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OBJECTIVE: We aimed to compare symptom frequency and severity in children with functional abdominal pain disorders (FAPDs) and to evaluate anxiety, quality of life (QoL) and global health during Coronavirus disease 2019 (COVID-19) related quarantine and after 17 months. METHODS: Children diagnosed with FAPDs between October 2019 and February 2020 at 5 different centers were enrolled and prospectively interviewed during the COVID-19 quarantine and 17 months later when schools, hospital services, and routine activities had re-opened to the public. The patients were asked to complete the Rome IV questionnaire, the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core Scale, the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and global health questionnaires. Data about COVID-19 infection and its clinical outcome were also collected. RESULTS: Ninety-nine out of 180 (55%) children completed the follow-up. The number of patients reporting a worsening of their symptoms was significantly higher at follow-up when compared to the quarantine period (24/99 [24.2%] vs. 12/99 [12.1%]; p = 0.04). The PedsQL 4.0 subtotal score at follow-up significantly decreased at 17 months of follow-up (65.57 [0-100]) when compared to the quarantine (71 [0-100], p = 0.03). Emotional functioning was the most significantly reduced (Follow-up: 64.7 [0-100] vs. Quarantine: 75 [0-100]; p = 0.006). We did not identify significant differences in symptoms and QoL between COVID-19 infected children and the remaining cohort at the two time points. CONCLUSIONS: An improvement of symptoms and QoL was observed during the quarantine, followed by a worsening at-follow-up. These findings reinforce the hypothesis that the nest effect overweighted COVID-19 fears during the quarantine and highlight the importance of psychological factors in symptom exacerbation.

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BACKGROUND: Biliary strictures are a significant cause of morbidity and graft loss in pediatric liver transplant recipients. Risk factors for the development of biliary strictures are not fully established. We aimed to evaluate the incidence of biliary strictures and treatment modalities outcomes and to identify potential risk factors for occurrence. METHODS: Pediatric patients who underwent liver transplantation in the single tertiary pediatric liver transplant center in Israel were evaluated. We compared demographics, presentation, laboratory results, imaging, treatment, and outcomes between patients with and without biliary stricture. Multivariate regression analyses were used to identify risk factors for biliary strictures. RESULTS: Among 121 pediatric liver transplant patients, 65 (53.7%) were males; the median age at the time of liver transplantation was 43 (3-215) months. Fifteen patients (12.4%) had biliary strictures following transplantation. One (7%) patient with biliary stricture was treated via endoscopic retrograde cholangiopancreatography, and 12 patients (80%) underwent interventions via a percutaneous transhepatic approach. Nine of the 12 patients were treated successfully, requiring one or multiple procedures, while the remaining had surgery or laser therapy. Risk factors for the development of biliary strictures were biliary leak, acute cellular rejection, and the presence of two biliary anastomoses. CONCLUSIONS: In our cohort, the presence of two biliary anastomoses and post-transplant complications including acute cellular rejection and early biliary leaks were associated with biliary strictures in pediatric liver transplantation recipients. Percutaneous transhepatic interventions result in good outcomes in most patients.

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Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth.

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OBJECTIVE: There is no gold standard to assess adherence to gluten-free diet (GFD) among patients with celiac disease (CeD). Gluten immunogenic peptides (GIPs) in urine and stool were suggested as novel markers for evaluating adherence to GFD. Our aim was to assess the presence of GIP in pediatric patients with CeD, and to compare the results with alternative methods for evaluating GFD adherence. METHODS: Pediatric patients diagnosed with CeD, who were on GFD for at least 1 year, were enrolled and followed prospectively between November 2018 and January 2021. Study visits included clinical assessment, a dietitian interview, Biagi score, food questionnaires, anthropometric and laboratory measurements, and urine and stool samples obtained for laboratory GIP analysis. RESULTS: The study included 74 patients (63.5% females), with median (interquartile range, IQR) age of 9.9 (7.8-11.7) years, and median (IQR) duration on GFD of 2.5 (2-5.5) years. Good GFD adherence, assessed by Biagi score, was reported in 93.1% of cases. GIP was evaluated during 134 visits, with GIP detected in 27 of 134 (20.1%) of the visits (16.3% of stool samples and 5.3% of urine samples). Positive GIP results were significantly more common in males compared to females (30.6% vs 14.1%, respectively, P < 0.05). Detection of positive GIP was not associated with dietary assessment of GFD adherence, celiac serology results, or reported symptoms. CONCLUSIONS: Stool and urine GIP can be detected in children with CeD, even when dietary assessment indicate good adherence to GFD. The role of GIP testing in clinical practice should be further explored.

