Colitis Infection Research Articles

Rising Incidence of Intestinal Infections in Inflammatory Bowel Disease: A Nationwide Analysis.

Intestinal infections are common in patients with inflammatory bowel disease (IBD) and may mimic IBD flares. In this study, we estimate the changing incidence of intestinal infections among IBD hospitalizations and assess the impact of intestinal infections on key hospitalization metrics. The National Inpatient Sample (NIS) was analyzed for hospitalizations from IBD between 1998 and 2014. Intestinal infections were identified using ICD-9-CM codes, and incidence for each infection was calculated for Crohn's disease (CD) and ulcerative colitis (UC). Linear and logistic regression analyses were used to assess the effects of intestinal infections on hospitalization duration, charges, and mortality. There were 4,030,620 hospitalizations for IBD between 1998 and 2014. The annual incidence of intestinal infections rose from 26.2 to 70.6 infections per 1000 IBD hospitalizations (Ptrend < 0.01). A main driver of this rising incidence was Clostridium difficile infections, which increased from 7.8 to 32.1 per 1000 CD hospitalizations and from 23.0 to 84.7 per 1000 UC hospitalizations (Ptrend < 0.01). The incidence of other intestinal infections increased from 10.2 to 15.3 per 1000 CD hospitalizations and 16.5 to 25.3 per 1000 UC hospitalizations. Intestinal infections and particularly C. difficile infections were associated with longer hospitalizations, greater hospital charges, and greater all-cause mortality. The incidence of intestinal infections among hospitalized IBD patients has increased over the past 15 years, primarily driven by C. difficile infections. Intestinal infections are associated with length of stay, hospital charges, and all-cause mortality. More aggressive measures for prevention of C. difficile infections are needed. 10.1093/ibd/izy086_video1izy086.video15779257979001.

276 - Risk Factors and Outcomes Associated with Clostridium Difficile Infection in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

276 - Risk Factors and Outcomes Associated with Clostridium Difficile Infection in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Amoebic Colonic Perforation Presenting as Peritonitis in Emergency, Incidence and Outcome: Our Experience

Amoebiasisis a common parasitic infection and fulminant amoebic colitis remains a very rare complication of this disease. The objective of the present study was to find the incidence and outcome of perforation peritonitis due to amoebic colitis in MMIMSR, Mullana, Ambala, India. 200 patients with perforation peritonitis were studied retrospectively, out of which 22 cases had colonic perforation, were selected over a period of five years, between 2012 to 2017, at MMIMSR Mullana. All patients had undergone emergency laparotomy and cases with amoebic colonic perforation established on histopathology were studied in terms of incidence, clinical presentation and outcomes. Out of 200 emergency exploratory laparotomies carried out during 2012-2017 at MMIMSR, Mullana, 22 (11%) patients had amoebic colonic perforation. The disease was more common among men as compared to women (21:1). The mean age of patients was 60±10 years. Symptom duration ranged from 1 to 8 days. 15 (68%) patients had historyof chronic alcohol intake and 2 (9%) had a recent episode of loose stools. Chest X-ray showed free gas under the diaphragm in 45% (10/22) of patients. Ultrasonography whole abdomen showing associated liver abscess was seen in 8/22 (36%) patients. Intraoperatively caecal perforation was seen in 20 cases, out of which 16 had concomitant ascending colon perforation and 2 sigmoid colon perforation. Bowel resection was performed depending upon the site and extent of the colon involved- right hemicolectomy (16), limited ileocolic resection (4) and sigmoidectomy (2). Proximal diversion stoma was made in all cases. Postoperative complications encountered were wound infection in 20 (91%) cases, followed by burst abdomen in 8 (36%) cases, stoma related complication in 6 (27%) cases. The overall mortality rate due to sepsis was 54% (12/22). Although amoebiasis is a common parasitic infection, fulminant amoebic colitis remains a very rare complication with a reported incidence of 1%. Even with aggressive management of this entity, patients have got a poor prognosis. Resection with exteriorization of bowel is the current gold standard treatment in such cases.

