Influence of Hemoglobin S Haplotypes on the Responses to Hydroxyurea Treatment in Children with Sickle Cell Disease in Abidjan, Côte d’Ivoire

Background: In Côte d’Ivoire so far, the circulating haplotypes have been inferred on the phenotypic profiling of SCD patients. The impact of the circulating haplotypes on the use of Hydroxyurea has not been assessed yet. Therefore the objective of this study is to identify in Abidjan the HbS haplotypes that modulate HU treatment responses. Methods: In a cross-sectional descriptive and analytical study, children aged 5 to 15 years with SCD, and carrying the hemoglobin phenotypes SSFA2 and SFA2, were recruited into a HU treatment cohort. Various parameters on the haplotypes and the outcomes of the treatment were analyzed. Results: Thirty nine children with SCD were included. The phenotypic profile of the cohort was 86.6% of SSFA2 and 15.4% of SFA2. Three haplotypes were found, the Benin haplotype, the Senegal haplotype, and an atypical one. The participants belonged to three genotypes, Benin/atypical (64.1%), Benin/Senegal (33.3%) and Senegal/Senegal (2.6%). Overall, HU treatment was successful in all haplotypes with 12 out of 39 patients failing treatment after 12 months in the Benin haplotype group. The association between HU treatment success and the Benin haplotype was found in terms of the decrease in the number of white blood cells and the students missing class. Conclusion: The study revealed that inferring haplotype based on the phenotypic profile could be inaccurate. The proportion of atypical haplotype that were not previously described in Côte d’Ivoire was high. All the haplotypes seemed to be associated with HU treatment success but some patients with Benin haplotype did not respond well.

Children with Sickle Cell Disease in Northern Benin: Follow up of a Cohort at the Borgou/Alibori Branch of Integrated Medical Healthcare Center for Infants and Pregnant Women with Sickle Cell Disease from 2017 to 2022

Introduction: Sickle cell disease is a public health problem in sub-Saharan Africa. A national referral center for the management of infants and pregnant women with sickle cell disease (CPMI-NFED) was created three decades ago in Cotonou, in the south of Benin with two regional branches including that of Parakou in the North for better access of patients to specialized care. This work is a review of five years of activities in order to describe the epidemiological, clinical, hematological and evolutionary profiles of the children followed up in the said branch. Method: This was a descriptive and retrospective cross-sectional study on the medical records of children with sickle cell disease, followed up at the regional branch of CPMI-NFED in Borgou/Alibori from June 1, 2017 to May 31, 2022. The variables studied were epidemiological, clinical, biological and evolutionary. Results: A total of 101 children with sickle cell disease were included in the study, including 78 homozygous SS (77.2%) and 23 heterozygous SC (22.8%). Their mean age at inclusion was 51.2 ± 37.6 months [6 - 204]. The sex ratio was 1.4. Vaso-occlusive crises were the main diagnostic circumstances in 42.3% of homozygotes. More than half of the children (51.5%) had a regular follow-up. The average baseline level of hemoglobin (Hb) in homozygous children was 8.8 ± 1.4 g/dl [5.8 - 11.5];and the rate of Hb S varied between 61.9 and 94.7%. In heterozygous SC children, the mean baseline level of Hb was 10.7 ± 0.6 g/dl [9.7 - 11.5]. Acute complications observed during follow-up were dominated by pneumonia and vaso-occlusive crises in both phenotypes. The overall mortality was 3% and only affected homozygous patients. Conclusion: On average, three out of four children were homozygous in our cohort. The main acute complications were infectious and vaso-occlusive. The mortality only affected homozygous carriers. Specialized follow-up has contributed to improving the quality of life of children with sickle cell disease. This could be implemented on a large scale for better survival of children with sickle cell disease.

Transmission Dynamics and Optimal Control Strategies of a Hand-Foot-Mouth Disease Model with Treatment and Vaccination Interventions

In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.

