Monocytes from infliximab-resistant patients with Crohn's disease exhibit a disordered cytokine profile

Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-alpha (TNF alpha) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-alpha therapy with infliximab (IFX). However, approximately 30-40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNF alpha, IL-23, IL-1 beta and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNF alpha, IL-1 beta, IFN gamma and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes' cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay

WSES-AAST guidelines: management of inflammatory bowel disease in the emergency setting

Background Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons. Method A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019. Conclusions Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.Peer reviewe

Antibiotic resistance and antibiotic sensitivity based treatment in Helicobacter pylori infection: advantages and outcome.

AIMS: To compare two strategies for the eradication of Helicobacter pylori infection. METHODS: Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment. RESULTS: In group 1, H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1 the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%). CONCLUSIONS: Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments

Diverticular abscess successfully treated by endoscopic transluminal drainage. (I.F. 1.348)

Since colonoscopy is typically contraindicated in com-plicated diverticular disease of the colon, very few casesof intraluminal diverticular abscesses have been described.Significant diverticular abscesses usually require CT scanner-guided percutaneous drainage [1]. However, this proceduremay be impossible in 15—30% of cases, mainly because ofthe interposition of small bowel loops between the abscessand the abdominal wall. Furthermore, abscess recurrence orfistula formation may occur. Over the last few years, endo-scopic transluminal diverticular abscess drainage has provenuseful in the management of diverticular abscess as a novelconservative treatment option [2,3]. Endoscopic drainageof other types of colonic abscesses using a simple biopsyforceps have also been reported in the caecum [4]

Infliximab for pediatric ulcerative colitis: a retrospective Italian multicenter study

. Dig Liver Dis. 2008 Jul;40 Suppl 2:S260-4. Infliximab for pediatric ulcerative colitis: a retrospective Italian multicenter study. Cucchiara S, Romeo E, Viola F, Cottone M, Fontana M, Lombardi G, Rutigliano V, de'Angelis GL, Federici T. Division Pediatric Gastroenterology and Hepatology, Department of Pediatrics, University of Rome "La Sapienza", Rome, Italy. [email protected] BACKGROUND: Infliximab (IFX), the chimeric anti TNFalpha antibody, an established treatment for Crohn's disease in adults and in children, is used less frequently in ulcerative colitis (UC). AIM OF THE STUDY: To report the clinical course of pediatric patients with active UC receiving IFX. PATIENTS AND METHODS: Charts of 22 patients were reviewed (13 male, 9 female): 4 with a severe UC attack refractory to systemic corticosteroids (CS); 18 with a protracted course, of which 16 CS-dependent and 2 CS-resistant. The baseline therapeutic program consisted of 3 consecutive intravenous infusions (0, 2, 6 weeks) of IFX (5 mg/kg), followed by a retreatment schedule (infusion every 8 weeks); azathioprine (AZA) was administered chronically in all. Clinical evaluation was done with the Lichtiger Colitis Activity Index (LCAI). Follow-up was performed until week 54. LCAI >/= 9 was considered treatment failure; a LCAI </= 2 was consistent with remission. RESULTS: All 22 patients began the study with a LCAI > 9: 12 had a full response and were on remission at week 54 and did not receive CS (8 on IFX re-treatment and AZA, 4 on AZA alone); 6 had a partial response; 4 were non responders. Colectomy was performed in 7 patients, beyond the period of the acute attack in all but one. CONCLUSIONS: In children with severe ulcerative colitis IFX is a valuable treatment for inducing remission, avoiding emergency colectomy; retreatment may be offered to maintain remission

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease.

