Objective:To explore the efficacy and safety of ustekinumab (UST) in the treatment of refractory Crohn′s disease (CD) in children.Methods:The clinical features, diagnosis and treatment of 6 patients with children refractory CD and CD-like monogenic inflammatory bowel disease (IBD) who were treated with ustekinumab (UST) at the Department of Gastroenterology, Beijing Children′s Hospital affiliated to Capital Medical University from August 2021 to January 2023 were retrospectively analyzed. The relevant literatures were reviewed and summarized by searching the articles on the treatment of refractory CD in children with UST published in Wanfang database, CNKI, PubMed and Medline.Results:All the six children with refractory CD and CD-like monogenic IBD were boys. Among them, 1 case was diagnosed as IL-10RA receptor defect, 1 case was diagnosed as IPEX syndrome, and 1 case diagnosed as X-linked lymphoproliferative syndrome (XLP-2) . Two patients were treated with UST only, three patients were treated with UST combined with thalidomide until presented clinical remission, and one patient was treated with UST in combination with IFX. Six children were treated with UST for over 24 weeks, and all of them presented clinical response. After treatment for more than 24 weeks, 4 cases presented endoscopic response.None of the 6 patients had special adverse drug reactions during follow-up for 24 weeks. A total of 16 literatures were retrieved. Conclusion:UST may induce and maintain remission in children with refractory CD.

Objective:To investigate the changes in symptoms of inflammatory bowel disease (IBD) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic, as well as the situation of IBD treatment medication use.Methods:A cross-sectional survey study method was used. A questionnaire survey was conducted on a voluntary sampling basis for IBD patients of multiple centers nationwide from December 1st to 31st 2022, collecting clinical data of patients diagnosed with COVID-19 through nucleic acid/antigen testing. Patients were divided into symptomatic exacerbation group and asymptomatic exacerbation group based on whether they felt an exacerbation of IBD symptoms including abdominal discomfort, increased bloody stool or the appearance of purulent bloody stool, increased frequency of diarrhea, etc. And the differences in age, gender, body mass index (BMI) , underlying disease conditions, SARS-CoV-2 vaccination status, IBD type, disease activity, COVID-19 symptoms, and treatment medication between the two groups were compared.Results:A total of 497 patients were included, 317 males and 180 females; age (35.27±11.54) years; 355 CD patients and 142 UC patients; more than 50% of patients exhibited respiratory system symptoms such as fever, muscle soreness, fatigue, cough, expectoration, nasal congestion, and some IBD patients exhibited digestive system symptoms and nervous system symptoms. The symptomatic exacerbation group consisted of 104 patients (20.93%) , and the asymptomatic exacerbation group consisted of 393 (79.07%) . There were no statistically significant differences in gender, age, BMI, underlying diseases, IBD type, and SARS-CoV-2 vaccine doses between the two groups (all P>0.05) . Compared with the asymptomatic exacerbation group, the proportion of patients in the disease active phase was higher [47.12% (49/104) vs. 24.68% (97/393) , P<0.001], and the proportion of patients using mesalazine/sulfasalazine was higher (35.58% vs. 23.41%, P = 0.012) , and the proportions of COVID-19 symptoms such as diarrhea, headache, and dizziness were all higher (all P<0.05) in the symptomatic exacerbation group. Among the 237 IBD patients using biologics, there was a statistically significant difference in the types of biologics used between the symptomatic and asymptomatic exacerbation groups (χ 2 = 9.351, P = 0.031) . Among the 240 patients using biologics, the proportion of delaying or interrupting the use of biologics was higher in symptomatic exacerbation group than that of the asymptomatic exacerbation group, and the difference was statistically significant [45.45% (20/44) vs. 23.98% (47/196) , χ 2 = 8.235, P = 0.004]. Among the 47 patients using immunosuppressants, there was no statistically significant difference in the proportion of stopping immunosuppressants between the symptomatic and asymptomatic exacerbation groups ( P = 0.263) . Conclusion:The main symptoms of IBD patients infected with COVID-19 are respiratory and systemic symptoms, and those in the active phase of the disease or those delaying or withdrawing biologics are more likely to experience an exacerbation of IBD symptoms during the infection.

