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Conjugated hyperbilirubinemia presenting in first fourteen days in term neonates

World Journal of Hepatology 2017年第26期9卷 1108-1114页

作者： Fang Kuan Chiou Christina Ong Kong Boo Phua Fares Chedid Ajmal Kader Gastro-enterology Service Paediatric Medicine KK Women’s and Children’s Hospital Neonatal Medicine Al Jalila Children’s Specialty Hospital Pediatric gastroenterology Dubai Hospital

AIM To describe the etiology and characteristics of earlyonset conjugated hyperbilirubinemia(ECHB) presenting within 14 d of life in term neonates.METHODS Retrospective review was performed of term infants up to 28-d-old who presented with conjugated hyperbilirubinemia(CHB) at a tertiary center over a 5-year period from January 2010 to December 2014. CHB is defined as conjugated bilirubin(CB) fraction greater than 15% of total bilirubin and CB greater or equal to 25 μmol/L. ECHB is defined as CHB detected within 14 d of life. "Late-onset" CHB(LCHB) is detected at 15-28 d of life and served as the comparison group.RESULTS Total of 117 patients were recruited: 65 had ECHB, 52had LCHB. Neonates with ECHB were more likely to be clinically unwell(80.0% vs 42.3%, P < 0.001) and associated with non-hepatic causes(73.8% vs 44.2%, P = 0.001) compared to LCHB. Multifactorial liver injury(75.0%) and sepsis(17.3%) were the most common causes of ECHB in clinically unwell infants, majority(87.5%) had resolution of CHB with no progression to chronic liver disease. Inborn errors of metabolism were rare(5.8%) but associated with high mortality(100%) in our series. In the subgroup of clinically well infants(n = 13) with ECHB, biliary atresia(BA) was the most common diagnosis(61.5%), all presented initially with normal stools and decline in total bilirubin but with persistent CHB. CONCLUSION Secondary hepatic injury is the most common reason for ECHB. BA presents with ECHB in well infants without classical symptoms of pale stools and deep jaundice.

关键词： Conjugated hyperbilirubinemia Biliary atresia Cholestasis Direct hyperbilirubinemia Neonatal jaundice

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Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion

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Chinese Medical Journal 2022年第6期135卷 707-713页

作者： Hua Li Yong Wang Changying Zhao Jian Liu Lei Zhang Anyuan Li Department of gastroenterology Cheeloo Children's HospitalShandong UniversityJinanShandong 250022China Department of Laboratory Medicine School of Stomatology and MedicineFoshan UniversityChancheng DistrictFoshanGuangdong 528000China Jinan Institute of paediatric Medicine Cheeloo Children's HospitalShandong UniversityJinanShandong 250022China Microbiome-X National Institute of Health Data Science of ChinaCheeloo College of MedicineShandong UniversityJinanShandong 250002China Department of Traditional Chinese Medicine Shandong Provincial HospitalShandong UniversityJinanShandong 250021China

Background:Tourette syndrome(TS)is a neuropsychiatric disorder with onset in childhood that warrants effective therapies.Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis.Therefore,the gut microbiota plays an important role in some mental illnesses.A small clinical trial showed that fecal microbiota transplantation(FMT)may alleviate TS symptoms in children.Herein,FMT effects and mechanisms were explored in a TS mouse model.Methods:TS mice model(TSMO)(n=80)were established with 3,3'-iminodipropionitrile,and 80 mice were used as controls.Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS,or were given probiotics.Fecal specimens were collected 3 weeks after FMT.16S rRNA sequencing,behavioral observation,and serum serotonin(5-HT)assay were performed.Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov(KS)tests.Results:A total of 18 discriminative microbial signatures(linear discriminant analysis score>3)that varied significantly between TS and healthy mice(CONH)were identified.A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed(P<0.05).Compared with non-transplanted TSMO,the symptoms of those transplanted with feces from CONH were alleviated(W=336,P=0.046).In the probiotic and FMT experiments,the serum 5-HT levels significantly increased in TSMO that received probiotics(KS=1.423,P=0.035)and in those transplanted with feces from CONH(W=336.5,P=0.046)compared with TSMO without transplantation.Conclusions:This study suggests that FMT may ameliorate TS by promoting 5-HT secretion,and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

