PMA - Zeolite (Clinoptilolite) in the Management of Irritable Bowel Syndrome - a Non-Interventional Study.

In clinical practice, the treatment of patients with irritable bowel syndrome (IBS) can be very challenging. The aims of the present non-interventional study (NIS) were to investigate the tolerability and efficacy of PMA-zeolite under everyday conditions in patients with diarrheic IBS type (IBS-D) or constipated type (IBS-C) or mixed type (IBS-M). METHODS: To document prospective data on tolerability and symptom frequency in the frame of a nationwide NIS, we recruited 204 IBS patients. The study focused on the IBS-related quality of life (measured by the SF-36 questionnaire) and improvements of IBS-related symptoms according to specific ROM-III criteria and stool consistency (Bristol stool scale). The participants documented their abdominal pain, bloating, number of bowel movements, and stool consistency through a web-based internet platform (initial and exit questionnaires) and daily diary entries over the period of intake (8 weeks). RESULTS: A total of 82.2% of the recruited patients had filled in the questionnaires before and after the 8-week treatment with PMA-zeolite. Seven of the eight subscales of the SF-36 improved significantly (p<0,001); the reduction in abdominal pain was especially significant (p<0,001). The diary entries confirmed the reduction in abdominal pain and revealed a significant reduction in days with bloating (p<0,001). The Bristol-stool-scale analysis showed improvements; particularly, patients with IBS-D benefited from the treatment (p<0,001). CONCLUSION: The treatment duration of 8 weeks was well tolerated by most patients. Under everyday life conditions, PMA-zeolite alleviated the global IBS-related symptoms and raised the quality of life (QOL). The PMA-zeolite, thus, may represent a good adjuvant therapeutic option for patients with irritable bowel syndrome.

Preexposition Prophylaxis With Truvada (Tenofovir/Emtricitabine) as Potential Cause of Celiac Disease-Like Enteropathy.

We present here a case of a 39-year-old patient who presented with celiac-disease-like symptoms and MARSH 3a histology in duodenal biopsies under normal diet. Interestingly, HLA genotyping and celiac-specific serology were negative, primarily leading to exclusion of celiac disease. However, biopsies from a second endoscopy a couple of months later (still under normal diet) showed histologic progression of the disease to MARSH 3b and led to the re-evaluation of the out-of-hospital-obtained histological samples by a pathologist experienced in celiac disease. The second biopsy described previously as MARSH 3b turned out to be non-specific and was therefore re-classified as MARSH 0. After all known causes of duodenal villous atrophy were excluded by a thorough evaluation, a correlation between the first biopsy (MARSH 3a) and Truvada intake could be established. After Truvada discontinuation and under normal diet, normalisation of duodenal mucosa was observed, leading to the assumption that Truvada could lead to celiac-like enteropathy.

Atypical enteropathogenic E. coli are associated with disease activity in ulcerative colitis.

With increasing urbanization and industrialization, the prevalence of inflammatory bowel diseases (IBDs) has steadily been rising over the past two decades. IBD involves flares of gastrointestinal (GI) inflammation accompanied by microbiota perturbations. However, microbial mechanisms that trigger such flares remain elusive. Here, we analyzed the association of the emerging pathogen atypical enteropathogenic E. coli (aEPEC) with IBD disease activity. The presence of diarrheagenic E. coli was assessed in stool samples from 630 IBD patients and 234 age- and sex-matched controls without GI symptoms. Microbiota was analyzed with 16S ribosomal RNA gene amplicon sequencing, and 57 clinical aEPEC isolates were subjected to whole-genome sequencing and in vitro pathogenicity experiments including biofilm formation, epithelial barrier function and the ability to induce pro-inflammatory signaling. The presence of aEPEC correlated with laboratory, clinical and endoscopic disease activity in ulcerative colitis (UC), as well as microbiota dysbiosis. In vitro, aEPEC strains induce epithelial p21-activated kinases, disrupt the epithelial barrier and display potent biofilm formation. The effector proteins espV and espG2 distinguish aEPEC cultured from UC and Crohn's disease patients, respectively. EspV-positive aEPEC harbor more virulence factors and have a higher pro-inflammatory potential, which is counteracted by 5-ASA. aEPEC may tip a fragile immune-microbiota homeostasis and thereby contribute to flares in UC. aEPEC isolates from UC patients display properties to disrupt the epithelial barrier and to induce pro-inflammatory signaling in vitro.

Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results.

BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. METHODS: This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. RESULTS: In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens. CONCLUSION: Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. CLINICALTRIALS: gov, Number: NCT002209456.

Role of fecal calprotection in predicting endoscopic recurrence in postoperative Crohn's disease.

BACKGROUND AND AIMS: Fecal calprotectin (fCP) has been shown to correlate with endoscopic disease activity in Crohn's disease (CD). The aim of this study was to evaluate its role in predicting early endoscopic recurrence in postoperative CD. METHODS: Patients who underwent CD-related intestinal resection with ileocolonic anastomosis were prospectively followed up until ileocolonoscopy was performed around 12 months post-surgery. Endoscopic recurrence (ER) was defined as modified Rutgeerts score i2b or higher. Endoscopic still images were reviewed by 2 independent reviewers blinded to fCP results. Stool specimens were collected 6 months post-surgery and a multivariate logistic regression model was established to explore the predictive value of fCP for ER. RESULTS: 79 patients were included. FCP was significantly associated with endoscopic recurrence (p = .036). A cut-off value of fCP of 267 µg/g at 6 months post-surgery predicted ER with a sensitivity of 61.8% and a specificity of 72.7% (AUC 0.669). A prediction model subsuming age at diagnosis and fCP 6 months post-surgery were significantly associated with ER (fCP at 6 months [p = .007] and age at diagnosis [p = .004], multivariate analysis). CONCLUSIONS: FCP 6 months after surgery and age at diagnosis predict early ER at 1 year postoperatively. However, the low sensitivity of fCP still suggests the necessity of endoscopy as a gold standard for the assessment of postoperative recurrence of CD.KEY SUMMARYWhat is already known? Fecal calprotectin (fCP) correlates with endoscopic disease activity. Endoscopic recurrence occurs in up to 70% of patients after intestinal resection within 1 year.What are the significant and/or new findings of this study? Fecal calprotectin 6 months post-surgery and age at diagnosis significantly predict endoscopic recurrence at 1 year. Due to low sensitivity fCP cannot replace the necessity of endoscopy for accurate assessment of postoperative recurrence.

Humoral response to COVID-19 infection in immunosuppressed patients with inflammatory bowel disease.

The course of coronavirus 19 (COVID-19) might be determined by certain comorbidities (e.g. diabetes, hypertension and other cardiovascular diseases) and advanced age. Because the impact of immunosuppression on disease severity is not entirely clear, management of patients under immunosuppressive treatment remains controversial. Six cases of inflammatory bowel disease (IBD) patients with COVID-19 on immunosuppressive medication are presented. The aim of this study was to describe patients' clinical manifestation and chronologic development of virus-specific antibodies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection before and after restart with immunosuppressive/biological therapy as an indicator for a specific immune response. All patients were tested for the presence of SARS-CoV-2-RNA with PCR, were in clinical remission prior to COVID-19 and only one patient continued his immunosuppressive treatment during the COVID-19 infection. Initial symptoms of COVID-19 were pyrexia, diarrhea, cephalea, and dysgeusia and anosmia. No patient needed admission to hospital or ICU. The SARS-CoV-2 antibody development was described to be late in three of the six patients. Late antibody development seems to be more frequent in older patients and in patients with combined immunosuppressive treatment. In this scenario, SARS-CoV-2 antibody testing could be useful prior to restarting immunosuppressive therapy.

Inflammatory Bowel Disease and Risk of Major Bleeding During Anticoagulation for Venous Thromboembolism.

