Diagnostic and therapeutic value of endoscopy and mucosal histology for digestive tract diseases in infants / 中华消化内镜杂志

Objectives:To investigate the clinical value of endoscopy and mucosal histology for digestive tract diseases in infants.Methods:Clinical data of 357 infants who underwent 422 gastrointestinal endoscopies from January 2010 to December 2021 were collected. The indications, endoscopic manifestations, histological features of mucosa and diagnosis were analyzed.Results:A total of 159 gastroscopies and 263 colonoscopies were performed. Diarrhea (185 cases), bloody stool (178 cases) and vomiting (46 cases) were common symptoms. Endoscopy showed manifestations including non-specific inflammatory changes (265 cases), ulcer-like changes (72 cases), and normal mucusa (48 cases). A total of 373 biopsies were performed, including 260 cases of abnormal mucosal histology, 109 cases of normal mucosal histology, and 4 cases of too small biopsy specimens for analysis. Diagnoses were 208 cases of anaphylactic disease, 45 cases of inflammatory bowel disease, 15 cases of variation of structure, 10 cases of intestinal lymphangiectasis, 2 cases of autoimmune enteropathy, and 1 case of celiac disease. There was only 1 colonic perforation complicating endoscopy in terms of endoscopic complication.Conclusions:It is safe and effective to perform endoscopy standardly for digestive tract diseases in infants. Endoscopy with biopsies is a greatly informative test for diagnosis in infants.

Clinical features and genetic variants of children with hepatic Wilson′s disease / 中华全科医师杂志

Objective:To analyze the clinical characteristics and genetic variants of children with hepatic Wilson disease (WD).Methods:The clinical data and genetic test results of 35 children, who were diagnosed as WD with primary hepatic manifestation in the Department of Gastroenterology, Children′s Hospital of Capital Institute of Pediatrics from March 2018 to March 2022, were retrospectively analyzed. The relationship between phenotype and genotype of patients was analyzed.Results:Among 35 children, there were 24 males and 11 females with a median age at diagnosis of 5.5 (4.0, 7.5) years. All patients had elevated transaminases. The elevated transaminases was found during routine physical examination in 33 cases (94.3%), in whom there was no fever, cough, recurrent vomiting, abdominal pain, diarrhea, jaundice, limb tremor, gait instability and other discomfort 2 weeks before admission, except 1 case with nausea; abdominal ultrasonography showed that 5 cases (15.2%) had no abnormality, and others had different degrees of hepatomegaly, splenomegaly, and echo enhancement in liver parenchyma. Among the remaining 2 cases, one 11-year-old child presented with edema, and had cirrhosis portal hypertension with esophageal varices; another 7-year-old child was diagnosed as acute liver failure manifested with nausea and jaundice. Thirty three patients(94.3%)had decreased serum ceruloplasmin levels (<100 mg/L); 24-h urinary copper concentration was>100 μg in 16 cases (45.7%) and<40 μg in 2 cases (5.7%). The tests of hepatitis B virus, hepatitis C virus, cytomegalovirus and EB virus were all negative in 35 children, and the autoimmune hepatitis antibodies were also negative. A total of 34 different ATP7B gene mutations were detected; the most frequent mutation was c.2333G>T (P.R778L) at exon 8, followed by c.2621C>T(p.A874V)at exon 11 and c.2621C>T(p.A874V)at exon 13. There was no significant difference in clinical phenotype between patients with nonsense mutation, frameshift mutation or splicing mutation and those with only missense mutations( Z=-1.00, t=-0.16, Z=-1.14, Z=-1.03,all P>0.05). Conclusions:The onset of WD in children is obscure, and clinicians should consider this disease in patients presenting with elevated transaminase. Ceruloplasmin and urine copper should be tested timely, the early diagnosis and treatment can improve the prognosis. And there is no significant correlation between genotype and clinical phenotype.

