Pediatricians' practices and knowledge of metabolic dysfunction-associated steatotic liver disease: An international survey.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in children. It is associated with significant intra- and extrahepatic comorbidity. Current guidelines lack consensus, potentially resulting in variation in screening, diagnosis and treatment practices, which may lead to underdiagnosing and/or insufficient treatment. The increasing prevalence of MASLD and associated long-term health risks demand adequate clinical management and consensus in guidelines. This study aims to evaluate the daily practices of pediatricians in screening, diagnosis and treatment of MASLD in children. METHODS: An online survey with 41 questions (single/multiple response options) was sent to pediatricians (with/without subspecialty) in Europe and Israel, via members of the ESPGHAN Fatty Liver Special Interest Group, between June and November 2022. The 454 pediatricians were included in this study. RESULTS: 51% of pediatricians indicated using any guideline for diagnosis and treatment of MASLD, with 68% reporting to follow recommendations only partially. 63% is of the opinion that guidelines need revision. The majority of pediatricians screen for MASLD with liver function tests and/or abdominal ultrasound. A large variety of treatment options is utilized, including lifestyle management, supplements and probiotics, with a notable 34% of pediatricians prescribing pharmacotherapy. When asked how often pediatricians request a liver biopsy in children with MASLD, 17% indicates they request a liver biopsy in more than 10% of cases. CONCLUSIONS: There is limited awareness and considerable variation in screening, diagnosis and treatment practices among European pediatricians, and a clear demand for new, uniform guidelines for MASLD in children.

Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis.

OBJECTIVES: To characterize the clinical course of acute pancreatitis (AP) in pediatric inflammatory bowel disease (IBD) patients compared to children with AP without IBD and to identify risk factors associated with AP among IBD patients. METHODS: This retrospective, single-center study compared clinical characteristics of children (<19 years) with AP with and without concomitant IBD who were hospitalized 2005-2019. We also conducted a risk factor analysis of AP development in pediatric IBD. RESULTS: Sixty-eight (54% males) patients with 120 episodes of AP were admitted at a median age of 15.3 years. Thirteen patients (14 episodes) had a co-diagnosis of IBD, representing 4% of our IBD patient population. The AP-IBD patients presented with lower amylase levels compared to the non-IBD patients (160 [interquartile range, IQR: 83-231] vs. 418 [IQR: 176-874] U/L, p > 0.01), all had a mild pancreatitis, and none required invasive intervention. The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. The only risk factor for AP development among IBD patients was IBD-associated arthritis (23% vs. 3% for IBD-non-AP, p = 0.04), while extracolonic Crohn's disease and induction therapy with nutrition were negative risk factors (15% vs. 51%, p = 0.05, and 8% vs. 44%, p = 0.04, respectively). Other parameters, including disease type and medications, were nonsignificant. CONCLUSION: The clinical course of AP in pediatric IBD patients is mild. Only IBD-associated arthritis emerged as a risk factor for the development of AP, while, unexpectedly, IBD medication did not.

Extended total colonic aganglionosis and total intestinal aganglionosis: Challenging enemies.

AIM: Extended total colonic aganglionosis (ETCA) represents uncommon forms of Hirschsprung disease (HD), with aganglionosis extending into the proximal small bowel. ETCA management is challenging and associated with poor outcomes and high mortality. This study compares management and outcomes of ETCA to more common HD forms. METHODS: A retrospective cohort of HD patients (2012-2023) from two institutions. Three HD forms were compared: short-segment HD (SSHD, n = 19), long-segment HD or total colonic aganglionosis (LS/TCA, n = 9) and ETCA (n = 7). RESULTS: Normally innervated segments in ETCA patients ranged 0-70 cm. Median times to first surgery were; ETCA = 3 days versus TCA = 21 days (p = 0.017) and SSHD = 95 days (p < 0.001), respectively. Median number of surgeries were; ETCA = 4, versus TCA = 2 (p = 0.17) and SSHD = 1 (p = 0.002), respectively. All the patients underwent a definitive pull-through procedure, except four ETCA patients with a permanent jejunostomy and residual aganglionic segment of 57-130 cm. ETCA patients had 92% lower odds of enterocolitis (14%) compared to TCA patients (67%, p = 0.054), and comparable odds to SSHD patients (16%, p = 0.92). ETCA mortality was 14%. CONCLUSION: Extended total colonic aganglionosis patients require earlier and multiple interventions. Leaving an aganglionic segment may be advantageous, without increasing risk for enterocolitis. Tailored surgical treatment and rehabilitation programmes may prevent mortality and need for transplantation.