BACKGROUND: Little is known about the bleeding risk in patients with inflammatory bowel disease (IBD) and venous thromboembolism (VTE) treated with anticoagulation. Our aim was to elucidate the rate of major bleeding (MB) events in a well-defined cohort of patients with IBD during anticoagulation after VTE. METHODS: This study is a retrospective follow-up analysis of a multicenter cohort study investigating the incidence and recurrence rate of VTE in IBD. Data on MB and IBD- and VTE-related parameters were collected via telephone interview and chart review. The objective of the study was to evaluate the impact of anticoagulation for VTE on the risk of MB by comparing time periods with anticoagulation vs those without anticoagulation. A random-effects Poisson regression model was used. RESULTS: We included 107 patients (52 women, 40 with ulcerative colitis, 64 with Crohn disease, and 3 with unclassified IBD) in the study. The overall observation time was 388 patient-years with and 1445 patient-years without anticoagulation. In total, 23 MB events were registered in 21 patients, among whom 13 MB events occurred without anticoagulation and 10 occurred with anticoagulation. No fatal bleeding during anticoagulation was registered. The incidence rate for MB events was 2.6/100 patient-years during periods exposed to anticoagulation and 0.9/100 patient-years during the unexposed time. Exposure to anticoagulation (adjusted incidence rate ratio, 3.7; 95% confidence interval, 1.5-9.0; P = 0.003) and ulcerative colitis (adjusted incidence rate ratio, 3.5; 95% confidence interval, 1.5-8.1; P = 0.003) were independent risk factors for MB events. CONCLUSION: The risk of major but not fatal bleeding is increased in patients with IBD during anticoagulation. Our findings indicate that this risk may be outweighed by the high VTE recurrence rate in patients with IBD.

Use of complementary and alternative medicine and low quality of life associate with the need for psychological and psychotherapeutic interventions in inflammatory bowel disease.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) suffer from various symptoms, impairing their quality of life and often affecting psychosocial issues. This may lead to the need for additional psychological care. This study investigated patients' subjective need for integrated psychosomatic support and psychotherapy and indicators for it. MATERIALS AND METHODS: This is a cross-sectional multicentre study in Austrian IBD patients who were in routine care at 18 IBD outpatient clinics. Patients filled in an anonymous, validated questionnaire (Assessment of the Demand for Additional Psychological Treatment Questionnaire [ADAPT]) assessing the need for psychological care. The ADAPT gives two separate scores: the need for integrated psychosomatic support and for psychotherapy. In addition, health-related quality of life and the use of complementary and alternative medicine as well as clinical and socio-demographic variables were queried. Multivariable regression analysis was performed to estimate the effect of the previously mentioned variables on the need for additional psychological care. RESULTS: Of 1286 patients, 29.7% expressed a need for additional psychological care, 19.6% expressed a need for integrated psychosomatic support and 20.2% expressed a need for psychotherapy. In the multivariable analysis, the two strongest indicators for the need for both types of psychological care were the use of complementary and alternative medicine (for integrated psychosomatic support: odds ratio = 1.64, 95% confidence interval 1.13-2.39, p = 0.010; for psychotherapy: odds ratio = 1.74, 95% confidence interval 1.20-2.53, p = 0.004), and a low health-related quality of life score (for integrated psychosomatic support: odds ratio = 0.95, 95% confidence interval 0.94-0.96, p < 0.001; for psychotherapy: odds ratio = 0.96, 95% confidence interval 0.94-0.97, p < 0.001). DISCUSSION: About 30% of the Austrian IBD patients expressed a need for integrated psychosomatic support and/or psychotherapy. The most important indicators for this need were the use of complementary and alternative medicine and low quality of life.

Passive Smoking Increases the Risk for Intestinal Surgeries in Patients With Crohn's Disease.

BACKGROUND: Despite substantial evidence on the negative effect of active smoking, the impact of passive smoking on the course of Crohn's disease (CD) remains largely unclear. Our aim was to assess passive smoking as a risk factor for intestinal surgeries in CD. METHODS: The study was conducted in a university-based, monocentric cohort of 563 patients with CD. Patients underwent a structured interview on exposure to passive and active smoking. For clinical data, chart review was performed. Response rate was 84%, leaving 471 cases available for analysis. For evaluation of the primary objective, which was the impact of exposure to passive smoking on the risk for intestinal surgery, only never actively smoking patients were included. RESULTS: Of 169 patients who never smoked actively, 91 patients (54%) were exposed to passive smoking. Exposed patients were more likely to undergo intestinal surgery than nonexposed patients (67% vs 30%; P < 0.001). Multivariate Cox regression analysis revealed that passive smoking was an independent risk factor for intestinal surgeries (hazard ratio, 1.7; 95% CI, 1.04-2.9; P = 0.034) after adjustment for ileal disease at diagnosis (hazard ratio, 2.9; 95% CI, 1.9-4.5; P < 0.001) and stricturing or penetrating behavior at diagnosis (hazard ratio, 1.9; 95% CI, 1.2-3.1; P = 0.01). Passive smoking during childhood was a risk factor for becoming an active smoker in later life (odds ratio, 2.2; 95% CI, 1.5-3.2; P < 0.001). CONCLUSION: Passive smoking increases the risk for intestinal surgeries in patients with CD.

