Gut microbiota predicts the diagnosis of ulcerative colitis in Saudi children

BACKGROUND Ulcerative colitis(UC)is an immune-mediated chronic inflammatory condition with a worldwide distribution.Although the etiology of this disease is still unknown,the understanding of the role of the microbiota is becoming increasingly strong.AIM To investigate the predictive power of the gut microbiota for the diagnosis of UC in a cohort of newly diagnosed treatment-naïve Saudi children with UC.METHODS The study population included 20 children with a confirmed diagnosis of UC and 20 healthy controls.Microbial DNA was extracted and sequenced,and shotgun metagenomic analysis was performed for bacteria and bacteriophages.Biostatistics and bioinformatics demonstrated significant dysbiosis in the form of reduced alpha diversity,beta diversity,and significant difference of abundance of taxa between children with UC and control groups.The receiver operating characteristic curve,a probability curve,was used to determine the difference between the UC and control groups.The area under the curve(AUC)represents the degree of separability between the UC group and the control group.The AUC was calculated for all identified bacterial species and for bacterial species identified by the random forest classification algorithm as important potential biomarkers of UC.A similar method of AUC calculation for all bacteriophages and important species was used.RESULTS The median age and range were 14(0.5-21)and 12.9(6.8-16.3)years for children with UC and controls,respectively,and 40%and 35%were male for children with UC and controls,respectively.The AUC for all identified bacterial species was 89.5%.However,when using the bacterial species identified as important by random forest classification algorithm analysis, the accuracy increased to 97.6%. Similarly, the AUC for all theidentified bacteriophages was 87.4%, but this value increased to 94.5% when the important bacteriophagebiomarkers were used.CONCLUSIONThe very high to excellent AUCs of fecal bacterial and viral species suggest the potential use of noninvasivemicrobiota-based tests for the diagnosis of unusual cases of UC in children. In addition, the identification ofimportant bacteria and bacteriophages whose abundance is reduced in children with UC suggests the potential ofpreventive and adjuvant microbial therapy for UC.

Crohn’s and colitis in children and adolescents

Crohn＇s disease and ulcerative colitis can be grouped as the inflammatory bowel diseases （IBD）. These conditions have become increasingly common in recent years, including in children and young people. Although much is known about aspects of the pathogenesis of these diseases, the precise aetiology is not yet understood, and there remains no cure. Recent data has illustrated the importance of a number of genes-several of these are important in the onset of IBD in early life, including in infancy. Pain, diarrhoea and weight loss are typical symptoms of paediatric Crohn＇s disease whereas bloody diarrhoea is more typical of colitis in children. However, atypical symptoms may occur in both conditions： these include isolated impairment of linear growth or presentation with extra-intestinal manifestations such as erythma nodosum. Growth and nutrition are commonly compromised at diagnosis in both Crohn＇s disease and colitis. Consideration of possible IBD and completion of appropriate investigations are essential to ensure prompt diagnosis, the- reby avoiding the consequences of diagnostic delay. Patterns of disease including location and progression of IBD in childhood differ substantially from adult- onset disease. Various treatment options are available for children and adolescents with IBD. Exclusive enteral nutrition plays a central role in the induction of remission of active Crohn＇s disease. Medical and surgical therapies need to considered within the context of a growing and developing child. The overall management of these chronic conditions in children should include multi-disciplinary expertise, with focus upon maintaining control of gut inflammation, optimising nutrition, growth and quality of life, whilst preventing disease or treatment-related complications.

Low trypsinogen-1 expression in pediatric ulcerative colitis patients who undergo surgery