Related factors of gastroesophageal reflux disease in children / 中华全科医师杂志

Objective:To investigate the factors related to gastroesophageal reflux disease (GERD) in children.Methods:Clinical data of 370 children who underwent 24h multi-channel impedance-pH monitoring (24h MII-pH) in Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2015 to December 2020 were enrolled in the study. The children were divided into GERD group ( n=202)and non-GERD group ( n=168) according to results of 24h MII-pH. The relationship of sex, age, body mass index (BMI), disease course, peripheral blood eosinophils count, IgE, Helicobacter pylori (Hp) infection, hiatus hernia of patients with GERD was analyzed by univariate and multivariate logistic regression analysis. Results:In GERD group 124 were males and 78 were females with a mean age of (6.4±4.1) years (2 months to 16.75 years), and in non-GERD group 82 were males and 86 were females with a mean age of (8.0±3.5) years (10 months to 15.17 years). Univariate logistic regression analysis showed that sex( OR=0.600,95% CI:0.396-0.908, P=0.016), age ( OR=0.537,95% CI:0.412-0.699, P<0.001)and hiatus hernia( OR=7.433,95% CI:2.567-21.520, P<0.001)were significantly associated with GERD of the children. Multivariate analysis showed that hiatus hernia ( OR=4.023,95% CI:1.298-12.470, P=0.016) was the independent risk factor, while male gender ( OR=0.567,95% CI:0.367-0.874, P=0.010) and younger age ( OR=0.613, 95%CI:0.459-0.819, P=0.001 ) were related factors of gastroesophageal reflux disease in children. Conclusion:Sex, age, and hiatal hernia are factors related to GERD in children.

Analysis of SLC25A13 gene variants in 16 infants with intrahepatic cholestasis caused by citrin protein deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the characteristics of SLC25A13 gene variants in 16 infants with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD).@*METHODS@#The infants were subjected to high-throughput DNA sequencing for coding exons and flanking regions of the target genes. Suspected variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Among the 16 NICCD cases, 15 were found to harbor pathogenic variants. Among these, IVS14-9A>G, c.1640G>A, c.762T>A, c.736delG, c.1098Tdel and c.851G>A were previously unreported.@*CONCLUSION@#Six novel SLC25A13 variants were found by high-throughput sequencing, which has enriched the spectrum of SLC25A13 gene variants and provided a basis for genetic counseling and prenatal diagnosis.

Clinical features of pancreatitis in children: a single center retrospective study / 中国小儿急救医学

Objective:To explore the clinical characteristics of children with pancreatitis, aiming to analyze the clinical differences of acute pancreatitis(AP), recurrent acute pancreatitis(RAP)and chronic pancreatitis(CP)in children.Methods:The clinical characteristics of AP, RAP, CP in children admitted to the Department of Gastroenterology at Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2015 to December 2020 were analyzed.Results:One hundred and nine cases were included in this study, including 69 cases of AP(63.3%), 22 cases of RAP(20.2%)and 18 cases of CP(16.5%). The proportion of school-age and adolescent children was 48.6% and 29.4%, and there was statistical difference between the composition of children at different ages( P<0.001). Idiopathic was the main cause of AP, RAP and CP.The other causes included biliary, viral infection, structural abnormalities, drug-induced, hypercholesterolemia and heredity.97.2%(106 cases)of the children were accompanied by abdominal pain, mainly in middle and upper abdomen(75 cases, 70.8%)and around umbilical cord(22 cases, 20.8%). The pancreatic enlargement in preschool children was mainly diffuse enlargement(11/12), while the older children with local enlargement and diffuse enlargement accounted for the same proportion, the difference was statistically significant( P=0.037). The height score of CP children was lower than the overall average of the population(0 score), and lower than those of AP and RAP children, with statistically significant difference[-0.65(-1.57, 0.25) vs.0.36(-1.03, 1.05) and -0.09(-0.30, 0.41), H=6.021, P=0.044]. Eight (11.6%) cases with AP progressed to RAP, and six (8.7%) cases with AP progressed to CP. Conclusion:Pancreatitis tends to occur in school-age and adolescent children, and idiopathic is the first cause of all types of pancreatitis.AP, RAP, and CP share common features of pancreatitis in terms of etiology composition and clinical manifestations.Compared with AP and RAP, CP is more likely to affect the growth and development of children.Some children with AP could progress to RAP or CP, so we should pay more attention to the etiological investigation of AP and eliminate the etiological factors in time to avoid the disease progression.