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Evidence‐based consensus on opportunistic infections in inflammatory bowel disease

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

BackgroundStudies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only).MethodV3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group.ResultsSignificant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT.ConclusionThe results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

Biologic-Induced Infections in Inflammatory Bowel Disease: The TNF-α Antagonists.

To review the mechanism and association of infectious risk among the tumor-necrosis factor α (TNF-α) antagonists used in inflammatory bowel disease. A PubMed literature search was performed using the following search terms: infliximab, adalimumab, certolizumab, golimumab, inflammatory bowel disease, crohn's, ulcerative colitis, adverse effects, adverse events, safety, and infection. Meta-analyses and cohort studies with outcomes pertaining to quantitative infectious risk were reviewed. Case reports and case series describing association between TNF-α inhibitors and infection were also reviewed. A total of 7 recent meta-analyses of randomized trials demonstrate inconclusive association of infection with TNF-α antagonists. Registry data suggest that medications carry an independent risk of opportunistic infections. Risk factors for infection include older age, malnutrition, diabetes, and possibly combination therapy. Reported infections vary widely but include intracellular and granulomatous bacteria, viruses, and fungi. TNF-α antagonists are associated with an increased risk of opportunistic infection, although this risk has not been demonstrated conclusively in randomized controlled trials. Knowledge of concomitant risk factors, mechanism of infectious risk, and available treatment options can improve patient care in the clinical setting.

Evidence-based consensus on opportunistic infections in inflammatory bowel disease (republication).

Inflammatory bowel disease (IBD) patients are a high-risk population for opportunistic infections. The IBD group of the Chinese Society of Gastroenterology of the Chinese Medical Association organized an expert group to discuss and develop this consensus opinion. This consensus opinion referenced clinical study results from China and other countries to provide guidance for clinical practices. Eight major topics, including cytomegalovirus infection, Epstein-Barr virus infection, viral hepatitis, bacterial infection, Mycobacterium tuberculosis infection, fungal infection, parasitic infection, and vaccines were introduced in this article.

Dasatinib-induced hemorrhagic colitis complicated with cytomegalovirus infection.

A 69-year-old man with chronic-phase chronic myeloid leukemia was initially treated with 100 mg dasatinib once a day. Despite a major molecular response within 9 months, he developed hemorrhagic colitis 32 months after starting dasatinib. Colonoscopy identified multiple hemorrhagic ulcers in the transverse colon. The pathological findings indicated cytomegalovirus infection. Dasatinib was stopped and he was started on ganciclovir. Three months later, colonoscopy confirmed the disappearance of the hemorrhagic ulcers. Dasatinib is a second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia. As a multi-kinase inhibitor that acts on SRC-family kinases, its broader off-target kinase-inhibitory activity may account for the adverse events of dasatinib. Although gastrointestinal bleeding is common in patients taking dasatinib, the combination of cytomegalovirus infection and hemorrhagic colitis in the absence of systemic immunodeficiency is rare. Based on this case of dasatinibinduced hemorrhagic colitis with cytomegalovirus infection, we describe a possible mechanism and effective treatment.

Expression of microRNA-155 in inflammatory bowel disease and its clinical significance

