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Background Crohn’s disease (CD) is a chronic relapsing inflammatory disease of the gastrointestinal tract. The etiology of CD may arise from complex interactions including host genetics, diet, and the intestinal microbiome. Increased consumption of saturated fats, characteristic of the Western diet, is a known risk factor for CD. Dietary fat (DF) is absorbed by the host through the release of primary bile acids (PBAs) and bio-transformed by the microbiome into secondary bile acids (SBAs). Altogether, bile acids (BAs) can act as signaling molecules involved in host immune regulation and potentially in CD onset. Purpose To investigate the relationship between CD risk, BAs, and DF, and evaluate the predictive performance of CD onset of these factors by developing machine learning models. Method We used samples healthy first-degree relatives (FDRs) recruited as part of the Crohn’s Colitis Canada- Genes, Environment, Microbial (GEM) project. Those who developed CD (n=87) were matched 1:4 by age, sex, follow-up time, and geographic location with control FDRs remaining healthy (n=347). Serum, urine, and stool BA were measured using ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy. DF types were derived from food frequency questionnaire data. We used conditional logistic regressions to identify associations between CD onset, BAs (n=93), and DFs (n=9). We further explored the relationships of significant CD-related BAs and DF via Generalized Estimation Equations. Finally, we used a tree-based machine-learning algorithm (XGBoost) with 5-fold cross-validation to assess the prediction performance of CD onset using BA from all sources as well as DF. Two-sided p Result(s) In total, 10 of 93 BAs, and two of nine DFs were significantly associated with increased odds of CD onset (p Conclusion(s) This study suggests that BAs are associated with the pathogenesis of CD and the effects may be influenced by DF. Serum-derived BAs may be able to better predict the risk of CD than other stool or urine derived BA, while DF is not directly implicated in CD risk. Submitted on behalf of the CCC-GEM consortium. Funding Crohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III The Leona M. and Harry B. Helmsley Charitable Trust Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) Jingcheng Shao is the recipient of a Data Science Institute Summer Undergraduate Data Science award Disclosure of Interest None Declared

Background Healthy individuals within families with multiple affected members (multiplex families) with Crohn’s disease (CD) have a notably high risk of developing CD. No large prospective pre-disease cohort has assessed differences in preclinical intestinal inflammation, permeability, fecal microbiome, and genetics in healthy at-risk subjects from multiplex families. Purpose We aimed to assess differences in subclinical gut inflammation, genetic risk, gut barrier function, and fecal microbiota composition between first-degree relatives (FDRs) from families with 2 or more affected members (multiplex) and families with only one affected member (simplex). Also, we aimed to assess the risk of future CD onset in subjects from multiplex versus simplex families. Method We utilized the GEM Project cohort of healthy FDRs of CD patients. Subclinical gut inflammation was assessed using fecal calprotectin (FCP) at recruitment. Gut barrier function was assessed using the lactulose-to-mannitol ratio (LMR). For assessment of the CD-related genetic risk, CD-polygenic risk scores (CD-PRS) were calculated. Microbiome composition was assessed by sequencing fecal 16S ribosomal RNA. Generalized estimating equations logistic regression and LEfSe (PMID: 21702898) were used to assess the associations between multiplex status and different outcomes. A Cox proportional hazards model was used to assess time-related risk of future onset of CD. Result(s) 4385 subjects were included. Median age was 17 [IQR 12-24] years, 52.9% were female, 69.4% were siblings and 30.6% were offspring. 4052 (92.4%) and 333 (7.6 %) were simplex and multiplex subjects, respectively. After adjusting for age, sex, family size, and relation to proband, multiplex status was significantly associated with higher baseline FCP (p=0.038), but was not associated with either baseline LMR or CD-PRS (p=0.19 and p=0.33, respectively). We found no significant differences in alpha diversity (Shannon index) (p=0.57) between simplex and multiplex subjects. Beta diversity analysis assessed by the Bray-Curtis dissimilarity index did not reveal significant differences (R2=3e-04, p=0.607). The genera Eisenbergiella, Eggerthellaceae uncultured, and Morganella, were significantly more abundant in multiplex subjects, whereas Lachnospira, Sutterella, Lachnospiraceae_NK4A136_group, and Lachnospiraceae_UCG_004 less abundant. The risk of CD onset was significantly higher in multiplex subjects. In multivariable analysis, multiplex status at recruitment was associated with increased risk of CD onset (adjusted HR 3.41, 95% CI 1.70-6.87, p=0.00055), after adjusting for demographics, FCP, LMR, and CD-PRS. Conclusion(s) Multiplex status compared to simplex is associated with a 3.4-fold increased risk of CD onset, a higher FCP, and fecal bacterial composition. A comprehensive assessment of environmental factors that increase CD risk in multiplex families remains to be elucidated in future studies. Disclosure of Interest None Declared