Clinical features of five children with hepatitis-associated aplastic anaemia / 中国小儿急救医学

Objective:To investigate the clinical characteristics of hepatitis-associated aplastic anaemia(HAAA)in children.Methods:A retrospective analysis was performed on the clinical manifestations, laboratory examinations, treatments and other clinical data of five children with aplastic anemia(AA)diagnosed by bone marrow examination after admission with acute liver dysfunction admitted to the Department of Gastroenterology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2016 to December 2020.Results:All five children were boys and the onset age of these children ranged from 2 to 13 years.All of the five cases were acute onset and presented with jaundice.The time frame of the diagnosis of HAAA was 0 to 12 weeks from the presentation of the liver disease.One patient had simultaneous onset of hepatitis and aplastic anemia.The liver function was significantly improved at the diagnosis of HAAA in three patients and worsen in one patient.Only one patient showed CMV-DNA positive and the pathogen results of other patients were negative.Lymphocyte immunity disorders were found in all five patients, and the proportion of inhibitory/cytotoxic T lymphocytes(CD3 + CD8 + ) increased.Two children received hematopoietic stem cell transplantation, of which one died and one improved after transplantation.One child improved after treated with antithymocyteglobulin and cyclosporin.One child died due to severe infection.There was no significant improvement in one child treated with cyclosporine. Conclusion:HAAA should be alerted in acute hepatitis patients.Blood routine should be monitored even if liver function improves.Bone marrow tests are needed if patients have peripheral cytopenia in two or more lineages.Early and timely treatments with immunosuppressive therapy and hematopoietic stem cell transplantation can improve the prognosis.

Clinical and genetic features of neonatal intrahepatic cholestasis caused by citrin deficiency in northern China: A single-center analysis of 23 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features and gene mutation characteristics of neonatal intrahepatic cholestasis caused citrin deficiency (NICCD) in northern China. MethodsA total of 23 pediatric patients in northern China who were diagnosed with NICCD by blood tandem mass spectrometry and/or gene detection in Department of Gastroenterology, Children’s Hospital Affiliated to Capital Institute of Pediatrics, from January 2015 to December 2018 were enrolled as NICCD group, and 36 pediatric patients with idiopathic neonatal cholestasis (INC) who had unclarified etiology after a series of examinations during the same period of time were enrolled as INC group. A retrospective analysis was performed for the clinical manifestation, laboratory examination, pathology, blood/urine metabolic screening, and gene sequencing results of the pediatric patients in the NICCD group, and follow-up was performed to observe their outcome; biochemical parameters were compared between the two groups. The independent samples t-test was used for comparison of normally distributed continuous data, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. ResultsAmong the 23 patients in the NICCD group, 10 had hypoglycemia, 13 had hypoalbuminemia, 17 had hyperammonemia, and 15 had hyperlactacidemia; 15 had an increase in low-density lipoprotein, 6 had an increase in cholesterol, and 7 had an increase in triglyceride; 17 had prolonged prothrombin time, and 16 had prolonged activated partial thromboplastin time (APTT). Compared with the INC group, the NICCD group had significantly higher gamma-glutamyl transpeptidase (GGT), total bile acid (TBA), and APTT and a significantly lower albumin (Alb) level (Z=-2.487, Z=-3.528, t=3.532, t=-2.24, all P＜0.05). For the patients with NICCD, blood tandem mass spectrometry showed that the most common abnormalities were the increased levels of arginine, citrulline, methionine, free carnitine, and long-chain acylcarnitine, while urinary gas chromatography showed the increased levels of 4-hydroxyphenyllactic acid, galactose, galactitol, and galactonic acid. Gene detection was performed for all 23 patients and identified 16 pathogenic mutations, among which 7 were newly discovered, namely ivs14-9a＞G, c1640 G＞A, c.762T＞A, c.736delG, c.1098 T del, c.851G＞A, and c.550G＞A. Except for the 2 patients who were lost to follow-up, the levels of aminotransferases and bilirubin gradually returned to normal in 21 patients after 2-6 months of treatment; none of them showed delayed growth and development after being followed up to the age of 1 year, and 2 of them developed dietary preference (they liked fish and meat and did not like staple food). ConclusionAbnormalities of blood GGT, TBA, Alb, and APTT may provide ideas for the differential diagnosis of NICCD and INC. NICCD gene mutations in northern China are heterogeneous and most patients tend to have a good prognosis.

