Microbiota signatures and mucosal healing in the use of enteral nutrition therapy v. corticosteroids for the treatment of children with Crohn's disease: a systematic review and meta-analysis.

Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn's disease (CD). This systematic review of randomised controlled trials (RCT) and cohort studies analyses the impact of EEN/PEN v. CS on intestinal microbiota, mucosal healing as well as other clinically important outcomes, including clinical remission, relapse, adherence, adverse events and health-related quality of life (HRQL) in paediatric CD. Three RCT (n 76) and sixteen cohort studies (n 1104) compared EEN v. CS. With limited available data (one RCT), the effect on intestinal microbiome indicated a trend towards EEN regarding Shannon diversity. Based on two RCT, EEN achieved higher mucosal healing than CS (risk ratio (RR) 2·36, 95 % CI (1·22, 4·57), low certainty). Compared with CS, patients on EEN were less likely to experience adverse events based on two RCT (RR 0·32, 95 % CI (0·13, 0·80), low certainty). For HRQL, there was a trend in favour of CS based on data from two published abstracts of cohort studies. Based on thirteen cohort studies, EEN achieved higher clinical remission than CS (RR 1·18, 95 % CI (1·02, 1·38), very low certainty). Studies also reported no important differences in relapse and adherence. Compared with CS, EEN may improve mucosal healing with fewer adverse events based on RCT data. While limited data indicate the need for further trials, this is the first systematic review to comprehensively summarise the data on intestinal microbiome, mucosal healing and HRQOL when comparing enteral nutrition and CS in paediatric CD.

Venous thromboembolism in pediatric inflammatory bowel disease: an 11-year population-based nested case-control study in Canada.

To investigate the occurrence of venous thromboembolism (VTE), clinical characteristics, risk factors, treatment outcomes, and anticoagulation safety in pediatric inflammatory bowel disease (IBD) over an 11-year period. A nested case-control study within an identified cohort was performed amongst children with IBD from 2009 to 2020 in Canada. There were 890 hospitalizations during the study period, and 15 venous thromboembolic events (1.69%) among 12 patients occurred, including 12 with ulcerative colitis and three with Crohn's disease. VTE proportions were significantly different between female (2.7%) and male (0.8%) patients (P = 0.03). VTE in the ulcerative colitis group (4.2%) was significantly higher than in the Crohn's disease group (0.6%) (P = 0.001). Central venous catheter and length of hospital stay were correlated to VTE development. Twelve of 15 (80%) with VTEs presented symptoms related to extremity thrombosis and pulmonary embolism. Nine of the 15 (60%) had a deep vein thrombosis, and 2 (13.3%) developed a severe pulmonary embolism. Seven of 15 (47%) received anticoagulation therapy for 1-6 months. VTE-related symptoms and repeat imaging tests improved with no bleeding complication in those treated with anticoagulation therapy. No patients received long-term thromboprophylaxis after antithrombotic treatment was discontinued. The VTE proportion in pediatric IBD patients was relatively low. Children with VTE were disproportionately females with ulcerative colitis compared with children without VTE. Patients with VTE had a good prognosis after anticoagulation therapy without mortality or increased bleeding events. The role of VTE screening and efficacy of thromboprophylaxis need to be further evaluated.

Risk factors for recurrence of Helicobacter pylori infection after successful eradication in Chinese children: A prospective, nested case-control study.

