Ustekinumab in pediatric patients with Crohn's disease: safety, and efficacy results from a multicenter retrospective study in China.

Background: Ustekinumab (UST) is approved as an effective therapy for Crohn's disease (CD) in adults. Off-label use is increasing in the pediatric population, more data on safety and efficacy in pediatric patients with CD is urgently needed. Aims: This study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease. Methods: This multicenter retrospective study carried out at three tertiary care centers, and identified children who received their first dose of UST at 18 years old or younger and followed up for a minimum of 24 weeks. Data on demographics, disease behavior, location and activity, treatment history were collected. The primary outcomes were clinical remission at weeks 24-32 and weeks 48-56 of UST therapy. Secondary outcomes were clinical response at the same time points, endoscopic remission, changes in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin and fecal calprotectin, improvement in growth parameters, and rate of adverse events. Results: Sixteen patients were included, and 11/13 (84.6%) continued to receive UST after 1 year. Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was lower than baseline (43.8, IQR: 31.3-51.9 vs.15, IQR: 5.6-25, p < 0.001) and 75% at weeks 48-56 with wPCDAI was lower than baseline (42.5, IQR: 23.8-50 vs. 7.5, IQR: 0-13.8, p = 0.004). Five of eleven children achieved endoscopic remission. No serious adverse events were recorded during the study period. Conclusions: UST is efficacious and safe in pediatric patients with CD. Pediatric patients could benefit from UST as either a primary or secondary biologic therapy for the induction, or maintenance of remission of CD.

Clinical application of endoscopic diaphragmotomy and dilation in a congenital duodenal diaphragm.

Background: A congenital duodenal diaphragm (CDD) is a rare cause of duodenal obstruction in infants and children. The traditional approach to treatment has been surgical intervention either with excision and duodenoplasty or with bypass through a duodenoduodenostomy, which is invasive and carries the risk of anastomotic leakage. Aims: To summarize the key points of differential diagnosis and treatment of a CDD under gastroscopy and to evaluate its efficacy and safety. Methods: The clinical data of patients with a duodenal obstruction diagnosed and treated by gastroscopy in our hospital between January 2019 and December 2022 were retrospectively analyzed. The gastroscopic features of the CDD were summarized. The clinical outcomes of patients with CDD treated by gastroscopy were collected and investigated. Results: A total of 13 children with a duodenal obstruction underwent a gastroscopic examination and/or treatment, and of these, 10 were diagnosed as having a CDD and 3 were finally diagnosed as having an annular pancreas. A dome-shaped structure during inspiration (9/10) and a guidewire that could be inserted through the opening into the distal lumen (6/10) were the gastroscopic features of the CDD, while the annular pancreas had none of these features. The 10 patients, 4 men and 6 women with the CDD, were treated through endoscopic diaphragmotomy and dilation. The age and weight at operation was 15 days to 7 years (M: 2.25 years) and 2.85-22 kg (M: 13.6 kg), respectively. A total of 11 endoscopic operations were performed in the 10 patients. The time of single operation was 15-55 min (M: 38 min). The patients did not experience complications such as bleeding, pneumoperitoneum, and duodenal papilla injury during the operation. Feeding was started 12-24 h after surgery, and the patients were discharged 2-10 days (M: 7 days) postoperatively. The patients were followed up for 3-36 months (M: 17 months), and none of them had a recurrence of vomiting. However, three showed a recurrence of stenosis in upper gastrointestinal imaging, one of whom underwent a partial diaphragm resection again 2 months after the primary treatment. Conclusions: A CDD can be confirmed by endoscopy based on its characteristic features. Endoscopic diaphragmotomy and balloon dilation are safe and effective, which can be a new option for minimally invasive treatment of a CDD.

Understanding endoscopic and clinicopathological features of patients with very early onset inflammatory bowel disease: Results from a decade of study.

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AIMS: This study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. METHODS: A retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. RESULTS: A total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. CONCLUSIONS: Endoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.

Intestinal ultrasound score predicts therapeutic outcomes of infliximab in pediatric patients with Crohn's disease.