Clinical and genotypic characteristics of infantile inflammatory bowel disease / 中华儿科杂志

Objective@#To analyze the clinical and genotypic characteristics of infantile inflammatory bowel disease (IBD).@*Methods@#The age of onset, family history, clinical manifestations, and treatment effect were retrospectively analyzed in 39 infants (male 23 cases, female 16 cases) with IBD who were admitted to the Department of Gastroenterology in Children′s Hospital, Capital Institute of Pediatrics from January 2007 to December 2017. Next generation sequencing (NGS) based on target gene panel was used for gene analysis in 17 patients.@*Results@#The median age of onset was 0.5 (0.5, 1.0) month. The most common clinical symptoms included diarrhea (39, 100%), malnutrition (38, 97%), hematochezia (34, 87%), fever (25, 64%), and perianal diseases (24, 61%). Four children had associated family history. Among the 17 patients whose gene was analyzed, 10 were found to have the pathogenic gene variation, within whom 7 had interleukin-10 receptor α subunit (IL-10RA) mutation, 2 had CYBB heterozygous mutation, 1 had interleukin-10 receptor β subunit (IL-10RB) mutation. The therapeutic medicine included mesalazine, steroids, and thalidomide. Eighteen children (46%) reached clinical remission (10 cases) or partial remission (8 cases).@*Conclusions@#The incidence of single gene mutation in infants with IBD is high, with IL-10RA mutation as the most common. Refractory diarrhea and malnutrition may indicate infantile IBD.

Interleukin-10 receptor gene mutations induced very early onset inflammatory bowel disease in 6 infants / 中华儿科杂志

Objective@#To analyze the clinical features and interleukin-10 receptor gene mutations in six infants with very early onset inflammatory bowel disease (VEO-IBD).@*Methods@#Four girls and two boys with VEO-IBD admitted to Children's Hospital Affiliated to Capital Institute of Pediatrics from June 2016 to September 2017 were reviewed. The clinical data including general condition, clinical symptoms, laboratory tests, and colonoscopy and pathological results were collected and analyzed. Interleukin-10 receptor α subunit (IL-10RA) gene was examined in all patients.@*Results@#Persistent diarrhea and fever were the most common symptoms and were found within 1 month after birth in all 6 patients. Anemia, oral ulcer or perianal lesions and growth retardation were common concomitant symptoms. All patients had colonoscopy examination and the results showed multiple ulcers affecting the colon with biopsies revealing acute and chronic inflammation. Three patients were found to have cryptitis and crypt abscesses. Gene sequencing revealed IL-10RA gene mutations in all six patients, including 3 cases with homozygous mutations (one with c.537G>A and two with c.301C>T) and 3 heterozygous mutations (paternal c.301C>T in all cases; maternal c.299T>G, c.350G>A and c.537G>A, respectively) . After conventional treatment, one got clinical and pathological improvement according to colonoscopy, three improved clinically, one worsened and died, and one died of septic shock secondary to intestinal perforation.@*Conclusions@#VEO-IBD is associated with IL-10RA mutation, usually with severe intestinal symptoms and significant extra-intestinal symptoms, as well as varied responses to conventional treatment. In our study, c.301C>T and c.537G>A are the most common mutations.

Clinical manifestations of celiac disease in two children / 临床儿科杂志

Objective To explore the diagnosis and treatment of celiac disease in children. Method The clinical data of 2 children with celiac disease were analyzed retrospectively. Results Both of them were 8-year and 2-year-old males. Chronic diarrhea and malnutrition were the main manifestations combined with anemia and hypoalbuminemia in both of them. The examinations showed that stool Sultan III staining, anti-endometrial antibody IgA, and anti-gliadin IgA were all positive. Endoscopic examination revealed mucosal lesions in duodenal and small bowel. Pathology showed small intestinal villus atrophy, infiltration of lymphocytes in crypt epithelium, and infiltration of lymphocytes and plasma cells in the lamina propria. Diarrhea was quickly improved in both of them after the gluten diet was avoided, and weight increased significantly. However, one of them failed to maintain a gluten free diet and diarrhea recurred. Conclusions The celiac disease in children is rare in China. It needs to have early diagnosis and treatment, and should be strictly followed by a lifelong gluten free diet.