Background Microbial composition-based risk score (MRS) was recently developed and validated to predict future risk of developing Crohn’s disease (CD) among healthy first-degree relatives (FDR) of CD patients. We hypothesized that stool metabolomic profiles, some of which are linked to the gut microbiome, are associated with future risk of CD. Aims To assess the association of stool metabolomic profile with onset of CD and to determine the correlation between stool metabolites and the MRS Methods Healthy FDR of CD patients were recruited as part of the nested case-control cohort of the CCC-GEM Project. Healthy FDRs who later developed CD (n=56) were matched approximately 1:1 by age, sex, follow-up duration, and geographical location with control FDRs remaining healthy (n=66). Stool metabolomics were assessed using the Metabolon’s DiscoveryHD4™ platform, and the stool microbiome characterised by 16s rDNA amplicon sequencing. We fitted a multivariable conditional logistic regression model on the disease status as a function of individual stool metabolites. We additionally performed Spearman correlation between each stool metabolite and the MRS. Results Among 1,029 stool metabolites that were analyzed, 79 were associated with future risk of CD (p Conclusions Stool metabolite profiles may predict future risk of CD. A subset of these metabolites have significant correlation with the MRS with consistent direction of effect. This may suggest that stool metabolites mediate the putative effect of the gut microbiome on CD risk. Further validation in the full GEM cohort is warranted. Funding Agencies CCC, CIHRThe Leona M. and Harry B. Helmsley Charitable Trust; Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases; Sun-Ho Lee is a recipient of the Imagine/ CIHR/CAG Fellowship Award; Sun-Ho Lee, Juan Antonio Raygoza Garay, and Williams Turpin are recipients of fellowship awards from the Department of Medicine, Mount Sinai Hospital, Toronto, Canada.

Background The recently developed TIGER endoscopy score was established to reliably describe disease severity as it can be utilized for both Ulcerative Colitis (UC) and Crohn’s disease (CD) patients.1The aim of this prospective study was to assess the TIGER score’s ability to predict UC and CD patient outcomes including biologic and steroid use. Methods A cohort of 78 patients with UC (n=40) and CD (n=38) were included in a 52-week multiple visit prospective study. Each visit included patient interviews using the IBD disk questionnaire, blood draws for C-reactive protein (CRP), and fecal calprotectin (FC). Endoscopy assessment was performed at baseline. Administration of steroids, immunomodulators (IMN), biologics, and dose escalations were recorded. Baseline total TIGER scores were dichotomized as Results At baseline, compared to patients with TIGER scores 100 both had a significantly increased likelihood of being prescribed or having to subsequently escalate biologic therapy (p Conclusion The TIGER endoscopy score demonstrates significant association with CRP, FC and IBD disk in UC and CD patients. Moreover, the TIGER endoscopy score can be utilized as a measure to predict the likelihood of UC and CD patients with moderate-to-severe disease burden requiring certain therapeutic interventions. These data suggest that the TIGER score reflects disease burden and the subsequent need for pharmacologic intervention in both UC and CD patients. 1. Zittan E, et al. J Crohns Colitis 2022;16:544-553.

Background The recently developed TIGER endoscopy score was established to reliably describe disease severity as it can be utilized for both Ulcerative Colitis (UC) and Crohn’s disease (CD) patients.1 The aim of this study was to assess the TIGER score’s ability to predict outcomes regarding complications such as surgeries, hospitalizations, and drug or disease-related side effects in a sample of both UC and CD patients. Methods A cohort of 78 patients with UC (n=40) and CD (n=38) were included in a 52-week multiple visit prospective study. Each visit included patient interviews, IBD disk questionnaire, blood draws for C-reactive protein (CRP), and fecal calprotectin (FC). Endoscopy was performed at baseline. Baseline total TIGER scores were dichotomized as Results At baseline, compared to patients with TIGER scores Conclusion The TIGER endoscopic score demonstrates significant association with CRP, FC and IBD disk in both UC and CD patients. Moreover, the TIGER score can be utilized as a measure to predict the likelihood of UC and CD patients with moderate-to-severe disease burden experiencing a disease complications. 1. Zittan E, et al. J Crohns Colitis 2022;16:544-553.

