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Introduction: We assessed the efficacy of taurolidine lock (TL) in preventing catheter-related bloodstream infections (CRBSIs) and related hospitalizations in children with parenteral nutrition (PN) in the home setting., Methods: This study is a retrospective case series study. All children with intestinal failure in a single center in southern Israel who were administered PN and treated with TL between 2017 and 2024 were included. The rates of CRBSI episodes, related hospitalizations and pathogen distribution in the pre-TL and post-TL periods were compared., Results: Overall, 14 patients were included. The median pre-TL and post-TL periods were 990 and 1260 days, respectively. The rate of CRBSI episodes due to bacterial infection per 1000 days declined by 45%, from 6.2 to 3.7, with p = 0.0008, while fungal CRBSI rates were low (<10% of all positive cultures) and did not decline significantly. Similarly, the hospitalization episode rate per 1000 days declined by 41%, from 7.6 to 4.5, with p = 0.001., Conclusions: Taurolidine lock treatment for children with central-line PN resulted in a substantial decrease in CRBSI episodes and related hospitalizations.

Background & Aims: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders., Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset., Results: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (P = .026) but not with baseline CD-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18-6.11, P < .001)., Conclusion: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the association between nonsyndromic esophageal atresia with tracheoesophageal fistula (EA-TEF) and consanguinity., Study Design: A retrospective study comparing the incidence of EA-TEF between a low-consanguineous Jewish population and a high-consanguineous Bedouin population. All patients were treated at Soroka University Medical Center, the only tertiary medical center in southern Israel., Results: From 2000 to 2022, 579 130 children were born in southern Israel, and 386 915 (66.8%) were Jewish, and 192 215 were Bedouin Muslims. A total of 96 patients were diagnosed with EA-TEF; 83 of them were nonsyndromic. The incidence of EA-TEF was 1.66 cases per 10 000 live births and was statistically higher among the Bedouin population (3 vs 0.95 cases per 10 000 live births; P < .001). The consanguinity rate among the Bedouin group was higher compared with the Jewish (67.8% vs 0%; P < .001). There were no differences in other risk factors., Conclusions: The incidence of EA-TEF is higher among the Bedouin population that lives in the same geographic region and has the same medical access as the Jewish population, proposing consanguinity as a risk factor for EA-TEF., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment., Methods: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort., Results: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia., Conclusion: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD., (Copyright © 2023 AGA Institute. All rights reserved.)

Background: The Lémann Index [LI] and the recently updated LI are tools for measuring structural bowel damage in adults with Crohn's disease [CD] but have not been evaluated in children. We aimed to validate the updated LI in the prospective multicentre ImageKids study of paediatric CD., Methods: We included children with CD undergoing magnetic resonance enterography [MRE], pelvic magnetic resonance imaging [MRI] and ileocolonoscopy. Half were followed for 18 months, when MRE was repeated. Serum was collected for fibrosis-related proteomic markers. The LI was calculated by central readers from the MRE, ileocolonoscopy, physical examination and surgical data. Reliability and construct validity were assessed at baseline, while responsiveness and test-retest reliability were explored longitudinally., Results: In total, 240 children were included (mean age, 14.2 ± 2.5 years; median disease duration, 2.2 years [interquartile range, IQR 0.25-4.42]; median baseline LI, 4.23 [IQR 2.0-8.8]). The updated LI had excellent inter-observer reliability (interclass correlation coefficient [ICC] = 0.94, 95% confidence interval [CI] 0.92-0.95) but poor, although statistically significant, correlation with radiologist and gastroenterologist global assessments of damage and with serum proteomic levels of fibrotic markers [rho = 0.15-0.30, most p < 0.05]. The updated LI had low discriminative validity for detecting damage (area under the receiver operating characteristic curve [AUC-ROC] 0.69, 95% CI 0.62-0.75). In 116 repeated MREs, responsiveness was suboptimal for differentiating improved from unchanged disease [AUC-ROC 0.58, 95% CI 0.45-0.71]. Test-retest reliability was high among stable patients [ICC = 0.84, 95% CI 0.72-0.91]., Conclusion: Overall, the updated LI had insufficient psychometric performance for recommending its use in children. An age-specific index may be needed for children with shorter disease duration than typical adult cohorts., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Infant exposure to macrolide antibiotics is a risk factor for infantile hypertrophic pyloric stenosis (IHPS). The aim of the study was to establish whether perinatal exposure to non-macrolide antibiotics was a risk factor for IHPS., Study Design: A retrospective matched case-control study was performed using a database including all children born at Soroka University Medical Centre between 2006 and 2018. Cases and controls were compared using Student T-test and multiple logistic regression., Result: Of 189 461 children in the database, 63 infants were diagnosed with IHPS and underwent pyloromyotomy. There was no association