Fertility preservation parameters in patients with haematologic malignancy: a systematic review and meta-analysis.

Patients with haematologic malignancies represent one of the most common groups referred for fertility preservation before gonadotoxic oncological treatment. The aim of this systematic review and meta-analysis was to evaluate the effect of haematologic cancer on ovarian reserve and response to ovarian stimulation compared with healthy controls. A total of eight observative studies were included in the final quantitative analysis. Despite a younger age (mean difference -4.17, 95% CI -6.20 to -2.14; P < 0.0001), patients with haematologic malignancy had lower serum anti-Müllerian hormone levels compared with the control group (MD -1.04, 95% CI -1.80 to -0.29; P = 0.007). The marginally higher total recombinant FSH dose (MD 632.32, 95% CI -187.60 to 1452.24; P = 0.13) and significantly lower peak oestradiol serum level (MD -994.05, 95% CI -1962.09 to -26.02; P = 0.04) were demonstrated in the study group compared with the healthy controls. A similar number of retrieved oocytes were achieved in both groups (MD 0.20, 95% CI -0.80 to 1.20; P = 0.69). In conclusion, haematologic malignancies may detrimentally affect ovarian function manifesting in decreased AMH serum levels despite a younger age compared with healthy controls. This effect can be overcome by the application of relevant IVF protocols and stimulation doses to achieve an adequate oocyte yield.

Helicobacter pylori-Associated Extranodal Marginal Zone Lymphoma of Mucosa-Associated Tissue in Children: A Multicenter Case Series.

OBJECTIVE: Data regarding Helicobacter pylori (H. pylori)-associated mucosa-associated lymphoid tissue (MALT) lymphoma in children are lacking. We aimed to characterize the diagnosis, management, and outcome of H. pylori-associated MALT lymphoma in pediatric patients. STUDY DESIGN: A retrospective multicenter case series of the pediatric patients with H. pylori-associated MALT lymphoma who were diagnosed during 2010-2022. RESULTS: Five children, of them three females, were identified. The mean age at diagnosis was 14.6 ± 2.4 years. The clinical presentation included abdominal pain (5/5), nausea (3/5), weight loss, night sweats, recurrent fever (1/5), and iron deficiency anemia (2/5). Endoscopic findings in both the stomach antrum and body included a fragile and hyperemic mucosa, large ulcers, extensive nodularity, and exudate. All the biopsies from the gastric mucosa were consistent with MALT lymphoma, and positive for H. pylori (by Giemsa stain). All the patients received triple therapy (amoxicillin, nitroimidazole, or a macrolide, and a proton pump inhibitor, for 14 days), and achieved H. pylori eradication. All had complete resolution of histological findings at the last follow-up. In one patient, the histology of MALT lymphoma persisted 12 months after H. pylori eradication, and only the 18-month-biopsy was free of residual disease. CONCLUSIONS: In this series of pediatric MALT lymphoma, complete resolution of disease occurred in all the patients, yet histological remission was delayed in one. This supports the importance of endoscopic follow-up.

Endomysial antibodies or anti-tissue transglutaminase type 2 IgA antibodies as a confirmatory test in children with celiac disease.

The no-biopsy approach to diagnose celiac disease (CD), introduced in the 2012 European Society for Gastroenterology and Hepatology and Nutrition guidelines, requires an anti-endomysial antibody (EMA) confirmatory serology test following a high-positive immunoglobulin A anti-tissue transglutaminase-2 (anti-TG2) antibody ≥10 times the upper limit of normal (ULN). The aim of this retrospective study is to compare EMA positivity and high-positive anti-TG2 in patients who had their confirmatory test within two month of their first high-positive anti-TG2 test. Among 933 patients who had high-positive anti-TG2 serology more than 10 times the ULN in their first sample, all had both high-positive anti-TG2 and positive EMA, most of them with very high EMA titers (99.6%) in their confirmatory test. In conclusion, we suggest that a repeated anti-TG2 test can replace the EMA test as the confirmatory serology test for the confirmation of the diagnosis of CD in the no-biopsy approach.

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.

Juvenile polyposis syndrome in children: The impact of SMAD4 and BMPR1A mutations on clinical phenotype and polyp burden.

OBJECTIVE: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS. METHODS: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group. RESULTS: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations. CONCLUSIONS: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status.

STEP-CD study: ustekinumab use in paediatric Crohn's disease-a multicentre retrospective study from paediatric IBD Porto group of ESPGHAN.

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7-17.2) with a median follow-up of 7.4 months (IQR 5.6-11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25-57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause.  Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12.

Sexual health in adolescents with inflammatory bowel disease - The paediatric gastroenterologists' point of view.

