Increased Risk of Celiac Disease in Patients with Uveitis.

PURPOSE: To examine whether patients with non-infectious uveitis (NIU) are at increased risk for celiac disease (CeD). METHODS: Celiac antibody testing was completed in 112 patients. The control group included patients who had undergone upper endoscopy for suspicion of CeD. RESULTS: 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, P = 0.049). Three additional patients had positive serology for CeD but the diagnosis was not confirmed. CONCLUSIONS: 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.

Sleep disorders in children with celiac disease: a prospective study.

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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 (P = .024). There was a significant difference in the disorders of arousal domain (P = .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 (P = .07). CONCLUSIONS: 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. CITATION: Reiter J, Abuelhija H, Slae M, et al. Sleep disorders in children with celiac disease: a prospective study. J Clin Sleep Med. 2023;19(3):591-594.

Endoscopic versus fluoroscopic esophageal dilatations in children with esophageal strictures: 10-year experience.

Esophageal strictures in children may cause dysphagia, choking during feeds, and failure to thrive. They can be treated by balloon dilatations, either under endoscopic or fluoroscopic guidance; there is no literature comparing the methods. Retrospective review of the medical records of children (0-18 years) who were treated with balloon dilatations between 2010 and 2020. The primary outcome was the number of dilatation sessions required until clinical success after 3 months. Secondary outcomes were long-term success at 12 months, and complications of bleeding and perforation. Forty-six patients underwent 174 dilatation sessions. Success rates in the endoscopy and fluoroscopy groups were similar: 62% versus 67% (p = 0.454) at 3 months and 57% versus 67% (p = 0.721) at 12 months. Complication rate was lower in the endoscopy group (0% vs. 15%, p < 0.001). Both endoscopic and radiologic-guided balloon dilatations were shown to be equally effective, but endoscopic guidance had fewer complications.

Tumor necrosis factor-α inhibitor-induced follicular psoriasiform eruption.

Tumor necrosis factor-α inhibitor-associated adverse cutaneous reactions are common in patients with inflammatory bowel disease. Infection-related dermatoses and psoriasiform eruptions are seen most frequently. We describe a follicular psoriasiform eruption that appeared during treatment with infliximab in two adolescents with Crohn's disease.

Efficacy and Outcomes of Faecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.

BACKGROUND: Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. METHODS: We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. RESULTS: A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. CONCLUSIONS: Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

The Relationship Between Self-Compassion, Concern for Others, and Parental Burnout in Child's Chronic Care Management.

OBJECTIVES: Parental burnout is a construct that reflects the exhaustion and emotional distancing of parents from their children due to the growing demands of caring for them. Research has pointed to a heightened risk for parental burnout among parents of children with special needs. Additional research has indicated that parents' personality traits and relational dynamics serve as resiliency factors regarding parental burnout. METHODS: In the present study, 91 primary parental caregivers of children receiving ongoing treatment at a pediatric ambulatory care unit were recruited. A theoretical model proposing the specific ways in which self-compassion and concern for others complement each other in predicting parental burnout was examined. In this model, the relationships between self-compassion, concern for others, and burnout respectively are mediated by different basic psychological needs, detailed in self-determination theory. Participants completed various questionnaires measuring these constructs. Regression and mediation analyses were used to examine our hypotheses. RESULTS: Results indicated that self-compassion and concern for others predicted levels of parental burnout. The covariance between concern for others and burnout was mediated by the psychological need of relatedness. CONCLUSIONS: The findings support the extension of a three-layered conceptual model of (a) self-compassion and concern for others, (b) psychological needs, and (c) burnout. The present study highlights self-compassion and concern for others as potential resilience factors regarding the risk of burnout in parental caregiving. These findings point to promising avenues for burnout prevention and preemptive facilitation of parental caregiving. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12671-021-01752-z.