Objective:To explore the efficacy and safety of dual targeted therapy（DTT）in the treatment of refractory inflammatory bowel disease（IBD）in children.Methods:The diagnosis and treatment processes of refractory IBD children treated with DTT in the Department of Gastroenterology,Beijing Children's Hospital Affiliated to Capital Medical University from April 2022 to May 2024 were analyzed retrospectively,and their clinical characteristics were summarized.Results:A total of ten children with refractory IBD were included,including five males and five females,with a median onset age of 12.58 (5.25,13.33) years old,and seven cases of Crohn's disease (CD) and three cases of ulcerative colitis (UC),with a median disease course of 1.25 (0.91,4.00) years，were treated with DTT for a median time of 6.08 (6.00,13.40)months.Two (2/7) cases of CD patients were partially effective with infliximab(IFX) treatment,while five (5/7) cases were partially effective with a combination of IFX and azathioprine treatment.These patients received DTT with UST in addition to continuous using of IFX.When the seven CD patients were treated with DTT for four weeks,12 weeks and 24 weeks,and the clinical remission rates were 42.9%(3/7),71.4%(5/7) and 100%(7/7)，respectively.The pediatric Crohn's disease activity index gradually decreased,which were significantly lower than those before treatment( P<0.05).Fecal calprotectin,C-reactive protein,erythrocyte sedimentation rate,and blood white blood cells all gradually decreased,which were lower than those before treatment,while hemoglobin and serum albumin were higher than those before treatment.Three children with UC were all resistant to glucocorticoids.One case was partially effective with adalimumab treatment,one case was partially effective with IFX combined with immunosuppressive agents,and one case was partially effective with vedolizumab.All the three UC patients received DTT treatment with UST in addition to continuous using of the original biological preparation.When the three UC patients were treated with DTT for four weeks and 12 weeks,one case showed clinical remission,one case showed clinical response,and one case showed no clinical response.After 24 weeks of DTT treatment,two cases achieved clinical remission and one case had no clinical response.Re-examination of colonoscopy showed that one case of clinical remission had mucosal healing and one case had mild disease activity.However,there was a slight improvement in disease activity under endoscopy compared with that before DTT in patient who had no clinical response.During DTT treatment,no adverse events occurred in all patients. Conclusion:DTT is effective and relatively safe for children with refractory IBD,and can be one of the attempts for children with IBD when they are partially effective with one biological agent.

Objective:To explore the efficacy and safety of ustekinumab (UST) in the treatment of refractory Crohn′s disease (CD) in children.Methods:The clinical features, diagnosis and treatment of 6 patients with children refractory CD and CD-like monogenic inflammatory bowel disease (IBD) who were treated with ustekinumab (UST) at the Department of Gastroenterology, Beijing Children′s Hospital affiliated to Capital Medical University from August 2021 to January 2023 were retrospectively analyzed. The relevant literatures were reviewed and summarized by searching the articles on the treatment of refractory CD in children with UST published in Wanfang database, CNKI, PubMed and Medline.Results:All the six children with refractory CD and CD-like monogenic IBD were boys. Among them, 1 case was diagnosed as IL-10RA receptor defect, 1 case was diagnosed as IPEX syndrome, and 1 case diagnosed as X-linked lymphoproliferative syndrome (XLP-2) . Two patients were treated with UST only, three patients were treated with UST combined with thalidomide until presented clinical remission, and one patient was treated with UST in combination with IFX. Six children were treated with UST for over 24 weeks, and all of them presented clinical response. After treatment for more than 24 weeks, 4 cases presented endoscopic response.None of the 6 patients had special adverse drug reactions during follow-up for 24 weeks. A total of 16 literatures were retrieved. Conclusion:UST may induce and maintain remission in children with refractory CD.