Intestinal Microecology in Children with Pneumonia: The Relationship Between Digestive Health and Disease Recovery

This paper explores the association between intestinal microecology and digestive health and disease recovery in children with pneumonia.Intestinal microecological imbalance is common in children with pneumonia,which is closely associated with digestive health and disease recovery.Intestinal microecological imbalance may affect digestive enzyme activity,intestinal mucosal barrier function,and nutrient absorption,which in turn affects digestive health.In addition,intestinal microecological imbalances may be associated with immune regulation,inflammatory responses,and pathogen suppression,affecting disease recovery.Strategies to regulate intestinal microecology include probiotic supplementation,dietary modification,and pharmacological treatment.Currently,the study of intestinal microecology in children with pneumonia faces challenges,and there is a need for improved research methods,individualized treatment strategies,and the development of novel probiotics.In conclusion,the intestinal microecology of children with pneumonia is closely related to digestive health and disease recovery,and the regulation of intestinal microecology is of great significance to the treatment of children with pneumonia.Furthermore,future research should further explore the application of the microecology of the intestinal microecology in the treatment of children with pneumonia.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

Gastroesophageal reflux disease in children: What’s new right now?

Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.

Gut microbiota predicts the diagnosis of celiac disease in Saudi children

BACKGROUND Celiac disease(CeD)is a multisystem immune-mediated multifactorial condition strongly associated with the intestinal microbiota.AIM To evaluate the predictive power of the gut microbiota in the diagnosis of CeD and to search for important taxa that may help to distinguish CeD patients from controls.METHODS Microbial DNA from bacteria,viruses,and fungi,was isolated from mucosal and fecal samples of 40 children with CeD and 39 controls.All samples were sequenced using the HiSeq platform,the data were analyzed,and abundance and diversities were assessed.For this analysis,the predictive power of the microbiota was evaluated by calculating the area under the curve(AUC)using data for the entire microbiome.The Kruskal-Wallis test was used to evaluate the significance of the difference between AUCs.The Boruta logarithm,a wrapper built around the random forest classification algorithm,was used to identify important bacterial biomarkers for CeD.RESULTS In fecal samples,AUCs for bacterial,viral,and fungal microbiota were 52%,58%,and 67.7%respectively,suggesting weak performance in predicting CeD.However,the combination of fecal bacteria and viruses showed a higher AUC of 81.8%,indicating stronger predictive power in the diagnosis of CeD.In mucosal samples,AUCs for bacterial,viral,and fungal microbiota were 81.2%,58.6%,and 35%,respectively,indicating that mucosal bacteria alone had the highest predictive power.Two bacteria,Bacteroides intestinalis and Burkholderiales bacterium 1-1-47,in fecal samples and one virus,Human_endogenous_retrovirus_K,in mucosal samples are predicted to be“important”biomarkers,differentiating celiac from nonceliac disease groups.Bacteroides intestinalis is known to degrade complex arabinoxylans and xylan which have a protective role in the intestinal mucosa.Similarly,several Burkholderiales species have been reported to produce peptidases that hydrolyze gluten peptides,with the potential to reduce the gluten content of food.Finally,a role for Human_endogenous_retrovirus_K in immune-mediated disease such as CeD has been reported.CONCLUSION The excellent predictive power of the combination of the fecal bacterial and viral microbiota with mucosal bacteria alone indicates a potential role in the diagnosis of difficult cases of CeD.Bacteroides intestinalis and Burkholderiales bacterium 1-1-47,which were found to be deficient in CeD,have a potential protective role in the development of prophylactic modalities.Further studies on the role of the microbiota in general and Human_endogenous_retrovirus_K in particular are needed.

