Shuvra Ray

Clinical evidence for allergy in orofacial granulomatosis and inflammatory bowel disease

BackgroundOrofacial granulomatosis (OFG) causes chronic, disfiguring, granulomatous inflammation of the lips and oral mucosa. A proportion of cases have co-existing intestinal Crohn’s disease (CD). The pathogenesis is unknown but has recently been linked to dietary sensitivity. Although allergy has been suggested as an aetiological factor in OFG there are few published data to support this link. In this study, we sought clinical evidence of allergy in a series of patients with OFG and compared this to a series of patients with inflammatory bowel disease (IBD) without oral involvement and to population control estimates.MethodsPrevalence rates of allergy and oral allergy syndrome (OAS) were determined in 88 patients with OFG using questionnaires, skin prick tests, total and specific serum IgE levels. Allergy was also determined in 117 patients with IBD without evidence of oral involvement (79 with CD and 38 with ulcerative colitis (UC)).ResultsPrevalence rates of allergy in patients with OFG were significantly greater than general population estimates (82% versus 22% respectively p = <0.0005). Rates of allergy were also greater in those with CD (39%) and, interestingly, highest in those with OFG and concurrent CD (87%). Conversely, whist OAS was common in allergic OFG patients (35%) rates of OAS were significantly less in patients with concomitant CD (10% vs 44% with and without CD respectively p = 0.006). Amongst CD patients, allergy was associated with perianal disease (p = 0.042) but not with ileal, ileocolonic or colonic disease location. Allergy in UC (18%) was comparable to population estimates.ConclusionWe provide compelling clinical evidence for the association of allergy with OFG whether occurring alone or in association with CD. The presence of gut CD increases this association but, conversely, reduces the expression of OAS in those with atopy. Interestingly, there is no evidence of increased allergy in UC.

The beta-adrenoceptor agonist isoproterenol rescues acetaminophen-injured livers through increasing progenitor numbers by Wnt in mice

Acetaminophen (APAP)‐induced acute liver injury (AILI) is a major health problem. Accumulating evidence suggests that the sympathetic nervous system (SNS) regulates neuronal and hematopoietic progenitors. SNS signaling affects hepatic progenitor/oval cells (HPCs) and β‐adrenoceptor agonism will expand HPCs to reduce AILI. Dopamine β‐hydroxylase‐deficient mice (Dbh−/−), lacking catecholamine SNS neurotransmitters, isolated HPCs, and immature ductular 603B cells were initially used to investigate SNS involvement in HPC physiology. Subsequently, control mice were treated with APAP (350 mg/kg) followed by the β‐adrenoceptor agonist, isoproterenol (ISO), or the β‐adrenoceptor antagonist, propranolol. Mechanistic studies examined effects of non‐SNS HPC expansion on AILI, involvement of the canonical Wnt/β‐catenin pathway (CWP) in the action of ISO on HPC expansion and comparison of ISO with the current standard of care, N‐acetylcysteine (NAC). Dbh−/− mice lacking catecholamines had low HPC numbers, reconstituted by ISO. In vitro, ISO‐induced proliferation of 603B cells was CWP dependent. In control mice, AILI raised HPC numbers, further increased by ISO, with attenuation of liver injury. Delayed administration of NAC did not, but delayed ISO did, reverse AILI. Propranolol worsened AILI. AILI activated the CWP, and ISO enhanced Wnt‐ligand production. HPCs were the major source of Wnt ligands. Recombinant Wnt3a and ISO‐603B‐conditioned media, but not ISO alone, protected isolated hepatocytes from death, reversed by DKK1—a Wnt antagonist. Additionally, tumor‐associated weak inducer of apoptosis expanded HPCs and protected against AILI. Furthermore, allotransplantation of HPCs from APAP+ISO‐treated mice to other APAP‐injured mice improved AILI, an effect antagonized by DKK1. Conclusion: SNS catecholamines expand HPCs, which are both targets and sources of Wnt ligands. Hepatoprotection by ISO is mediated by para‐ and autocrine effects of Wnt signaling. ISO represents novel pharmacotherapy for AILI. (Hepatology 2014;60:1023–1034)

In vitro and in vivo modeling of lipid bioaccessibility and digestion from almond muffins: The importance of the cell-wall barrier mechanism

Highlights • We investigated the mechanisms of lipid bioaccessibility from almond muffins.• An in vitro dynamic gastric model was used to simulate human digestion.• A pilot ileostomy study was performed to define the rate of lipid release.• Microstructural analysis proved that some lipid remained encapsulated within matrix.• The cell-wall is the main factor regulating the lipid bioaccessibility.