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Background: The increased intake of FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyol) rich foods has been suggested as a possible trigger of functional gastrointestinal disorders (FGIDs). Despite the high FODMAP content, the Mediterranean diet (MD) appears to have beneficial effects on health. Our aim was to evaluate whether the prevalence of FGIDs in different Mediterranean countries may be influenced by FODMAP consumption and adherence to the MD. Methods: A school-based, cross-sectional, multicenter study was performed in six countries in the Mediterranean area: Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects 4-18 years were examined in relation to their eating habits and the presence of FGIDs, using Rome IV criteria, 3-day food diaries and Mediterranean Diet Quality Index in Children and Adolescents (KIDMED) questionnaires. Results: We enrolled 1972 subjects between 4 and 9 years old (Group A), and 2450 subjects between 10 and 18 years old (Group B). The overall prevalence of FGIDs was 16% in Group A and 26% in Group B. FODMAP intake was significantly different among countries for both age groups. In both groups, no significant association was found between FGIDs and FODMAPs. Adherence to the MD in all countries was intermediate, except for Serbia, where it was low. In both groups, we found a statistically significant association between FGIDs and the KIDMED score (Group A: OR = 0.83, p < 0.001; Group B: OR = 0.93, p = 0.005). Moreover, a significant association was found between the KIDMED score and functional constipation (Group A: OR = 0.89, p = 0.008; Group B: OR = 0.93, p = 0.010) and postprandial distress syndrome (Group A: OR = 0.86, p = 0.027; Group B: OR = 0.88, p = 0.004). Conclusions: Our data suggest that the prevalence of FGIDs in the Mediterranean area is not related to FODMAP consumption, whereas adherence to the MD seems to have a protective effect.

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OBJECTIVES: Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. METHODS: This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. RESULTS: We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. CONCLUSIONS: We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.

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PURPOSE: Kasai portoenterostomy (KPE) is the only treatment currently available for biliary atresia (BA). Age at KPE and surgical experience are prognostic factors for a successful KPE. Here, we aimed to assess whether the size of bile ductules at the porta hepatis during KPE correlates with KPE success and transplant-free survival (TFS). METHODS: A retrospective analysis of patients diagnosed with BA during 2000-2019. Porta hepatis biopsies were reviewed for diameters of five representative ducts, and a mean ductal diameter (MDD) was calculated. Laboratory values including pre- and postoperative bilirubin levels were analyzed. RESULTS: The cohort included 77 patients; for 33, ductal plate biopsy was available. KPE was successful in six of eight patients with MDD ≥ 50 µm, and in five of 25 with MDD < 50 µm, p = 0.008, OR = 12.0 (95% CI 1.83-78.3). Ten-year survival with native liver was higher in patients with MDD ≥ 50 µm than in patients with MDD < 50 µm, p < 0.001, HR 0.038 (95% CI 0.007-0.207). Direct bilirubin < 1 mg/dl 3 months post-KPE was associated with improved 2-year post-KPE TFS (27.7% vs. 13.9%, p < 0.0001). CONCLUSIONS: MDD ≥ 50 µm correlates with KPE success and a higher rate of TFS. Direct bilirubin < 1 mg/dl 3 months post-operation may serve as a marker of successful biliary excretion, and a predictor of 2-year TFS.