Having a Partner and Having Children:Comparisons of Adults with Congenital Heart Disease and the General Population:A 15-Year Case-Control Study

Objectives:To examine whether patients with congenital heart disease(CHD)are less likely to have a partner or children than individuals from the general population.Methods:Longitudinal study with two assessments of the same patients(n=244)from a hospital population and controls(n=238)from the German Socio-Economic Panel(GSOEP)using parental education,patients age,and sex as matching criteria.The first patient study was conducted between 5/2003 and 6/2004,the second one between 5/2017 and 4/2019.Controls were drawn from GSOEP-surveys 2004 and 2018.CHD-severity was classified according to type of surgery:curative,reparative,or palliative.Living single was used as outcome measure,for offspring the outcome was having children or not.Results:Among women with CHD the rate of those living single was higher than among controls with the differences depending on disease complexity(curative:OR=5.5;reparative:OR=1.9;palliative:OR=2.7).No statistically significant differences between patients and controls emerged in the male study population.With respect to children a marked difference emerged between women with CHD and controls.Among patients the odds of having children were lower than among controls(curative:OR=0.3;reparative:OR=0.3;palliative:OR=0.2).The rate of patients with children with CHD(women:5.6%;men:4.9%)was higher than expected(1%)if compared with the general population.Conclusions:Using partnership and children as outcome criteria,patients with CHD are disadvantaged if compared to subjects from the general population.In female patients the social consequences of the disease turned out as more pervasive than in women.

The Prevalence of Congenital Heart Disease among School-Age Children in China:A Meta-Analysis and Systematic Review

Objectives:To estimate the prevalence of Congenital Heart Disease(CHD)in school-age children,to identify the extent to which altitude affects the prevalence of the disease,and to examine trends in prevalence over time in China.Methods:Seven databases were systematically searched and last retrieved on September 10,2021 for all studies reporting the prevalence of CHD in children after 1970 in China,which were then divided into high and low altitude regions based on 2500 meters above sea level.The random-effected model was used to combine prevalence data and subgroups analysis.The baseline data of all cases and individuals were used for comparison to calculate the odds ratio(OR)for overall and different altitude prevalence.Results:A total of 12,926,083 individuals(aged 3-18 years),with 31,835 cases from 86 studies,were included in the analysis.The pooled CHD prevalence of total children was 4.69[95%confidence interval(CI):4.10 to 5.29]per 1000 children.Overall,temporal trends analysis indicated that the prevalence of CHD in children continuously decreased with time,from 6.19(95%CI:4.50 to 7.88)per 1000 children in 1976-1985 to 3.30(95%CI:2.49;4.38)per 1000 children in 2016-2021.The OR for the prevalence of CHD in children from high and low altitudes with baseline data was 2.84(95%CI:2.48 to 3.27)and 1.31(95%CI:1.13 to 1.53)(χ^(2)=53.89,p<0.01),respectively.The OR of the prevalence of CHD in male children compared to females was 0.60(95%CI:0.53 to 0.68)at high altitudes and 0.79(95%CI:0.71 to 0.89)at low altitudes.Among the seven most common subtypes,patent ductus arteriosus was the most common at high altitudes,while atrial septal defects were the most common at low altitudes.Conclusion:This study provides valuable insights for further disease prevention and etiological exploration.The overall decreasing trend in the prevalence of CHD in children over time may indicate a positive effect of perinatal management and treatment during infancy.

Effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease

Objective: To investigate the effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease. Methods: A total of 116 children with hand-foot-mouth disease who were treated in this hospital between September 2016 and February 2018 were selected as the study subjects and divided into the control group (n=58) and the Potassium Sodium Dehydroandrograpolide Succinate group (n=58) by random number table method. Control group received symptomatic + interferon therapy, and Potassium Sodium Dehydroandrograpolide Succinate group received symptomatic + interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy, and they were treated for 1 week. The differences in the serum contents of inflammatory factors, adhesion molecules and humoral immunity indexes were compared between the two groups before and after treatment. Results:Before treatment, serum levels of inflammatory factors, adhesion molecules and humoral immunity indexes were not significantly different between the two groups. After 1 week of treatment, serum inflammatory factors IL-1β, IL-10, PCT and hs-CRP levels of Potassium Sodium Dehydroandrograpolide Succinate group were lower than those of control group;serum adhesion molecules CD44, ICAM-1 and VCAM-1 levels were lower than those of control group;serum humoral immunity indexes IgA, IgG, C3 and C4 levels were lower than those of control group. Conclusion: Interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy can effectively reduce the systemic inflammatory response and improve the humoral immune function in children with hand-foot-mouth disease.

Correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease complicated by encephalitis

Objective:To study the correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease (HFMD) complicated by encephalitis.Methods:Children who were diagnosed with hand-foot-mouth disease in Yulin Third Hospital between May 2015 and February 2017 were selected, children who were combined with central nervous system were selected as severe group, and children who were not combined with central nervous system were selected as mild group;children who received physical examination during the same period were selected as the control group. Serum was collected to determine the contents of NSE, S100β and inflammatory response mediators, and peripheral blood was collected to determine the contents of T cell subsets and NK cells.Results: Serum NSE and S100β levels of severe group and mild group were significantly higher than those of control group, and serum NSE and S100β levels of severe group were significantly higher than those of mild group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group and mild group were significantly higher than those of control group while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of control group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group were significantly higher than those of mild group and positively correlated with NSE and S100β levels while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of mild group and negatively correlated with NSE and S100β levels.Conclusion: The increase of serum NSE and S100β levels in children with HFMD complicated by encephalitis is closely related to inflammatory response activation and immune response disorder.

Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”

Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver-which generally follows a benign, non-progressive clinical course-to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of "pediatric" NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.

Clinical and neuroimaging features of enterovirus71 related acute flaccid paralysis in patients with hand-foot-mouth disease

Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.

Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children

AIM: To investigate the effect of lifestyle intervention on non-alcoholic fatty liver disease (NAFLD) in Chinese obese children. METHODS: Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided randomly into three groups. Group1, consisting of 38 obese children, was an untreated control group without any intervention. Group 2, consisting of 19 obese children in summer camp, was strictly controlled only by life style intervention. Group 3, consisting of 19 obese children, received oral vitamin E therapy at a dose of 100 mg/d. The height, weight, fasting blood glucose (FBG), fasting serum insulin (FINS), plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TCHO) and homeostasis model assent- insulin resistance (HOMA-IR) were measured at baseline and after one month. All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups. RESULTS: The monitor indices of BMI, ALT, AST, TG, TCHO and HOMA-IR were successfully improved except in group 1. BMI and ALT in group 2 were reduced more significantly than in group 3 (2.44 ± 0.82 vs 1.45 ± 0.80, P = 0.001; 88.58 ± 39.99 vs 63.69 ± 27.05, P = 0.040, respectively).CONCLUSION: Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children. Compared with vitamin E, lifestyle intervention is more effective. Therefore, lifestyle intervention should represent the first step in the management of children with NAFLD.

Cardiovascular disease risk factor profiles in children with celiac disease on gluten-free diets

AIM:To describe the cardiovascular disease(CVD)risk factors in a population of children with celiac disease(CD)on a gluten-free diet(GFD).METHODS:This cross-sectional multicenter study was performed at Schneider Children’s Medical Center of Israel(Petach Tiqva,Israel),and San Paolo Hospital(Milan,Italy).We enrolled 114 CD children in serologic remission,who were on a GFD for at least one year.At enrollment,anthropometric measurements,blood lipids and glucose were assessed,and compared to values at diagnosis.The homeostasis model assessment-estimated insulin resistance was calculated as a measure of insulin resistance.RESULTS:Three or more concomitant CVD risk factors[body mass index,waist circumference,low density lipoprotein(LDL)cholesterol,triglycerides,blood pressure and insulin resistance]were identified in 14%of CD subjects on a GFD.The most common CVD risk factors were high fasting triglycerides(34.8%),elevated blood pressure(29.4%),and high concentrations of calculated LDL cholesterol(24.1%).On a GFD,four children(3.5%)had insulin resistance.Fasting insulin and HOMA-IR were significantly higher in the Italian cohort compared to the Israeli cohort(P<0.001).Children on a GFD had an increased prevalence of borderline LDL cholesterol(24%)when compared to values(10%)at diagnosis(P=0.090).Trends towards increases in overweight(from 8.8%to 11.5%)and obesity(from 5.3%to 8.8%)were seen on a GFD.CONCLUSION:This report of insulin resistance and CVD risk factors in celiac children highlights the importance of CVD screening,and the need for dietary counseling targeting CVD prevention.

Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease(NAFLD).METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction(HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue(VAT), pancreatic fat fraction(PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance(HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index(WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either:(1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/d L to < 126 mg/d L;(2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/d L and < 200 mg/d L; or(3) hemoglobin A1 c value of ≥ 5.7% to < 6.5%.RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index(BMI)-SD score, and VAT. In multiple regression analysis withWBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI(standardized coefficient B,-0.398; P = 0.001) as well as HOMA-IR(0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes(OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.

Fatigue in children and adolescents with inflammatory bowel disease

AIM To identify factors other than active disease and anemia that contribute to fatigue in pediatric inflammatory bowel disease(IBD).METHODS We performed an electronic search in Medline and EMBASE from their inception to May 2017 using the search term "fatigue" or the related keywords "physical impairment" and "inflammatory bowel disease" with the filter "child"(age 0-18 years). Cross-sectional and case-control studies were included. We restricted our search to studies published in English. We used the PRISMA checklist and flow diagram. Duplicate articles were manually deleted in End Note. To identify further relevant studies, we checked the reference lists of the selected articles.RESULTS We identified 149 papers, of which 19 were retrieved for full text review. Eleven studies were subsequently excluded because fatigue was not evaluated as an outcome measure. Eight papers focused on the desired topic and were discussed in the final analysis. A lack of uniformity of outcome measures made the pooling of data impossible. In all but one study, questionnaires were used to evaluate fatigue. In the remaining study, an accelerometer was used to measure daily activities, sleeping time and their relationships with fatigue in a more quantifiable manner. Adolescents with IBD are significantly more fatigued than healthy controls. In addition to active disease, increased anxiety or depression and disturbed family relationships were frequently reported predictors of fatigue. Quantitative measurement of physical activity in patients with Crohn's disease showed a reduction in the number of steps per day, and patients with ulcerative colitis had a shorter duration of physical activity during the day.CONCLUSION Fatigue in pediatric IBD is related to a combination of biological, functional and behavioral factors, which should all be taken into account when managing fatigue.

Comparison of the use of wireless capsule endoscopy with magnetic resonance enterography in children with inflammatory bowel disease

BACKGROUND Magnetic resonance enterography (MRE) and wireless capsule endoscopy (WCE) are equally accepted modalities for noninvasive screening of small bowel involvement (SBI) in children with Crohn’s disease (CD) and indeterminate colitis (IC) albeit there is a paucity of data comparing the two and thereby guiding the clinician in selecting the ideal diagnostic approach. Therefore, the goal of this study is to provide additional evidence for capsule endoscopy role in the evaluation of established Crohn’s disease exacerbation compared to MRE in relation to Pediatric Crohn's Disease Activity Index (PCDAI), and histological indices. AIM To prospectively compare the findings of MRE and WCE and their agreement with PCDAI or histology in children with CD or IC. METHODS Consecutive patients diagnosed with CD and IC were screened for inclusion. After informed consent, patient’s demographic and clinical data was abstracted. The current pediatric disease activity index (PCDAI) and endoscopic findings were included. Patients underwent MRE and WCE including preprocedural patency capsule within a maximum of 7 d of each other. Pathological presence of active small bowel disease in ileal and duodenal biopsies were collected if the endoscopy was performed within 2 mo of the WCE study. Patients who failed to pass the PC were excluded from the study. WCE was read by two different experienced gastroenterologists (Attard TM and Colombo JM) blinded to each other's findings and to the findings on MRE (Mardis NJ). Agreement between WCE reviewers, WCE and MRE findings and concordance between positive PCDAI and SBI based on MRE compared with WCE was computed. RESULTS Forty-five patients were included in the study, 18 withdrew and 27 (20 males and 20 CD), mean age (standard deviation) 13.46 (2.4) years, completed the study protocol. There were no instances of capsule retention. Concordance between gastroenterologist reviewers was excellent for the diagnosis of small intestinal CD with good correlation between the two Lewis scores (r=0.875, P<0.001). Concordance between WCE and MRE was poor (69%). In CD patients, when both MRE and WCE were compared using PCDAI>10 as the standard reference reflecting active small intestinal CD, the sensitivity of MRE and WCE were 100% and 83% respectively and the specificity of MRE and WCE were 57.14% and 78.6%, respectively. If the histology in ileum or/and duodenum was used as the reference for active small bowel involvement, WCE had a higher specificity as compared to MRE (83.3% vs 50%). In patients with Crohn’s disease, those with a positive PCDAI (>10) were more likely to have a positive WCE as compared to those with a negative PCDAI (83% vs 21%;P=0.018). CONCLUSION We suggest that MRE and WCE have a complementary role in the assessment of SBI in CD. WCE detected SBI with a much higher specificity while MRE had a higher sensitivity.