关键词： Tourette syndrome Fecal transplantation Microbiota Serotonin

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Changes of smooth muscle contractile filaments in small bowel atresia

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World Journal of gastroenterology 2012年第24期18卷 3099-3104页

作者： Stefan Gfroerer Henning Fiegel Priya Ramachandran Udo Rolle Roman Metzger Department of paediatric Surgery Goethe-University Frankfurt60590 FrankfurtGermany Kanchi Kamakoti Childs Trust Hospital Chennai 600034India Department of paediatric Surgery University of Leipzig04317 LeipzigGermany

AIM:To investigate morphological changes of intestinal smooth muscle contractile fibres in small bowel atresia patients.METHODS:Resected small bowel specimens from small bowel atresia patients(n = 12) were divided into three sections(proximal,atretic and distal).Standard histology hematoxylin-eosin staining and enzyme immunohistochemistry was performed to visualize smooth muscle contractile markers-smooth muscle actin(SMA) and desmin using conventional paraffin sections of the proximal and distal bowel.Small bowel from agematched patients(n = 2) undergoing Meckel's diverticulum resection served as controls.RESULTS:The smooth muscle coat in the proximal bowel of small bowel atresia patients was thickened compared with control tissue,but the distal bowel was unchanged.Expression of smooth muscle contractile fibres SMA and desmin within the proximal bowel was slightly reduced compared with the distal bowel and control tissue.There were no major differences in the architecture of the smooth muscle within the proximal bowel and the distal bowel.The proximal and distal bowel in small bowel atresia patients revealed only minimal differences regarding smooth muscle morphology and the presence of smooth muscle contractile filament markers.CONCLUSION:Changes in smooth muscle contractile filaments do not appear to play a major role in postoperative motility disorders in small bowel atresia.

关键词：平滑肌收缩小肠闭锁形态学变化组织学免疫组化肌动蛋白石蜡切片

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Upper gastrointestinal tract involvement of pediatric inflammatory bowel disease: A pathological review

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World Journal of gastroenterology 2019年第16期25卷 1928-1935页

作者： Dua Abuquteish Juan Putra Division of Pathology Department of Paediatric Laboratory Medicine Hospital for Sick Children

Upper gastrointestinal(UGI) tract involvement of inflammatory bowel disease(IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis(UC), atypical UC, Crohn's disease(CD) and IBD unclassified.Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid(non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD,is histologically characterized by increased intraepithelial lymphocytes(> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis,villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.

关键词： Pediatric Inflammatory bowel disease Lymphocytic esophagitis Focally enhanced gastritis Epithelioid granuloma Crohn’s disease Ulcerative colitis

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Management of hyperplastic gastric polyp following upper gastrointestinal bleeding in infant with Menkes' disease

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World Journal of Gastrointestinal Endoscopy 2017年第7期9卷 341-345页

作者： Dalia Belsha Priya Narula Arun Urs Mike Thomson Centre of paediatric gastroenterology Sheffield Children’s HospitalSheffeld S10 2THUnited Kingdom

We report a case of an infant with Menkes' disease(MD) presented at the age of five months,with coffee ground vomiting,melaena with a significant drop of haemoglobin.Urgent endoscopic assessment revealed a friable bleeding trans-pyloric multi-lobulated sessile polyp.Due to further significant upper gastrointestinal bleeding,polypectomy occurred.Endoscopic mucosal resection was performed with a grasp-and-snare technique using a dual channel operating gastroscope.Haemostasis was achieved by application of argon plasma coagulation where required.No perforation occurred.Repeated debridement was required 6 wk after which the growth was excised completely with no further blood transfusion required after that procedure.Histological examination confirmed ulcerated and inflamed hyperplastic polyp.We discuss our endoscopic technique and discuss the reported gastrointestinal manifestation of MD in the literature.