between non-macrolide antibiotic exposure and IHPS. Maternal diabetes (DM) had an adjusted odds ratio for infants developing IHPS of 4.53 (p = 0.004)., Conclusion: The lack of association between exposure to non-macrolide antibiotics and IHPS suggests a quality unique to macrolides. An association between DM and IHPS may suggest elevated levels of IGF-1 have a role., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective and Aim: Infantile-onset inflammatory bowel disease (IO-IBD), defined as IBD diagnosed at age 2 years or younger, tends to be more severe and refractory to conventional treatment than IBD diagnosed at a later age. However, data about IO-IBD and its long-term follow up are limited. We thus aimed to evaluate the presentation and long-term outcomes of patients with IO-IBD in a retrospective multicenter study., Methods: Medical records of patients diagnosed with IO-IBD in eight medical centers during 2000-2017 with at least 1-year follow up were reviewed. Demographics and disease characteristics at diagnosis including age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions were recorded., Results: Twenty-three patients with IO-IBD (16 males, 70%) were identified and followed for a median (range) of 51.2 (26.0-110.3) months. The mean ages at presentation and at the last follow up were 14 ± 9.8 and 101 ± 77 months, respectively. Six (26%) patients needed ileostomy already at the time of diagnosis and 20 (87%) were treated with corticosteroids. During long-term follow up, remission was achieved in 16 (73%) patients; of whom, 3 (14%) were without medications and 7 (32%) were in remission with the use of 5-aminosalicylic acid only. One patient needed hemicolectomy and one developed a severe EBV related infection., Conclusion: The majority of patients with IO-IBD achieved long-term remission, despite a severe disease presentation at diagnosis. Surgery rate however is high, mainly during the first months from diagnosis., Competing Interests: The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JO declared a shared consortium [Very Early Onset Inflammatory Bowel Disease Consortium] with the author DS to the handling editor., (© 2023 Krauthammer, Weintraub, Shaoul, Lev-Tzion, Broide, Wilschanski, Lerner, Yerushalmi, Shouval, Shamaly, Haberman-Ziv and Weiss.)

Aim: Telomeres are DNA sequences of tandem TTAGGG repeats that protect chromosome ends from degradation and instability. Constitutional loss-of-function telomerase mutations result in rapid telomere shortening, premature senescence and cell death. Liver cirrhosis is rare and has only been reported in adults. We present five family members of Bedouin-Muslim origin, all of which carry the same mutation, and yet demonstrate an extremely variable phenotypical presentation, including liver cirrhosis during early childhood., Methods: A multidisciplinary long-term follow-up of two healthy and three affected patients was analysed. The mutation (r.95G>C) was identified in all patients using Sanger sequencing. Telomere length samples were obtained and analysed., Results: Clinical phenotypes were extremely variable, including age at first symptoms, organ involvement, disease severity and patient prognosis. The most prominent clinical phenotype is liver involvement, including end-stage liver disease early in life, which affects three members of the family. Affected patients had markedly shorter telomeres., Conclusion: We describe an unusual presentation of early liver failure in telomere disease patients. Little, if any, is known about the association between the genotype and phenotype among children with telomere disease and whether the mutation we have described (r.95G>C) is predisposed to early severe hepatic involvement., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: We set out to ascertain a possible association between mode of delivery (cesarean vs. vaginal delivery) and gastrointestinal hospitalization of the offspring., Study Design: A population based cohort analysis including all uncomplicated singleton deliveries occurring between the years 1991-2014 at a tertiary medical center was performed, comparing long-term gastrointestinal hospitalization of offspring, according to mode of delivery. Multiple gestations, fetuses with congenital malformations and perinatal deaths were excluded, as were cases of urgent cesarean delivery and pregnancy complications. Gastrointestinal hospitalizations (up to age 18 years) were defined using predefined ICD9 codes, as recorded in hospital records. A Kaplan Meier survival curve was constructed to compare cumulative incidence of first gastrointestinal hospitalizations. A Cox proportional hazard model was used to control for confounders., Results: During the study period 139,232 deliveries met the inclusion criteria; 13,242 (9.5%) of which were elective cesarean deliveries, and the remaining 125,990 (90.5%) were delivered vaginally. Cesarean delivery was associated with more offspring hospitalizations for gastrointestinal morbidity ( p  < .001). The Kaplan Meier survival curve demonstrated higher cumulative incidence of gastrointestinal hospitalizations in the cesarean delivery group (log rank test p < .001 ). Utilizing a Cox proportional hazards model to control for confounders, cesarean delivery was found to be an independent risk factor for long-term gastrointestinal hospitalization of the offspring (adjusted HR 1.409, 95%CI 1.306-1.521, p  < .001). Specifically, inflammatory bowel disease was more common among offspring following cesarean delivery aHR 1.386 95% CI 1.215-1.582 p  < .001., Conclusion: Elective cesarean delivery is an independent risk factor for long-term gastrointestinal-related hospitalization of the offspring.