Crohn's disease: prevalence, MR features, and clinical significance of enteric and colonic sinus tracts.

OBJECTIVES: Enteric and colonic sinus tracts are inflammatory complications that precede intestinal fistulas in patients with Crohn's disease (CD). The aim of this study was to retrospectively determine the prevalence, morphologic features, and outcome of sinus tracts using MR imaging. METHODS: A consecutive cohort of 642 patients with known CD, referred for MR enterography or MR enteroclysis (study period 01/2014-09/2019), was evaluated retrospectively for the presence of sinus tracts, their locations, presence and length of coexisting strictures, bowel wall thickness, CDMI score, upstream dilation, and bowel distension. Clinical outcome was assessed using medical records. For metric data, means and standard deviation, as well as one-way ANOVA and Pearson's correlation coefficient, were calculated. RESULTS: In 36/642 patients with CD undergoing MRE, 49 sinus tracts (forty in small intestine, nine in left-sided colon) were detected with a prevalence of 6.9% in patients with MR-visible signs of CD (n = 519, overall prevalence of 5.6%). Mean segmental bowel wall thickness was 8.9 mm, and mean CDMI score was 9.3. All sinus tracts were located within a stenotic segment, showing mesenteric orientation within the small bowel and upstream dilation in 13 patients. Of 36 patients, 19 underwent immediate surgery and seven developed clinical progression within the segment containing the sinus tract. CONCLUSIONS: Sinus tracts occur in 6.9% of patients with visible signs of CD. They are located within stenotic, severely thickened bowel segments with high MR inflammation scores. Their detection is clinically important, because they indicate a more aggressive phenotype and, if left untreated, may show severe progression. KEY POINTS: • Sinus tracts occur in 6.9% of patients with MR-visible signs of Crohn's disease. • Sinus tracts are a radiological indicator of early penetrating Crohn's disease, with a high risk of progression, and require dedicated treatment. • Sinus tracts can be recognized by characteristic findings and typically occur in stenotic, severely thickened bowel segments with high MR inflammation scores.

Prevalence and indicators of use of complementary and alternative medicine in Austrian patients with inflammatory bowel disease.

OBJECTIVE: Complementary and alternative medicine (CAM) seems to be frequently used among patients with inflammatory bowel disease (IBD). We aimed to determine the prevalence and indicators of CAM use in Austrian IBD patients. METHODS: In a multicentre cross-sectional study, adult patients with IBD attending 18 Austrian outpatient clinics completed a multi-item questionnaire that recorded use of CAM as well as medical and socioeconomic characteristics. Patients were recruited between June 2014 and June 2015. The study outcome was the prevalence of CAM use and its socioeconomic and disease-related associations. RESULTS: A total of 1286 patients (Crohn's disease 830, ulcerative colitis 435, IBD unclassified 21; females 651) with a median age of 40 years (interquartile range 31-52 years) and a median disease duration of 10 years (4-18 years) were analysed. The prevalence of previous and/or current CAM use was 50.7%, with similar results for Crohn's disease and ulcerative colitis. In the multivariable analysis, female gender and a university education were independent socioeconomic indicators of CAM use. IBD-related indicators were longer duration of the disease and previous and/or current treatment with steroids and TNF-α inhibitors. CONCLUSION: CAM use for IBD is frequent in Austrian IBD patients and associated with female gender, higher educational level of university degree, longer duration of the disease, and treatment with steroids and TNF-α inhibitors.

Diagnostic delay in patients with inflammatory bowel disease in Austria.

BACKGROUND: Delayed diagnosis seems to be common in inflammatory bowel diseases (IBD). The study was carried out to investigate the diagnostic delay and associated risk factors in Austrian IBD patients. METHODS: In a multicenter cross-sectional study adult patients with IBD attending 18 Austrian outpatient clinics completed a multi-item questionnaire that recorded medical and socioeconomic characteristics. The study outcome was diagnostic delay defined as the period from symptom onset to diagnosis of IBD. RESULTS: A total of 1286 patients (Crohn's disease 830, ulcerative colitis 435, inflammatory bowel disease unclassified 21; females 651) with a median age of 40 years (interquartile range 31-52 years) and a median disease duration of 10 years (4-18 years) were analyzed. The median diagnostic delay was 6 months (2-23 months) in Crohn's disease and 3 months (1-10 months) in ulcerative colitis (p < 0.001). In the multivariable regression analysis Crohn's disease, greater age at diagnosis and a high educational level (compared to middle degree level) were independently associated with longer diagnostic delay. CONCLUSION: The diagnostic delay was longer in Crohn's disease than in ulcerative colitis patients and was associated with greater age at diagnosis and a higher educational level.