AIM: To investigate whether matrix metalloproteinases-9 (MMP-9) or trypsinogens could serve as histological markers for an aggressive disease course in pediatric ulcerative colitis (UC). METHODS: We identified 24 patients with pediatric onset (≤ 16 years) UC who had undergone surgery during childhood/adolescence a median of 2.1 years (range 0.1-7.4 years) after the diagnosis (between 1990 and 2008) in Children's Hospital, Helsinki, Finland. We also identified 27 conservatively treated UC patients and matched them based on their age at the time of diagnosis and follow-up at a median of 6 years (range 3-11 years) to serve as disease controls. Twenty children for whom inflammatory bowel disease (IBD) had been excluded as a result of endoscopy served as non-IBD controls. Colon biopsies taken by diagnostic endoscopy before the onset of therapy were stained using immunohistochemistry to study the expression of MMP-9, trypsinogen-1 (Tryp-1), Tryp-2, and a trypsin inhibitor (TATI). The profiles of these proteases and inhibitor at diagnosis were compared between the surgery group, the conservatively treated UC patients and the non-IBD controls. RESULTS: The proportions of Tryp-1 and Tryp-2 positive samples in the colon epithelium and in the inflammatory cells of the colon stroma were comparable between the studied groups at diagnosis. Interestingly, the immunopositivity of Tryp-1 (median 1; range 0-3) was significantly lower in the epithelium of the colon in the pediatric UC patients undergoing surgery when compared to that of the conservatively treated UC patients (median 2; range 0-3; P = 0.03) and non-IBD controls (median 2; range 0-3; P = 0.04). For Tryp-2, there was no such difference. In the inflammatory cells of the colon stroma, the immunopositivities of Tryp-1 and Tryp-2 were comparable between the studied groups at diagnosis. Also, the proportion of samples positive for TATI, as well as the immunopositivity, was comparable between the studied groups in the colon epithelium. In the stromal inflammatory cells of the colon, TATI was not detected. In UC patients, there were significantly more MMP-9 positive samples and a higher immunopositivity in the stromal inflammatory cells of the colon when compared to the samples from the non-IBD patients (P = 0.006 and P = 0.002, respectively); the immunopositivity correlated with the histological grade of inflammation (95%CI: 0.22-0.62; P = 0.0002), but not with the other markers of active disease. There were no differences in the immunopositivity or in the proportions of MMP-9 positive samples when examined by epithelial staining. The staining profiles in the ileal biopsies were comparable between the studied groups for all of the studied markers.CONCLUSION: For pediatric UC patients who require surgery, the immunopositivity of Tryp-1 at diagnosis is lower when compared to that of patients with a more benign disease course.

How has the disease course of pediatric ulcerative colitis changed throughout the biologics era?A comparison with the IBSEN study

BACKGROUND In Korea,infliximab was approved for use in children with ulcerative colitis(UC)in October 2012.AIM To compare the clinical course of UC before and after the introduction of biological agents,and to compare with the IBSEN study.METHODS Patients under 18 years of age,who were diagnosed with UC and followed from January 2003 to October 2020,were included in the study.Group A(n=48)was followed for at least 2 years between January 2003 and October 2012,and Group B(n=62)was followed for at least 2 years between November 2012 and October 2020.We compared endoscopic remission,drug composition,relapse rate,steroidfree period,and the quality of life of each group.We plotted the clinical course of the included patients using the pediatric UC activity index score,and compared our patients with those in the IBSEN study.RESULTS After 2 years of treatment,colonoscopy evaluation revealed different outcomes in the two treatment groups.Remission was confirmed in 14 patients(29.2%)of Group A,and in 31 patients(50.0%)of Group B(P<0.012).The median cumulative corticosteroid-free period was 3.0 years in Group A and 4.4 years in Group B.Steroid-free period of Group B was significantly longer than that of Group A(P<0.001).There was a statistically significant difference between the two groups in evaluation of the relapse rate during the observation period(P<0.001).The plotted clinical course graphs of Group A showed similar proportions to the graphs in the IBSEN study.However,in Group B,the proportion of patients corresponding to curve 1(remission or mild severity after initial high activity)was high at 76%(47/62).CONCLUSION The incidence of relapse has decreased and the steroid-free period has increased after the introduction of the biological agent.The clinical course also showed a different pattern from that of IBSEN study.The active use of biological agents may change the long-term disease course in moderate to severe pediatric UC.