BACKGROUND: Limited research has been published on the recurrence of Helicobacter pylori infection and risk factors in Chinese children. Our study aimed to identify risk factors for Helicobacter pylori infection recurrence after successful eradication in children. MATERIALS AND METHODS: A prospective, nested case-control study was performed. A cohort of 230 children with successful eradication of Helicobacter pylori in Baoding (China) was selected from January 2018 to February 2019. A standardized questionnaire was used to obtain socioeconomic details. Eradication regimens and Helicobacter pylori antibiotic susceptibility testing results were also recorded. Interleukin-1ß level, interferon-γ level, and genetic susceptibility (IFNGR1 and PTPRZ1 gene polymorphisms) were analyzed. All children were followed for 1 year. RESULTS: Among 218 (94.8%) children who were successfully followed, 41 children (18.8%) had a Helicobacter pylori infection recurrence. The recurrence rate was higher in children ≤10 years old than >10 years old (22.8% vs 7.1%, P = .01). There was no significant difference between the recurrence group and the non-recurrence group in terms of types of therapy and antibiotic sensitivity (P > .05). Multivariable regression results indicated that residence in urban areas, higher household income, and having lunch at home were significantly protective against recurrence (OR 0.155, 0.408, and 0.351 respectively), whereas Helicobacter pylori infection in family members increased the risk of recurrence (OR 2.283). The levels of IL-1ß and IFN-γ exhibited no significant difference between the recurrence group and the non-recurrence group. The allele frequency of G in the IFNGR1-56 site, A in the IFNGR1-600 site, and T in the IFNGR1-565 site was significantly higher in the recurrence group when compared to the non-recurrence group (P < .05). CONCLUSIONS: The Helicobacter pylori infection recurrence rate is high in children in Baoding region and is closely correlated to socioeconomic factors. The IFNGR1 gene polymorphism may be an independent risk factor for Helicobacter pylori infection recurrence.

[Clinical analysis of 2 cases with chylothorax due to primary lymphatic dysplasia and review of literature].

OBJECTIVE: To analyze the clinical characteristics and diagnosis of 2 cases with chylothorax due to primary lymphatic dysplasia and to elevate pediatrician's recognition level for this disease. METHOD: Clinical manifestations of the children were retrospectively analyzed. Primary lymphatic dysplasia was diagnosed by lymphoscintigraphy. RESULT: The first patient was a male aged 2-year-7-month who presented with a history of tachypnea for 43 days, fever and sore throat for 5 days at the early stage of the illness. He had a history of external injury before his illness. Physical examination showed his left chest bulging and left side diminished breath sound. His pleural effusion showed dark red (It was divided into two layers after standing, the upper layer turned into milky white, and the lower turned into hemorrhagic liquid) . White blood cell (WBC) count was 9 000×10(6)/L, mononuclear cell was 0.9, polykaryocytes was 0.1, triglyceride was 12.37 mmol/L in the pleural effusion. Contrast-enhanced lung CT (revascularization) showed pericardial effusion and a massive left sided pleural effusion. The second patient was a male aged 9 years and 6 months, who presented with a history of cough for 24 days, intermittent fever, vomiting, abdominal pain for 19 days, and edema of lower limbs for 4 days. Physical examination showed edema in both eyelids, lower extremities and scrotum. The level of albumin was 14 g/L and the titer of Mycoplasma pneumoniae IgM was 1: 320 in the serum. His hydrothorax pleural effusion showed milk white. White blood cell (WBC) count was 74×10(6)/L, mononuclear cell was 0.78, polykaryocytes was 0.22, triglyceride was 1.01 mmol/L in the pleural effusion. Chyle test showed positive in his pleural effusion and seroperitoneum. High-resolution CT of the lung revealed bilateral interstitial and parenchymal infiltration and both sided pleural effusion. Abdominal ultrasound showed giant hypertrophy of the gastric mucosa and massive ascites. Gastroscopy showed giant hypertrophy of the gastric mucosa. Lymphoscintigraphy revealed primary lymphatic dysplasia in both children. CONCLUSION: Primary lymphatic dysplasia might occur in children and result in dropsy of serous cavity (chylothorax, chylopericardium, chylous ascites). Dropsy of serous cavity showed bloody or milk white. WBC count might elevate with lymphocyte increasing mostly, triglyceride was often higher than 1.0 mmol/L in dropsy of serous cavity. Primary lymphatic dysplasia can be diagnosed by lymphoscintigraphy.

[Antibiotic resistance of Helicobacter pylori in children and macrolide-resistant genotypes in Helicobacter pylori].