BACKGROUND AND AIMS: Objective evaluation of treatment response is critical in the management of Crohn's disease (CD). Compared with endoscopy, intestinal ultrasound (IUS) is non-invasive and well-tolerated. This study is aimed to assess the predictive value of IUS score for treatment response in pediatric CD patients. METHODS: We conducted a retrospective study in pediatric CD patients who underwent endoscopy and IUS at start of infliximab treatment [T0] and after 22-38 weeks [T1] between February 2021 and January 2023. Pediatric Crohn's Disease Activity Index (PCDAI), biochemical parameters, the Simple Endoscopic Score for Crohn's disease (SES-CD) and IUS parameters were collected at two timepoints. IUS scores were assessed by International Bowel Ultrasound Segment Activity Score (IBUS-SAS). RESULTS: Thirty patients were included, with 53.3% reaching endoscopic response and 43.3% endoscopic remission. After infliximab treatment, IBUS-SAS (58.5 ± 24.2 vs 34.4 ± 21.6, p = .0001) was significantly decreased. At T1, change in IBUS-SAS (-38.2 ± 22.0 vs -7.9 ± 24.1, p = .0015) were pronounced in patients with endoscopic response compared with endoscopic non-response. Significant correlation were observed between IBUS-SAS and SES-CD, PCDAI, C-reaction protein, erythrocyte sedimentation rate, hemoglobin, albumin. The most accurate cutoff values for predicting endoscopic response were 57.4% decrease of IBUS-SAS (AUROC: 0.862, p < .001). The optimal cut-off of IBUS-SAS to correlate endoscopic remission was 26.0 (AUROC: 0.686, p = .017). CONCLUSIONS: The validated ultrasound-base score, IBUS-SAS is an effective index for monitoring endoscopic response to infliximab therapy in CD. IUS evaluation could guide treatment decision for pediatric CD.

Long-term outcomes after enterostomy for very early-onset inflammatory bowel disease with interleukin-10 signaling deficiency.

BACKGROUND: Very early-onset inflammatory bowel disease (VEOIBD) with interleukin-10 (IL10R) signaling deficiency usually requires enterostomy in patients who are refractory to traditional treatment. This study aimed to evaluate long-term outcomes after enterostomy for VEOIBD patients with IL10R signaling deficiency. METHODS: The medical records of all patients undergoing enterostomy for signaling deficiency were retrospectively assessed during 2012.1-2022.7 in a tertiary teaching hospital, Children's Hospital of Fudan University, Shanghai, China. Data on disease history, diagnosis and details of enterostomy and stoma closure and follow-up were collected. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors associated with the long-term outcome of delayed stoma closure. RESULTS: A total of 46 patients underwent an enterostomy, 19 who required emergency enterostomy and 27 with selective enterostomy. After ten years of follow-up, 35 patients underwent hematopoietic stem cell transplantation (HSCT), and 25 patients were alive after HSCT. The median timeframe between HSCT and stoma closure was 19.6 [15.9,26.2] months. Nineteen patients underwent stoma closure and had an average age of 3.9 ± 1.5 years; 6 patients were waiting for stoma closure. Based on a univariate logistic model, risk factors significantly associated with late stoma closure were age at enterostomy and age at HSCT. However, multivariate logistic regression showed no statistically significant factor associated with late stoma closure. There was no significant difference between the stoma closure group and delay closure group in the z scores of weight for age at follow up. CONCLUSIONS: This study determined the long-term outcomes after enterostomy for VEOIBD with interleukin-10 signaling deficiency. The appropriate time point of enterostomy and HSCT may improve quality of life in the long term.

Efficacy of Phenotype-vs. Genotype-Guided Therapy Based on Clarithromycin Resistance for Helicobacter pylori Infection in Children.