High-dose infliximab for treatment of pediatric ulcerative colitis:A survey of clinical practice

AIM:To assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis(UC).METHODS:A 19-item survey was distributed to subscribers of the pediatric gastroenterology(PEDSGI) listserv.Responses were submitted anonymously and results compiled in a secure website.RESULTS:A total of 113 subscribers(88% based in the United States) responded(101 pediatric gastroenterology attendings and 12 pediatric gastroenterology fellows).There were 46% in academic medical institutions and 39% in hospital-based practices.The majority(91%) were treating >10 patients with UC;13% were treating >100 patients with UC;91% had prescribed infliximab(IFX) 5 mg/kg for UC;72% had prescribed IFX 10 mg/kg for UC.Using a 5-point Likert scale,factors that influenced the decision not to increase IFX dosing in patients with UC included:"improvement on initial dose of IFX"(mean:3.88) and "decision to move to colectomy"(3.69).Lowest mean Likert scores were:"lack of guidelines or literature regarding increased IFX dosing"(1.96) and "insurance authorization or other insurance issues"(2.34)."Insurance authorization or other insurance issues" was identified by 39% as at least somewhat of a factor(Likert score ≥ 3) in their decision not to increase the IFX dose.IFX 10 mg/kg was more commonly used for the treatment of pediatric UC among responders based in the United States(75/100) compared to non-United States responders(6/13,P = 0.047).Induction of remission was reported by 78% of all responders and 81% reported maintenance of remission with IFX 10 mg/kg.One responder reported one death with IFX 10 mg/kg.CONCLUSION:IFX 10 mg/kg is more commonly used in the United States to treat pediatric UC.Efficacy and safety data are required to avoid insurance barriers for its use.

Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis

AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years(median) after proctocolectomy.Expression of MMPs-3,-7,-8,-9,-12 and-26 and TIMPs-1,-2 and-3 in samples was examined using immunohistochemichal methods,and another biopsy was used to evaluate the grade of histological inflammation.Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion,using a scale marking staining intensity as follows:0 = less than 20 positive cells;1 = 20-50 positive cells;2 = 50-200 positive cells;3 = over 20 positive cells.Fecal calprotectin and blood inflammatory markers [serum C-reactive protein(CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS:Of the 28 patients with pediatric onset UC,nine had not experienced pouchitis,whereas thirteen reported a single episode,and six had recurrent pouchitis(≥ 4 episodes).At the time of the study,six patients required metronidazole.In all of the others,the most recent episode of pouchitis had occurred over one month earlier,and none were on antibiotics.Only four samples depicted no sign of inflammation,and these were all from patients who had not had pouchitis.Two samples were too small to determine the grade of inflammation,but both had suffered pouchitis,the other recurrent.No sample depicted signs of colonic metaplasia.Most pouch samples showed expression of epithelial(e) and stromal(s) MMP-3(e,n = 22;s,n = 20),MMP-7(e,n = 28;s,n = 27),MMP-12(e,n = 20;s,n =24),TIMP-2(e,n = 23;s,n = 23) and MMP-3(e,n = 23;s,n = 28) but MMP-8(e,n = 0;s,n = 1),MMP-9(e,n = 0;s,n = 9) and MMP-26(e,n = 0;s,n = 3) and TIMP-1(n = 0,both) were lacking.In samples with low grade of inflammatory activity,the epithelial MMP-3 and MMP-7 expression was increased(r =-0.614 and r =-0.472,respectively,P < 0.05 in both).MMPs and TIMPs did not correlate with the markers of inflammation,fecal calprotectin,erythrocyte sedimentation rate,or CRP,with the exception of patients with low fecal calprotectin(< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMPor TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes.Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP-or TIMP-expression.CONCLUSION:The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease,but inflammation cannot be classified as a reactivation of the disease.

Ulcerative Colitis and Acute Thrombocytopenia in a Pediatric Patient: A Case Report and Review of the Literature

We report the case of a 14-year-old boy affected by ulcerative colitis (UC) and acute thrombocytopenic purpura (ITP) with simultaneous onset. UC diagnosis was based on symptoms, endoscopy and histology findings. ITP diagnosis was based on the normal bone marrow megakaryocyte count, the presence of platelet associated IgG and the absence of splenomegaly. Medical treatments including high doses of steroids, intravenous immunoglobulins were ineffective on ITP course, while UC course was mild for several months after the onset. When colonic inflammation became untractable not responsive at steroids and immunosuppressive agents, colectomy resolved both pathologies.