Background Several environmental factors are associated with Crohn’s disease (CD) in large case-control studies; however, it is not clear how these factors maybe be influenced by age of exposure and if they are related to alterations in pre-disease biological markers of CD risk. Purpose To investigate the association between environmental factors in different age groups with future risk of CD onset and assess their relation to other pre-disease biomarkers. Method We used an environmental risk assessment questionnaire (ERA) to collect information from healthy first-degree relatives(FDR) of CD enrolled in the CCC-GEM project. ERA was a multi-item questionnaire querying 69 questions under 7 section headings: background, cultural/ethnic, smoking history, medical history, family history, environmental history and pet history. For the environmental and pet sections, current and historical ( Result(s) A total of 4289 FDRs were recruited, 47% were male, median recruitment age was 17.0 years[6-35]. After a median follow-up of 5.6-years (IQR=3.42-8.67), 86 FDRs developed CD. Living with a dog between age 5-15 (Hazard Ratio (HR)=0.61; 95% confidence interval (CI)=0.39-0.95), and a large family size (>3) in the first year of life (HR=0.41; 95% CI=0.22-0.89) were protective against CD onset. Conversely, having a bird at time of survey (HR=2.84; CI=1.37-5.90), and having a sibling with CD (HR=2.07; 95% CI=1.18-3.63) were risk factors for CD onset. We found that owning a dog between age of 5-15 (Odd Ratio(OR)=0.77, 95% CI=0.65-0.90) was significantly associated with LMR, nine taxa bacterial and higher chao1 diversity index. Having a bird at time of survey was significantly associated with FCP (OR=2.04, 95% CI=1.33-3.11). There was no association between large family size and having a CD sibling with gut microbiome, FCP or LMR. Conclusion(s) The study identified four environmental factors associated with future development of CD. Among them, exposure to dogs during early life was protective against CD onset and might be explained by its association with normal gut permeability and microbiome. We also identified that having a bird at recruitment increased risk of CD onset which might be mediated by an increase in subclinical inflammation. Submitted on behalf of the CCC-GEM consortium Disclosure of Interest None Declared

Background The incidence of Crohn’s disease (CD) is increasing globally, indicating a significant environmental influence such as diet. A plethora of dietary adherence (DA) patterns exist in the literature: the Mediterranean Diet (MD), Empirical Dietary Inflammatory Pattern (EDIP), Specific Carbohydrate Diet (SCD), and low Fermentable Oligosaccharide, Disaccharide, Monosaccharide, or Polyol diet (FODMAP) are all potential candidates to maintain a reduced level of inflammation, improving gastrointestinal function. Contrary, the Westernized diet (WD) is generally reported as a diet promoting inflammation in humans. Purpose To determine if DA to literature-derived dietary indices in a cohort of first-degree relatives (FDRs) of CD patients can modulate pre-disease biomarkers. Method We used food frequency questionnaire (FFQ) data from 2,696 healthy FDR subjects of the Crohn’s Colitis Canada- Genes, Environment, Microbial (CCC-GEM) project. We rederived each of the following scores using our FFQ data, utilizing originally described methods for the MD, EDIP, SCD, low FODMAP, and WD to obtain DA. Each diet was correlated pairwise via Kendall’s Tau. We fit multivariable regression models to identify the association of DA (top quintile vs remaining) and: i) intestinal permeability using urinary fractional excretion of lactulose to mannitol ratio (LMR), LMR≥0.03 defined abnormal; ii) subclinical inflammation using fecal calprotectin (FCP) measured with BÜHLMANN fCAL® ELISA, FCP≥250µg/g defined inflammation; and iii) fecal microbiome richness and composition using 16S rRNA sequencing. Two-sided p Result(s) There were positive correlations between the MD, SCD, and low FODMAP, these diets negatively correlated with the WD. The EDIP negatively correlated with the SCD and low FODMAP, did not correlate with the MD, and positively correlated with the WD. No diet was associated with abnormal LMR or FCP. Only the SCD was associated with increased microbial richness (q=0.03). All diets were associated with microbial genera: the MD (n=18 taxa, (2.0-7 Conclusion(s) This study shows that literature-derived dietary indices correlate generally with each other, yet none were not associated with abnormal LMR or FCP. However, we found that diet can impact microbiome richness and composition. Thus, it is tempting to speculate that diet is a possible intervention capable of maintain microbiome homeostasis to reduce future risk of CD. Submitted on behalf of the CCC-GEM consortium. Funding Crohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III The Leona M. and Harry B. Helmsley Charitable Trust Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Disease Disclosure of Interest None Declared