Body composition in pediatric celiac disease and metabolic syndrome component risk-an observational study.

BACKGROUND: Celiac disease (CD) in children and adolescents has been linked with increased susceptibility for cardiometabolic disease in adulthood. We explored the interaction between body composition and metabolic syndrome (MetS) components in pediatric CD. METHODS: We conducted a retrospective observational study of patients with CD followed at our Pediatric Endocrine and Gastroenterology Units between 1/2018-1/2022. Data on sociodemographic, clinical, laboratory, and body composition parameters (bioelectrical impedance analysis, BIA) were collected. RESULTS: Forty-four patients with MetS components and 67 patients without them were enrolled. The cohort's mean age at BIA assessment was 11.5 ± 3.6 years. Individuals with MetS components were older (P = 0.045), had higher BMI z-scores (P < 0.001), higher total and truncal fat percentage levels (P < 0.001), lower muscle-to-fat ratio z-scores (P = 0.018), higher sarcopenic indices (P = 0.05), higher systolic blood pressure percentiles (P = 0.001), higher triglycerides levels (P = 0.009), and higher triglycerides/HDL-c ratios (P < 0.001) than those without MetS components. A sex- and age-adjusted model revealed that the diagnosis of MetS components was positively associated with fat percentage (odds ratio = 1.087, confidence interval [1.010-1.171], P = 0.027), but not with BMI z-scores (P = 0.138). CONCLUSIONS: We found that fat percentage but not weight status is associated with risk for MetS components in individuals with childhood-onset CD. Preventive interventions should target an improvement in body composition. IMPACT: The literature on cardiometabolic risk in pediatric patients with celiac disease (CD) is sparse. Our analysis revealed that at least one metabolic syndrome (MetS) component was present in two out of every five children and adolescents with CD. An increase in fat percentage but not in body mass index z-scores predicted the presence of MetS components in our cohort. These findings suggest that the weight status of children and adolescents with CD does not mirror their risk for MetS components. Body composition analysis should be considered as an integral part of the clinical evaluation in young patients with CD.

Laparoscopic Sleeve Gastrectomy Versus One Anastomosis Gastric Bypass in Adolescents With Obesity.

OBJECTIVE: Large studies comparing outcomes between laparoscopic sleeve gastrectomy (LSG) and one anastomosis gastric bypass (OAGB) are scarce and involve adult populations. The aim of the study was to compare perioperative, early postoperative, and 1-year postoperative outcomes of adolescents with obesity who underwent LSG or OAGB surgery. METHODS: The medical records of adolescents with obesity who underwent LSG or OAGB at the Tel Aviv Sourasky Medical Center from January 2017 to January 2021 were retrospectively reviewed. Data on their gastrointestinal (GI) symptoms and postoperative quality of life were obtained by a telephone interview. RESULTS: Included were 75 adolescents (median [interquartile range, IQR] age 17.3 [16-18] years) of whom 22 underwent OAGB and 53 underwent LSG. There were no significant preoperative group differences in age, sex, and body mass index score. A low rate of perioperative (5.7% vs 0) and postoperative complication (15.1% vs 10%) with no statistical differences between LSG and OAGB group, respectively, was noted. At 12 months, the percent excessive weight loss + IQR was 42.40% [30.00, 45.00] and 38.00% [33.550, 44.20] in the LSG and OAGB group, respectively ( P = NS). The results of the Pediatric Quality of Life Inventory Gastrointestinal Symptoms scale revealed significantly less food limitation and heartburn after OAGB compared to LSG (food limitation 71.63 vs 53.85 and heartburn 83.654 vs 61.6, P = 0.03 and P = 0.029, respectively). CONCLUSIONS: Both surgeries are effective and safe for weight loss in the adolescent population. OAGB was associated with significantly fewer GI symptoms compared to LSG.

Chronic Mucosal Inflammation in Pediatric Intestinal Failure Patients-A Unique Phenomenon.