Risk of venous thromboembolism in children and adolescents with inflammatory bowel disease: A systematic review and meta-analysis

BACKGROUND A two-to three-fold increased risk of venous thrombotic events(VTE) has been demonstrated in patients with inflammatory bowel disease(IBD) compared to the general population, but less is known about the risk of VTE in child-and pediatric-onset IBD. In recent years, several studies have reported the rising incidence rate of VTE in juvenile patients with IBD, and the related risk factors have been explored.AIM To evaluate the risk of VTE in children and adolescents with IBD.METHODS Articles published up to April 2021 were retrieved from Pub Med, Embase, Cochrane Library, Web of Science, Sino Med, CNKI, and WANFANG. Data from observational studies and clinical work were extracted. The outcome was the occurrence of VTE according to the type of IBD. The available odds ratio(OR) and the corresponding 95% confidence interval(CI) were extracted to compare the outcomes. Effect size(P), odds ratio(OR), and 95%CI were used to assess the association between VTE risk and IBD disease. Subgroup analyses stratified by subtypes of VTE and IBD were performed.RESULTS Twelve studies(7450272 IBD patients) were included in the meta-analysis. Child and adolescent IBD patients showed increased VTE risk(P = 0.02, 95%CI: 0.01-0.03). Subgroup analyses stratified by IBD(ulcerative colitis(UC): P = 0.05, 95%CI: 0.03-0.06;Crohn’s disease(CD): P = 0.02, 95%CI: 0.00-0.04) and VTE subtypes(portal vein thrombosis: P = 0.04, 95%CI: 0.02-0.06;deep vein thrombosis: P = 0.03, 95%CI: 0.01-0.05;central venous catheter-related thrombosis: P = 0.23, 95%CI: 0.00-0.46;thromboembolic events: P = 0.02, 95%CI: 0.01-0.03) revealed a significant correlation between VTE risk and IBD. Patients with IBD were more susceptible to VTE risk than those without IBD(OR = 2.99, 95%CI: 1.45-6.18). The funnel plot was asymmetric, suggesting the presence of significant publication bias. Pediatric and adolescent IBD patients have an increased VTE risk. UC and CD patients exhibited a high risk of VTE. The risk of VTE subtypes was increased in IBD patients.CONCLUSION The current meta-analysis showed that the incidence and risk of VTE are significantly increased in pediatric and adolescent IBD patients. Thus, IBD might be a risk factor for VTE in children and young adults. High-quality prospective cohort studies are necessary to confirm these findings.

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.

Cognitive functioning and depressive symptoms in adolescents with inflammatory bowel disease

AIM:To investigate cognitive functioning and depressive symptoms in adolescents with inflammatory bowel disease(IBD).METHODS:A neuropsychological test battery,including subtests of the Wechsler Adult Intelligence ScaleRevised and Ⅲ,Wechsler Memory Scale-Revised,California Verbal Learning Test(CVLT),Stroop Color-Word Test,and Trail Making Test,which assessed verbal and visual short-and long-term memory,processing speed,logical reasoning,verbal intelligence,attention,and executive functioning,was administered to 13-to 19-year-old patients with IBD(n = 34;active disease n = 20).Depressive symptoms were measured with the Beck Depression Inventory.The findings were compared with peers with non-acute juvenile idiopathic arthritis(JIA;n = 23).Patients with coexisting psychiatric disorders were excluded.RESULTS:The IBD group,especially patients in the acute phase,made more perseverative errors in the CVLT test that assessed verbal memory than the JIA group(6.0 ± 4.3 vs 3.3 ± 2.9,P < 0.01),but no other differences between the IBD and JIA groups were observed in the neuropsychological tests.The difference was close to statistical significance,even when glucocorticoid medication was controlled for(P < 0.052).The IBD group had more depressive symptoms than the JIA group(7.9 ± 7.6 vs 4.0 ± 4.0,P < 0.05).Approximately one third of the IBD group had at least mild depressive symptoms,and those with acute illness had the highest scores.However,depressive symptoms were not related to the difference in the verbal memory test(perseverative errors in the CVLT) between the IBD and JIA groups.CONCLUSION:Adolescents with acute IBD may have mild verbal memory problems but no major cognitive deficits compared to peers with JIA.