Background: Clarithromycin resistance reduces the eradication rate of Helicobacter pylori (H. pylori). Cultures with susceptibility testing and molecular determination of genotypes are recommended to guide-tailored therapy. Methods: We retrospectively enrolled patients aged 6 and 18 years with H. pylori infection, who underwent an endoscopy and agreed to undergo both culture and genetic testing for clarithromycin resistance. Patients receiving tailored therapy based on traditional culture results (phenotype-guided therapy) or genetic testing results (genotype-guided therapy) were included in the study. 13C-urea breath test was used to evaluate the success of eradication at least 4 weeks after the completion of treatment. We aimed to determine whether the eradication rate of phenotype- or genotype-guided therapy based on clarithromycin resistance is greater than 90% in children. Results: Between September 2017 and October 2020, 226 eligible patients were enrolled. There were 71 with clarithromycin-sensitive strains in the phenotype-guided therapy group and 87 without 23S rRNA point mutations (A2142G, A2142C, and A2143G) in the genotype-guided therapy group. Eradication rates were 70.4% (50/71, [95% CI: 58.4-80.7%] for phenotype-guided therapy and 92.0% (80/87, [95% CI: 84.1-96.7%]) for genotype-guided therapy (P < 0.01). The incidence of side effects was 4.2% (3/71) and 10.3% (9/87), with no major differences between these two groups (P = 0.15), respectively. The compliance rate was also similar (97.2 vs. 95.4%, P = 0.87). Conclusion: Tailored therapy according to genetic testing results achieved eradication rates of 92% and was superior to tailored therapy guided by traditional culture results.

Clinical outcome of infantile-onset inflammatory bowel disease in 102 patients with interleukin-10 signalling deficiency.

BACKGROUND: Infantile-onset inflammatory bowel disease can be caused by defects in interleukin-10 signalling. The natural history and clinical outcomes of allogeneic haematopoietic stem cell transplantation, medical treatment and surgery have not been thoroughly described. AIMS: This study evaluates disease progression and clinical outcome in patients with interleukin-10 signalling deficiency. METHODS: One hundred and nine patients with interleukin-10 signalling deficiency were retrospectively reviewed from a single tertiary centre. The Kaplan-Meier method was applied to calculate probabilities of survival and interval between transplant and stoma closure. RESULTS: One hundred and nine patients were reviewed, and 102 patients were included in the survival analysis. One hundred and eight patients were identified with IL10RA mutations, and one patient harboured IL10RB mutation. Seventy-three patients received haematopoietic stem cell transplantation. The overall survival after transplantation was 64.2% (95% confidence interval, 52.8 to 75.6), and without transplantation, it was 47.5% (95% confidence interval, 14.8 to 80.2, P = 0.47). The median timeframe between transplant and stoma closure was 19.6 months. The probability of survival was significantly lower in patients with perforation (P < 0.001), ileus (P = 0.038) and without thalidomide treatment (P < 0.001) among patients who did not receive haematopoietic stem cell transplantation. The survival probability was not associated with timeframe between transplant and onset, graft source and genotypes. CONCLUSIONS: The survival probability was not significantly different between patients with transplantation and the non-transplanted patients.

The Association Between Genetic Variants, Pharmacokinetics, and Infliximab Efficacy in Pediatric Patients With Crohn's Disease in China.

Background: Infliximab is an effective therapy for Crohn's disease (CD). Early non-invasive predictors of disease remission allow for modification of treatments. The aim of this study was to investigate the associations between genetic variants, pharmacokinetics, and infliximab efficacy in pediatric patients with CD. Methods: This retrospective observational study included CD patients under infliximab therapy between August 2015 and December 2020. Information on demographics, laboratory tests, medication data, and disease activity index was collected. The trough levels of infliximab (TLI) and antibodies to infliximab (ATI) were measured at week 14, and reactive drug monitoring was performed during follow-up. Ten single-nucleotide polymorphisms involved in the NF-κB-mediated inflammatory response, pharmacokinetics, and therapeutic response to infliximab were genotyped. Results: A total of 62 pediatric CD patients were enrolled. The clinical remission (CR) rate was 69.4 and 63.2% at week 14 and week 30, respectively. TLI at week 14 was significantly independently associated with CR at week 14 and mucosal healing (MH) at week 30 (p = 0.007 and p = 0.025, respectively). The optimal TLI threshold level capable of distinguishing between the CR and non-CR groups was 2.62 µg/ml (p < 0.001, area under the curve = 0.79, sensitivity = 69.2%, specificity = 78.9%), while that capable of distinguishing between the MH and non-MH groups was 3.34 µg/ml (p < 0.001, area under the curve = 0.85, sensitivity = 78.6%, specificity = 79.4%). Rs3397 in TNFRSF1B was associated with time to ATI production in CD patients (p < 0.001). Conclusions: Higher TLI contributed to achieving MH. Genotyping rs3397 in TNFRSF1B may identify patients who are prone to generating immunogenicity to drugs.