Clinical manifestations of celiac disease in two children / 临床儿科杂志

Objective To explore the diagnosis and treatment of celiac disease in children. Method The clinical data of 2 children with celiac disease were analyzed retrospectively. Results Both of them were 8-year and 2-year-old males. Chronic diarrhea and malnutrition were the main manifestations combined with anemia and hypoalbuminemia in both of them. The examinations showed that stool Sultan III staining, anti-endometrial antibody IgA, and anti-gliadin IgA were all positive. Endoscopic examination revealed mucosal lesions in duodenal and small bowel. Pathology showed small intestinal villus atrophy, infiltration of lymphocytes in crypt epithelium, and infiltration of lymphocytes and plasma cells in the lamina propria. Diarrhea was quickly improved in both of them after the gluten diet was avoided, and weight increased significantly. However, one of them failed to maintain a gluten free diet and diarrhea recurred. Conclusions The celiac disease in children is rare in China. It needs to have early diagnosis and treatment, and should be strictly followed by a lifelong gluten free diet.

Six cases of Brucella infection in children and review of literatures / 中华儿科杂志

<p><b>OBJECTIVE</b>To present six cases of Brucella infection in children, analyze the characteristics of the disease, diagnostic and therapeutic process.</p><p><b>METHOD</b>The clinical manifestations, laboratory test results and diagnostic process of 6 confirmed cases of brucellosis seen between 2011-2012 were retrospectively analyzed and domestic and foreign literature was reviewed.</p><p><b>RESULT</b>All the 6 children had a history of either exposure to, travelling to endemic area, or consuming infected lamb/beef. After the relevant examinations for these children, either positive etiologic or serologic evidence of brucellosis infection was obtained. The main clinical manifestation was fever in all cases, the peak body temperature was 37.5-38.0 °C in 3 cases, 38.1-39.0 °C in 2 cases, 39.1-41 °C in 1 case. Except for 1 case whose fever type was undulant fever, all the rest had irregular fever.Joint pain existed in 3 cases, orchitis in 1 case, cervical lymphadenopathy in 3 cases, hepatosplenomegaly in 2 cases, and impaired liver function in 4 cases. The Brucella agglutination test was positive in 5 cases. The blood culture was positive for all cases. In 4 cases the sulfamethoxazle and rifampicin were used for treatment, 1 case was treated with rifampicin and erythromycin, parents of 1 case refused to use the drug. The "brucellosis in children" was used to search literature at Wanfang database, Pubmed database for literature of recent 10 years, and a total of 13 articles including 15 cases were retrieved. All the patients had fever, 6 cases had joint swelling and pain, 10 cases had hepatosplenomegaly, 6 cases had cervical lymphadenopathy, 4 cases were complicated with central nervous system infection. Brucella agglutination test was positive in 9 cases and blood culture was positive for Brucella infection in all cases.</p><p><b>CONCLUSION</b>Childhood Brucella infections are usually presented with various clinical manifestations, and are often accompanied by symptoms of systemic infection. For fever of unknown origin, one should include tests associated with brucellosis and pay special attention to differential diagnosis against other diseases.</p>

Clinical features of childhood eosinophilic gastroenteritis / 临床儿科杂志

ObjectiveTo analyze clinical manifestations and treatment of eosinophilic gastroenteritis (EGE) in children.MethodsThe clinical data of 10 children with EGE under the treatment from June 2014 to June 2012 were analyzed retrospectively.ResultsThere were 10 children (6 males and 4 females) aged from 9 months to 14 years. Clin-ical symptoms of eight preschool and school age children included abdominal pain (8 cases), vomiting (4 cases), diarrhea (3 cases), ascites (3 cases), rash (3 cases), fever (2 cases) and hypoalbuminemia (2 cases). Clinical symptoms of two in-fant and toddler were diarrhea and hematochezia. Peripheral blood eosinophils were increased in 10 children. IgE was elevated in 9 children. One child had very high C-reactive protein. Endoscopic examination showed mucosal congestion, swelling, erythema, erosion. Multiple sites of biopsy showed eosinophil count> 20/HP. One child was diagnosed by lap-aroscopic exploration. The treatment included diet avoidance, omeprazole, anti-allergic drug. Four children were treated with corticosteroids. All children had been followed up for 6 months to 2 years. One child had relapsed.Conclusion The clinical manifestations of EGE are various. Endoscopic biopsy is necessary for diagnosis. Laparoscopy also is help-ful for diagnosis. Dietary and glucocorticoid therapy were effective.