INTRODUCTION/OBJECTIVES: As intestinal failure (IF) management improves and long-term survival rate increases, its physiological complications have become more apparent. The development of chronic intestinal inflammation resembling inflammatory bowel disease (IBD) in this population has been reported, but the literature describing it in detail is sparse. The present study was designed to characterize children with IF who developed chronic intestinal inflammation and identify the potential predisposing clinical factors. METHODS: This retrospective study was based on the electronic medical records of pediatric patients seen at the Cincinnati Children's Hospital Medical Center between January 2000 and July 2022. Demographic and medical history data were collected and compared between children with IF that developed chronic intestinal inflammation and children with IF that did not develop chronic intestinal inflammation. RESULTS: During the follow-up period, 23 children were diagnosed with chronic intestinal inflammation. Of these, 12 (52%) were males, with a median age of 4.5 (3-7) years at diagnosis. Nearly one-third of the patients had gastroschisis (31%), followed by necrotizing enterocolitis (26%), and malrotation and volvulus (21.7%). More children in the chronic intestinal inflammation group lacked an ileocecal valve (ICV) and adjoining distal ileum as compared to the short bowel syndrome (SBS)-IF control group (15 patients, 65% vs 8 patients, 33%). Moreover, more children in the chronic intestinal inflammation group had undergone a prior lengthening procedure than the SBS-IF control group (5 patients, 21.7% vs. 0, respectively). DISCUSSION: SBS patients are at risk of relatively early onset chronic intestinal inflammation. The absence of an ICV (and adjoin ileum) and prior lengthening procedures emerge as factors associated with the risk of IBD in these patients.

The Yield of Routine Tissue Sampling in Pediatric Gastrointestinal Endoscopy.

OBJECTIVES: Societies' guidelines suggest routine tissue sampling in all children undergoing esophagogastroduodenoscopy and ileocolonoscopy, even in the absence of visible endoscopy abnormalities. We aimed to determine the agreement between endoscopic and histopathological findings in pediatric endoscopy and to assess the yield of routine biopsies from all sites. METHODS: Since January 2019, our endoscopy institute protocol has included routine biopsies sampling from the esophagus, stomach, duodenum, ileum, and colon in all diagnostic procedures. Agreement between tests was done using the kappa coefficient ( κ ). The study included all endoscopies performed during 2019. RESULTS: In total, 541 diagnostic endoscopies were done during the study period with 434 (80%) esophagogastroduodenoscopy and 107 (20%) were ileocolonoscopy. Compared to histology, endoscopic findings performance were: esophagus-sensitivity 33%, specificity 98%; stomach-sensitivity 60%, specificity 89%; duodenum-sensitivity 50%, specificity 97%; duodenal bulb-sensitivity 47%, specificity 89%; terminal ileum-sensitivity 82%, specificity 100%; colon-sensitivity 84%, specificity 96%. Assessment of concordance between endoscopic and histopathologic findings reveals an overall low level of agreement in esophagogastroduodenoscopy ( κ of 0.39, 0.51, 0.53, and 0.24 for the esophagus, stomach, duodenal second part, and bulb, respectively), and good agreement in ileocolonoscopy ( κ of 0.88 and 0.81 for the ileum and colon, respectively). CONCLUSIONS: Endoscopy findings are highly specific for histologic pathology, whereas the absence of findings correlates poorly with histologic findings. Ileocolonoscopy shows better agreement than esophagogastroduodenoscopy. Our data support routine tissue sampling in pediatric endoscopy.

Pediatric feeding disorders among children with parental history of feeding disorders: a distinct group of patients with unique characteristics.