Characterization of novel and large fragment deletions in exon 1 of the IL10RA gene in Chinese children with very early onset inflammatory bowel diseases.

BACKGROUND: Defects in interleukin 10 (IL10) and its receptors are particularly involved in very early onset inflammatory bowel disease (VEOIBD). However, large fragment deletions of IL10 receptor A (IL10RA) are rare. METHODS: VEOIBD patients with confirmed mutations in the IL10RA gene were enrolled from January 1, 2019 to June 30, 2020. The clinical features and endoscopic-radiological findings of the patients with large fragment deletions of the IL10RA gene were determined and followed up. RESULTS: Thirty-five patients with IL10RA gene mutations, namely, 28 compound heterozygous mutations and 7 homozygote mutations, were enrolled in this study. Six patients carried the reported point mutation c.301C > T (p. R101RW) or c.537 G > A (p. T179T) in one locus and a large fragment deletion in exon 1 in another locus, which were novel mutations in this gene. A 333-bp deletion of exon 1 (117857034-11857366 del) was the main mutation in this locus in 85.7% of the patients with large fragment deletions. The time of disease onset ranged from birth to 4 years, and diarrhea was the main initial symptom. In total, 6/7 patients had perianal complications, including perianal abscess, fistula and skin tags. Six patients accepted thalidomide treatment, 5/7 accepted mesalamine, 3/7 accepted hematopoietic stem cell transplantation (HSCT), and 3/7 were waiting for HSCT. CONCLUSIONS: We identified a novel large deletion of exon 1 involving the IL10RA gene for the first time and showed the characteristics of VEOIBD patients. This study expands the spectrum of Chinese VEOIBD patients with IL0RA gene mutations.

Tibetan Macaques with Higher Social Centrality and More Relatives Emit More Frequent Visual Communication in Collective Decision-Making.

Animals on the move often communicate with each other through some specific postures. Previous studies have shown that social interaction plays a role in communication process. However, it is not clear whether the affinity of group members can affect visual communication. We studied a group of free-ranging Tibetan macaques (Macaca thibetana) at Huangshan Mountain, China, and answered whether and how social centrality or relatives matter in visual signals during group movement using Tobit regression modeling. All individuals emitted the signals of back-glances and pauses in collective movement. The emission of two signals decreased with the number of participants increased. The back-glance and pause signals emitted by the participating individuals were stronger as the position moved backward in the group. Sex, age, and rank had no significant influence on back-glance and pause signals. Individuals with higher social centrality would emit more pause signals, but social centrality had no effect on the back-glance signal. Individuals with more relatives in the group had more back-glance signals, but this had no effect on the pause signal. This study verifies that social centrality and the number of relatives have effects on visual signals in Tibetan macaques. We provide insights into the relationship between communication behaviors and group cooperation in social animals.

The diagnostic value of capsule endoscopy in children with intestinal lymphangiectasia.

BACKGROUND: intestinal lymphangiectasia is an unusual cause of protein-losing enteropathy due to either congenital malformation or obstruction of the intestinal lymphatics. However, few reports have investigated the use of video capsule endoscopy in children with intestinal lymphangiectasia. This study was performed to evaluate the diagnostic value of video capsule endoscopy for pediatric intestinal lymphangiectasia. METHODS: in this retrospective study, all patients who underwent video capsule endoscopy between January 2014 and July 2020 were included. Clinical information and video capsule endoscopy data were analyzed. RESULTS: twelve children were enrolled, 7 males and 5 females, with an age at disease onset of 4.5 (range: 3.2-9.3) years and a disease duration of 12.0 (range: 1.3-30.0) months. The most common symptoms were hypoproteinemia (10, 83.3 %), diarrhea (7, 58.3 %), edema (6, 50.0 %), and abdominal pain (3, 25.0 %). Eight patients had low lymphocyte counts, whereas 10 had reduced serum albumin levels (23.2 ± 5.8 g/L). Video capsule endoscopy revealed an overall white snowy appearance due to the presence of whitish, swollen villi in all patients. Regarding the macroscopic lesions of lymphangiectasia, 7 cases involved the entire small bowel from the duodenum to the ileocecal valve, while 5 cases involved part of the small bowel. All patients were treated with medium-chain triglyceride diets, and albumin infusions were administered to 10 patients; sirolimus treatment was administered to 3 patients. At the last follow-up, 5 patients still had hypoalbuminemia and one patient had died of intestinal lymphoma. CONCLUSION: video capsule endoscopy is useful for the diagnosis of intestinal lymphangiectasia and should be applied as a valuable and less invasive examination to confirm or establish a diagnosis.