关键词： Menkes 疾病胃肠的流血掌握和圈套技术 Polypectomy 胃的息肉

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Efficacy,effectiveness,immunogenicity- are not the same in vaccinology

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World Journal of gastroenterology 2013年第41期19卷 7217-7218页

作者： Aleksandra Banaszkiewicz Andrzej Radzikowski Department of paediatric gastroenterology and Nutrition the Medical University of Warsaw01-184 WarsawPoland

Manuscript of Carrera et al is devoted to immunization in inflammatory bowel disease(IBD)that is very important issue in gastroenterology.However,some specific definitions used in the article need clarification.Efficacy of vaccine is measured in a randomised,placebo-controlled studies,that are expensive and difficult to plan.Moreover,it is unethical to offer a placebo instead of vaccine.For all of these reasons,efficacy of vaccine is measured in IBD patients rarely.Effectiveness of vaccine is measured as an epidemiological affect from observational studies.These studies are also uncommon in IBD because it would be difficult to perform a study that assess the prevalence of one rare disease(vaccine-preventable)in patients with a chronic rare condition,such as IBD.Immunogenicity of vaccine refers to the ability of a vaccine to induce an immune response in a vaccinated individual that is,in fact,the matter of the article.

关键词： Efficacy Effectiveness Immunogenicity vaccine

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Effects of dual sofosbuvir/daclatasvir therapy on, chronic hepatitis C infected, survivors of childhood malignancy

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World Journal of Clinical Cases 2019年第16期7卷 2247-2255页

作者： Mortada HF El-Shabrawi Laila M Sherief Mostafa Yakoot Naglaa M Kamal Mohamed A Almalky Manal M AbdElgawad Aml A Mahfouz Sherine Helmy Enas M Kamal Dina Attia Hisham R El-Khayat paediatric Hepatology Department Cairo Faculty of MedicineCairo 11559Egypt paediatric Hematology-Oncology Department Zagazig Faculty of MedicineZagazig 21121Egypt Internal medicine Pediatrics and HepatologyGreen Clinic and Research CenterAlexandria UniversityAlexandria 21121Egypt paediatric Hepatology Department Alexandria Faculty of medicineAlexandria 21121Egypt Innovations & Research Pharco CorporationAlexandria 21121Egypt Endemic medicine and Hepatology Department Minia UniversityMinia 22233Egypt Endemic medicine and Hepatology Department Beni-suef UniversityBeni-suef 62511Egypt gastroenterology and Endemic Medicine Department Theodore Research InstituteCairo 23323Egypt

BACKGROUND Childhood cancer survivors are potentially at a higher risk of infection with hepatitis C virus (HCV).The effects of all-oral direct-acting antiviral therapy (DAA) on both the HCV infection as well as the state of cancer remission have not been well investigated in this population.AIM To test the effects of dual sofosbuvir/daclatasvir (SOF/DCV) therapy in the treatment of chronic HCV in survivors of hematologic malignancy in pediatric age group.METHODS We conducted a prospective,uncontrolled,open-label multicenter study.A total of 20 eligible,chronic HCV,genotype-4,infected children who had been in continuous complete remission from hematologic cancer (leukemia/lymphoma) for at least one year were included in the study.All patients were treated with combined SOF/DCV for 12 wk.Patients were monitored throughout the study till 12 wk after end of treatment for safety and efficacy outcomes including the sustained virologic response 12 (SVR12) rate,hematological indices,liver and kidney functions.RESULTS The intent-to-treat SVR12 rate was 20 of 20 (100%;95%CI: 84%-100%).All patients showed normalized liver enzymes from week-4.All hematological indices,liver and kidney functions were kept normal throughout the study.No fatalities or treatment-emergent serious or severe adverse events were reported throughout the study.CONCLUSION SOF/DCV combined therapy could be used safely and effectively in the treatment of chronic HCV genotype-4 infection in leukemia/lymphoma treated children.No relapses were detected during treatment and throughout the follow up period for either the original malignant disease or the HCV infection.