To investigate factors associated with pediatric feeding disorders (PFD) among children of parents that reported to have had feeding disorders during their own childhood compared to children with PFD with no history of parental PFD. We retrospectively reviewed the medical records of children diagnosed with PFD according to the recent WHO-based definition. The demographic and clinical characteristics of children with PFD with a parental history of PFD were compared to those of children with a PFD with no history of parental PFD. Included were 231 children with PFD (median [interquartile range] age 10 months [5.5-29] at diagnosis, 58% boys) of whom 133 children had parents without PFD and 98 children had parents with PFD. Unexpectedly, children of parents without PFD had a higher rate of low birth weight (28% vs. 19%, respectively, p = 0.007), more delivery complications (10% vs. 2%, p = 0.006), more hospitalizations (33% vs. 17%, p = 0.004), more prescription medications (27% vs. 18%, p = 0.05), and a higher percent of gastrostomy tube use (6% vs. 0, p = 0.02). Moreover, more parents with PFD had academic background compared with parents without PFD (72% vs. 59%, p = 0.05). There were no significant group differences in sex, history of breastfeeding, parental marital status, or type of the child's feeding disorder.  Conclusion: PFD among children with a parental history of PFD comprise a distinct group of patients with unique characteristics and outcomes. Since parental feeding history may explain their child's PFD in highly differing ways, such information may help in devising a specific family-based and multidisciplinary treatment plan for those children. What is Known: • Pediatric feeding disorder (PFD) is relatively common and its prevalence is increasing. • Information on an association between parental PFD and their child's feeding disorder is limited. What is New: • PFD among children with a parental history of PFD comprise a distinct group of patients with various characteristics and outcomes. • The parents' feeding history during childhood may provide important clues to their child's PFD.

Anemia, Hepcidin, and Vitamin D in Healthy Preterm Infants: A Pilot Study.

OBJECTIVE: The etiology of anemia in premature neonates is multifactorial and may involve anemia of inflammation mediated by hepcidin. Hepcidin expression is suppressed by vitamin D. We aimed to investigate the interrelationship between hepcidin, anemia, and vitamin D status in preterm infants. STUDY DESIGN: Preterm infants aged 1 to 5 weeks were prospectively recruited at the neonatal intensive care unit of the Dana Dwek Children Hospital. Blood counts and serum levels of hepcidin, ferritin, iron, 25-hydroxyvitamin D [25(OH)D] and C-reactive protein (CRP) were measured and compared between anemic and nonanemic preterm infants. RESULTS: Forty-seven preterm infants (mean ± standard deviation gestational age at birth 32.8 ± 1.1 weeks, 66% males) were recruited. In total, 36% of the preterm infants were vitamin D deficient [25(OH)D < 20 ng/mL] and 15% were anemic. Hepcidin levels were significantly higher in anemic premature infants than in the nonanemic group (55.3 ± 23.9 ng/mL vs. 30.1 ± 16.3 ng/mL, respectively, p < 0.05). No differences were found in iron, ferritin, 25(OH)D, and CRP levels between anemic and nonanemic premature newborn infants. A positive correlation was found between hepcidin and ferritin (R 2 = 0.247, p = 0.02) and a negative correlation was found between 25(OH)D and CRP (R 2 = 0.1, p = 0.04). No significant correlations were found between 25(OH)D and hepcidin, iron, ferritin, or CRP. CONCLUSION: Anemia of prematurity was associated with high hepcidin serum levels. The exact mechanisms leading to anemia and the role of vitamin D warrant further investigation. KEY POINTS: · Hepcidin levels were significantly higher in anemic premature infants.. · A positive correlation was found between hepcidin and ferritin.. · Negative correlation was found between 25(OH)D and CRP..

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3 months and all within 1 year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Increasing rate of a positive family history of inflammatory bowel disease (IBD) in pediatric IBD patients.

The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15 years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041).Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome. What is Known: •Familial clustering of inflammatory bowel disease (IBD) has been reported in 5%-15% of IBD patients. •The investigation of the impact of a positive family history upon IBD characteristics and severity revealed conflicting results. What is New: •In this cohort of 325 children with IBD, 25.2% had a positive family history. •The rate of a positive family history of IBD in the pediatric IBD population is increasing. •A positive family history may have some impact upon IBD phenotype but none on IBD outcome.

The role of gastrostomy feeding during intestinal rehabilitation for children with short bowel syndrome.