Effect of Exclusive Enteral Nutrition on the Disease Process, Nutrition Status, and Gastrointestinal Microbiota for Chinese Children With Crohn's Disease.

BACKGROUND: The aim of this study was to prospectively study the effect of exclusive enteral nutrition (EEN) treatment on Chinese pediatric Crohn's disease (CD) patients. METHODS: Thirty-one newly diagnosed CD patients were enrolled in this study and treated with EEN for 8 weeks. Twelve healthy controls (HCs) donated their fecal samples. Statistical methods were used to compare the differences. RESULTS: According to the Simple Endoscopic Score for CD (SES-CD) at the end of the EEN treatment, 21 patients with SES-CD ≤4 were classified into the remission group (CD-RE), and 10 patients with SES-CD >4 were classified into the nonremission group (CD-NRE). After EEN therapy, there was a significant decrease in the SES-CD, the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), and fecal calprotectin (FCP) in the CD-RE group (all P < .001). The wPCDAI and FCP also decreased in the CD-NRE group (both P < .05). In terms of nutrition improvement, the CD-RE group patients showed more improvement in weight gain, hemoglobin, and serum albumin level than the CD-NRE group patients (all P < .05). For the microbiota, the CD patients had a lower bacterial diversity and different bacterial community compared with HCs. EEN increased overall diversity and was able to shift the dysbiosis in CD patients toward a healthier state. Absence of improvement in wPCDAI and Shannon index at 2 weeks predicts poor response at the end of EEN. CONCLUSION: EEN can be used in most Chinese pediatric CD patients to induce remission and improve nutrition.

Clinical features of capsule endoscopy in 825 children: A single-center, retrospective cohort study.

Video capsule endoscopy (VCE) can detect mucosal lesions in the intestine, especially in the small bowel.Our study aims to evaluate the applications of VCE for pediatric gastrointestinal diseases.In this retrospective study, we included all patients who underwent VCE between December 2012 and December 2018. Clinical information and VCE data were analyzed.Among 828 patients, the completion rate was 99.6% (n = 825), with an average age of 10.2 ±â€Š3.3 years old. A total of 459 VCE procedures showed abnormalities, and the overall diagnostic yield was 55.6%. The most common indications for VCE were abdominal pain among 505 (61.2%) patients and hematochezia (10.1%) among 83. Among the positive results of VCE, small bowel ulcers accounted for the highest percentage (57.7%), of which 164 cases were diagnosed as inflammatory bowel disease. For obscure gastrointestinal bleeding, 12 cases were diagnosed as Meckel's diverticulum. In terms of the small bowel transit time of VCE, compared with the negative group [288 (216.5, 390.3) min] and the enteritis group [277 (192.5, 374.8) min], a longer transit time was needed in the small bowel ulcer group [332.5 (240, 451.5) min, P < .01]. There were no correlations of positive VCE findings with anemia, the white blood cell count, the C-reactive protein level or the small bowel transit time according to Spearman rank analysis.VCE is relatively well tolerated and safe in children and has great value for the diagnosis and treatment of abdominal pain, especially inflammatory bowel disease and obscure gastrointestinal bleeding.

[Value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint].