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BACKGROUND: The COVID-19 pandemic has affected medical care worldwide. Thus, we aimed to assess the impact of the COVID-19 pandemic on pediatric LT recipients. METHODS: A cross-sectional study based on a structured internet or telephone survey was conducted among pediatric LT recipients. Survey results were compared with results of a survey conducted among pediatric patients with IBD. RESULTS: Seventy-six pediatric LT patients participated in the study. Of them, 58 (76.3%) reported fear of severe COVID-19 infection due to LT or LT-associated medications. Half of the patients reported needing emotional support. Most patients (51, 67.1%) reported strictly following official guidance, while more stringent protective measures were taken by 64 (84.2%) patients. None of the patients discontinued their medications due to COVID-19. Compared to pediatric patients with IBD, a higher proportion of pediatric LT recipients reported fears of contracting severe COVID-19 infection due to their illness or medications (45, 59.2% vs. 110, 45.1%). CONCLUSION: Among pediatric LT recipients a higher proportion reported fear of severe COVID-19 infection, implemented additional protective measures and expressed a need for emotional support, compared to patients with IBD. Medical teams should provide adequate information and offer a support system for this vulnerable population.

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OBJECTIVES: The aim of this study was to assess the prevalence of functional gastrointestinal disorders (FGIDs) in children of Mediterranean area using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV and Rome III criteria. METHODS: This was a cross-sectional study enrolling children and adolescents living in Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects were examined in relation to the presence of FGIDs, using the Rome IV criteria. Data were compared with the results of a previous study using Rome III data. RESULTS: We analyzed 1972 children ages 4 to 9 years (group A), and 2450 adolescents 10 to 18 years old (group B). The overall prevalence of FGIDs was 16% in group A and 26% in group B, with statistical differences among countries in both groups (P < 0.001). In group A, the prevalence of FGIDs and of functional constipation (FC) was significantly lower than in the previous study (P < 0.001), whereas in group B no significant difference was found. In both groups of age, the prevalence of abdominal migraine and irritable bowel syndrome decreased significantly (P < 0.001 and P < 0.001, respectively) using Rome IV versus Rome III criteria, conversely functional dyspepsia increased (P < 0.001). CONCLUSIONS: FGIDs are common in children and adolescents, their frequency increases with age, and there is a significant variation in the prevalence of some FGIDs among different European countries. The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs in children compared with Rome III criteria.

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AIM: Infants with biliary atresia (BA) generally have chronic malnutrition. However, the best anthropometric measure to assess malnutrition and its correlation with disease severity is unknown. We aimed to assess correlations of various anthropometric measurements, including air displacement plethysmography (ADP), with laboratory parameters and with the pediatric end-stage liver disease (PELD) score in infants with BA. METHODS: Infants with BA were followed at a pediatric liver transplantation center during 2014-2018. Follow-up comprised laboratory tests and nutritional assessment by a dietitian including dietary intake, weight, height, mid-upper arm circumference (MUAC), and skin-fold thickness. Fat-free mass (FFM) and fat mass (FM) were measured by ADP. RESULTS: Forty-three nutritional evaluations were performed in 28 infants with BA (13 boys, 44.4%). The median age was 20.7 weeks (IQR: 13-25.9). Based on the various anthropometry modalities, infants with BA were found to be malnourished on most of the visits; 63% had a MUAC-Z score lower than -2 standard deviations. High serum bilirubin level predicted lower weight for age, length for age, and MUAC-Z. Lower MUAC-Z was associated with a higher PELD score. Neither FM mass nor FFM correlated with PELD or with serum bilirubin level. However, FM correlated with skin-fold thickness-Z and was low in most patients. CONCLUSIONS: The majority of BA infants suffer from malnutrition as assessed by most anthropometrics modalities; low MUAC correlated best with disease severity and serum bilirubin level. Further studies are warranted to determine the contribution of FM measurement by ADP to the anthropometric assessment of infants with BA.

