31%, this corresponded to an odds ratio of 5.77 (95% CI 1.4118 to 23.4737,
= 0.049). Three additional patients had positive serology for CeD but the diagnosis was not confirmed.
An increased risk of CeD was detected in patients with NIU. We therefore recommend screening for CeD in NIU patients. Larger prospective studies are required to further validate these results.
Childhood cases of cyanoacrylates generally do not cause moderate or severe gastrointestinal complications. We report the case of a 3-year-old boy referred to our pediatric emergency room and ...admitted to the pediatric department with signs of upper gastrointestinal obstruction that required invasive intervention. Although it is rare, cyanoacrylate ingestion may injure esophageal and gastric mucosa in the pediatric population.
To characterize the clinical manifestations, outcomes, and complications of hijab pin ingestion in adolescents and to identify risk factors for a need for intervention.
A retrospective review of ...patients <25 years of age who presented to our emergency department because of hijab pin ingestion between 2007 and 2018. Comparison was performed between impaled and nonimpaled pins.
We reviewed 1558 foreign-body ingestion cases. Of these, 208 (13.3%) patients presented because of hijab pin ingestion, with a total of 225 ingested pins. The mean patient age was 14.7 ± 4.1 years, and 88% of patients were girls. Time from ingestion to presentation was 24 ± 49.5 hours. Most pins were located in the stomach (46.6%), and 18.6% of all pins were impaled. Location in the stomach (odds ratio = 4.3 95% confidence interval: 1.9-9.2;
< .001) and abdominal tenderness on examination (odds ratio = 2.7 95% confidence interval: 1.3-5.6;
= .007) were strong independent risk factors for an impaled pin. Time to intervention was 22.9 hours, and 41 endoscopies were performed. One patient required laparoscopic surgery. No complications were observed.
The hijab pin is an increasingly encountered foreign body in pediatric practice. Its specific clinical features distinguish it from other sharp objects. A delayed interventional approach in selected patients does not carry a higher risk of complications and results in significantly fewer interventions compared to existing guidelines. These findings will help guide pediatric specialists in this prevalent clinical scenario. Management recommendations are proposed.
Reports of vitiligo associated with metastases and rare cases of spontaneous regression of disease have fueled enthusiasm for immunologic approaches to the treatment of advanced melanoma. More recent ...strategies have focused on using antigen-presenting dendritic cells as vaccines.
We observed 3 cases of leukoderma associated with a novel adenovirus-mediated gp100/MART-1-transduced dendritic cell (MART indicates melanoma antigen recognized by T cells). All 3 patients had advanced metastatic melanoma. Despite the development of this leukodermic response, all patients experienced disease progression while under treatment.
We provide the initial evidence for effective induction of a leukodermic response with a gp100/MART-1-transduced dendritic cell vaccine.
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