Mucosal bacterial microflora and mucus layer thickness in adolescents with inflammatory bowel disease

AIM:To assess the mucosa-associated bacterial microflora and mucus layer in adolescents with inflammatory bowel disease(IBD) .METHODS:Sixty-one adolescents(mean age 15 years,SD ± 4.13) were included in the study.Intestinal biopsies from inflamed and non-inflamed mucosa of IBD patients and from controls with functional abdominal pain were cultured under aerobic and anaerobic conditions.The number of microbes belonging to the same group was calculated per weight of collected tissue.The mucus thickness in frozen samples was measured under a fluorescent microscope.RESULTS:The ratios of different bacterial groups in inflamed and non-inflamed mucosa of IBD patients and controls were specific for particular diseases.Streptococcus spp.were predominant in the inflamed mucosa of Crohn's disease(CD) patients(80% of all bacteria) ,and Lactobacillus spp.were predominant in ulcerative colitis patients(90%) .The differences were statistically significant(P = 0.01-0.001) .Lower number of bifidobacteria was observed in the whole IBD group.A relation was also found between clinical and endoscopic severity and decreased numbers of Lactobacillus and,to a lesser extent,of Streptococcus in biopsies from CD patients.The mucus layer in the inflamed sites was significantly thinner as compared to controls(P = 0.0033) and to non-inflamed areas in IBD patients(P = 0.031) .CONCLUSION:The significantly thinner mucosa of IBD patients showed a predominance of some aerobes specific for particular diseases,their numbers decreased in relation to higher clinical and endoscopic activity of the disease.

英夫利西单抗治疗儿童溃疡性结肠炎的疗效及安全性

目的评价英夫利西单抗(IFX)治疗儿童溃疡性结肠炎(UC)的疗效以及安全性。方法回顾性分析2018年1月至2022年12月在济南市儿童医院接受IFX治疗的21例溃疡性结肠炎患儿临床资料。比较治疗前后儿童UC疾病活动指数(PUCAI)、内镜严重程度评分和实验室检查结果,评估IFX疗效及安全性。结果21例UC患儿中男12例、女9例。IFX疗效分析显示,第14周诱导缓解期临床应答率76.2%(16/21),临床缓解率66.7%(14/21)。第30周维持缓解期临床应答率76.4%(13/17),持续缓解率58.5%(10/17)。与治疗前相比,IFX治疗第14周及30周PUCAI、C反应蛋白(CRP)、红细胞沉降率(ESR)、粪便钙卫蛋白均明显下降(P<0.05),血红蛋白、白蛋白均有显著改善(P<0.05)。14周复查结肠镜,8例达到黏膜愈合,6例由重度炎症减轻为中度炎症,4例黏膜炎症中度炎症减轻为轻度炎症,2例黏膜炎症无好转。IFX输液反应发生率为43%(9/21),包括急性输液反应、迟发性输液反应、转氨酶升高,其中治疗期间感染最常见,发生率为38%(8/21)。结论IFX对儿童UC疗效显著,但治疗期间需警惕不良事件的发生。

Disease impact on the quality of life of children with inflammatory bowel disease

To assess the impact of disease characteristics on the quality of life (QOL) in children with inflammatory bowel diseases (IBD).METHODSThis was a cross-sectional study conducted at the First Department of Pediatrics of the University of Athens at the “Aghia Sophia” Children’s Hospital. Children diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC), who were followed as outpatients or during a hospitalization, participated, after informed consent was obtained from their legal representative. QOL was assessed by the IMPACT-III questionnaire. Demographic data and disease characteristics were also collected. Statistical analyses included parametric (Student’s t-test and Pearson’s r) and non-parametric (Mann-Whitney test, Fisher’s test and Spearman’s rho) procedures.RESULTSNinety-nine patients (UC: 37, 73.0% females, CD: 62, 51.6% females), aged 12.8 ± 2.6 years were included. Overall, as well as, sub-domain scores did not differ between UC and CD (overall score: 73.9 ± 13.3 vs 77.5 ± 11.2, respectively, P = 0.16). In the entire sample, total score was related to physician’s global assessment (PGA, patients classified as “mild/moderate” active disease had, on average, 14.8 ± 2.7 points lower total scores compared to those “in remission”, P < 0.001) and age at IMPACT completion (Pearson’s r = 0.29, P = 0.05). Disease activity assessed by the indices Pediatric Ulcerative Colitis activity index, Pediatric Crohn’s disease activity index or PGA was significantly associated with all subdomains scores. Presence of extraintestinal manifestations had a negative impact on emotional and social functioning domains.CONCLUSIONDisease activity is the main correlate of QOL in children with IBD, underlining the importance of achieving and sustaining clinical remission

