Safwat Girgis

Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: A pilot study

Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that has periods of exacerbated symptoms and periods that are symptom‐free. The treatment of active UC with probiotic bacteria could possibly induce remission. We evaluated the clinical efficacy and safety profile of probiotic preparation VSL#3 in the treatment of mild to moderate acute UC in the pediatric population. Methods: Eighteen eligible patients between the ages of 3–17 with mild to moderate acute UC received open‐label VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre‐ and post‐VSL#3 therapy was assessed by the simple clinical colitis activity index (SCCAI); Mayo ulcerative colitis endoscopic score; inflammatory markers: erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP); serum cytokine profiling; and rectal tissue microbial profiling done at baseline and at week 8. Results: Thirteen patients completed 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission (defined as SCCAI ≤3) was achieved in 56% of children (n = 10); response (decrease in SCCAI ≥2, but final score ≤5) in 6% (n = 1); and no change or worsening in 39% (n = 7). Post‐VSL#3 treatments demonstrated a bacterial taxonomy change in rectal biopsy. The VSL#3 was well tolerated in clinical trials and no biochemical and clinical adverse effects attributed to VSL#3 were identified. Conclusions: Treatment of pediatric patients diagnosed with mild to moderate UC with VSL#3 resulted in a remission rate of 56% and a combined remission/response rate of 61%.

Diagnostic criteria for eosinophilic esophagitis: a 5-year retrospective review in a pediatric population.

Background: The diagnostic criterion based on the number of eosinophils (Eos) per high-power field (HPF) does not appear to capture all patients with eosinophilic esophagitis (EE). Objectives: To determine whether EE has been underrecognized at our institution, clinical variables predicting EE, and whether the Luna eosinophil granule (LEG) stain detects eosinophils better than hematoxylin and eosin (HE). Materials and Methods: Esophageal biopsies of 202 children younger than 18 years old from 2000 to 2004 were reviewed and Eos/HPF was recorded. Clinical variables from charts were reviewed and a marginal logit model was used to determine significance. LEG stains for 60 randomly selected patients were prepared and compared to HE originals. Results: EE diagnoses have risen from none in 2000 to 23 in 2004. The clinically significant variables that predicted EE were improvement from EE treatment (160 times more likely to have EE; P < 0.0005), final endoscopic diagnosis of EE (31 times; P = 0.004), absence of vascular pattern on endoscopy (20 times; P = 0.008), and vertical furrows on endoscopy (29 times; P = 0.039). LEG stain appeared to be superior to HE in detecting low Eos/HPF (mean 24.82 and 38.53, respectively). Peak counts of eosinophils in the most involved HPF significantly correlated with highest average count of eosinophils per HPF in the most involved specimen (Pearson correlation 0.958). Conclusions: Misdiagnosed EE cases decreased but prevalence appeared to increase. LEG potentially can be a more sensitive stain. The key variables that predict EE were typical endoscopic findings and improvement from specific EE treatment.

Disease manifestations of Helicobacter pylori infection in Arctic Canada: using epidemiology to address community concerns.

Objectives Helicobacter pylori infection, linked to gastric cancer, is responsible for a large worldwide disease burden. H pylori prevalence and gastric cancer rates are elevated among indigenous Arctic communities, but implementation of prevention strategies is hampered by insufficient information. Some communities in northern Canada have advocated for H pylori prevention research. As a first step, community-driven research was undertaken to describe the H pylori-associated disease burden in concerned communities. Design Participants in this cross-sectional study completed a clinical interview and gastroscopy with gastric biopsies taken for histopathological examination in February 2008. Setting Study procedures were carried out at the health centre in Aklavik, Northwest Territories, Canada (population ∼600). Participants All residents of Aklavik were invited to complete a clinical interview and gastroscopy; 194 (58% female participants; 91% Aboriginal; age range 10–80 years) completed gastroscopy and had gastric biopsies taken. Primary and secondary outcome measures This analysis estimates the prevalence of gastric abnormalities detected by endoscopy and histopathology, and associations of demographic and clinical variables with H pylori prevalence. Results Among 194 participants with evaluable gastric biopsies, 66% were H pylori-positive on histology. Among H pylori-positive participants, prevalence was 94% for acute gastritis, 100% for chronic gastritis, 21% for gastric atrophy and 11% for intestinal metaplasia of the gastric mucosa, while chronic inflammation severity was mild in 9%, moderate in 47% and severe in 43%. In a multivariable model, H pylori prevalence was inversely associated with previous gastroscopy, previous H pylori therapy and aspirin use, and was positively associated with alcohol consumption. Conclusions In this population, H pylori-associated gastric histopathology shows a pattern compatible with elevated risk of gastric cancer. These findings demonstrate that local concern about health risks from H pylori is warranted and provide an example of how epidemiological research can address health priorities identified by communities.