OBJECTIVE: To evaluate the value of capsule endoscopy in children with small intestinal diseases with hematochezia as the chief complaint. METHODS: A retrospective analysis was performed on the clinical data and capsule endoscopy findings of 93 children with hematochezia who were admitted to Children's Hospital of Fudan University from May 2015 to January 2019 and underwent capsule endoscopy. According to the capsule endoscopy findings of the jejunum and the ileum, they were divided into a positive lesion group with 39 patients and a negative lesion group with 54 patients. Related clinical data and the features of lesion on capsule endoscopy were analyzed for the two groups. RESULTS: There were no significant differences in age, sex, duration of capsule endoscopy, gastric transit time, and small intestinal transit time between the positive lesion and negative lesion groups (P>0.05). The positive lesion group had a significantly lower level of hemoglobin than the negative lesion group (P<0.05). Hemoglobin level was negatively correlated with the rate of positive lesions on capsule endoscopy (r=-0.342, P=0.001). Among the 39 patients with positive lesions on capsule endoscopy, the detection of Meckel's diverticulum was the highest (41%), followed by inflammatory bowel disease (21%). CONCLUSIONS: Capsule endoscopy has a certain value in detecting small intestinal diseases, especially diseases in the jejunum and the ileum, in children with lower gastrointestinal hemorrhage.

The diagnostic value of video capsule endoscopy for Meckel's diverticulum in children

BACKGROUND: Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract and is also an important cause of bloody stool and anemia in children. However, there are few data about video capsule endoscopy (VCE) for MD in children. This study aimed to evaluate the diagnostic value of VCE for MD in children. MATERIALS AND METHODS: children who underwent VCE for obscure gastrointestinal bleeding from October 1st 2015 to August 31st 2019 at the Children's Hospital of Fudan University were included in this retrospective study. Medical data, VCE data and Meckel's scans, etc. were collected for each patient. RESULTS: sixteen patients were diagnosed with MD by VCE, including 13 males and 3 females. The age of the patients ranged from 4 years to 13 years, with an average of 7.8 ± 2.7 years. Lower gastrointestinal tract bleeding was the main symptom for patients with MD, including hematochezia (75 %) and melena (25 %). Of the VCE findings, 14 patients had double lumen signs and 2 showed protruding lesions. Among the 16 patients diagnosed with MD by VCE, 14 patients were diagnosed with MD by Meckel's scan, 3 with MD by abdominal enhanced CT and 14 patients were diagnosed with MD by surgery. During the follow-up, bleeding occurred sporadically in patient 12 and the reason is still unknown. CONCLUSIONS: VCE is useful for the diagnosis of MD and should be used as a valuable and less invasive examination to confirm or establish a diagnosis

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The diagnostic value of video capsule endoscopy for Meckel's diverticulum in children.

BACKGROUND: Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract and is also an important cause of bloody stool and anemia in children. However, there are few data about video capsule endoscopy (VCE) for MD in children. This study aimed to evaluate the diagnostic value of VCE for MD in children. MATERIALS AND METHODS: children who underwent VCE for obscure gastrointestinal bleeding from October 1st 2015 to August 31st 2019 at the Children's Hospital of Fudan University were included in this retrospective study. Medical data, VCE data and Meckel's scans, etc. were collected for each patient. RESULTS: sixteen patients were diagnosed with MD by VCE, including 13 males and 3 females. The age of the patients ranged from 4 years to 13 years, with an average of 7.8 ± 2.7 years. Lower gastrointestinal tract bleeding was the main symptom for patients with MD, including hematochezia (75 %) and melena (25 %). Of the VCE findings, 14 patients had double lumen signs and 2 showed protruding lesions. Among the 16 patients diagnosed with MD by VCE, 14 patients were diagnosed with MD by Meckel's scan, 3 with MD by abdominal enhanced CT and 14 patients were diagnosed with MD by surgery. During the follow-up, bleeding occurred sporadically in patient 12 and the reason is still unknown. CONCLUSIONS: VCE is useful for the diagnosis of MD and should be used as a valuable and less invasive examination to confirm or establish a diagnosis.

Comparison of four different regimens against Helicobacter pylori as a first-line treatment: A prospective, cross-sectional, comparative, open trial in Chinese children.