AIM: Although sexual health (SH) impairment and sexually transmitted infections (STI) are occasionally encountered in patients with inflammatory bowel disease (IBD), paediatric gastroenterologists (PedGI) do not often discuss these issues. Literature about SH in the paediatric IBD population is limited. We aimed to assess PedGI knowledge and common practice related to sexual advice and STI workups in patients with IBD. METHODS: A questionnaire comprising 25 questions addressing sexual activity in youth, SH, recommendations, and workup for STI in adolescents with IBD was sent to all registered PedGI in Israel. RESULTS: Fifty-two physicians completed the questionnaire (27 males,52%). Only 50% correctly predicted the mean age that Israeli youth start practicing sex. Seventy-five per cent responded that providers should discuss sexual activity with their patients, but only 19% do so, most often in response to a patient's query. Ninety six percent answered that they do not have enough knowledge about SH in IBD. Finally, only 2% obtain rectal swabs for STI in patients with refractory proctitis. CONCLUSION: Sexual issues and recommendations are not routinely discussed by the majority of PedGI in paediatric IBD clinics. Providers should obtain more knowledge in the field and initiate discussion of these issues with adolescent patients with IBD.

Accidental uterine extensions in cesarean deliveries - outcome of subsequent pregnancy.

OBJECTIVES: To explore the obstetric, maternal and neonatal outcome in the subsequent pregnancy after a pregnancy with an accidental uterine extension (AUE) during cesarean delivery (CD), as well as the relationship between the different types of AUE (inferior, lateral and superior). METHODS: A retrospective cohort study of all CD with AUE in a tertiary medical center between 01/2011-01/2022. Women with a prior CD with AUE were compared to a 1:3 ratio matched control group of women with a prior CD without AUE. All AUE were defined in their direction, size and mode of suturing. CD with deliberate uterine extensions were excluded. We evaluated obstetric, maternal and neonatal outcomes in the subsequent pregnancy after a pregnancy with AUE during CD. RESULTS: Comparing women with a prior CD with AUE (n=177) to the matched control group of women with a prior CD without AUE (n=528), we found no significant differences in proportions of uterine rupture or any other major complication or adverse outcome between the groups. There were no significant differences in the outcomes of the subsequent pregnancy in relation to the characteristics of the AUE (direction, size and mode of suturing). CONCLUSIONS: Subsequent pregnancies after AUE are not associated with higher maternal or neonatal adverse outcomes including higher proportions of uterine rupture compared to pregnancies without previous AUE. Different characteristics of the AUE do not impact the outcome.

Pregnancy Outcomes after Uterine Preservation Surgery for Placenta Accreta Spectrum: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to investigate maternal and neonatal outcomes in subsequent pregnancies of women with a history of placenta accreta spectrum (PAS) compared with women without history of PAS. STUDY DESIGN: A retrospective cohort study conducted at a single tertiary center between March 2011 and January 2022. We compared women with a history of PAS who had uterine preservation surgery and a subsequent pregnancy, to a control group matched in a 1:5 ratio. The primary outcome was the occurrence of a composite adverse outcome (CAO) including any of the following: uterine dehiscence, uterine rupture, blood transfusion, hysterectomy, neonatal intensive care unit admission, and neonatal mechanical ventilation. Multivariable logistic regression was performed to evaluate associations with the CAO. RESULTS: During the study period, 287 (1.1%) women were diagnosed with PAS and delivered after 25 weeks of gestation. Of these, 32 (11.1%) women had a subsequent pregnancy that reached viability. These 32 women were matched to 139 controls. There were no significant differences in the baseline characteristics between the study and control groups. Compared with controls, the proportion of CAO was significantly higher in women with previous PAS pregnancy (40.6 vs. 19.4%, p = 0.019). In a multivariable logistic regression analysis, previous PAS (adjusted odds ratio [aOR] = 3.31, 95% confidence interval [CI] = 1.09-10.02, p = 0.034) and earlier gestational age at delivery (aOR = 3.53, 95% CI = 2.27-5.49, p < 0.001) were independently associated with CAOs. CONCLUSION: A history of PAS in a previous pregnancy is associated with increased risk of CAOs in subsequent pregnancies. KEY POINTS: · The uterine-preserving approach for PAS delivery is gaining more attention and popularity in recent years.. · Women with a previous pregnancy with PAS had higher rates of CAOs in subsequent pregnancies.. · Previous PAS pregnancy is an independent factor associated with adverse outcomes..

Neonatal outcomes in pregnancies complicated by placenta accreta- a matched cohort study.