Lack of effect of Maraviroc intensification on blood and gut reservoir

We show that intensification of treatment with maraviroc in patients chronically infected with HIV-1 receiving successful long-term antiretroviral therapy was not associated with improvements in HIV-related morbidity, HIV reservoir, microbial translocation, immune activation, or immune exhaustion in either gut or peripheral blood. The measurement of reservoir in both gut and blood longitudinally contributes to a paucity of data in the area.Abstract We show that intensification of treatment with maraviroc in patients chronically infected with HIV-1 receiving successful long-term antiretroviral therapy was not associated with improvements in HIV-related morbidity, HIV reservoir, microbial translocation, immune activation, or immune exhaustion in either gut or peripheral blood. The measurement of reservoir in both gut and blood longitudinally contributes to a paucity of data in the area.

Sa1255 Higher Red Blood Cell Methotrexate Polyglutamates Correlate With Increased Disease Activity, and Are Useful in Assessing Adherence

Introduction Methotrexate (MTX) is commonly used in patients with inflammatory bowel disease (IBD). Within red blood cells (RBC), MTX is activated by sequential addition of glutamic acid residues to form polyglutamates (MTXPG 1–5 ). In rheumatoid arthritis, low [MTXPG] has been associated with active disease, whereas other studies have demonstrated an inverse relationship, including the only published data in IBD. The aim of this study was to determine if RBC [MTXPG] reflect clinical response in IBD patients and whether they are useful in assessing adherence. Methods This was a single-centre, retrospective pilot study of 21 IBD patients treated with weekly MTX. RBC MTXPG 1–5 was measured using high-performance liquid chromatography. Clinical status (active disease or remission) was assessed by 2 IBD physicians blinded to [MTXPG], using a combination of prospectively recorded clinical activity indices (Simple Colitis Activity Index, Harvey Bradshaw Index), endoscopy, faecal calprotectin and C reactive protein (CRP). Pearson correlation coefficient, r was calculated to assess the relationship between MTX dose and [MTXPG]. Association between [MTXPG] and clinical response was analysed with unpaired t-test. Results 4/21(22%) patients (3 of whom admitted non-adherence) had undetectable MTXPGs and were excluded from further analysis. MTXPG 2–4 were detected in all adherent patients. PG 3 was the predominant polyglutamate accounting for a mean of 43% of total MTXPG. A linear relationship between dose of MTX and PG 1–5 was observed. 12/21(57%) patients were assessed as having active disease. No significant difference in mean [MTXPG n ] was observed between those with active disease and remission. For each MTXPG n , a non-significant trend towards a higher concentration was observed in patients with active disease. Conclusion In this study, the largest to date in IBD, measuring RBC MTXPG was useful in assessing adherence to MTX. A trend towards higher PG concentrations was associated with active disease confirming the findings in the only other study in IBD. Whether this is confounded by higher doses being used in patients with more active disease warrants further study in larger, prospective trials. Reference Disclosure of Interest None Declared.

Su1101 Indeterminate and Inconclusive Results Are Common When Using Interferon Gamma Release Assay As Screening for TB in Patients With IBD

Introduction Anti-TNF treatment is widely used in inflammatory bowel disease (IBD) but has been linked with reactivation of tuberculosis (TB). Screening for active and latent TB prior to initiation of anti-TNF therapy is therefore mandated. ECCO recommends interferon gamma release assays (IGRAs) as, unlike tuberculin skin test, positive tests are not caused by previous Bacillus Calmette–Guerin (BCG) vaccine. However, immunosuppressive agents can result in indeterminate or unreportable results[i] and there is no clear guidance on managing them. We quantified the prevalence of indeterminate or unreportable TB IGRA Elispot results in a large tertiary centre cohort of patients with IBD. Methods A single centre retrospective study of IGRA tests performed on IBD patients prior to commencement of anti-TNF therapy between Oct 2010 and Oct 2013. Results We included 140 patients (median age 34, range 24–86, 50% males). 92% had Crohn’s disease, 4% ulcerative colitis, and 4% IBD-unclassified. At the time of IGRA testing, 115 patients were on immunomodulators and 6 on prednisolone. 3 were positive for latent TB and were referred to infectious disease (ID) department prior to anti-TNF therapy. 3 had indeterminate results; all were on immunosuppressants (2=azathioprine, 1=methotrexate). 2 had a lymphocyte count 10 had unreportable results, 9 of whom were on azathioprine. On repeat testing, 4 were negative, and the remainder were still unreportable, one of whom had risk factors for TB and was treated with isoniazid chemoprophylaxis on the advice of the ID team. The remaining 5 patients started anti-TNF based on the absence of risk factors for TB. No patient had reactivation of latent TB at follow up (range 1–18 months). Lymphopaenia was found to be associated with non-reportable cases as compared to the reported cases (median lymphocyte count unreportable = 0.4, reportable = 1.2; p = 0.015). Conclusion Our results demonstrate TB IGRA is a useful test to screen for latent infection before initiating anti-TNF therapy. However, a minority of results are indeterminate or unreportable. In such cases repeat testing can produce definitive results. Low lymphocyte counts in association with immunosuppression may contribute to unreportable and indeterminate results; clinical risk stratification appears to be a safe way of managing such cases in this small cohort. Reference Papay P et al . Predictors of indeterminate IFN-γ release assay in screening for latent TB in inflammatory bowel diseases. Eur J Clin Invest. 2011 Disclosure of Interest None Declared.