关键词： Chronic hepatitis C Survivors of childhood cancer Sofosbuvir Daclatasvir Efficacy

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Use of thiopurines in inflammatory bowel disease: Safety issues

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2014年第2期5卷 63-76页

作者： Anastasia Konidari Wael El Matary Department of paediatric gastroenterology Alder Hey Children’s NHS Foundation TrustLiverpool L12 2APUnited Kingdom Section of paediatric gastroenterology Department of Paediatrics Faculty of MedicineUniversity of Mani-tobaManitoba R3A 1S1Canada

Thiopurines are widely used for maintenance treatment of inflammatory bowel disease. Interindividual variability in clinical response to thiopurines may be attributed to several factors including genetic polymorphisms, severity and chronicity of disease, comorbidities, duration of administration, compliance issues and use of concomitant medication, environmental factors and clinician and patient preferences. The purpose of this review is to summarise the current evidence on thiopurine safety and toxicity, to describe adverse drug events and emphasise the significance of drug interactions, and to discuss the relative safety of thiopurine use in adults, elderly patients, children and pregnant women. Thiopurines are safe to use and well tolerated, however dose adjustment or discontinuation of treatment must be considered in cases of non-response, poor compliance or toxicity. Drug safety, clinical response to treatment and short to long term risks and benefits must be balanced throughout treatment duration for different categories of patients. Treatment should be individualised and stratified according to patient requirements. Enzymatic testing prior to treatment commencement is advised. Surveillance with regular clinic follow-up and monitoring of laboratory markers is important. Data on long term efficacy, safety of thiopurine use and interaction with other disease modifying drugs are lacking, especially in paediatric inflammatory bowel disease. High quality, collaborative clinical research is required so as to inform clinical practice in the future.

关键词： Thiopurines Azathioprine Mercaptopurine Inflammatory bowel disease Adult Children Therapeutic drug monitoring

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Lymphocytic esophagitis:Report of three cases and review of the literature

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World Journal of Clinical Cases 2016年第12期4卷 413-418页

作者： Bilel Jideh Andrew Keegan Martin Weltman Department of gastroenterology and Hepatology Nepean Hospital

Lymphocytic esophagitis(LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema("spongiosis"). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn's disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. Ly E has been reported to run a benign course; however there has been a case of esophageal perforation associated with Ly E. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature.

关键词： Esophagitis Lymphocytes Gastroesophageal reflux disease Eosinophilic esophagitis Esophageal dysmotility

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Differential changes in intrinsic innervation and interstitial cells of Cajal in small bowel atresia in newborns

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World Journal of gastroenterology 2010年第45期16卷 5716-5721页

作者： Stefan Gfroerer Roman Metzger Henning Fiegel Priya Ramachandran Udo Rolle Department of paediatric Surgery Johann Wolfgang Goethe-University Frankfurt/MTheodor-Stern-Kai 760590 Frankfurt/MGermany Department of paediatric Surgery University of Leipzig04103 LeipzigGermany Department of Pediatric Surgery Kanchi Kamakoti Childs Trust Hospital12-A ChennaiIndia

AIM: To investigate morphological changes of the enteric nervous system (ENS) and the interstitial cells of Cajal (ICCs) in small bowel atresia.METHODS: Resected small bowel specimens from affected patients (n = 7) were divided into three parts (proximal, atretic, distal). Standard histology and enzyme immunohistochemistry anti-S100, anti-protein gene product (PGP) 9.5, anti-neurofilament (NF), antic-kit-receptor (CD117) was carried out on conventional paraffin sections of the proximal and distal part. RESULTS: The neuronal and glial markers (PGP 9.5, NF, S-100) were expressed in hypertrophied ganglia and nerve fibres within the myenteric and submucosal plexuses. Furthermore, the submucous plexus contained typical giant ganglia. The innervation pattern of the proximal bowel resembled intestinal neuronal dysplasia. The density of myenteric ICCs was clearly reduced in the proximal bowel, whereas a moderate number of muscular ICCs were found. The anti-CD117 immunore- action revealed additional numerous mast cells. The distal bowel demonstrated normal morphology and density of the ENS, the ICCs and the mast cells.CONCLUSION: The proximal and distal bowel in small bowel atresia revealed clear changes in morphology and density of the ENS and ICCs.

关键词： Small bowel atresia Enteric nervous system Gastrointestinal motility Interstitial cells of Cajal

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