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OBJECTIVE: We aimed to assess how the first phase of coronavirus disease 2019 (COVID-19) pandemic influenced symptoms in children with functional abdominal pain disorders (FAPDs) and to characterize their quality of life (QoL), anxiety and global health. METHODS: This was a multicenter, observational, international study conducted between April and July 2020 at six different referral centers. Children diagnosed with FAPDs between October 2019 and February 2020 were enrolled and prospectively interviewed at 4 months of follow-up during the first pandemic phase (Quarantine group). Patients were asked to complete PedsQL 4.0 Generic Core Scale and PROMIS Anxiety and Global Health questionnaires. A cohort of children diagnosed with FAPDs between October 2018 and February 2019 was used as a Control group. RESULTS: Three-hundred-fifty-six children were enrolled of whom 180 (mean age at diagnosis: 14 ±â€Š2.8 years) in the Quarantine group and 176 (mean age at diagnosis: 13 ±â€Š2.8 years) in the Control group. At 4 months of follow-up, we observed a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline, in both groups (Quarantine group: 63.9% vs 42.2%, P < 0.001; Control group: 83.5% vs 50%, P < 0.001). The Quarantine group had median QoL values of 84.8 with 16.6% of children showing high anxiety values and 55% having decreased global health score. CONCLUSIONS: We demonstrated symptoms' improvement at 4 months of follow-up in both cohorts. During the first months of the COVID-19 quarantine children with FAPDs showed satisfactory QoL and anxiety scores, suggesting positive effects of school closure and increased parental attention.

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OBJECTIVES: Celiac disease (CD) is a common intestinal autoimmune disorder with diverse presenting features. We aimed to determine age-dependent patterns in CD presentation, diagnosis and management at a large tertiary referral center. METHODS: A retrospective review of electronic medical records of pediatric patients diagnosed with CD between January 1999 and December 2018 at Schneider Children's Medical Center of Israel. We compared demographics, clinical and laboratory parameters between four age groups at CD presentation. RESULTS: A cohort of 932 children was divided into four groups by age (in years) at diagnosis: 0-3 (17.9%), 3-6 (31.8%), 6-12 (34.5%), 12-18 (15.8%). The youngest age group presented more frequently with diarrhea, weight loss, abdominal distention, vomiting and lower weight z scores, P < 0.01. Hypoalbuminemia and zinc deficiency were also more frequent in this age group, compared to older patients (P < 0.05, each). Rates of anemia were higher in younger age groups (0-3 and 3-6 years), compared to older age groups, P < 0.05. Patients in the younger age groups (0-3 and 3-6 years) presented more frequently with tissue transglutaminase (TTG) levels above 10 times the upper limit of normal (ULN; P < 0.05), and more often normalized their CD serologies by 24 months of gluten-free diets (GFD) compared to older age groups (P < 0.05). CONCLUSION: There is an age-dependent variation in CD presentation during childhood. Younger patients present more often with malabsorptive features, and higher TTG levels, yet normalize TTG while on GFD more rapidly than older patients. Clinicians should be aware of the diversity in CD presentation and course at the various presentation age.