PURPOSE: Following extensive bowel resection, many children with short bowel syndrome (SBS) are routinely offered a placement of gastrostomy tube (G-tube) for feeding. This nutritional pathway is aimed to accommodate the gastric and small bowel motor disturbances related to SBS, and to promote weaning off parenteral nutrition (PN) to achieve enteral autonomy (EA). The aim of this study was to investigate the effect of gastrostomy feeding in outcomes of children with SBS. METHODS: A retrospective cohort of all SBS children managed at our multidisciplinary Intestinal Rehabilitation Center as part of an Intestinal Rehabilitation Program. SBS was defined as PN dependence for more than six weeks following extensive bowel resection. Patients treated with G-tube feeding were compared with patients without G-tube in terms of PN duration, reaching EA, physical development, and surgical parameters. RESULTS: A total of 36 SBS patients diagnosed between 2003 and 2022 were included. The most common etiologies included congenital intestinal atresia (31%) and necrotizing enterocolitis (25%). SBS-G-tube (group A) contained 20 children, and SBS (group B) contained 16 children. A total of 21 children reached EA (58%); ten from group A (50%), and 11 from group B (69%) (p > 0.05). Within EA patients, mean PN duration was 49 ± 44 months in group A, and 24 ± 33 months in group B (p > 0.05). Patients who reached EA had 22% longer residual small bowel when compared with PN-dependent patients (p = 0.003). However, the outcomes were adjusted for residual small and large bowel length and percentages, a residual ileocecal valve, and a colon in continuity with no differences between the groups. Two-thirds of children from group A reported G-tube related complications (mechanical, bleeding, or infections). We did not find differences in mean height and weight percentiles between the groups (p > 0.05). CONCLUSION: We did not find significant advantage of gastrostomy feeding in reaching EA. Because there are surgical and mechanical complications related to this procedure, further prospective studies are required to determine G-tube relevance for children with SBS.

Motility disorders in children with intestinal failure: a national tertiary referral center experience.

PURPOSE: Intestinal dysmotility (ID) problems are common in patients with pediatric-onset intestinal failure (IF) and short bowel syndrome (SBS), leading to significant morbidity and delays in the advancement of enteral nutrition (EN). We aimed to investigate the clinical features and complications of ID in children with IF and SBS. METHODS: Retrospective chart review of all children with IF and/or SBS who required parenteral nutrition (PN) > 6 weeks or small-intestinal resection ≥ 50%. Patients were divided into SBS and non-SBS groups. SBS group was divided into two subgroups: with and without ID. Patients with ID were identified (clinically, radiologically and functionally) and analyzed with regard to demographics, intestinal anatomy, complications and outcomes (short and long term). RESULTS: A total of 42 children with IF were treated in our institution during 2003-2022. In non-SBS group (n = 10), ID was the most common cause of IF (80%). SBS-group included 32 children; 18 children (56%) developed ID. The clinical profile of SBS-ID patients (vs SBS) was: female gender (56%), remaining small bowel length ≤ 55 cm, estimated residual small bowel ≤ 28% (p = 0.045) and absence of ICV (56%). Common symptoms of the SBS-ID group were: food intolerance (61%), abdominal distension (50%), vomiting (44%), malabsorption and severe constipation. Complications included FTT (67%) (p = 0.003), bacterial overgrowth with subsequent bloodstream infection (33%) (p = 0.75), and lactic acidosis (11%). Lengthening procedure (STEP) was performed in 11 SBS-ID patients (61%) (p = 0.002). In all patients, STEP operation "rescued" their dysfunctional intestine. Eight of these patients (73%) were weaned from TPN. Survival rate was 100%; however, one SBS-ID patient is a candidate for combined intestinal and liver transplantation. CONCLUSIONS: ID is the most common complication of SBS and is the most common cause of IF in non-SBS patients. ID has a high morbidity rate and various clinical manifestations. Successful treatment of these infants may be achieved with the use of tapering enteroplasty.

Intestinal dysmotility after bowel resection in rats is associated with decreased ghrelin and vimentin expression and loss of intestinal cells of Cajal.