Objective: To explore the expression of microRNA-155 in colonic mucosa and peripheral blood in patients with inflammatory bowel disease(IBD), and to examine the clinical value and significance of microRNA-155 in the diagnosis of IBD. Methods: Quatitative reverse-transcription PCR was performed to detect the expression of microRNA-155 in 20 patients with Crohn disease(CD), 21 patients with ulcerative colitis (UC), 18 patients with IBD type unclassified(IBDU), 25 healthy people(control group), 12 patients with infection colitis and 19 patients with ischemia colitis.Receiver operating characteristic (ROC) curve was performed to analyze the clincal value of microRNA-155 in diagnosis of IBD. Results: The expression of microRNA-155 in colonic mucosa in CD, UC and IBDU group was significantly higher than that in control group(P<0.05). MicroRNA-155 expression was also significantly higher in UC group in comparison to CD group (35.4±3.0 vs 18.6±5.9, P<0.01), IBDU group in comparison to CD group (23.0±3.7 vs 18.6±5.9, P<0.05) and UC group in comparison to IBDU group (35.4±3.0 vs 23.0±3.7, P<0.01). The plasma level of microRNA-155 in UC group (55.6±2.5) and IBDU group (48.1±6.2) was significantly higher than that in control group(P<0.05), while no significant difference in CD group was observed when compared with control group(P>0.05). ROC curve shows an AUC of 0.83 and 95%CI of 0.679-0.986 of microRNA-155 expression in colonic mucosa.The sensitivity and specificity of microRNA-155 expression in colonic mucosa in diagnosis of IBD was 68.4% and 78.6%, respectively. Conclusions: MicroRNA-155 showed high expression in colonic mucosa and peripheral blood in patients with IBD.MicroRNA-155 shows promise as a biomarker in diagnosis of IBD.Furthermore, the aberrant expression indicates that microRNA-155 may be involved in pathogenesis and progression of IBD.

Treatment Regimens of C. difficile Infection in Inflammatory Bowel Disease

Treatment Regimens of C. difficile Infection in Inflammatory Bowel Disease

Prevalence of hepatitis B and C and factors for infection and nonimmune in inflammatory bowel disease patients in China.

The aims of this study were to investigate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in inflammatory bowel disease (IBD) patients and the risk factors related to the infection and nonimmune status. A retrospective study was carried out at two clinical centers. The prevalence of viral markers and risk factors related to HBV and HCV infection and nonimmune status were analyzed in IBD patients. Age-matched and sex-matched healthy individuals were recruited as the controls. A total of 980 IBD patients were included in this study. Present and past HBV infection was detected in 41.21% of the IBD group, which was higher than that in the general population (P=0.003). Age older than 30 years (P=0.000), ulcerative colitis (P=0.002), and previous surgery (P=0.039) were found to be significant risk factors for HBV infection in the multivariate analysis. 36.43% of the patients in the IBD group had nonimmune status against HBV, and age less than 40 years (P=0.011) and Crohn's disease (P=0.002) were identified as independent risk factors in the multivariate analysis. The prevalence of HCV infection was low and similar to that of the general population. The prevalence of HBV infection in IBD patients in China was higher than that in Europe, USA, and the general population in China, but the prevalence of HCV infection in IBD patients was similar to that in the general population in this study. The frequency of nonimmune status against HBV was high, especially in young Crohn's disease patients, and HBV vaccination should be intensified and have a targeted coverage.

Clostridium difficile infection in inflammatory bowel disease: challenges in diagnosis and treatment.

The problem of Clostridium difficile infection (CDI) has reached epidemic proportions, particularly in industrialized nations. The pathophysiology, disease course and the potential complications are well appreciated in the general hospitalized patient. However, when CDI occurs in the setting of inflammatory bowel disease (IBD), a number of distinct differences in the diagnosis and clinical management of the infection in this population should be appreciated by gastroenterologists, hospitalists and other care providers. This review highlights the unique aspects of CDI when it occurs in IBD patients with an emphasis on the challenge of distinguishing persistent infection from exacerbation of underlying chronic colitis. An understanding of how CDI may differ in presentation and how management should be altered can prevent serious and life-threatening complications.

P517 Features of cytomegalovirus infection in inflammatory bowel disease

P517 Features of cytomegalovirus infection in inflammatory bowel disease

Management of Clostridium difficile Infection in Inflammatory Bowel Disease: Expert Review from the Clinical Practice Updates Committee of the AGA Institute.

The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection. Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection. Best Practice Advice 3: Clinicians should consider treating Cdifficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole. Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis. Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations. Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.