Nutritional status of children with inflammatory boweldisease in Saudi Arabia

AIM: To assess the prevalence of nutritional disorders in children with inflammatory bowel disease(IBD) in Saudi Arabia.METHODS: The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn's disease(CD) and ulcerative colitis(UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index(BMI) of each child [weight(kg)/height^2(m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and <-2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age-related variation in the prevalence of nutritional status between children < 10 years of age and older.RESULTS: There were 374 children from 0.33 to 17 years of age, including 119(32%) children with UC and 255(68%) with CD. All of the children were Saudi nationals, and 68(57%) of the UC and 150(59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30(25%) patients with UC and 99(39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC(P = 0.037) only in the age group of 10-17 years(P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years(P = 0.020). CONCLUSION: A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care.

Hepatobiliary manifestations in children with inflammatory bowel disease:A single-center experience in a low/middle income country

BACKGROUNDThere has been a worldwide increase in the reported incidence of inflammatorybowel disease (IBD) in children over the past 2-3 decades. The hepatobiliary (HB)manifestations of IBD have been well-studied in children in industrialized anddeveloped countries but are infrequently reported in low- and middle-incomecountries (LMIC) such as Egypt.AIMTo determine the prevalence of the HB manifestations in a cohort of Egyptianchildren with IBD.METHODSThis cross-sectional observational study was carried out over a period of 6 mo(between June 2013 to December 2013, at the Paediatric Hepatology andGastroenterology Units of Cairo University Children's Hospital, which is thelargest paediatric tertiary care centre in the country.RESULTSThe study included 48 patients with confirmed IBD based upon clinical,laboratory, endoscopic and histopathological features, 29 (60.4%) were male.Twenty-four patients (50%) had ulcerative colitis (UC), 11 (22.9%) had Crohn'sdisease (CD) and 13 (27.1%) had unclassified-IBD (IBD-U), which was formerlyknown as indeterminate colitis. The mean age of the patients at the time ofpresentation was 8.14 (± SD 4.02) years and the mean age at the time of studyenrolment was 10.16 (± SD 4.19) years. All patients were screened for HBmanifestations by physical examination, liver function tests, imaging and liver biopsy when indicated. HB disorders were confirmed in 13 patients (27.1%).Transaminases were elevated in 3 patients (6.3%). Two patients (4.2%) hadelevated biliary enzymes (one was diagnosed as primary sclerosing cholangitis(PSC) and the other was diagnosed with PSC/autoimmune hepatitis overlapsyndrome and the third patient had hepatitis C virus infection. Ten patients(20.8%) had bright echogenic liver on ultrasound suggesting fatty infiltration as asequel of malnutrition or medication toxicity.CONCLUSIONThe commonest HB disorders in Egyptian children with IBD were abnormal liverfunction tests, fatty infiltration and PSC. These HB manifestations in paediatricpatients in LMIC may be relatively more common than in industrializedcountries. Therefore, IBD patients in LMIC should be meticulously screened forliver disease to allow prompt diagnosis and management.

Inflammatory bowel disease incidence in Czech children:A regional prospective study,2000-2015

AIM To examine the incidence and trends in pediatric inflammatory bowel diseases(IBDs) over 2000-2015 and project the incidence to 2018. METHODS A 16-year prospective study of IBD patients < 19 years of age was conducted in the Czech Republic(the Pilsen region). All incident IBD cases within a well-defined geographical area were retrieved from a prospectively collected computerized clinical database. Historical Czech data were used for comparison(1990-2001). Our catchment population was determined from the census data. We calculated the incidence by relating the number of newly diagnosed cases to the size of thepediatric population-at-risk in each calendar year. Age/sex, disease type, place of residence, and race/ethnicity were identified. RESULTS In total, 170 new IBD cases [105 Crohn's disease(CD), 48 ulcerative colitis(UC), and 17 IBD-unclassified(IBD-U)] were identified. The median age at IBD diagnosis was 14.2 years, 59.4% were males, and 97.1% were Caucasians. A male preponderance of IBD(P = 0.026) and CD(P = 0.016) was observed. With 109209 person-years in the catchment area, the average incidence of IBD per 100000 person-years was 10.0(6.2 for CD, 2.8 for UC, and 1.0 for IBD-U) for children aged 0 to 19 years; for those aged 0 to 15 years, the incidence rate was 7.3(4.6 for CD, 2.0 for UC, and 0.7 for IBD-U). An increase in incidence with age was observed(P = 0.0003). Over the 16-year period, the incidence increased for IBD patients(P = 0.01) and CD in particular(P < 0.0001), whereas the incidence for UC(P = 0.09) and IBD-U(P = 0.339) remained unchanged. IBD-projected data from 2016 to 2018 were 12.1, 12.3 and 12.6 per 100000 personyears, respectively.CONCLUSION Pediatric-onset IBD incidence is around its highest point. The increase, which is particularly pronounced for CD, may be challenging to relate to causes of pediatric disease.