Background: Pre- and perinatal events may be associated with an increased risk of inflammatory bowel disease [IBD]. We aimed to investigate the role of pre- and perinatal factors as potential risk factors for the development of IBD in a population with a follow-up of 50 years., Methods: We conducted a nested case-control study, reporting IBD incidence among individuals born in 1964-76, for whom pre- and perinatal exposures were reported as part of the Jerusalem Perinatal Study [JPS], by linking them to the database of the epidemiology group of the Israeli IBD Research Nucleus [epi-IIRN], including all IBD patients in Israel since 2005 and their matched controls., Results: We identified 2789 individuals within the epi-IIRN cohort who were also included in the JPS cohort [n = 90 079]: 746 IBD patients (405 with Crohn's disease [CD] and 341 with ulcerative colitis [UC]) and 2043 non-IBD controls. Those with a 'Non-western' family origin had decreased odds of developing CD and UC. High socioeconomic status was associated with CD but not UC. Low birth weight [≤2500 g] occurred less frequently in IBD cases compared to controls, especially in UC patients, showing a protective effect. Being the first born was associated with CD, and having older siblings lowered the odds of developing CD, decreasing 7% with each additional sibling. Smoking and breastfeeding data were available for a subset of individuals, but neither was associated with IBD development., Conclusion: This population-based study identifies several pre- and perinatal variables as predictors of IBD development. This information may be helpful to facilitate implementation of early diagnosis interventions and family follow-up protocols., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To describe the extent of prisoner/detainee cuffing and characterize cuffing methods., Background: Thousands of prisoners and detainees receive medical treatment in Israeli hospitals every year. According to the Israeli law, cuffing during hospital stay should be an exceptional measure, to be considered only in cases of real threat of violence or escape, based on individual assessment. There is no documentation of cuffing rates in hospitals., Methods: A multi-center study in 12 hospitals was performed during 2020-2021. Data were collected prospectively or retrieved retrospectively from security records, when available., Results: A total of 1857 prisoners/detainees were documented, of whom 1794 (96.6%) were cuffed. Of the 241 hospitalized patients, 230 (95.4%) were cuffed. Details regarding cuffing methods were available for 185 hospitalized patients, revealing that at least 63 patients (68% of patients for whom details regarding cuffing to bed were available) were cuffed to the bed with opposite arm and leg in a cross position. Cuffing rates of prisoners under custody of the Prisons Authority, police and the Israeli Defense Forces, were 98.5%, 96.6%, and 83%, respectively. Impaired mobility for medical reasons was documented in 64 cases, of whom 85.9% were cuffed regardless., Conclusions: Cuffing of prisoners/detainees in Israeli hospitals is performed non-selectively, in violation of the law. During hospitalization, cuffing is usually performed in a cross position, severely impairing mobility. Our findings highlight the need for routine documentation of cuffing due to its medical consequences and the responsibility of medical staff towards patients according to rules of ethics and regulations.