BACKGROUNDS: Due to the decreasing eradication rate of Helicobacter pylori, some novel alternatives have been developed, such as bismuth-containing quadruple therapy and non-bismuth-containing quadruple therapy (sequential and concomitant treatment). Little is known about whether a success rate above 90% can be achieved with these regimens in Chinese children. METHODS: In this prospective, open, comparative cross-sectional study, we recruited treatment-naïve children (aged between 6 and 18 years) with H pylori infection. The patients were assigned either standard triple therapy, sequential therapy, bismuth-based quadruple therapy, or concomitant therapy at the discretion of the prescribing physician. H pylori infection was evaluated at least 4 weeks after the completion of the treatment. A negative urea breath test (UBT) indicated successful eradication. The primary endpoint was the eradication frequency of H pylori in the full analysis set (FAS), which included all children who received at least one dose of the treatment and with available follow-up data. RESULTS: Between September 2017 and December 2018, 228 patients were finally included in the FAS analyses. The eradication rates were 74.1% for standard triple therapy (43/58, [95% CI: 62.8%-85.5%]), 69.5% for sequential therapy (41/59, [95% CI: 57.8%-81.2%]), 89.8% for bismuth-based quadruple therapy (53/59, [95% CI: 82.1%-97.5%]), and 84.6% for concomitant therapy (44/52, [95% CI: 74.8%-94.4%]). Bismuth-based therapy was superior to triple therapy, while sequential therapy and concomitant therapy were not superior to triple therapy. The frequency of adverse events was 12.1% (7/58) in standard triple therapy, 6.8% (4/59) in sequential therapy, 15.3% (9/59) in bismuth-based therapy, and 15.4% (8/52) in concomitant therapy. The rate of adverse events was similar among the four groups. CONCLUSION: Bismuth quadruple therapy can achieve an eradication rate of 89.8% as first-line treatment and is safe and well tolerated. Bismuth could be a promising alternative as a first-line regimen in Chinese children.

Complications of enterostomy and related risk factor analysis of very early onset inflammatory bowel disease with interleukin-10 signalling deficiency: a single-centre retrospective analysis.

BACKGROUND: Interleukin-10 (IL10) signalling pathway deficiency results in severe very early onset inflammatory bowel disease (VEOIBD), and enterostomy is often inevitable. However, studies in these surgical populations are lacking. This study aims to determine the enterostomy characteristics, postoperative complications and related risk factors in enterostomy patients. METHODS: From March 1, 2015, to December 31, 2018, patients with IL10R-mutation who underwent enterostomy were recruited for analysis. We collected data on the patients' clinical characteristics, enterostomy characteristics, postoperative complications and related risk factors. RESULTS: Twelve patients required emergency enterostomy, and 10 patients underwent elective enterostomy. Twelve patients experienced postoperative complications, including wound infection (27.3%), wound dehiscence (18.2%), reoperation (18.2%), etc. Compared with the pre-enterostomy values, there was a decrease in C-reactive protein (CRP) (P = 0.001), an increase in albumin (P = 0.001) and an improvement in the weight-for-age (P = 0.029) and body mass index (BMI) Z-scores (P = 0.004) after enterostomy. There was a significant difference between the pre-operation and postoperation medicine expenses (P = 0.002). Univariate binary logistic regression analysis revealed a statistically significant influence of CRP (OR: 1.43, 95% CI: 1.07-1.91, P = 0.016) and a tendency towards a significant influence of intestinal perforation, albumin level, BMI Z-score and weighted paediatric Crohn's disease activity index (wPCDAI). Multivariate logistic regression analysis showed that CRP (OR: 1.40), wPCDAI (OR: 2.88) and perforation (OR: 1.72) showed a tendency to behave as independent risk factors for postoperative complications, but the results were not significant (all P > 0.05). CONCLUSIONS: Surgery and enterostomy showed benefits for VEOIBD with IL-10 signalling deficiency. The timing of intervention, potential postoperative complications, economic burden and other related problems should be considered.

Phenotypic Characterization of Very Early-Onset Inflammatory Bowel Disease with Interleukin-10 Signaling Deficiency: Based on a Large Cohort Study.