Objective:To investigate the changes in symptoms of inflammatory bowel disease (IBD) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic, as well as the situation of IBD treatment medication use.Methods:A cross-sectional survey study method was used. A questionnaire survey was conducted on a voluntary sampling basis for IBD patients of multiple centers nationwide from December 1st to 31st 2022, collecting clinical data of patients diagnosed with COVID-19 through nucleic acid/antigen testing. Patients were divided into symptomatic exacerbation group and asymptomatic exacerbation group based on whether they felt an exacerbation of IBD symptoms including abdominal discomfort, increased bloody stool or the appearance of purulent bloody stool, increased frequency of diarrhea, etc. And the differences in age, gender, body mass index (BMI) , underlying disease conditions, SARS-CoV-2 vaccination status, IBD type, disease activity, COVID-19 symptoms, and treatment medication between the two groups were compared.Results:A total of 497 patients were included, 317 males and 180 females; age (35.27±11.54) years; 355 CD patients and 142 UC patients; more than 50% of patients exhibited respiratory system symptoms such as fever, muscle soreness, fatigue, cough, expectoration, nasal congestion, and some IBD patients exhibited digestive system symptoms and nervous system symptoms. The symptomatic exacerbation group consisted of 104 patients (20.93%) , and the asymptomatic exacerbation group consisted of 393 (79.07%) . There were no statistically significant differences in gender, age, BMI, underlying diseases, IBD type, and SARS-CoV-2 vaccine doses between the two groups (all P>0.05) . Compared with the asymptomatic exacerbation group, the proportion of patients in the disease active phase was higher [47.12% (49/104) vs. 24.68% (97/393) , P<0.001], and the proportion of patients using mesalazine/sulfasalazine was higher (35.58% vs. 23.41%, P = 0.012) , and the proportions of COVID-19 symptoms such as diarrhea, headache, and dizziness were all higher (all P<0.05) in the symptomatic exacerbation group. Among the 237 IBD patients using biologics, there was a statistically significant difference in the types of biologics used between the symptomatic and asymptomatic exacerbation groups (χ 2 = 9.351, P = 0.031) . Among the 240 patients using biologics, the proportion of delaying or interrupting the use of biologics was higher in symptomatic exacerbation group than that of the asymptomatic exacerbation group, and the difference was statistically significant [45.45% (20/44) vs. 23.98% (47/196) , χ 2 = 8.235, P = 0.004]. Among the 47 patients using immunosuppressants, there was no statistically significant difference in the proportion of stopping immunosuppressants between the symptomatic and asymptomatic exacerbation groups ( P = 0.263) . Conclusion:The main symptoms of IBD patients infected with COVID-19 are respiratory and systemic symptoms, and those in the active phase of the disease or those delaying or withdrawing biologics are more likely to experience an exacerbation of IBD symptoms during the infection.

Objective:To investigate the clinical features and risk factors of the extraintestinal manifestations(EIM)in children with ulcerative colitis(UC).Methods:A retrospective case-control study was conducted.The clinical data of 99 children with UC diagnosed in Department of Gastroenterology, Beijing Children′s Hospital, Capital Medical University from January 2016 to December 2021 were analyzed.According to whether the patients had EIM or not, they were divided into EIM-positive group and EIM-negative group.Rank sum test, χ2test or Fisher′s exact test were used to compare the variables between the 2 groups, including the clinical features, laboratory examination results and treatments.The Logistic regression was used to analyze the risk factors of EIM in children with UC. Results:A total of 99 children with UC were enrolled, including 57 males and 42 females; the age of onset was 10.3(6.4, 12.6)years, and the course of disease was 4.2(1.6, 10.1)months.The patients were mainly characterized by extensive disease(E3)and pancolitis(E4)(69/99, 69.7%), moderate to severe activity(63/99, 63.6%)and moderate to severe inflammation of colonic mucosa(89/99, 89.9%). There were 77 patients(77.8%)in the EIM-negative group and 22 patients(22.2%)in the EIM-positive group, of which 5 patients had two types of EIMs; the most common EIMs were oral ulcers(9 cases), joint lesions(7 cases), and skin lesions(6 cases). Compared with the EIM-negative group, those in the EIM-positive group, such as the E4 type(77.3% vs 44.2%, χ2=7.513, P=0.006), moderate to severe activity(81.8% vs 58.4%, χ2=4.041, P=0.044), pediatric ulcerative colitis activity index score[47.5(35.0, 57.5)score vs 35.0(25.0, 50.0)score, Z=-2.260, P=0.024], the proportion of C-reactive protein≥8mg/L at diagnosis(54.5% vs 19.5%, χ2=10.607, P=0.001), erythrocyte sedimentation rate[30.0(13.8, 47.8)mm/h vs 10.0(4.0, 19.5)mm/h, Z=-3.918, P<0.001], the proportion of glucocorticoid treatment within one year after diagnosis(77.3% vs 49.4%, χ2=5.403, P=0.020)and the proportion of biological agents treatment(45.5% vs 23.4%, χ2=4.112, P=0.043)were significantly higher; the E3 type were significantly lower than those in the EIM-negative group(0 vs 23.4%, χ2=4.813, P=0.028), and the differences were statistically significant.Multivariate Logistic regression analysis showed that erythrocyte sedimentation rate at diagnosis was an independent risk factor of EIM in children with UC( OR=1.063, 95% CI: 1.025~1.103, P=0.001). Conclusion:The UC patients with EIM had more extensive lesions, more severe disease activity, significantly increased inflammatory indicators, and more commom glucocorticoid and biologic therapy.Increased erythrocyte sedimentation rate was an high risk factor of EIM in children with UC.