Objectives: In this quality improvement program, named quality in pediatric inflammatory bowel disease, we constructed a nation-wide platform that prospectively recorded clinically important quality indicators in pediatric inflammatory bowel diseases (PIBD), aiming at improving clinical management across the country., Methods: Representatives of all 21 PIBD facilities in Israel formed a Delphi group to select quality indicators (process and outcomes), recorded prospectively over 2 years in children with Crohn's disease 2-18 years of age seen in the outpatient clinics. Monthly anonymized reports were distributed to all centers, allowing comparison and improvement. Trends were analyzed using the Mann-Kendall test, reporting τ (tau) values., Results: The indicators of 3254 visits from 1709 patients were recorded from September 2017 to September 2019 (mean age 14.7 ± 3.1 years, median disease duration 1.8 years (interquartile range 0.69-4.02)). An increase in three of five process indicators was demonstrated: obtaining drug levels of anti-tumor necrosis factor (TNF) (τ = 0.4; P = 0.005), utilization of fecal calprotectin (τ = 0.38; P = 0.008) and bone density testing (τ = 0.45; P = 0.002). Among outcome indicators, three of nine improved as measured during the preceding year: calprotectin <300 μg/mg (τ = 0.35; P = 0.015), and "resolution of inflammation" defined as a composite of endoscopy, imaging and fecal calprotectin (τ = 0.39; P = 0.007). Endoscopic healing reached borderline significance (τ = 0.28; P = 0.055). An increase in the use of biologics throughout the study was observed (τ = 0.47; P = 0.001) with a concurrent decrease in the use of immunomodulators (τ = -0.47; P = 0.001)., Conclusions: Quality improvement nationwide programs can be implemented with limited resources while facilitating standardization of care, and may be associated with improvements in measured indicators., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: Advances in genetic technologies provide opportunities for patient care and ethical challenges. Clinical care of patients with rare Mendelian disorders is often at the forefront of those developments. Whereas in classical polygenic inflammatory bowel disease (IBD), the predictive value of genetic variants is very low, predictive prenatal genetic diagnosis can inform families at high risk of severe genetic disorders. Patients with IL-10 signalling defects because of pathogenic variants in IL10RA, Il10RB, and IL10 develop severe infantile onset inflammatory bowel disease that is completely penetrant and has a high morbidity and substantial mortality despite treatment., Methods: We performed a survey among tertiary specialist paediatric centers of 10 countries on the utilization of predictive prenatal genetic diagnosis in IL-10 signalling defects. We retrospectively report prenatal genetics in a series of 8 families., Results: International variation in legislation, guidelines, expert opinion, as well as cultural and religious background of families and clinicians results in variable utilization of preimplantation and prenatal genetic testing for IL-10 signalling defects. Eleven referrals for prenatal diagnosis for IL-10 signalling defects were identified across 4 countries. We report on 8 families who underwent prenatal preimplantation monogenic testing after in vitro fertilization (n = 2) and/or by amniocentesis/chorion villus sampling (n = 6). A genetic diagnosis was established in 1 foetus and excluded in 7 foetuses (all IL10RA variants)., Conclusions: Prenatal genetic testing for IL10R-defects is feasible, yet the legal and ethical considerations are complex and controversial. In some countries, predictive genetics for IL-10-related signalling defects is entering clinical practice., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn's disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction., Methods: Participants were children 6-17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies., Results: Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group., Conclusions: Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462)., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Alterations in the microbiome have been postulated to drive inflammation in IBD. In this pilot randomized controlled trial, we evaluated the effectiveness of quadruple antibiotic cocktail in addition to intravenous-corticosteroids (IVCSs) in acute severe colitis (ASC)., Methods: Hospitalized children with ASC (pediatric ulcerative colitis activity index [PUCAI] ≥65) were randomized into 2 arms: the first received antibiotics in addition to IVCS (amoxicillin, vancomycin, metronidazole, doxycycline/ciprofloxacin [IVCS+AB]), whereas the other received only IVCS for 14 days. The primary outcome was disease activity (PUCAI) at day 5. Microbiome was analyzed using 16S rRNA gene and metagenome., Results: Twenty-eight children were included: 16 in the AB + IVCS arm and 12 in the IVCS arm (mean age 13.9 ± 4.1 years and 23 [82%] with extensive colitis). The mean day-5 PUCAI was 25 ± 16.7 vs 40.4 ± 20.4, respectively (P = 0.037). Only 3 and 2 children, respectively, required colectomy during 1-year follow-up (P = 0.89). Microbiome data at time of admission were analyzed for 25 children, of whom 