OBJECTIVE: To explore the antibiotic resistance of Helicobacter pylori (H.pylori ) in children and identify 23 S rRNA gene mutations in macrolide-resistant strains. METHODS: From December 2008 to December 2010, a total of 73 H.pylori strains were isolated from 120 gastric mucosa specimens obtained from children of gastrointestinal symptoms with a diagnosis of gastritis or peptic ulcer underwent gastroscopy. The antibiotic resistance to 9 antibiotics of 73 H.pylori strains isolated from gastric biopsies was detected by E-test method. Mutations in 23 S rRNA gene of macrolide-resistant of isolated H.pylori strains were examined by polymerase chain reaction (PCR). RESULTS: Seventy-three H.pylori strains (60.8%) were isolated from gastric biopsies.Seventy were drug resistance strains and only 3 sensitive strains.No resistance to amoxicillin, gentamicin and tetracycline was observed. The resistance rate to azithromycin, clarithromycin, metronidazole, rifampicin, levofloxacin and moxifloxacin was 79.5% (58/73), 80.8% (59/73), 58.9% (43/73), 6.8% (5/73), 12.3% (9/73) and 13.7% (10/73) respectively. The dual, triple and quadruple antibacterial resistant percentage was 47.9% (35/73), 8.2% (6/73) and 1.4% (1/73) respectively. And the multi-drug resistance rate to clarithromycin, azithromycin and metronidazole was 43.8% (32/73). The gene mutation rate of A2142C,A2142G, and A2143G in 23 S rRNA gene was 1.6% (1/64), 6.3% (4/64) and 85.9% (55/64) respectively. CONCLUSIONS: There is a high rate of multi-drug resistance to clarithromycin, azithromycin and metronidazole in H.pylori strains isolated from children at our hospital. Therefore amoxicillin and rifampicin sensitive to H.pylori strains should be considered for H.pylori eradication. A2143G is the most populated mutation in macrolide-resistant strains.

[Therapeutic mechanism of diaphragm training at different periods in patients with gastroesophageal reflux disease].

OBJECTIVE: To explore the effects of postprandial diaphragm training (DT) on esophageal acid exposure, esophageal motility and proximal gastric volume at different postprandial periods in patients with gastroesophageal reflux disease (GERD). METHODS: Thirty GERD patients and 9 healthy subjects (HS) with matched demographic characteristics were enrolled from June 2005 to June 2006 at Peking Union Medical College Hospital. Esophageal manometry with a Dent sleeve catheter and simultaneous esophageal pH monitoring were recorded in a 30-min fasting period and a 120-min postprandial period. The GERD patients were divided into 3 groups: 9 patients received diaphragm training at 1(st) hour after meal (group DT1 h) and another 10 at 2(nd) hour after meal (group DT2 h) whereas no diaphragm training after meal in 11 (group NDT). Ultrasonic imaging of proximal gastric volume was undertaken at 0, 30, 60, 90 and 120 min after meal. RESULTS: (1) The percentage time with pH<4 in group DT1 h was lower than that in group NDT in the 120-min postprandial period (0.2% (0-4.1%), 6.6% (2.2%-18.2%), P < 0.05) and no significant difference of esophageal acid exposure was observed between groups DT2 h and NDT (3.7% (0.1%-17.8%), 6.6% (2.2%-18.2%), P > 0.05) . (2) Esophagogastric junction (EGJ) and crural diaphragm pressures at the 1(st) hour after meal in group DT1 h were both significantly higher than those in group NDT during diaphragm training ((44.4 ± 8.1) vs(16.2 ± 4.5) mm Hg, (38.2 ± 4.2) vs (9.8 ± 4.5) mm Hg, 1 mm Hg = 0.133 kPa, both P < 0.05). EGJ and crural diaphragm pressures at the 2(nd) hour after meal in group DT2 h were significantly higher than those in group N-DT during diaphragm training ((53.2 ± 7.5) vs (14.0 ± 3.7) mm Hg, (48.2 ± 6.3) vs (8.9 ± 2.7) mm Hg, both P < 0.05). There was no change of lower esophageal sphincter pressure (all P > 0.05). (3) After test meal, the groups DT1 h, DT2 h and N-DT had similar proximal stomach volume (all P > 0.05). CONCLUSIONS: Diaphragm training at the 1(st) hour after meal might reduce the 120-min postprandial esophageal acid exposure in GERD patients. The reduction in esophageal acid exposure may result from enhanced antireflux barrier of EGJ function. Therefore postprandial diaphragm training provides a new approach to conservative treatment of GERD.