Evaluation of gastrointestinal symptoms in pediatric patients post hematopoietic stem cell transplantation: Ileo-colonoscopy versus sigmoidoscopy. A single-center experience and review of literature.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a curative therapy used to treat high-risk hematological malignant disorders and other life-threatening nonmalignant diseases. Gastrointestinal (GI) symptoms post-HSCT might be due to GI graft-versus-host disease (GVHD) or GI infections or both. GI endoscopy with biopsies is safe and beneficial in guiding the management of GI symptoms in children after HSCT, justifying the therapeutic management and contributing to improved outcomes. METHODS: A retrospective cohort study including 16 children with malignant and nonmalignant diseases that underwent allogeneic HSCT who had 24 ileo-colonoscopies performed for GI symptoms. To facilitate an evidence-based approach to the endoscopic evaluation of GI symptoms in pediatric patients post HSCT, we examined whether a full ileo-colonoscopy, which includes right colon and terminal ileum (TI), as opposed to a limited sigmoidoscopy, was more accurate in the evaluation of GI symptoms in pediatric patients post HSCT. RESULTS: Specific findings on the right colon/TI were found in nine out of 24 ileo-colonoscopies (38%, CI = 19%-59%). The macroscopic findings on ileo-colonoscopy were compared with the histopathologic findings. When macroscopic findings were present, there were matching histopathologic findings in 100% of cases. However, even in the absence of any macroscopic findings on ileo-colonoscopy, there were histopathological findings in 29% of the cases (p-value = .016). CONCLUSIONS: This cohort favors ileo-colonoscopy over sigmoidoscopy, with systematic biopsy sampling, in evaluating GI symptoms in pediatric patients post HSCT.

Chronic demodicosis in patients with immune dysregulation: An unexpected infectious manifestation of Signal transducer and activator of transcription (STAT)1 gain-of-function.

Signal transducer and activator of transcription (STAT)1 heterozygous gain-of-function (GOF) mutations are known to induce immune dysregulation and chronic mucocutaneous candidiasis (CMCC). Previous reports suggest an association between demodicosis and STAT1 GOF. However, immune characterization of these patients is lacking. Here, we present a retrospective analysis of patients with immune dysregulation and STAT1 GOF who presented with facial and ocular demodicosis. In-depth immune phenotyping and functional studies were used to characterize the patients. We identified five patients (three males) from two non-consanguineous Jewish families. The mean age at presentation was 11.11 (range = 0.58-24) years. Clinical presentation included CMCC, chronic demodicosis and immune dysregulation in all patients. Whole-exome and Sanger sequencing revealed a novel heterozygous c.1386C>A; p.S462R STAT1 GOF mutation in four of the five patients. Immunophenotyping demonstrated increased phosphorylated signal transducer and activator of transcription in response to interferon-α stimuli in all patients. The patients also exhibited decreased T cell proliferation capacity and low counts of interleukin-17-producing T cells, as well as low forkhead box protein 3+ regulatory T cells. Specific antibody deficiency was noted in one patient. Treatment for demodicosis included topical ivermectin and metronidazole. Demodicosis may indicate an underlying primary immune deficiency and can be found in patients with STAT1 GOF. Thus, the management of patients with chronic demodicosis should include an immunogenetic evaluation.

Hijab Pin Ingestions.

OBJECTIVES: To characterize the clinical manifestations, outcomes, and complications of hijab pin ingestion in adolescents and to identify risk factors for a need for intervention. METHODS: 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. RESULTS: 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]; P < .001) and abdominal tenderness on examination (odds ratio = 2.7 [95% confidence interval: 1.3-5.6]; P = .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. CONCLUSIONS: 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.

Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.

Fecal Microbiomes in Premature Infants With and Without Parenteral Nutrition-Associated Cholestasis.

INTRODUCTION: Premature infants often require parenteral nutrition (PN) until they reach enteral autonomy which puts them at risk of developing PN-associated cholestasis (PNAC). We sought to compare longitudinal changes in fecal microbiomes of premature infants who developed PNAC versus those who did not despite being on similar PN doses. METHODS: Stool samples from premature infants (gestational age <30 weeks) who developed direct bilirubin ≥1.5 mg/dL while receiving PN were classified as precholestasis, cholestasis, or postcholestasis based on bilirubin levels at the time of sample acquisition and were compared to matched control groups 1, 2, and 3, respectively. RESULTS: A total of 102 fecal samples from 8 cases and 10 controls were analyzed. Precholestasis samples were more abundant in phylum Firmicutes and genus Staphylococcus, whereas control 1 was more abundant in phylum Proteobacteria and genus Escherichia-Shigella. Nonmetric multidimensional scaling ordination plots based on the taxonomic composition of early fecal samples revealed significant separation between cases and controls. On indicator species analysis, genus Bacilli was more prevalent in samples from the precholestasis group, whereas genus Escherichia-Shigella was more prevalent in control 1. With feeding advances, weaning of PN and resolution of PNAC, most differences in microbiota resolved with the exception of control 3 group being more diverse compared to the postcholestasis group. CONCLUSIONS: Premature neonates who develop PNAC, compared to those who do not, show significantly different fecal microbiomes preceding the biochemical detection of cholestasis.

Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.

Effects of Ethanol Lock Therapy on Central Line Infections and Mechanical Problems in Children With Intestinal Failure.

OBJECTIVES: Although use of 70% ethanol lock therapy (ELT) has been shown to decrease the rate of catheter-related bloodstream infections (CRBSIs) in patients with intestinal failure and central venous catheters (CVCs), concerns have been raised about its association with higher rates of mechanical problems and CVC replacements (CVC-Rs). We sought to compare the rates of CRBSI, mechanical problems, and CVC-Rs in a cohort of pediatric patients with intestinal failure, with and without ELT (ELT+ and ELT-, respectively). METHODS: Data were collected in a retrospective chart review from February 2007 to May 2014. Mann-Whitney and Wilcoxon signed-rank tests were used to compare nonparametric and paired data, respectively. RESULTS: Twenty-nine children had 9033 catheter days (CDs). The ELT+ group (vs ELT-) had lower rate of infection and significantly fewer CVC-Rs due to infection but significantly more mechanical events and related CVC-Rs with significantly shorter mean CVC survival. In 13 children who had a pre-ELT and post-ELT period, ELT was associated with a decrease in the rate of CVC-Rs due to infection (0.36 vs 4.74/1000 CDs, P = .046) and an increase in the rate of CVC-Rs due to mechanical problems (5.05 vs 0/1000 CDs, P = .018). CONCLUSIONS: While ELT+ is associated with a lower rate of CRBSIs and related CVC-Rs, it is also associated with higher rates of mechanical problems and related CVC-Rs. In addition to investigating the ideal concentration, duration, and timing of ELT to preserve the integrity of the CVC, alternatives to exclusively ethanol-based lock solutions should be developed.

Improved Delivery of Fat From Human Breast Milk via Continuous Tube Feeding.

BACKGROUND: Human breast milk is used sparingly in infants with intestinal failure due to observations from studies using syringe pumps that show loss of macronutrients with continuous feeding. Because of the potential benefits of using human milk, we sought to assess macronutrient losses using human milk as continuous tube feeds as done in the inpatient and home setting using a feeding bag and pump. METHODS: Using in vitro simulations of human milk to assess macronutrient losses with continuous tube feeds, hourly samples were analyzed using the SpectraStar Near-Infrared Analyzer (Unity Scientific, Columbia, MD). Effects of agitation and positional changes of the feeding bag on macronutrient delivery were investigated in 249 total samples. Pairwise comparisons were performed using repeated-measures analysis of variance. RESULTS: Significant fat losses were observed at all rates at hours 1-4, averaging to 73% at 5 mL/h. Caloric losses correlated strongly with fat losses. Significant gains in the fat content (+116% at hour 4 at 5 mL/h) were seen in the preinfusion aliquots (feeding bags). Horizontal positioning and continuous agitation of the feeding bag only partially limited fat losses. Fat delivery at 5 mL/h was significantly enhanced to 87% when the feeding bag was placed in an inverted position and improved further up to 98% with higher infusion rates. No carbohydrates and proteins losses were seen. CONCLUSIONS: Enabling the delivery of the human milk from the top of the feeding bag optimizes fat delivery and limits losses. Such top infusing feeding bags should be developed and could decrease healthcare costs for intestinal rehabilitation programs.

Transition to a Tube Feeding Formula With Real Food Ingredients in Pediatric Patients With Intestinal Failure.