17 (68%) had a predominant bacterial species (>33% abundance); response was not associated with the specific species, whereas decreased microbiome diversity at admission was associated with day-5 response in the IVCS arm., Conclusion: Patients with ASC have alterations in the microbiome characterized by loss of diversity and presence of predominant bacterial species. Quadruple therapy in addition to IVCS improved disease activity on day 5, but larger studies are needed to determine whether this is associated with improved long-term outcomes (clinicaltrials.gov NCT02033408)., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The prevalence of celiac disease (CD) has dramatically increased with wide variability in clinical presentations between different geographical areas. However, the contribution of ethnic disparities in pediatric celiac disease is still unclear, especially in patients of Bedouin origin. Objective: We aimed to compare the clinical presentation and histological severity of celiac disease between Bedouin and Jewish children in southern Israel. Methods: This is a retrospective study in which we collected the demographic and clinical data, laboratory results, and histological severity of CD in two ethnic groups: Bedouins and Jews. The study included patients who were diagnosed between 1997 and 2015 in a tertiary hospital in southern Israel. Results: Data from 844 children with CD (271 Jewish and 573 Bedouins), 505 females (59.8%), were analyzed. Gastrointestinal symptoms and diabetes were more prevalent among the Jewish population ( p < 0.001 and p = 0.008, respectively), while family history, failure to thrive, iron deficiency anemia, and histological severity were significantly more prevalent among the Bedouin group. Upon multivariate logistic regression analysis, only the presence of iron deficiency anemia and Bedouin origin were associated with more advanced histological disease (OR of 2.03 (95% C.I 1.31; 4.308) ( P < 0.009) and OR 1.78 (95% C.I 1.31; 4.308) ( P < 0.003) respectively). Conclusion: The clinical presentation of celiac disease in Bedouin children is characterized by anemia with less gastrointestinal symptoms, but more severe histological damage. These differences might be explained either by a delay in the diagnosis of the disease in this population or by variable environmental, cultural, and nutritional factors unique to this ethnic group., (Copyright © 2020 Yerushalmi, Vosko, Ling, Raanan, Cohen, Shirin, Shalem, Matalon and Broide.)

Ciliopathies are a heterogeneous group of disorders, related to abnormal ciliary function. Severe biliary ciliopathy, caused by bi-allelic mutations in TTC26, has been recently described in the context of a syndrome of polydactyly and severe neonatal cholestasis, with brain, kidney and heart involvement. Pituitary involvement has not been previously reported for patients with this condition. Pituitary stalk interruption syndrome (PSIS) is a congenital anomaly of the pituitary gland, diagnosed by characteristic MRI findings. We now describe four patients with TTC26 ciliopathy due to a homozygous c.695A>G p.Asn232Ser mutation and delineate PSIS as a novel clinical feature of this disorder, highlighting an important role of TTC26 in pituitary development., (© 2020 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Objectives: Growth impairment is common in children with Crohn disease (CD). We aimed to assess the effect of adalimumab (ADL) treatment on linear growth in children with CD in a post-hoc analysis of the Pediatric Crohn's Disease AdalImumab Level-based Optimization Treatment randomized controlled trial., Methods: Children 6 to 17 years who responded to ADL induction were assessed consecutively for anthropometric parameters. Associations of these parameters with disease characteristics and disease activity were analyzed., Results: Overall, 66 patients completed 72 weeks of follow-up (25% girls, mean age of 15.6 ± 2.5 years). Median (interquartile range [IQR]) height z score improved from -0.6 (-1.6-0.15) at baseline to -0.33 (-1.3-0.5) at week 72 (P = 0.005) with lesser improvement in patients with perianal disease. Similar effect was noted in children with growth potential (boys younger than 16 years, girls younger than 14 years). Median (IQR) height velocity standard deviation was -0.32 (-1.5-0.8) at week 26, and +0.11 (-1.1-1.3) at week 72. Median weight z score increased from -0.54 (-1.2-0.15) to -0.1 (-0.9-0.6), P < 0.001 and body mass index from -0.4 (-1.0-0.5) to 0.0 (-0.8-0.9), P = 0.005. Pediatric CD activity index and erythrocyte sedimentation rate at week 4 correlated negatively with height z score changes (P = 0.043 and P = 0.048, respectively), whereas sustained clinical and biologic remission (week 4-72) were positively associated with changes in height z scores. Significant improvement in linear growth was predicted by lower pediatric CD activity index and erythrocyte sedimentation rate at the end of induction and sustained clinical remission (P = 0.05) and sustained normal C-reactive protein (P = 0.001) at all visits., Conclusion: In children with moderate-to-severe CD, ADL treatment had a significant effect on linear growth, with normalization of weight and body mass index (clinicaltrials.gov no: NCT02256462).