PURPOSE: Pregnancies complicated by placenta accreta spectrum (PAS) are associated with severe maternal morbidities. The aim of this study is to describe the neonatal outcomes in pregnancies complicated with PAS compared with pregnancies not complicated by PAS. METHODS: A retrospective cohort study conducted at a single tertiary center between 03/2011 and 01/2022, comparing women with PAS who underwent cesarean delivery (CD) to a matched control group of women without PAS who underwent CD. We evaluated the following adverse neonatal outcomes: umbilical artery pH < 7.0, umbilical artery base excess ≤ - 12, APGAR score < 7 at 5 min, neonatal intensive care unit (NICU) admission, mechanical ventilation, hypoxic ischemic encephalopathy, seizures and neonatal death. We also evaluated a composite adverse neonatal outcome, defined as the occurrence of at least one of the adverse neonatal outcomes described above. Multivariable regression analysis was used to determine which adverse neonatal outcome were independently associated with the presence of PAS. RESULTS: 265 women with PAS were included in the study group and were matched to 1382 controls. In the PAS group compared with controls, the rate of composite adverse neonatal outcomes was significantly higher (33.6% vs. 18.7%, respectively, p < 0.001). In a multivariable logistic regression analysis, Apgar score < 7 at 5 min, NICU admission and composite adverse neonatal outcome were independently associated with PAS. CONCLUSION: Neonates in PAS pregnancies had higher rates of adverse outcomes. Apgar score < 7 at 5 min, NICU admission and composite adverse neonatal outcome were independently associated with PAS.

Obstetric and Early Neonatal Outcomes Following Second and Third COVID-19 Vaccination in Pregnancy.

BACKGROUND: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective. OBJECTIVES: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses. METHODS: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose. RESULTS: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (212 vs. 315 weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048-0.926, P = 0.039). CONCLUSIONS: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

Neutrophil Extracellular Traps in Pediatric Inflammatory Bowel Disease: A Potential Role in Ulcerative Colitis.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gut affecting both adults and children. Neutrophil extracellular traps (NETs) are structures released by activated neutrophils, potentially contributing to tissue damage in various diseases. This study aimed to explore the presence and role of NETs in pediatric IBD. We compared intestinal biopsies and peripheral blood from 20 pediatric IBD patients (UC and CD) to controls. Biopsy staining and techniques for neutrophil activation were used to assess neutrophil infiltration and NET formation. We also measured the enzymatic activity of key NET proteins and evaluated NET formation in UC patients in remission. Both UC and CD biopsies showed significantly higher levels of neutrophils and NETs compared to controls (p < 0.01), with UC exhibiting the strongest association. Peripheral blood neutrophils from UC patients at diagnosis displayed increased NET formation compared to controls and CD patients. Interestingly, NET formation normalized in UC patients following remission-inducing treatment. This pilot study suggests a potential role for NETs in pediatric IBD, particularly UC. These findings warrant further investigation into the mechanisms of NET involvement and the potential for targeting NET formation as a therapeutic strategy.

Trends and Correlates of Early-Life Exposure to Acid-Suppressant Therapy in Israel (2005-2020).

OBJECTIVES: To describe trends and correlates of acid-suppressant therapy usage during the first year of life. STUDY DESIGN: A population-based cohort in a large state-mandated health fund in Israel, including members born between 2005 and 2020, was conducted. Acid-suppressant therapy initiation was defined by any purchase within the first year of life. The association between acid-suppressant therapy initiation with medical and sociodemographic characteristics was assessed via logistic regression. RESULTS: Among 595 860 children, acid-suppressant therapy was initiated in 22 412 (37.6 per 1000). The incidence rate increased by 2.8-fold from 18.2 per 1000 in 2005 to 51.0 per 1000 in 2020, furthermore the median age at initiation decreased. Primary care providers accounted for 74.8% of prescribing physicians in 2005 vs 96.1% in 2020, whereas the prevalence of prescribing gastroenterologists decreased from 18.8% to 2.8%. Preterm birth and small weight per gestational age were associated with acid-suppressant therapy usage, with an aOR of 4.23 (95% CI 3.59-4.99), 3.05 (95% CI 2.72-3.42), and 1.65 (95% CI 1.58-1.74) for extreme, very, and moderate preterm vs term birth and aOR 1.22 (95% CI 1.16-1.28) for small weight per gestational age. Birth order was inversely associated with acid-suppressant therapy initiation, with aOR 0.62 (95% CI 0.60-0.65) for third born vs firstborns. High socioeconomic status was linearly associated with initiation, with aOR 1.12 (95% CI 1.11-1.12) per 1-point increase on a 10-point score. CONCLUSIONS: Our analysis demonstrates a substantial increase in early life exposure to acid-suppressant therapy during recent years in Israel. Correlates for initiation in early life were identified to define a population for intervention to reduce potential unnecessary use.

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.

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.

Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN.

OBJECTIVES: Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD. METHODS: This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up. RESULTS: Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported. CONCLUSIONS: Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.

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.

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.