Childhood autism and eosinophilic colitis.

Background/Aims: The significance of the association between many gastrointestinal pathologies and autism is yet to be discovered. The aim of this report is to highlight an association between autism and microscopic eosinophilic colitis in 2 children. The possible mechanisms that may connect these two conditions are discussed. Methods and Results: A rare association between autism and microscopic eosinophilic colitis in 2 children is reported through retrospective chart review. Common causes of secondary eosinophilic colitis were excluded. Conclusion: This report suggests the possibility of either impaired intestinal barrier function or an aberrant immune system that predisposes autistic children to sensitization to environmental antigens. Large controlled studies are needed to examine this hypothesis.

Pre-pouch ileitis after colectomy in paediatric ulcerative colitis

Colectomy and ileal pouch anal anastomosis (IPAA) is a potentially curative option for patients with ulcerative colitis (UC). A rare, postoperative complication is terminal ileitis which has been poorly documented in paediatric patients. A search of our paediatric inflammatory bowel disease (IBD) database revealed two boys with UC who were resistant to medical therapy. They each underwent colectomy with IPAA. One year later, both children represented with bloody diarrhoea and weight loss. Several endoscopies and biopsies showed acute on chronic mucosal inflammation in the pouch and up to 50 cm into the terminal ileum (TI). Biopsies revealed mixed inflammatory infiltrate with no granulomas.

Impact of combination antiretroviral therapy in the NOD.c3c4 mouse model of autoimmune biliary disease

The NOD.c3c4 mouse model develops autoimmune biliary disease characterized by spontaneous granulomatous cholangitis, antimitochondrial antibodies and liver failure. This model for primary biliary cirrhosis (PBC) has evidence of biliary infection with mouse mammary tumour virus (MMTV), suggesting that the virus may have a role in cholangitis development and progression of liver disease in this mouse model. We tested the hypothesis that MMTV infection is associated with cholangitis in the NOD.c3c4 mouse model by investigating whether antiretroviral therapy impacts on viral levels and liver disease.

Fulminant hepatic failure necessitating transplantation following the initiation of infliximab therapy: a cautionary tale times two

Dear Sirs, Infliximab (IFX) is a human-murine chimeric antibody with well-established efficacy in the treatment for several autoimmune diseases [1,2]. However, it is known to be hepatotoxic [3–6]. While the appreciation of IFX-associated liver disease is increasing, only one other documented case of IFX-related liver failure has been reported [7]. We herein report two patients with fulminant hepatic failure temporally linked to initiation of IFX, which likely precipitated a need for urgent liver transplantation. A 40-year-old female with a lupus background complicated by hydradenitis suppurativa was started on IFX and 4 months after initiating this later treatment she developed fatigue, jaundice and encephalopathy. There was no prior history of alcohol abuse, and baseline liver and renal function were entirely normal (aspartate aminotransferase (AST) 27 U/l, bilirubin (Bili) 15 lM, alkaline phosphatase (ALP) 72 U/l and INR 0.6), although an abdominal ultrasound (US) showed moderate enlargement of the spleen (12 cm) at the time of IFX administration. At the time of presentation with liver failure, bloodwork showed severe cholestasis (Bili 262 lM, AST 292 U/l, ALP 193 U/l and INR 2.6), with a model for end-stage liver disease (MELD) score of 28 points. Repeat US showed a small, shrunken, nodular liver without biliary obstruction, and marked ascites. Subsequent transjugular liver biopsy showed diffuse parenchymal collapse with extensive areas of lobular necrosis with ductal proliferation and portal fibrosis (Fig. 1a). She deteriorated rapidly with encephalopathy and progressed to fulminant liver failure, requiring inotropic pressure, ventilatory and renal support followed by a whole liver transplant from a deceased donor. Her postoperative course was complicated by renal failure secondary to hepatorenal syndrome, pneumonia and acute cellular rejection. Over the next 2 weeks her renal and liver function normalized. She was discharged on a corticosteroid taper, with mycophenolate mofetil and tacrolimus for maintenance immunosuppression. Intensive care unit (ICU) stay was 27 days, and the total hospital stay was 58 days. (a)

Insulinoma or non-insulinoma pancreatogenous hypoglycemia? A diagnostic dilemma.

Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. An alternate etiology, non-insulinoma pancreatogenous hypoglycemia (NIPH), is rare. Clinically, NIPH is characterized by postprandial hyperinsulinemic hypoglycemia, negative 72-h fasts, negative preoperative localization studies for insulinoma and positive selective arterial calcium infusion tests. Histologically, diffuse islet hyperplasia with increased number and size of islet cells is present and confirms the diagnosis. Differentiating NIPH from occult insulinoma preoperatively is challenging. Partial pancreatectomy is the procedure of choice; however, recurrence of symptoms, although less debilitating, occurs commonly. Medical management with diazoxide, verapamil and octreotide can be used for persistent symptoms. Ultimately, near-total or total pancreatectomy may be necessary. We report a case of a 67-year-old male with hypoglycemia in whom preoperative workup, including computerized tomography abdomen, suggested insulinoma, but whose final diagnosis on pathology was NIPH instead.

1029 Community-Driven Research on Helicobacter pylori Infection in the Canadian Arctic: the Fort Mcpherson H. pylori Project

Background: The Canadian North Helicobacter pylori (CANHelp) Working Group conducts community Helicobacter pylori projects to address public concerns about health risks from this infection in Arctic Canada, where H.pylori prevalence and stomach cancer rates are elevated. At the request of community leaders of Fort McPherson, Northwest Territories (population~800, ~95% Aboriginal), the ongoing Fort McPherson H. pylori Project launched in 2012 to investigate the disease burden related to H.pylori infection and identify strategies for reducing related health risks. Methods: A local planning committee guided the design and implementation of the project, which includes six components: surveys of risk factors, urea breath test (UBT) screening for H. pylori infection, upper gastrointestinal endoscopy with biopsies collected and histopathology, treatment, knowledge exchange, and policy development. During 2012-13, all residents of Fort McPherson were invited to participate in UBT screening and questionnaire-based risk factor interviews; residents ≥15 years of age were invited to undergo endoscopy in temporary endoscopy units in the local health centre. Participants could also enrol in a randomized trial comparing two 10-day H.pylori therapies: sequential therapy (ST) consisted of a proton pump inhibitor (PPI) and amoxicillin for days 1-5, followed by a PPI, clarithromycin, and metronidazole for days 6-10; quadruple therapy (QT) consisted of a PPI, bismuth, metronidazole, and tetracycline for days 1-10. Treatment outcomes were classified by UBT at >=10 weeks after treatment. Results: To date, 226 residents, aged 4-98 years, have consented to participate. Parental consent and childs assent were obtained for residents <17 years of age. Of the 226 project participants, 180 have completed risk factor interviews, 217 had a UBT (positivity=59%), 53 had endoscopy with biopsies collected, 71 consented to treatment and 60 enrolled in the treatment trial, with 24 to date completing a post-treatment UBT. Of the 53 participants who had endoscopy, gastroenterologists identified gastritis in 15%, gastric ulcer in 4%, gastric erosion in 11%, duodenitis in 4%, duodenal erosion in 2%, and esophagitis in 11%. Histopathology (Sydney classification) of gastric biopsies from 53 Fort McPherson H. pylori Project participants is shown in table 1. Preliminary findings from the treatment trial to date are: 86% treatment success for participants randomized to ST (12/14; 95% CI 57%-98%) and 100% treatment success for participants randomized to QT (10/10; 95% CI 74%-100%). Discussion: These results add to evidence that shows Arctic Aboriginal communities to be disproportionately affected by H. pylori infection. The high prevalence of moderate-severe gastritis shows that public concern over risks from H. pylori infection is warranted. Histology Results

Changes in the Linear Attenuation Coefficient of Canine Appendicular Bone Following Intravenous Infusion of Strontium Lactate, Measured Using Gamma-Ray Computed Tomography

SummaryChanges in the average linear attenuation coefficient (LAC) within a fixed measurement volume in the proximal end of the dog tibia, which contains trabecular bone and associated soft tissues (the trabecular bone “space”), were monitored continuously using gamma-ray computed tomography (γ-CT) prior to, during, and following intravenous infusion of strontium (Sr) lactate. An infusion of 1.3–4.7 g of Sr over a period of 110–160 minutes into 20-kg dogs resulted, within 6–8 hours, in an increase of 0.019–0.045 cm-1 (P<0.002) in the LAC. Calibration of the γ-CT system showed that 0.44 mg/cm3 of Sr produced a change of 0.01 cm-1 in the LAC. Using this conversion factor, the Sr concentration in the trabecular bone space resulting from infusion, as measured by flame atomic absorption spectroscopy, agreed with that predicted by the change observed in the LAC. Sr present in the serum and urine was consistent with the changes observed in the LAC over the study period. Control dogs infused with mineral-free solutions showed no change in LAC. Calcium equivalents required to give the changes observed in the LAC using Sr indicate that variations in skeletal turnover in man can be monitored in the peripheral skeleton using γ-CT.