[Second Austrian consensus on the safe use of anti-TNFα-antibodies in patients with inflammatory bowel diseases]. / Zweiter österreichischer Konsensus zur sicheren Anwendung von anti-TNF-α-Antikörpern bei chronisch-entzündlichen Darmerkrankungen.

Anti-TNFα-antibodies have revolutionized the therapy of inflammatory bowel diseases and other immune-mediated inflammatory diseases. Due to the increasing application of these substances, the Working Group of Inflammatory Bowel Diseases of the Austrian Association of Gastroenterology and Hepatology intended to update their consensus report on the safe use of Infliximab (published in 2010) and to enlarge its scope to cover all anti-TNFα-antibodies. The present consensus report summarizes the current evidence on the safe use of anti-TNFα-antibodies and covers the following topics: general risk of infection, bacterial infections (i. e., Clostridium difficile, Tuberculosis, food hygiene), Pneumocystis jiroveci, viral infections (i. e., Hepatitis B, Hepatitis C, HIV, CMV, VZV), vaccination in general and recommendation for vaccines, gastrointestinal aspects (i. e., perianal fistula, abdominal fistula, intestinal strictures, stenosis and bowel obstruction), dermatologic aspects (skin malignancies, eczema-like drug-related skin eruption), infusion reactions and immunogenicity, demyelinating diseases, hepatotoxicity, haematotoxicity, congestive heart failure, risk and history of malignancies, and pregnancy and breast feeding. For practical reasons, the relevant aspects are summarized in a checklist which is divided into two parts: issues to be addressed before therapy and issues to be addressed during therapy.

Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel Disease by a Bayesian Dashboard System.

Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are easy-to-use programs incorporating complex Bayesian statistics to determine individual pharmacokinetics. We evaluated various infliximab detection assays and the number of samples needed to precisely forecast individual SICs using a Bayesian dashboard. We assessed long-term infliximab retention in patients being dosed concordantly versus discordantly with Bayesian dashboard recommendations. Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab maintenance therapy were analyzed by 3 commercially available assays. Data from each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter precision and residual variability were assessed. Forecast concentrations from both systems were compared with observed concentrations. Infliximab retention was assessed by prediction for dose intensification via Bayesian dashboard versus real-life practice. Forecast precision of SICs varied between detection assays. At least 3 SICs from a reliable assay are needed for an accurate forecast. The Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed concordantly with Bayesian dashboard recommendations had a significantly longer median drug survival than those dosed discordantly (51.5 versus 4.6 months, P < .0001). The Bayesian dashboard helps to assess the diagnostic performance of infliximab detection assays. Three, not single, SICs provide sufficient information for individualized dose adjustment when incorporated into the Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with longer drug retention of infliximab.

Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating ß7+ T Cells in Crohn's Disease: Report of the TOSCA Study.

BACKGROUND AND AIMS: Progressive multifocal leukoencephalopathy [PML], a brain infection associated with anti-integrin drugs that inhibit lymphocyte translocation from bloodstream to tissue, can be fatal. Decreased central nervous system [CNS] immune surveillance leading to this infection has been reported in patients with multiple sclerosis or Crohn's disease treated with anti-integrin antibody natalizumab. PF-00547659 is an investigational human monoclonal antibody for inflammatory bowel disease, targeted against α4ß7-mucosal addressin cell-adhesion molecule-1 [the integrin ligand selectively expressed in the gut]. We hypothesised that this selective agent would not affect central nervous system immune surveillance. METHODS: Cerebrospinal fluid from five healthy volunteers, and from 10 patients with Crohn's disease previously treated with immunosuppressants, was evaluated to assess the feasibility of the study. Subsequently, 39 patients with active Crohn's disease and previous immunosuppression were evaluated over 12 weeks of PF-00547659-induction therapy. We measured total lymphocytes, T cell subsets in cerebrospinal fluid, and circulating ß7+ memory cells. Disease activity was assessed using the Harvey-Bradshaw Index. RESULTS: Patients treated with PF-00547659 had no reduction of cerebrospinal fluid lymphocytes, T-lymphocyte subsets, or CD4:CD8 ratio, whereas circulating ß7+ memory cells increased significantly. A total of 28/35 [80%] patients had a clinical response and 27/34 [79%] had disease remission. Treatment-related adverse events, none serious, were reported in 23/49 [47%] patients. CONCLUSIONS: In patients with active Crohn's disease, natalizumab therapy increases the risk for PML, and the increased risk is thought to be associated with iatrogenic leukopenia within the CNS. PML under PF-00547659 may be a lesser concern, as this agent did not reduce lymphocytes or T cell subsets in the cerebrospinal fluid.