[Follow-up of pediatric inflammatory bowel disease].

OBJECTIVE: To analyze the clinical characteristics and prognosis of pediatric inflammatory bowel disease (IBD) through a long-term follow-up so as to improve the diagnosis and management of IBD in children. METHODS: Seventy-three IBD patients admitted into our hospital from May 2000 to September 2010 were re-evaluated with the uniform diagnostic criteria proposed by the 2010 consensus diagnostic criteria for pediatric IBD. All patients were followed up by questionnaire, telephone and face-to-face interview. RESULTS: Among them, 56 cases (76.7%) (ulcerative colitis (UC): n = 34, Crohn's disease (CD): n = 22) were available for follow-up study. Among 34 UC cases, 13 cases had their diagnosis confirmed and 21 cases were diagnosed as probable UC. Meanwhile, among 22 CD cases, 14 and 8 had definite and probable diagnoses respectively. At diagnosis, 46.9% (15/32) of UC patients had extensive colitis, 40.6% (13/32) left-sided colitis while 72.7% (16/22) of CD patients with had ileocolonic. And 28 cases (82.4%) of UC patients and 20 cases (90.9%) of CD patients fulfilled the criteria for moderate to severe grade. Among 56 IBD cases, there was no death for CD, but 5 died for UC (14.7%). In the remaining 29 UC and 22 CD patients, 16 cases (55.2%) and 15 cases (68.2%) stayed symptom-free (P > 0.05). Moreover, 8 cases (27.6%) of UC and 3 cases (13.6%) of CD patients belonged to chronic relapsing type while 16 cases (55.2%) of UC and 15 cases (68.2%) of CD patients were of chronic persistent type. The physical activities of most IBD patients (n = 49) were unrestricted. The surgical rate for IBD was 19.6% (n = 11), 8.8% for UC (n = 3) and 36.4% for CD (n = 8) (P < 0.05). The incidences of surgical complications such as intestinal obstruction, intestinal perforation and hemorrhage of gastrointestinal tract were 7.1% (n = 4), 7.1% (n = 4) and 1.8% (n = 1). And it was more common in the CD group. CONCLUSIONS: Most IBD patients belong to chronic persistent type and then chronic relapsing type. Their physical activities are unrestricted. The surgical rate for CD is significantly higher than UC. And surgical complications such as intestinal obstruction, intestinal perforation and hemorrhage of gastrointestinal tract occur more frequently in the CD group.

Primary antibiotic resistance of Helicobacter pylori isolated from Beijing children.

BACKGROUND: The antimicrobials resistance of Helicobacter pylori (H. pylori) was able to sharply decline the eradication rate of H. pylori both in adults and children, but there are limited studies about the primary antibiotic resistance and the related gene mutations, specifically in China. MATERIALS AND METHODS: The primary resistance to 9 antibiotics of 73 H. pylori strains isolated from gastric biopsies of children recruited at Beijing Children's Hospital was assessed, and the mutations in 23S rRNA gene of 65 macrolide-resistant strains and in gyrA and gyrB of 12 quinolone-resistant strains were investigated. RESULTS: The resistance rate to clarithromycin, azithromycin, metronidazole, levofloxacin, moxifloxacin, and rifampicin was 84.9%, 87.7%, 61.6%, 13.7%, 15.1%, and 6.8%, respectively. No resistance to amoxicillin, gentamicin, and tetracycline was observed. Dual, triple, and quadruple antibacterial resistant percentage was 46.6% (34/73), 15.1% (11/73), and 2.7% (2/73), respectively. The gene mutation rate of A2142C, A2142G, and A2143G in 23S rRNA gene was 1.5% (1/65), 6.2% (4/65), and 84.6% (55/65), respectively. The detection rate of mutations of Asn87, Asp91, and Met191 in GyrA was 41.7% (5/12), 25% (3/12), and 25% (3/12), respectively. CONCLUSION: The high prevalence of primary antibiotic resistance was out of expectation in H. pylori strains isolated from the children in Beijing. Antibiotic susceptibility should be made clear before the antibiotic was used in the anti-H. pylori therapy in this population. The A2143G was the most populated mutation in macrolide-resistant strains, and Asn87 and Asp91 of GyrA were the most common mutation points in quinolone resistance strains.