Objective:To assess the value of double-balloon enteroscopy(DBE)in the treatment of Peutz-Jeghers syndrome(PJS)polyp with intussusception in children.Methods:A total of 14 cases with PJS polyp with intussusception were collected in Gastroenterology Department of Beijing Children′s Hospital Affiliated to Capital Medical University from July 2019 to January 2023.The general information, clinical manifestations, history of surgeries, abdominal ultrasound, enteroscopy and postoperative outcomes were retrospectively analyzed.Results:Fourteen cases with intussusception of PJS(including nine boys and five girls) were enrolled, and the average age was(10.25±2.52)years.There were 21 small intestinal intussusceptions in 14 cases, including eight cases of single intussusception and six cases of multiple intussusceptions.All the patients underwent DBE examination and treatment.A total of 215 small intestinal polyps were removed, no direct complications such as bleeding or perforation were found during the operation.Twelve cases were confirmed intussusception relieved by DBE, and the average maximum diameter of polyps causing intussusception was(4.38±1.43)cm.In addition, DBE did not reach the site of intussusception polyp in one case, and another case developed intestinal obstruction after DBE operation, which were treated by surgery.Conclusion:DBE provides a relatively effective method for the treatment of PJS polyps with intussusception without complete ileus in children.

Objective:To compare the efficacy of combination therapy on cyclic vomiting syndrome(CVS)in children, and improve the efficacy of CVS treatment in the future.Methods:This study retrospectively analyzed patients′ medical records of CVS, which were admitted to Digestive Department of Beijing Children′s Hospital from 2012 to 2019.The treatment regimen was A(Cyproheptadine+ Doxepin+ Valproate), B(Propranolol+ Cyproheptadine), or C(Propranolol+ Amitriptyline). Meanwhile, the patients should take drugs more than three months.The clinical data of 42 cases were analyzed retrospectively, and the treatment effect after discharge was followed up by telephone until October, 2020.Results:Among the 42 cases, 17 were male and 25 were female, whose mean age of onset was (4.65±3.23) years, and the age of diagnosis was (6.79±3.58) years.The main accompanied symptoms were abdominal pain and upper gastrointestinal bleeding.Forty-two patients were moderate/severe CVS.The regimens A, B and C were observed in 7, 11, and 24 patients, respectively.The age at improvement was(8.17±4.12)years.The course of treatment was(1.37±0.96)years.The age at follow-up was(10.32±4.03)years.During the 1-year follow-up, 35 cases were effective, and the efficiency was 83.3%.Among them, 23 cases had no paroxysmal vomiting and 7 cases had no effect.There was no significant difference in therapy effects among group A, B and C. Between the effective group and non-effective group, there were statistical differences in the personal history of hiatus hernia( P=0.024), the weight at follow-up ( P=0.042), and the course of medication( P=0.020). Conclusion:The combination regimen has a higher effective rate in the treatment of CVS.There was no significant difference among the three regimens in the treatment of CVS.For children with refractory CVS, who can not be treated with combination therapy, individualized therapy should be further developed.