Platelets Toll-like receptor-4 in Crohns disease.

BACKGROUND: Platelets are activated in Crohn's disease (CD) and interplay with leukocytes. Engagement of Toll-like receptor-4 (TLR-4), which is expressed in human platelets, may be involved in crosstalks between platelets and leukocytes leading to their mutual activation for host defense. MATERIALS AND METHODS: Human neutrophil peptides (HNPs), lipoprotein binding peptides, and sCD14 were determined by enzyme-linked immunosorbent assays in 42 patients with active CD, in 43 patients with CD in remission, and in 30 healthy individuals. Neutrophil-platelet aggregates and binding of the TLR-4 monoclonal antibody to platelets were determined by flow cytometry. RESULTS: Levels of HNPs were higher in patients with CD than in controls (P = 0.0003 vs. active CD and P = 0.01 vs. CD in remission). Likewise, neutrophils with adhering platelets were higher in patients with active CD than in controls (P = 0.004). Binding of the TLR-4 antibody in patients with active CD was similar to that in controls, while patients in remission had significantly higher binding capacities (P = 0.59 and P = 0.003). Incubation of plasma from patients with active disease or patients in remission with platelets from healthy controls confirmed lower binding of the TLR-4 antibody in the presence of plasma from active diseased patients compared to controls (P = 0.039), possibly due to high levels of lipopolysaccharides, as suggested by high levels of sCD14 and lipoprotein binding protein. CONCLUSION: Our study indicates involvement of platelet TLR-4 in enhancing the secretion of antimicrobial peptides from neutrophils. While platelet aggregation can be due to a variety of mechanisms in inflammatory disease, the mutual activation of platelets and neutrophils may augment host defense.

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults.

Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.

Prime and boost aerosol exposure via fog machine or shisha smoke followed by cinnamon hypersensitivity and anaphylaxis to spiced food.

BACKGROUND: Cinnamon aldehyde (alias cinnamaldehyde) is widely used in food, textile or cosmetic industry. It is mostly associated with contact allergy, but immediate type allergies have been reported. The present study was triggered by a case of anaphylactic events to cinnamon in food and upon skin prick test. We investigated a possible correlation of exposure to a disco fog machine and/or shisha consumption with immediate type hypersensitivity to cinnamon aldehyde in the patient and healthy volunteers. METHODS & RESULTS: In both fog machines and shisha pipes heating of glycerol-based fluids before evaporation renders chemical transversion to malodorous acrolein. Therefore, both methods are frequently operated with aroma additives. Cinnamon aldehyde and derivatives could be detected by gas chromatography in sampled fog flavored with cola fragrance. The patient as well as healthy (mostly female) volunteers were skin prick tested using cinnamon aldehyde diluted in 0.9 % NaCl, Vaseline® or fog fluid. Persons with a history of exposure to disco fog or shisha (n = 10, mean 32.8 years) reacted with a significantly larger wheal and flare reaction in the skin test (p = 0.0115, p = 0.0146, or p = 0.098) than the non-exposed (n = 8, mean 37.3 years). Both groups were gender matched, but differed in the mean age by 4.5 years. This reaction was specific as compared to skin reactivity to cinnamon alcohol, with only a trend to higher reactivity in exposed persons (ns). CONCLUSION: From our data we conclude that hapten fragrances such as cinnamon aldehyde may during heating in glycerol fluids associate to complete antigens and via inspiration lead to specific immediate type hypersensitivity. In some cases the hypersensitivity may be unmasked by spiced food containing cinnamon aldehyde or related chemicals, and lead to severe adverse reactions.