[Diagnostic value of reflux disease questionnaires in children with gastroesophageal reflux disease].

OBJECTIVE: To evaluate the value of reflux diagnostic questionnaire in the diagnosis of children with gastroesophageal reflux disease (GERD). METHODS: Forty-five children aged 7-16 years old referred for suspected GERD with vomiting/regurgitation, nausea, heartburn/retrosternal pain, abdominal pain, epigastric pain, acid regurgitation and pain while swallowing were assessed. Each symptom was rated from 0 to 3 according to its severity and frequency. The items of questionnaire were validated against the results from upper gastrointestinal endoscopy and esophageal 24 h pH monitoring. And the results were compared with symptom scores to determine the threshold value for GERD. RESULTS: In 45 patients, the ratio of male to female was 1.37:1 and the mean age (11.1±2.6) years old. Composite score in 23 patients with GERD (20±10) was significantly higher than that in 22 patients without GERD (13±4) (P<0.05). There was no significant difference of composite scores among patients with grades 0, I, II and III according to upper gastrointestinal endoscopy (P>0.05). With 13.0 as threshold score for GERD, the sum of sensitivity and specificity was maximal. The area under the receiver operating characteristic curve (ROC) was 0.79 while true positive diagnostic rate 72.0% and true negative diagnostic rate 75.0% with a sensitivity of 78.3%, a specificity of 68.2% and an accuracy of 73.3%. CONCLUSION: Reflux diagnostic questionnaire is a suitable method in initial diagnosis of GERD. It may serve as a screening test for GERD in 7-16-year-old children.

[Multi-channel electrogastrography and autonomic nervous system function in patients with non-erosive reflux disease and reflux esophagitis].

OBJECTIVE: To investigate the gastric myoelectrical activity and autonomic nervous system (ANS) function in patients with non-erosive reflux disease (NERD) and reflux esophagitis (RE). METHODS: 42 patients with gastroesophageal reflux disease (GERD), 21 with NERD and 21 with RE, and 20 healthy volunteers (controls) underwent multi-channel electrogastrography (MEGG) and electrocardiography simultaneously for 30 min in the fasting state and 60 min after a standard test meal. The MEGG parameters included dominant frequency (DF), dominant power (DP), normal percentage of 2 - 4 times/min gastric slow waves (N%), and percentage of slow wave coupling (%SWC). ANS was determined according to power spectra analysis of heart rate variability (HRV) which was conducted by using electrocardiogram recording, including the parameters of sympathetic activity, vagal activity, and sympathovagal balance ratio so as to evaluate the ANS function. RESULTS: The DF levels of the NERD and RE patients and healthy volunteers after test meal were all significantly higher than those in fasting state (all P < 0.05). The %SWC levels of the 3 groups after test meal were all significantly lower than those when fasting (all P < 0.05), and the %SWC level of the NERD patients was significantly lower than that of the healthy volunteers in fasting state [70.5% (40.6% - 81.9%, 76.3% (66.4% - 91.4%), P < 0.05]. Test meal significantly increased the sympathetic activity and sympathovagal balance ratio of the NERD and RE patients and healthy volunteers (all P < 0.05), and the vagal activity levels of the 3 groups after test meal were all significantly lower than those when fasting (all P < 0.01). The sympathovagal balance ratio of the NERD group was significantly lower than that of RE group after meal [1.4 (0.8 - 2.5), 2.2 (1.3 - 4.4), P < 0.05]. CONCLUSION: The spatial regularity of gastric slow waves and ANS function in NERD patients are significantly different from those in RE patients.

[Effect of combined drug treatment on megacolon with severe constipation].