Background Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro-esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease. Methods Fifteen children (median age: 11.2years) with NERD, and 11 with ERD (median age: 9.6years) were prospectively studied. All patients underwent upper endoscopy. Biopsies were taken 2-3cm above the Z-line, and ISD was measured using transmission electron microscopy. All patients underwent impedance pH-monitoring, and baseline impedance levels were assessed in the most distal impedance channel. Key Results Mean (±SD) ISD did not differ between NERD (1.0±0.3?m) and ERD (1.1±0.3?m, ns). Considering all patients together, no correlation was found between distal baseline impedance and ISD (r: -0.15; ns). Conversely, negative correlations were found between distal baseline impedance and acid exposure time (r: -0.76; P<0.001), long-lasting reflux episodes (r: -0.78; P<0.001), acid reflux episodes (r: -0.62; P<0.001), and acid clearance time (r: -0.79; P<0.001). Distal baseline impedance was significantly lower in ERD [1455 (947-2338) ?] than in NERD children [3065 (2253-3771) ?; P<0.01]. Conclusions & Inferences In children with GERD baseline impedance levels are not useful in predicting reflux-induced ultrastructural changes in the esophageal mucosa, despite their ability to discriminate between NERD and ERD

Anti-gastric antibodies and gastritis in insulin-dependent diabetes in children.

Adult patients with insulin-dependent diabetes mellitus frequently also show gastric disturbances. Knowledge of the prevalence of such abnormalities in children with insulin-dependent diabetes and the predictive value of anti-gastric parietal cell antibodies in blood may be of practical importance. PATIENTS AND METHODS: 68 patients (29 boys and 39 girls), aged from 5 yr 2 mo to 19 yr 10 mo, and treated for insulin-dependent diabetes from 1 mo to 14 yr 6 mo, were included in the study. Fasting blood concentrations of gastrin (G), pepsinogen (PG1), anti-gastric parietal cell antibodies (PCA) were measured. Fiberoptic endoscopy and biopsy of the gastroduodenal mucosa were performed in PCA+ patients and biopsy samples were examined for Helicobacter pylori (HP). RESULTS: 12 patients were PCA+; 3 of them had blood gastrin levels above 104 pg/ml and 4 had blood pepsinogen levels 24 ng/ml. Histologically, 3 patients had chronic diffuse gastritis (2 were HP+); 2 had chronic gastritis restricted to the antro-pyloric area (both were HP+); 3 had follicular lymphoid hyperplasia (without HP) and 4 had normal mucosa (without HP). CONCLUSION: The presence of PCA can predict the risk of chronic gastritis, possibly auto-immune in origin, in children with insulin-dependent diabetes

Celiac disease in children with type 1 diabetes: impact of gluten free diet on diabetes management.

Background and aim of the work: the coexistence of Type 1 Diabetes (T1D) and celiac disease (CD) has been long established. Methods: Between January 2000 and December 2009, biopsy-proven CD was diagnosed in 12 children with T1D, giving a prevalence of 4.8% in our out-patient clinic population. For each patient with coexisting T1D and CD, two control subjects with T1D and without CD who matched for age, sex and duration of diabetes were chosen. Prospective study follow up lasted 24 months. At the enrolment time, and at 2-month intervals, time from diagnosis of T1D to diagnosis of CD, presence of gastrointestinal symptoms, HbA1c value, body mass index (BMI), Height and Weight SDS were collected by a single observer. Daily insulin requirements were also retained. Results: In 3 children, CD predated the onset of T1D and these children were excluded from the analysis. The 9 children who subsequently developed CD became earlier diabetic than control group (p=0.002). Eight of these children had CD diagnosis within 1 year after T1D onset. Seven out of 9 children were positive for TTG antibodies and all were positive for EMA. A significant increase in insulin requirement was found in CD children after 1 year of GFD (p= 0.02). The mean HbA1c value in CD children was higher than in the control subjects (p< 0.01).A significant increase in the insulin requirement after 1 year in the GFD compliant children was found. There was a significant improvement in height-SDS after institution of GFD in the GFD-compliant children. Families of children with both T1D and CD reported higher burden than those affected by T1D only (p= 0.001). The health care providers perceived family burden to increase with CD appearance (p< 0.05). Conclusion: Our study supports the importance of screening for CD in children with T1D 1. The early treatment with GFD of biopsy-confirmed CD children promotes a significant catch-up growth and prevents a growth failure during the follow-up. (www.actabiomedica.it). © Mattioli 1885