Objective:To investigate endoscopic and clinical characteristics of intestinal Behcet′s disease (BD) in children.Methods:General information, clinical manifestations, laboratory tests, imaging examinations and endoscopic characteristics of 14 children with intestinal BD treated in the Department of Gastroenterology, Beijing Children′s Hospital Affiliated to Capital Medical University from January 2016 to March 2020 were retrospectively analyzed.Results:Fourteen children with intestinal BD were recruited, involving 5 males and 9 females with the age of 1 month to 12 years and 11 months [(6.68±3.73) years old], and a median disease course of 6 months.All of them had gastrointestinal symptoms, including 11 cases with abdominal pain, 7 cases with diarrhea and 2 cases with vomiting.Complications of children with intestinal BD included gastrointestinal bleeding, intestinal perforation and stenosis.Extragastrointestinal symptoms included recurrent oral aphthosis in all the 14 cases, fever in 11 cases, skin lesions in 9 cases, vascular manifestations in 8 cases, positive pathergy test in 6 cases, joint manifestations in 5 cases, neurological manifestations in 1 case, and malnutrition in 6 cases.Observed by the endoscopy, lesions were mainly distributed in the distal ileum [61.5%(8/13 cases)]and ileocecal part[53.8%(7/13 cases)], with the main manifestation of ulcer.There were 3 cases with single ulcer and 10 cases with multiple ulcers, including 7 cases with deep and large ulcers.Pathological examinations of endoscopic lesions showed that the main features were mucosa chronic nonspecific inflammation, mucosa chronic active inflammation with ulcer and vasculitis.Conclusions:Clinical manifestations of intestinal BD vary a lot and are non-specific.Some children with intestinal BD may develop severe complications.Endoscopic lesions of intestinal BD have certain characteristics, which contribute to the diagnosis.Gastroenterologists need to be fully aware of intestinal BD.

Objective:To evaluate the clinical efficacy and safety of Infliximab (IFX) in pediatric Crohn′s disease (CD).Methods:The efficacy of IFX therapy in 30 patients suffering from active CD who were not completely improved with traditional medicine and enteral nutrition or had intolerance to the medicine in Beijing Children′s Hospital Affiliated to Capital Medical University from December 2014 to December 2019 were retrospectively analyzed.Pediatric Crohn′s Disease Activity Index (PCDAI), blood biochemistry indices, mucosal healing, nutritional status, and adverse reactions were compared and evaluated.Results:Thirty active CD cases, with 18 males and 12 females, were enrolled, and the average age was (8.63±4.76) years old.Three cases who didn′t complete 3 times of IFX injection and 1 case who lost to be followed up were excluded.A total of 26 cases of CD in active period were enrolled in this study on efficacy.The clinical remission and response rate of 26 cases were 61.5% and 84.6%, respectively, at 14-week of IFX therapy.The clinical remission and response rate of 21 cases were 71.4% and 85.7%, respectively, at 30-week.The clinical remission and response rate of 15 cases were 86.7% and 93.3%, respectively, at 54-week.At week 14 th, PCDAI score [(9.56±8.05) scores vs.(29.02±10.86) scores] decreased compared with before treatment ( t=7.339, P<0.05). The levels of erythrocyte sedimentation rate [(15.54±10.26) mm/1 h vs.(33.77±21.30) mm/1 h] and C-reactive protein [(4.79±12.94 ) mg/L vs.(16.33±23.43) mg/L] were obviously decreased, and the hemoglobin [(126.27±16.51) g/L vs.(110.58±16.45) g/L], hematocrit [(37.03±3.95)% vs.(33.52±4.32)%], and albumin levels [(42.30±3.03) g/L vs.(37.13±5.68) g/L] were remarkably increased compared with those before treatment ( t=3.932, 1.993, -3.398, -3.060, -4.009, all P<0.05). Height for age Z score and body mass index Z score were increased after IFX treatment, without statistically significant differences (all P>0.05). Conclusions:IFX therapy had good clinical efficacy in controlling inflammatorys and inducing clinical remission in pediatric CD.