Due to concerns related primarily to allergic response and malabsorption, enteral nutrition therapy has traditionally relied on the use of elemental formulas in children with intestinal failure (IF). Blended food diets via a gastrostomy tube have been reported to improve feeding tolerance in pediatric populations receiving long-term enteral nutrition therapy. Complex macronutrients have been shown to stimulate intestinal adaptation in animal models. We report on our experience in children with IF who had an overall improvement in stool output when transitioned from an elemental formula to a tube feeding formula with real food ingredients (TFRF). Data were collected in a retrospective chart review of children with IF, >1 year of age, who were receiving enteral nutrition via continuous infusion, bolus feeding, or both. Indications for the TFRF trial were diarrhea or inconsistent stooling patterns. Ten children with a mean small bowel length of 48.3 cm were trialed on TFRF. Nine of 10 (90%) children tolerated the transition to 100% TFRF, of which 7 of 9 (78%) had their entire colon in continuity. The average age at successful transition was 29.2 months, and the average length of time to transition to 100% TFRF was 67.3 days. TFRF is well tolerated in children >1 year of age with IF; it also improves their stooling patterns. A commercially available TFRF is a cost-effective and nutritionally adequate means of providing nutrition to this patient population.

Fecal Transplantation Successfully Treats Recurrent D-Lactic Acidosis in a Child With Short Bowel Syndrome.

D-lactic acidosis can occur in patients with short bowel syndrome (SBS) when excessive malabsorbed carbohydrate (CHO) enters the colon and is metabolized by colonic bacteria to D-lactate. D-lactate can be absorbed systemically, and increased serum levels are associated with central nervous system toxicity manifested by confusion, ataxia, and slurred speech. Current therapy, usually directed toward suppressing intestinal bacterial overgrowth and limiting ingested CHO, is not always successful. Fecal transplantation, the infusion of donor feces into a recipient's intestinal tract, has been used for decades to treat recurrent Clostridium difficile infection, and case reports document its use in the successful treatment of constipation, diarrhea, and abdominal pain. The exact mechanism of action is unknown, but it is surmised that the alteration of the intestinal microbiome, as well as the reintroduction of potential beneficial microbes, helps mediate disease. Here we present the case of a child with SBS and recurrent, debilitating D-lactic acidosis, which was successfully treated with fecal transplantation.

The Fecal Microbiome in Pediatric Patients With Short Bowel Syndrome.

BACKGROUND: Changes in the intestinal microbiome of patients with short bowel syndrome (SBS) are thought to significantly affect clinical outcome. These changes may not only delay enteral diet advancement but may also predispose patients to bacterial translocation, bacteremia, and liver disease. Patients with SBS are thought to be more susceptible to changes in gut microbial communities due to intestinal dysmotility and/or lack of anatomic safeguards such as the ileocecal valve. MATERIALS AND METHODS: We analyzed the bacterial composition of 21 fecal specimens from 9 children with SBS and 8 healthy children ages 4 months to 8 years by 16S ribosomal RNA gene sequencing. The sequences were quality filtered and analyzed using QIIME, the Ribosomal Database Project Classifier, and the randomForest supervised learning algorithm. RESULTS: The fecal microbiome of patients with SBS is different from that of healthy controls. Stool from patients with SBS had a significantly greater abundance of the bacterial classes Gammaproteobacteria and Bacilli. Stool from patients with SBS who experienced increased stool frequency tended to have increased abundance of Lactobacillus (P = .057) and decreased abundance of Ruminococcus. CONCLUSION: This study shows that the fecal microbiome of patients with SBS is significantly different from that of healthy controls when analyzed by 16S metagenomics. Differences in the composition and function of gut microbiomes in children with SBS may affect bowel physiology, and these findings may provide new opportunities for intestinal rehabilitation and clinical management.

Fecal transplantation: re-discovering the value of stool.

PURPOSE OF REVIEW: For over 1000 years, stool in various forms has been used to treat disease. Within the past few decades, fecal infusion either rectally or via a nasogastric tube has become a viable option for the treatment of refractory Clostridium difficile infection (CDI), and, more recently, it has shown promise in treating inflammatory bowel disease (IBD) and metabolic disease. The purpose of this article is to review the use of feces as a treatment option in pediatric disease. RECENT FINDINGS: The majority of publications detailing the use of fecal infusion as a medical treatment have been case reports. In the first randomized controlled trial of its kind, fecal infusion via nasogastric tube was shown to be beneficial in treating refractory CDI in adults. In another first of its kind, a pilot study on the use of fecal enemas to treat ulcerative colitis in pediatric patients found it to be well tolerated and effective. SUMMARY: The infusion of feces into the intestinal tract shows great promise for treatment and modulation of a variety of intestinal and extraintestinal diseases. Defining the underlying mechanism, microbes, and metabolites that mediate this effect will lead to more directed, safer, and potentially more effective treatments.