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OBJECTIVES: Severe obesity in the pediatric population has lifelong consequences. Bariatric surgery has been suggested for selected adolescents with severe obesity after careful evaluation. The indications for preoperative esophagogastroduodenoscopy (EGD) in this age group are not clear, despite its established usefulness in adults. We aimed to assess the usefulness of EGD before bariatric surgery in pediatric patients with severe obesity and metabolic comorbidities. METHODS: We conducted a retrospective chart review in a single tertiary pediatric medical center of adolescents treated during 2011 to 2018. Data collected from electronic medical records included patient demographics, endoscopic findings, and laboratory parameters. RESULTS: A total of 80 patients (40 boys) underwent evaluation. Macroscopic abnormalities were detected in 54% of the endoscopies, including gastritis, esophagitis, and duodenitis in 46%, 16%, and 13%, respectively. Forty-nine percentage of the biopsies showed histological abnormalities; in 35 (44%) patients, Helicobacter pylori was detected. Thirty-three patients (41%) received medical treatment and 2 (2.5%) required a second EGD. Metabolic comorbidities included hypertriglyceridemia (38% of the patients), low high-density lipoprotein (23%), and prediabetic (16%) or diabetic levels of HbA1C (4%). Fifty-five percentage of the cohort had elevated alanine aminotransferase (ALT), suggestive of nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: Endoscopies performed before bariatric surgeries suggest a higher prevalence of clinically significant findings, many of which required treatment. These findings support incorporating an EGD into the preoperative evaluation of this patient population.

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Adenosine kinase (ADK) deficiency is characterized by liver disease, dysmorphic features, epilepsy and developmental delay. This defect disrupts the adenosine/AMP futile cycle and interferes with the upstream methionine cycle. We report the clinical, histological and biochemical courses of three ADK children carrying two new mutations and presenting with neonatal cholestasis and neurological disorders. One of them died of liver failure whereas the other two recovered from their liver damage. As the phenotype was consistent with a mitochondrial disorder, we studied liver mitochondrial respiratory chain activities in two patients and revealed a combined defect of several complexes. In addition, we retrospectively analyzed methionine plasma concentration, a hallmark of ADK deficiency, in a cohort of children and showed that methionine level in patients with ADK deficiency was strongly increased compared with patients with other liver diseases. ADK deficiency is a cause of neonatal or early infantile liver disease that may mimic primary mitochondrial disorders. In this context, an elevation of methionine plasma levels over twice the upper limit should not be considered as a nonspecific finding. ADK deficiency induced-liver dysfunction is most often transient, but could be life-threatening.

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BACKGROUND: Celiac disease (CD) is common worldwide with increasing prevalence and changing presentation. AIMS: To evaluate changes in the presentation and management of CD over the last two decades. METHODS: Retrospective chart review of pediatric patients with CD between 01.1999 to 12.2018 was performed. Comparisons were made between an early (1999 to 2008) and late (2009 to 2018) decade, regarding clinical and laboratory parameters at presentation and follow-up. RESULTS: In a cohort of 932 patients (early decade n = 316, late decade n = 616), patients from the late decade presented with lower rates of weight loss and abdominal distention (24.2% vs 34.7% and 6% vs 11%, respectively p < 0.01), and with higher rates of abdominal pain or asymptomatic presentation (41.4% vs 27.4%, p < 0.01, and 18% vs 13%, p < 0.05, respectively). Good adherence to gluten-free diet was reported more often in the late decade (64% vs 50.6%, p < 0.001), and fewer patients were lost to follow-up. During the late decade, significantly higher rates of celiac serology normalization were achieved during the first two years of follow-up. CONCLUSION: In recent years, children with CD were diagnosed with milder symptoms, showed better adherence and demonstrated earlier normalization of celiac serology.