Utility of Prophylactic Antibiotics in Nonoperative Facial Fractures.

Facial fractures are commonly managed nonoperatively. Patients with facial fractures involving sinus cavities commonly receive 7 to 10 days of prophylactic antibiotics, yet no literature exists to support or refute this practice. The aim of this study was to compare the administration and duration of antibiotic prophylaxis on the incidence of soft tissue infection in nonoperative facial fractures. A total number of 289 patients who were admitted to our level I trauma center with nonoperative facial fractures from the beginning of 2012 to the end of 2014 were studied. Patients were categorized into 3 groups: no antibiotic prophylaxis, short-term antibiotic prophylaxis (1-5 days), and long-term antibiotic prophylaxis (>5 days). The primary outcome was the incidence of facial soft tissue infection and Clostridium difficile colitis. Fifty patients received no antibiotic prophylaxis. Sixty-three patients completed a short course of antibiotic prophylaxis and 176 patients received long-term antibiotics. Ampicillin/sulbactam, amoxicillin/clavulanic acid, or a combination of both were used in 216 patients. Twenty-three patients received clindamycin due to penicillin allergy. Short and long courses of antibiotic prophylaxis were administered more commonly in patients with concomitant maxillary and orbital fractures (P <0.0001). No mortality was found in any group. Soft tissue infection was not identified in any patient. C. difficile colitis was identified in 1 patient who had received a long course of antibiotic prophylaxis (P = 0.7246). There was no difference in the outcome of patients receiving short-term, long-term, and no antibiotic prophylaxis. Prospective randomized studies are needed to provide further clinical recommendations.

Fulminant Ulcerative Colitis Complicated by Treatment-Refractory Bacteremia

Severe ulcerative colitis is defined by more than six bloody stools daily and evidence of toxicity, demonstrated by fever, tachycardia, anemia, or an elevated erythrocyte sedimentation rate. Fulminant disease represents a subset of severe disease with signs and symptoms suggestive of increased toxicity. Treatment of severe colitis includes intravenous corticosteroid administration, with consideration of intravenous infliximab 5 mg/kg. Failure to show improvement after 3 to 5 days is an indication for colectomy or treatment with intravenous cyclosporine. We report a 23-year-old Hispanic woman with decompensated cirrhosis presenting with new-onset fulminant ulcerative colitis and resulting polymicrobial bacteremia, requiring colectomy for infection source control and colitis treatment.

Clostridium difficile Infection in Inflammatory Bowel Disease: A Nursing-Based Quality Improvement Strategy.

Patients with inflammatory bowel disease (IBD) have a higher prevalence of Clostridium difficile infection (CDI) and worse outcomes. Research has highlighted the inconsistent care that is provided to patients with IBD, and at our institution, the CDI testing rate was 41%. The present quality improvement intervention sought to increase CDI testing for inpatients with IBD with a flare. Eighty-nine patients admitted to our gastrointestinal unit over a 9-month period with IBD flare were eligible for the study. If a patient did not have a test for CDI ordered, the floor nurse collected stool and alerted the provider to order the test. The primary outcome was percent of eligible patients receiving a test. Secondary outcomes included rate of CDI, length of hospital stay, and readmission rate within 6 months. There was a significant increase in testing for CDI to 75% (p = .0151). Patients who received a test were more likely to have CDI (p = .0316), shorter hospital stays (p = .0095), and fewer readmissions (p = .0366). This study used the nursing admission workflow to increase the rate of CDI testing. Future studies should further characterize inconsistencies in IBD care and implement quality improvements.