This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 wk after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (ICC; downregulation of transmembrane member 16A (TMEM16A) and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to a decrease in final body weight, suggesting less effective nutrient absorption. The purpose of this study was to evaluate the mechanisms of intestinal motility in a rat model of short bowel syndrome (SBS). Rats were divided into three groups: Sham rats underwent bowel transection; SBS-NSI rats underwent a 75% bowel resection and presented with normal intestinal size (NSI) at euthanasia and hypermotility patterns; SBS-DYS showed dysmotile (DYS) enlarged intestine and inhibited motility patterns. Animals were euthanized after 2 wk. Illumina's digital gene expression (DGE) analysis was used to determine the intestinal motility-related gene expression profiling in mucosal samples. Intestinal motility-related and ICC genes and protein expression in intestinal muscle layer were determined using real-time PCR, Western blotting, and immunohistochemistry. Gastrointestinal tract motility was studied by microcomputer tomography. From 10 Ca2+ signaling pathway-related genes, six genes in jejunum and seven genes in ileum were downregulated in SBS vs. Sham animals. Downregulation of TMEM16A mRNA and protein was confirmed by real-time PCR. Rapid intestinal transit time in SBS-NSI rats correlated with a mild decrease in TMEM16A, c-kit, and vimentin mRNA and protein expression (vs/. Sham animals). SBS-DYS rats demonstrated enlarged intestinal loops and delayed small intestinal emptying (on imaging studies) that were correlated with marked downregulation in TMEM16A, c-kit, vimentin, and ghrelin mRNA and protein levels compared with the other two groups. In conclusion, 2 wk following massive bowel resection in rats, impaired intestinal motility was associated with decreased vimentin and ghrelin gene and protein levels as well as loss of ICC (c-kit and TMEM16A).NEW & NOTEWORTHY This study provides novel insight into the mechanisms of intestinal dysmotility following massive small bowel resection. We show that 2 weeks after bowel resection in rats, impaired intestinal motility was associated with loss of interstitial cells of Cajal (downregulation of TMEM 16A, and c-kit expression) as well as with decreased vimentin, desmin, and ghrelin levels. Impaired intestinal motility led to decrease in final body weight, suggesting less effective nutrient absorption.

BMI in the lower and upper quartiles at diagnosis and at 1-year follow-up is significantly associated with higher risk of disease exacerbation in pediatric inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition, but obesity may also serve as a negative prognostic factor. This study aimed to present the longitudinal course of height, weight, and body mass index (BMI) of children from IBD diagnosis to 18 months of follow-up, and to describe the impact of BMI on the clinical course of the disease. One hundred and fifty-two children were identified, of whom 85 had Crohn's disease (CD) and 67 had ulcerative colitis (UC). During a median (interquartile range) follow-up of 2.95 (1.73-4.5) years, weight and BMI Z-scores increased in the first 18 months since diagnosis in both the CD (P < 0.001) and UC (P < 0.028) groups. BMI in lower and upper quartiles at diagnosis was associated with higher risk of hospitalization (hazard ratio [HR] = 2.72, P = 0.021). In a multivariate analysis, BMI in the lower quartile at diagnosis and at 6, 12, and 18 months was associated with higher risk of disease exacerbation (HR = 2.36, 1.90, 1.98, and 2.43, respectively, P < 0.021), as was BMI in the upper quartile (HR = 2.59, 2.91, and 2.29, respectively, P < 0.013).Conclusion: BMI in the lower and upper quartiles at diagnosis and during follow-up was associated with a more severe disease course in children with IBD. What is Known: • Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition. • The impacts of weight and body mass index (BMI) on the presentation and course of IBD have been mainly investigated in the adult population. What is New: • In the era of the obesity epidemic, this study identifies both low and high BMIs at diagnosis and at follow-up as a marker for poor outcome in pediatric IBD. • The results support using BMI as a predictor of IBD course and prognosis.

Higher BMI predicts liver fibrosis among obese children and adolescents with NAFLD - an interventional pilot study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. TRIAL REGISTRATION: TRN NCT04561804 (9/17/2020).

The effect of gluten-free diet on body mass index in paediatric celiac disease.

AIM: More normal weight and overweight children are currently diagnosed with celiac disease (CD). We aimed to describe the relation between body mass index (BMI) and the clinical characteristics of paediatric CD and to determine the effect of a gluten-free diet (GFD) on BMI. METHODS: Data on all children diagnosed with CD during 7/2010-7/2019 with documented anthropometric data at diagnosis were retrospectively analysed. The children were divided into three groups according to BMI status at diagnosis: underweight, normal weight and overweight (BMIs <5%, 5%-85% and >85%, respectively). RESULTS: Of the 236 children [median age 7.87 (4.91-11) years] included in the study, 24 (10.1%) were underweight at diagnosis and 32 (13.6%) were overweight. Diarrhoea as the presenting symptom was significantly more common in the overweight group (p = 0.012), while short stature was more common in the underweight group (p = 0.002). Following a GFD had no significant effect on the children's BMI during a median follow-up of 15.7 (0-85) months, but there was a significant shift of patients between the BMI categories (p < 0.001). CONCLUSION: Although a shift of patients between the BMI categories was observed, following a GFD did not significantly affect the overall BMI in children with CD.