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BACKGROUND & AIMS: Little is known about the prevalence of functional gastrointestinal disorders (FGIDs) in children from the Mediterranean area of Europe. We aimed to assess the prevalence of FGIDs in children and adolescents in this region. METHODS: We collected data on 13,750 children (4-18 years old) enrolled in the Mediterranean-European Area Project, a school-based health study performed in Croatia, Greece, Israel, Italy, Jordan, Lebanon, Macedonia, Serbia, and Spain. Data were collected from March to June and in September of 2016. We analyzed data from 6602 students 4 to 10 years old (group A; mean age, 7.7 ± 1.9 y), and 7148 subjects 11 to 18 years old (group B; mean age, 13.8 ± 2.1 y). Children with FGIDs were identified based on answers to questionnaires on pediatric gastrointestinal symptoms, selected based on Rome III criteria. RESULTS: In group A, the prevalence of FGIDs was 20.7%. The most frequent disorders were functional constipation (11.7%), irritable bowel syndrome (IBS, 4%), aerophagia (3.5%), and abdominal migraine (3.1%). The prevalence of abdominal migraine was significantly higher in girls than in boys (P = .007). In group B, the overall prevalence of FGIDs was 26.6%. The most frequent disorders were functional constipation (13.1%), abdominal migraine (7.8%), aerophagia (6.3%), and IBS (5.6%). In group B, FGIDs had a higher prevalence among girls than boys (P < .001). In both groups, we found significant differences in the prevalence of specific disorders among specific countries. CONCLUSIONS: In an analysis of data on children 4 to 18 years old from the Mediterranean-European Area Project, we found FGIDs to be more frequent in girls. Functional constipation, aerophagia, abdominal migraine, and IBS are the most common disorders. However, the prevalence of FGIDs varies significantly among countries.

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OBJECTIVES: Childhood functional gastrointestinal disorders (FGIDs) are common conditions associated with significant morbidity and high healthcare costs. This multicenter study aimed at assessing the clinical approach to infants (0-6 months) and children/adolescents (4-18 years) with suspected FGIDs by pediatricians from the Mediterranean Area. METHODS: A survey evaluating the diagnostic approach, including the use of Rome II and III criteria, and the therapeutic management of some of the most prevalent FGIDs, such as irritable bowel syndrome (IBS), functional constipation (FC), and functional regurgitation (FR), was distributed to a sample of pediatricians. RESULTS: We collected 278 questionnaires from 9 countries (Croatia, Greece, Israel, Italy, Lebanon, Montenegro, Serbia, Slovenia, and Spain). Rome III criteria are used to diagnose FC by 28.8%. Treatment of FC is based on dietary modifications (97.5%) and osmotic laxatives (93.5%). Rome III criteria are used to diagnose FR by 22.3% of the responders, in contrast to 79.5% who rely on personal experience for diagnosis. Reported treatments mainly consist of reassurance (96.8%) and thickened feedings (77.3%). Nevertheless, 21.2% prescribe proton pump inhibitors or H2-blockers to infants with FR. Rome III criteria are used to diagnose IBS by only 25.9%. Moreover, 86% of the pediatricians base IBS therapy on the predominant symptom. The most prescribed treatments are analgesics (36.6%) for pain control, dietary advice (41.5%) for diarrhea-predominant IBS, and dietary advice (47.8%) for constipation-predominant IBS. CONCLUSIONS: Our data show that the use of Rome III diagnostic criteria is not sufficiently widespread among pediatricians, and that large variability remains in the management of FGIDs within the different Mediterranean countries surveyed.

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No broadly protective vaccine is available for the prevention of group B meningococcal disease. One promising candidate is factor H-binding protein (fHbp), which is present in all strains but often sparsely expressed. We prepared seven murine immunoglobulin G monoclonal antibodies (MAbs) against fHbp from antigenic variant group 2 (v.2) or v.3 ( approximately 40% of group B strains). Although none of the MAbs individually elicited bactericidal activity with human complement, all had activity in different combinations. We used MAb reactivity with strains expressing fHbp polymorphisms and site-specific mutagenesis to identify residues that are important for epitopes recognized by six of the v.2 or v.3 MAbs and by two v.1 MAbs that were previously characterized. Residues affecting v.2 or v.3 epitopes resided between amino acids 174 and 216, which formed an eight-stranded beta-barrel in the C domain, while residues affecting the v.1 epitopes included amino acids 121 and 122 of the B domain. Pairs of MAbs were bactericidal when their respective epitopes involved residues separated by 16 to 20 A and when at least one of the MAbs inhibited the binding of fH, a downregulatory complement protein. In contrast, there was no cooperative bactericidal activity when the distance between residues was >or=27 A or

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