Nonalcoholic fatty liver disease and the heart in children and adolescents

Over the last two decades, the rise in the prevalence rates of overweight and obesity explains the emergence of nonalcoholic fatty liver disease(NAFLD) as the leading cause of chronic liver disease worldwide. As described in adults, children and adolescents with fatty liver display insulin resistance, glucose intolerance, and dyslipidemia. Thus NAFLD has emerged as the hepatic component of the metabolic syndrome(MetS) and a strong cardiovascular risk factor even at a very early age. Several studies, including pediatric populations, have reported independent associations between NAFLD and markers of subclinical atherosclerosis including impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, after adjusting for cardiovascular risk factors and MetS. Also, it has been shown that NAFLD is associated with cardiac alterations, including abnormal left ventricular structure and impaired diastolic function. The duration of these subclinical abnormalities may be important, because treatment to reverse the process is most likely to be effective earlier in the disease. In the present review, we examine the current evidence on the association between NAFLD and atherosclerosis as well as between NAFLD and cardiac dysfunction in the pediatric population, and discuss briefly the possible biological mechanisms linking NAFLD and cardiovascular changes. We also address the approach to treatment for this increasingly prevalent disease, which is likely to have an important future global impact on the burden of ill health, to prevent not only end-stage liver disease but also cardiovascular disease.

Magnetic resonance imaging in children and adolescents with chronic inflammatory bowel disease

Inflammatory bowel diseases(IBD) represent challenges, both from a diagnostic, and therapeutic point of view. Deep-seated anatomic structures are difficult to assess by ultrasound technique alone. As radiation-free alternative cross-sectional imaging method, magnetic resonance imaging of the intestinal structures is costly and time-consuming. Examination of pediatric patients imply additional considerations: reduction of body motions in younger children and consideration of the most appropriate preparation, and examination technique. The demanding Sellink technique is the only means for appropriately distending the lesser intestine in order to detect small bowel strictures. Oral intake of contrast medium(CM) alone shows its limitations regarding distensibility. The need for intravenous contrast media application needs to be considered, too. Active inflammation of both intestinal wall, and mesentery can be demonstrated accurately. Nevertheless, viable alternatives to CM application is desirable, considering non-negligible adverse reactions. Recent data suggest diffusion weighted imaging might fill this diagnostic gap. Irrespective of sequence technique chosen, bowel movement remains a major obstacle. Antispasmolytics in their function as smooth muscle relaxants help in improving image quality, however, their use in children might be off-label. Optimal preparation for the examination and appropriate imaging technique allow for diagnosing typical patterns of changes in IBD, such as bowel wall thickening, ulcers, mural stratification, strictures, creeping fat, and comb sign, and lymphadenopathy. The article gives a detailed overview of current significance of magnetic resonance imaging pediatric patients suffering from IBD, considering indications, limitations, and safety aspects.