儿童炎症性肠病合并急性胰腺炎11例病例系列报告

背景国内尚缺乏儿童炎症性肠病(IBD)合并急性胰腺炎(AP)的临床病例报道。目的 总结单中心收治的儿童IBD合并AP病例的临床特征、治疗和转归。设计病例系列报告。方法 回顾性纳入2017年1月至2022年6月在复旦大学附属儿科医院消化科住院的IBD合并AP的连续病例。截取患儿的临床表现,实验室检查、影像学检查和消化内镜检查结果,治疗和转归情况。主要结局指标AP相关实验室指标和IBD内镜评分。结果 研究期间收治的406例IBD患儿中11例(2.7%)合并AP,男9例、女2例,IBD和AP的中位确诊年龄分别为9.8(5.5,13.1)和10.2(5.7,14.0)岁;AP病程中位时间为22(7,56)d。8例在诊断IBD后出现AP,其中5例克罗恩病(CD)、3例溃疡性结肠炎(UC);3例先诊断AP,后诊断CD。确诊IBD和AP时血淀粉酶为238(158,573)U·L^(-1),血脂肪酶为466(360,1 376)U·L^(-1),3、6、12个月后均下降,较确诊时差异有统计学意义。9/10例患儿影像学检查提示胰腺病变。8例CD患儿在确诊CD合并AP时的儿童克罗恩病活动指数(PCDAI)和克罗恩病简化内镜评分(SES-CD)分别为36.3(25.6,49.4)分和17.5(7.8,22.2)分,3个月后均降低,差异有统计学意义。3例UC患儿在AP发病时的儿童溃疡性结肠炎疾病活动指数(PUCAI)评分和Mayo内镜评分(MES)分别为40(25,42.5)分和2(2,2.5)分,出院3个月后分别为15(0,30)分和2.5(2,3)分。随访3年,11例患儿均无AP复发;1例UC患儿AP发病前采用5-氨基水杨酸和英夫利昔单抗治疗,AP发病后家长自行停用上述两种药物,随访2年时有持续性高淀粉酶血症、高脂肪酶血症,并出现胰管扩张,随访3年时进展为慢性胰腺炎。结论 儿童IBD活动期可合并AP,AP可能是IBD的一种少见的肠外表现。在IBD的诊治过程中要注意胰腺功能的评估及随访。

代币激励法联合自制动画微视频对溃疡性结肠炎患儿的护理效果评价

目的 观察代币激励联合自制动画微视频在溃疡性结肠炎患儿护理中的应用效果。方法 按照组间基本特征具有可比性的原则,将2021年2月—2022年2月医院收治的溃疡性结肠炎患儿92例分为对照组和观察组,每组46例。对照组采用常规护理,观察组接受代币激励联合自制动画微视频干预。比较两组患儿干预前后心理状态、服药依从性、营养状况、健康行为及生活质量。结果 代币激励联合自制动画微视频干预前,两组患儿家属焦虑自评量表(SAS)及抑郁自评量表(SDS)评分比较差异无统计学意义(P>0.05);干预后,观察组患儿家属SAS、SDS评分低于对照组,组间比差异有统计学意义(P<0.05)。代币激励联合自制动画微视频干预前,两组患儿Morisky服药依从性量表评分等级比较差异无统计学意义(P>0.05);干预后,观察组患儿Morisky服药依从性量表评分等级高于对照组,组间比差异有统计学意义(P<0.05)。干预前,两组患儿健康行为比较差异无统计学意义(P>0.05);干预后,观察组患儿情绪稳定、遵医服药、规律饮食率高于对照组,组间比差异有统计学意义(P<0.05)。干预前,两组患儿营养状况评估量表(PG-SGA)评分比较差异无统计学意义(P>0.05);干预后,观察组患儿PG-SGA评分低于对照组,组间比差异有统计学意义(P<0.05)。干预前,两组患儿炎症性肠病生存质量量表(IBDQ)的肠道症状、全身症状、情绪变化评分及总分比较差异无统计学意义(P>0.05);干预后,观察组患儿IBDQ中肠道症状、全身症状、情绪变化评分及总分高于对照组,组间比差异有统计学意义(P<0.05)。结论 代币激励联合自制动画微视频护理在溃疡性结肠炎患儿中能有效减轻患儿家属焦虑、抑郁,提高患儿服药依从性,提升患儿情绪稳定、遵医服药、规律饮食率,降低PG-SGA评分,改善生活质量。