Abstract LB-317: Energy distruptor 2-deoxyglucose mitigates bacterial infection responsive hyperplasia and/or colitis

Abstract Transmissible murine crypt hyperplasia (TMCH) is a pathological outcome of Citrobacter rodentium (CR) infection, accompanied by intestinal inflammation during colitis though excessive induction of epithelial regeneration and repair mechanisms. The TMCH model, provides an excellent template to determine how alterations in intestinal stem cells promote trans-differentiation, crypt regeneration or colon carcinogenesis following bacterial infection. CR is a valuable infection model for the study of pathogenesis of the clinically significant human pathogens, enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC). During TMCH, there is a complex interplay between the Notch and Wnt/β-catenin pathways in colonic crypt hyperplasia. Blocking Notch signaling via chronic dibenzazepine (DBZ) administration inhibits both Notch and Wnt signaling, and disrupts the intestinal barrier during CR induced colitis. 2-deoxyglucose (2DG) is a glycolytic inhibitor has been used for cancer therapy exploiting the cancer cell's high metabolic state. Added, the similarity of 2DG to mannose produces improper N-linked glycosylation resulting in an unfolded protein response (UPR) slowing growth of tumors. Here, using CR infection model, we show that dietary treatment of 2DG (0.4%) mitigates C. rodentium- and Notch signaling blocker dibenzazepine (DBZ)-induced colitis in NIH:Swiss mice. The survival curve shows no loss in mice administered with 2DG, compared to 40% loss in mice with vehicle alone during CR infection together with DBZ treatment. At tissue level, 2DG dietary intervention resulted in restoration of Hes-1, and β-catenin protein levels as observed from the western analyses of the C. rodentium-infected and DBZ-treated mice crypts. Histological staining show reduced dysbiosis upon 2DG intervention, as seen from reduced infiltration of inflammatory response cells during CR infection and the therapeutic effects are further substantiated with the Ki-67 staining. Thus, the energy distruptor 2-deoxyglucose (2DG) is described for the first time here to mitigate bacterial infection and its responsive hyperplasia/colitis. The current model in this novel mechanism of action will be presented. Citation Format: Ishfaq Ahmed, Shahid Umar, Rao V. Papineni. Energy distruptor 2-deoxyglucose mitigates bacterial infection responsive hyperplasia and/or colitis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-317.

Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study

Objective: It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease.Materials and methods: In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry.Results: Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA.Conclusions: Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.

H. pylori infection promotes intestinal inflammation and colitis-associated colon cancer in mice with a lineage-restricted deletion of the Smad4 gene in T cells.

Abstract Recent data suggest a protective effect of Helicobacter pylori (H. pylori) infection in inflammatory bowel disease (IBD), but the mechanisms mediating this protective effect are poorly understood. We previously reported that selective deletion in T cells of the TGF-β signaling intermediate in mice, Smad4 (Smad4TKO mice) leads to spontaneous gastrointestinal inflammation which progresses to mucosal epithelia cancers. Thus we infected Smad4TKO mice with H. pylori SS1 and PMSS1. Smad4TKO mice developed thickened intestinal mucosa, epithelial hyperplasia, crypt abscesses, and abundant inflammatory cell infiltrates between 2 and 3 months post infection. Some mice also developed colonic adenocarcinoma while wild type (WT) infected mice exhibited no gross or histologic signs of colitis. Smad4TKO mice infected with H. pylori had a increase in the number of mucosal effector CD4+ T cells producing IFN-g and IL-17 and a decrease in the mucosal Foxp3+CD4+ T cells (Tregs) in vivo, compared to WT mice infected with H. pylori. We also observed enhanced epithelia expressing PD-L1 in colon of Smad4TKO mice with H. pylori infection. The colon epithelia of Smad4TKO mice with H. pylori infection exhibited an oncogenic signature with an increase in the expression of iNOS and p-STAT1. Mutations in Smad4 are found in large percentage of human Juvenile Polyposis Syndrome (JPS) and Hereditary Hemorrhagic Telangiectasia (HTT) patients who are at risk of developing both adolescent and adult colon cancer. Our results raise the intriguing possibility that H. pylori infection could be a co-factor in the development of colon cancer by JPS/HTT patients.