OBJECTIVE: To assess the effectiveness of combined drug treatment on megacolon complicated by severe constipation. METHODS: Ten patients with megacolon confirmed by barium enema examination, 4 males and 6 females, aged 38 (15 - 66), with a mean course of 10 years (2 weeks - 23 years), all complicated by severe constipation and 5 cases with colonic obstruction confirmed by X-ray examination, 1 being diagnosed as with Hirschsprung' disease, 3 secondary to chronic constipation, 1 with diabetes mellitus, 1 with a history of anorectal malformation, 4 with colonic pseudo-obstruction, and 4 with colonic pseudo-obstruction, were treated with combined conservative therapy including tegaserod (6 mg 2/d), polyethylene glycol (PEG) 4000 (20 - 40 g/d), and liuweianxiao (traditional Chinese medicine, 5 # 3/d). Colon enema was used in the first week if necessary. Follow-up was conducted for 1 - 7 months. The major clinical data included bowel symptoms, complications and adverse effects. RESULTS: After 1 - 2 weeks of treatment, properties of feces, defecation times, defecation difficulty, and abdominal symptoms, and X-ray findings were all notably improved. No relapse of colonic obstruction was found. The 5 patients with colonic obstruction all showed release. Regarding adverse effect, mild diarrhea was found in 2 cases and was relieved when the dosage was decreased. CONCLUSION: Combined drug treatment including tegaserod, PEG 4000 and traditional Chinese medicine is effective in treating megacolon with severe constipation and may help avoid surgical treatment.

[Barrier function of esophagogastric junction in patients with gastroesophageal reflux disease].

OBJECTIVE: To investigate the barrier function of esophagogastric junction (EGJ) in the patients with gastroesophageal reflux diseases (GERD). METHODS: Ninety-six GERD patients and 18 healthy subjects (HSs) underwent esophageal manometry. Forty-two of the 96 patients were with reflux esophagitis (RE) and were divided into 2 subgroups according to the LA typing: 31 subgroup of LA-A or B (n = 31), and subgroup of LA-C or D (n = 11). Fifty-four of the 96 patients suffered from non-erosive reflux disease (NERD) and were divided into 2 subgroups based on 24 h esophageal pH monitoring: 31 patients with normal acid exposure (pH < 14.72 according to DeMeester scoring) and 23 with excessive acid exposure (pH > 14.72). The EGJ functions, including lower esophageal sphincter pressure (LESP), crura of diaphragm pressure (CDP), esophagogastric junction pressure (EGJP, sum of LESP and CDP), and post-lower esophageal sphincter relaxation pressure (post-LESRP), and the contractive pressure of esophageal body, including proximal esophageal contractive pressure (PECP) and distal esophageal contractive pressure (DECP), were measured. RESULTS: The levels of LESP, CDP, EGJP, and post-LESRP of the RE patients were (8 +/- 3), (13 +/- 7), (20 +/- 9), and (31 +/- 13) mm Hg respectively, all significantly lower than those of the NERD patients [(9 +/- 3), (18 +/- 6), (28 +/- 8), and (39 +/- 15) mm Hg, all P < 0.05]. The levels of LESP and post-LESRP of the NERD patients were significantly lower than those of the HSs [(32 +/- 7) and (50 +/- 15) mm Hg, both P < 0.05], however, the levels of CDP and EGJP of the NERD patients were both not significantly different from those of the HSs [(16 +/- 6) and (32 +/- 7) mm Hg, both P > 0.05]. The PECP and DECP of the RE and NERD patients were all significantly lower than those of the HSs (all P < 0.05), however, there were not significant differences in DECP and PECP between the RE and NERD patients (both P > 0.05). Among the NERD patients there were not significant differences in the PECP and DECP between the LA-A and B subgroup and RE LA-C and D subgroup, and among the NERD patients there were not significant differences in PECP and DECP between the subgroups with and without excessive esophageal acid exposure (all P > 0.05). CONCLUSION: The EGF anti-reflux function of the GERD patients is impaired. The function of crura of diaphragm of the NERD patients is almost normal, however, that of the RE patients is impaired. NERD and RE have different path physiological basis.