溃疡性结肠炎患儿血清炎症因子及氧化应激水平变化及意义

目的探讨溃疡性结肠炎患儿血清降钙素原(PCT)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)、超氧化物歧化酶(SOD)变化及其临床意义。方法检测61例溃疡性结肠患儿(结肠炎组)、30例慢性感染性腹泻病患儿(慢性腹泻组)和30例健康儿童(对照组)血清PCT、CRP、TNF-α、NO和SOD水平。结果结肠炎组血清PCT、CRP、TNF-α和NO水平均明显高于其他2组(P均<0.05),SOD水平均明显低于其他2组(P均<0.05),其中PCT、CRP和TNF-α水平慢性腹泻组高于对照组(P均<0.05);重度和活动期溃疡性结肠炎患儿血清PCT、CRP、TNF-α和NO水平均明显高于轻中度和缓解期溃疡性结肠炎患儿(P均<0.05),SOD水平则明显低于轻中度和缓解期溃疡性结肠炎患儿(P均<0.05)。结论血清PCT、CRP、TNF-α、NO、SOD水平可能成为评价溃疡性结肠炎病情活动及严重程度的辅助指标,其中NO、SOD水平有助于溃疡性结肠炎和慢性感染性腹泻的鉴别诊断。

CD4阳性T细胞分泌的Bcl2L12蛋白在小儿溃疡性结肠炎中促进Th2细胞活化对疾病进展的影响

目的:探讨CD4阳性T(CD4+T)细胞分泌的Bcl2L12蛋白介导Th2细胞活化对小儿溃疡性结肠炎(UC)进展的影响。方法:分别收集20例UC患儿及健康儿童的外周血样本,测量血清中Th2细胞因子(IL-2,IL-5,IL-13)和Bcl2L12蛋白水平,检测并对比两组外周血单个核细胞(PBMC)中Th2细胞比例。以CD4+T细胞内Bcl2L12特异性敲除小鼠(Bcl2L12-KO)及野生型(WT)小鼠为动物模型,通过硫酸葡聚糖(DSS)进行UC造模,比较Bcl2L12-KO和WT经DSS造模后结肠病变的严重程度、血清炎症因子水平及结肠组织内Th2细胞凋亡比例等。结果:UC患儿血清中IL-4、IL-5、IL-13和Bcl2L12水平均显著高于对照组儿童,PBMC中Th2细胞比例也显著高于对照组儿童,差异均存在统计学意义(P<0.05)。经DSS诱导的UC模型中,Bcl2l12-KO小鼠的结肠炎症情况体及重降低程度明显低于WT小鼠,结肠长度长于WT小鼠。此外,Bcl2L12-KO小鼠的外周血Th2细胞、IL-4、IL-5、IL-13和Bcl2L12水平也显著低于WT小鼠,差异均存在统计学意义(P<0.05)。通过分离结肠组织中的免疫细胞并进行凋亡流式分析后发现,Bcl2l12-KO小鼠的Th2凋亡细胞比例显著高于WT小鼠,差异存在统计学意义(P<0.05)。结论:UC患儿血清中Bcl2L12和Th2细胞因子水平显著升高,处于Th2细胞偏向性炎症反应状态,而CD4+T细胞分泌的Bcl2L12蛋白能够抑制Th2细胞凋亡、促进Th2细胞活化和Th2细胞因子分泌增加而促进UC进展。