BACKGROUND: Interleukin-10 (IL10)/interleukin-10 receptor (IL10R) deficiency is a rare disease with life-threatening infantile-onset colitis. We sought to accurately phenotype this disorder based on a large cohort of patients with a proven defect of IL10 signaling and to clarify the effects of allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We analyzed the phenotypes of our 61 patients and reviewed 78 other previously reported cases with identified mutations in the genes encoding IL10 or IL10R. We also compared the clinical features of patients with interleukin-10 receptor B (IL10RB), interleukin-10 receptor A (IL10RA), and IL10 mutations. The therapeutic effects of allogeneic HSCT were evaluated. RESULTS: We found that the disease onset time was extremely early: 70.3% within 30 days postnatal and 94.9% within the first 6 months of life. In addition, 94.2% of patients typically presented with perianal lesions. Oral ulcers and skin rash were common extra-intestinal manifestations (33.8% and 51.8%, respectively). There was no statistically significant difference in disease onset time, perianal lesion involvement, or mortality rate among patients with IL10RB, IL10RA, or IL10 deficiency. However, the surgery rate was higher in patients with IL10RB mutations than in those with IL10 or IL10RA mutations (P < 0.05). Compared with those with IL10RA deficiency, a higher percentage (32%, 9 of 28) of patients with IL10RB mutations developed B-cell lymphoma (P < 0.01). Compared with other regions, a higher percentage (98.7%) of IL10RA mutations was detected among patients in East Asia countries (P < 0.01), with hot-spot mutation sites of c.C301T and c.G537A. Allogeneic HSCT is efficacious but has a high mortality rate (17.5%, 7 of 40). CONCLUSIONS: Our study expands the current knowledge on the genotype-correlated phenotypes with a defect of IL10 signaling. B-cell lymphoma was more frequent than would be expected in patients with IL10RB mutations. There may be a unique genetic architecture among Eastern Asia compared with other populations. Although allogeneic HSCT represents a causal therapeutic approach for IL10-and IL10R-deficient patients, a word of caution is warranted.

MicroRNA-15a - cell division cycle 42 signaling pathway in pathogenesis of pediatric inflammatory bowel disease.

AIM: To determine whether cell division cycle (Cdc)42 is regulated by microRNA (miR)-15a in the development of pediatric inflammatory bowel disease (IBD). METHODS: We cultured 293T cells, used plasmids and performed dual-luciferase assay to determine whether Cdc42 is a miR-15a target gene. We cultured Caco-2 cells, and stimulated them with tumor necrosis factor (TNF)-α. We then employed lentiviruses to alter the expression of miR-15a and Cdc42. We performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence to determine whether Cdc42 is regulated by miR-15a in Caco-2 cells. Finally, we collected ileocecal tissue by endoscopy from patients and performed qRT-PCR to examine the expression of miR-15a and Cdc42 in pediatric IBD patients. RESULTS: Target Scan and dual-luciferase assay revealed that Cdc42 was a miR-15a target gene. MiR-15a expression increased (P = 0.0038) and Cdc42 expression decreased (P = 0.0013) in cells stimulated with TNF-α, and the expression of the epithelial junction proteins zona occludens (ZO)-1 (P < 0.05) and E-cadherin (P < 0.001) decreased. Cdc42 levels decreased in miR-15a-mimic cells (P < 0.001) and increased in miR-15a inhibitor cells (P < 0.05). ZO-1 and E-cadherin decreased in miR-15a-mimic cells (P < 0.001) but not in the miR-15a inhibitor + TNF-α cells. In Lv-Cdc42 + TNF-α cells, ZO-1 and E-cadherin expression increased compared to the Lv-Cdc42-NC + TNF-α (P < 0.05) or miR-15a-mimic cells (P < 0.05). Fifty-four pediatric IBD patients were included in this study, 21 in the control group, 19 in the Crohn's disease (CD) active (AC) group, seven in the CD remission (RE) group, and seven in the ulcerative colitis (UC) group. MiR-15a increased and Cdc42 decreased in the CD AC group compared to the control group (P < 0.05). miR-15a decreased and Cdc42 increased in the CD RE group compared to the CD AC group (P < 0.05). miR-15a was positively correlated with the Pediatric Crohn's disease Activity Index (PCDAI) (P = 0.006), while Cdc42 was negatively correlated with PCDAI (P = 0.0008). Finally, miR-15a expression negatively correlated with Cdc42 in pediatric IBD patients (P = 0.0045). CONCLUSION: MiR-15a negatively regulates epithelial junctions through Cdc42 in Caco-2 cells and pediatric IBD patients.