Age and pain score before gastrointestinal endoscopies in children are predictors for post procedure pain.

BACKGROUND: Gastrointestinal endoscopy may be associated with pain and anxiety. Predictors for high pain scores after endoscopies in children are not known. The aim of our study was to identify risk factors for prolonged recovery and higher pain scores after gastrointestinal endoscopy in children. METHODS: All the children that were electively admitted for gastrointestinal endoscopies were included. We retrospectively collected demographic, clinical and endoscopic data as well as information on the recovery process. A numerical rating scale and the Faces, Legs, Activity, Cry, and Consolability Scale were used for pain scoring. RESULTS: During the study period (01/2016-10/2016), 284 children (median age 10.7 years, interquartile range 6.7-14.8) were recruited. In a univariate analysis, older age, higher pre-procedure pain scores, longer procedure durations, higher number of biopsies and longer recovery duration were associated with higher post-procedure pain scores. In a multivariate analysis higher pain scores before the procedure (OR 12.42, 95% CI 3.67-42, P < 0.001) and older age (OR 1.016, 95% CI 1.007-1.025, P < 0.001) were associated with higher pain scores after the procedure. Children with a higher pain score before the procedure also had a longer recovery period (OR 5.28, 95% CI (1.93-14.49), P = 0.001). CONCLUSION: Older age and higher pain score before the procedure were identified as predictors for higher pain score after pediatric gastrointestinal endoscopies. Children with these risk factors should be identified before the procedure in order to personalize their post-procedure management.

Predictors for Complicated Disease Course after Stepping Down from Combination to Antitumor Necrosis Factor Alpha Monotherapy in Children with Inflammatory Bowel Disease.

OBJECTIVE: Combinations of antitumor necrosis factor alpha (TNFα) and immunomodulators may be indicated in high-risk inflammatory bowel disease patients. Our aims were to compare disease course between children that did and did not step down to anti-TNFα monotherapy and to define risk factors for complicated disease course after stepping down. METHODS: A retrospective review of the medical records of consecutive children who were treated with combination therapy. RESULTS: Of 64 children, 32 continued combination therapy while the others stepped down to monotherapy (median duration of 6 months [range 6-10]). Children that stepped down had a trend of lower anti-TNFα levels (median [interquartile range] of 2.4 [1-4.2] µg/mL) compared to those that did not step down (4.5 [2.2-6.23] µg/mL, p = 0.065). Children with Crohn's disease that stepped down had a significantly higher risk for disease exacerbation, hospital admission, and operation (p < 0.025). Univariate analysis revealed that penetrating phenotype, upper gastrointestinal involvement, higher disease activity at diagnosis, and lower anti-TNFα levels under combination therapy were predictors for complicated course after stepping down. CONCLUSION: Stepping down to anti-TNFα monotherapy may be related to lower anti-TNFα levels and to a more complicated disease course thereafter. Predictors for a complicated course were identified.

"Bariatric families"- a new phenomenon with unique characteristics.

BACKGROUND: Many obese children have at least one obese parent, and some of them have one parent who had undergone bariatric surgery ("bariatric families"). The perceptions and attitudes towards child obesity of parents in bariatric families vs. non-bariatric families have not been explored. We assessed how parents who underwent bariatric surgery for obesity perceived their child's obesity compared to those perceptions of obese parents who did not undergo bariatric surgery. METHODS: We conducted a cross-sectional survey by interviewing families in which one or both parents underwent bariatric surgery (bariatric group) and comparing their responses to those of families in which one or both parents had been treated conservatively for obesity (control group). The children of both groups were attending the Obesity Clinic of our children's hospital. RESULTS: Thirty-six children (median age 10.6 years, 18 in each group, matched for age and sex) were recruited. More parents in the bariatric group replied that weight plays an important role in determining self-image (p < 0.03), and more replied that their child's obesity is a current and future health problem (p < 0.03 and p < 0.007, respectively, Table 1). Five children (28%) in the bariatric group had expectations of undergoing bariatric surgery compared to none in the control group (p < 0.02), with a similar trend among their parents (44% vs. 11%, respectively, p < 0.07). CONCLUSION: Families in which one or both parents underwent bariatric surgery for obesity revealed different perceptions of their child's obesity and different opinions about interventions for treating it compared to families with no bariatric surgery.