The impact of immunoglobulin in acute HIV infection on the HIV reservoir: a randomized controlled trial

Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV‐specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone.

Outcomes following Serial Intragastric Balloon Therapy for Obesity and Nonalcoholic Fatty Liver Disease in a Single Centre

Background The incidence of nonalcoholic fatty liver disease (NAFLD) continues to parallel the rise in obesity rates. Endobariatric devices such as the intragastric balloon (IGB) may provide an alternative treatment option. Methods Outcomes following IGB treatment in 135 patients with obesity and NAFLD (mean baseline weight 117.9 kg; BMI 41.7 kg/m2; HOMA-IR 3.6) were retrospectively examined. Clinical, anthropometric, and biochemical changes were analysed at six months and after consecutive treatment with two and three serial IGBs. Results After six months, significant changes were seen with weight and BMI (mean reductions of 11.3 kg and 4.1 kg/m2, resp., p < 0.01 for both). Significant improvements were also seen with ALT, GGT, and HOMA-IR, with all changes corresponding with weight loss. Forty-eight patients received two IGBs, and 20 were treated with three serial IGBs. The greatest amount of total weight loss was observed after the first 6 months (mean weight lost 7.4 kg, versus 3.6 kg and 1.9 kg with two and three IGBs, resp.). Conclusions IGB therapy is an effective, alternative nonsurgical means for weight loss in the management of obesity and NAFLD over the short term, with greatest outcomes observed after six months. Improvements in insulin resistance and hepatic transaminases correlated with weight change.

PTU-044 Tertiary Centre Experience Of 360 Degree Side-viewing Video Capsule Endoscopy

Introduction Since it’s development in 1999, video capsule endoscopy (VCE) has become the investigation of choice for examining the small bowel. Recently, a novel panoramic 360 degree side-viewing VCE (Capsovision, Medical Innovations, USA) was launched. It differs from previous capsules in that no data recorder or sensors are required. The images are stored on the capsule itself, which when passed, must be retrieved and sent to the endoscopy reader for analysis. We report our initial experience of this novel VCE. Methods We retrospectively analysed the first 51 side-viewing VCE over a 6-month period at our institution. All patients had a clear liquid diet as preparation the day before. Results 51 patients (26 males) underwent examination with the side-viewing VCE. 39 (76.4%) examinations were completed and 12 were incomplete. This included 4 which were lost due to being flushed away. Over the same time period, forward-viewing VCE complete results were available in 83.2% patients. 1 of the incomplete examinations was due to a NSAID-induced stricture, subsequently diagnosed with a forward-viewing VCE. 31 patients had good bowel preparation, 11 satisfactory preparation and 6 were reported as having poor bowel preparation. The duodenal ampulla was reliably identified in 3/47 (6.4%) examinations. Pathology was identified in 11/47 (23.4%) examinations. Conclusion Side-viewing VCE was well tolerated and completed examination results were available for 76.4% of patients examined. Our findings did not correlate with previous reported results (71%) regarding the identification rate of the duodenal papilla as a small bowel landmark with side-viewing VCE. Advantages of the side-viewing VCE are not needing the patient to wear a recorder, with the data being stored in the capsule itself. This enables multiple patients to be examined on the same day and the number of examinations is not limited by available data recorders. Patients can also take the capsule home and take the capsule at any time which can be useful in the investigation of obscure GI bleeding. Side-viewing VCE is comparable to forward viewing VCE with respect to cost and accuracy. Disclosure of Interest None Declared.

5‐ASAs in Crohn's disease: are they any better than placebo?

5‐ASAs are widely employed in the management of Crohns disease despite limited evidence for their effectiveness. Here, the authors assess the evidence base and current guidance for their use in inducing and maintaining remission in CD.