Background and Aims We constructed the Toronto IBD Global Endoscopic Reporting [TIGER] score for inflammatory bowel disease [IBD]. The aim of our study was to develop and validate the TIGER score against faecal calprotectin [FC], C-reactive protein [CRP], and IBD Disk. Methods A cross-sectional study was performed among 113 adult patients (60 Crohn’s disease [CD] and 53 ulcerative colitis [UC]). In the development and usability phase, blinded IBD experts reviewed and graded ileocolonoscopy videos. In the validity phase the TIGER score was compared with: [1] the Simple endoscopic Score for CD [SES-CD] and the Mayo endoscopic score in CD and UC, respectively; [2] FC and CRP; and [3] IBD Disk. Results Inter-observer reliability of the TIGER score per segment between reviewers was excellent: interclass correlation coefficient [ICC] = 0.94 [95% CI: 0.92–0.96]. For CD patients, overall agreement per segment between SES-CD and TIGER was 91% [95% CI: 84–95] with kappa coefficient 0.77 [95% CI: 0.63–0.91]. There was a significant correlation between TIGER and CRP [p Conclusions The TIGER score is a reliable and simple novel endoscopic score that can be used for both CD and UC patients and captures full endoscopic disease burden.

Background The Mediterranean Diet (MD) is proposed to reduce the risk of Crohn’s disease (CD) onset in cohort studies, with inconsistent results. This inconsistency may be due to heterogeneity in defining MD scores. Additionally, relationships between MD compliance and intestinal permeability or sub-clinical inflammation are not defined. Aims We examined correlations between different MD scores, and determined associations between MD compliance and intestinal permeability or subclinical inflammation in a cohort of first degree relatives of CD patients. Methods We used food frequency questionnaire data from 2,112 subjects of the Crohn’s Colitis Canada- Genes, Environment, Microbial (CCC-GEM) project. We obtained 12 MD definitions from the literature and calculated daily percent compliance, we further compared MD scores via pairwise correlations (Kendall’s Tau). We measured intestinal permeability via urinary fractional excretion ratio of lactulose to mannitol (LMR) (LMR≥0.03 defined abnormal), and subclinical inflammation via fecal calprotectin (FCP) measured with BÜHLMANN fCAL® ELISA (FCP≥250 defined abnormal). We fit multivariable regression models between MD compliance and abnormal LMR and FCP, respectively. Two-sided p Results There was large variation in cross-correlations among MD scores, from nil (t=0.0, p=0.54) to highly significant (t=0.97, p Conclusions Currently MD definitions vary widely. Despite discrepancies, we expected consistent directions of effect for MD compliance on LMR or FCP. The largely non-significant associations between MDs suggest limitations in definition, interpretation, and relation to biological outcomes. Submitted on behalf of the CCC-GEM consortium. Funding Agencies CIHRCrohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III;The Leona M. and Harry B. Helmsley Charitable Trust; Justine Timpano is a recipient of a fellowship award from Mount Sinai Hospital; Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases

Background We recently developed and validated a microbial composition-based risk score (MRS) that predicts future risk of Crohn’s disease (CD) development among healthy first-degree relatives (FDR) of CD patients. We hypothesized that stool metabolomic profiles may mediate the effect of microbiome-based risk on future onset of CD. Methods Healthy FDRs of CD patients were recruited as part of the CCC-GEM Project. Stool metabolomics data were available in the nested case-control cohort (a subset of CCC-GEM cohort) whereby FDRs who later developed CD (n=56) were matched approximately 1:1 by age, sex, follow-up duration, and geographical location with control FDRs remaining healthy (n=66). Stool metabolomics were assessed using the Metabolon’s DiscoveryHD4™ platform, and the stool microbiome characterized by 16s rDNA amplicon sequencing. A multivariable conditional logistic regression model was evaluated on the disease development as a function of individual stool metabolites. Spearman correlation evaluated the rank values between stool metabolites and the MRS. Results 122 healthy FDRs (median age 15 years, 60% female) were followed for a median 5.2 years. Among 1,029 stool metabolites that were analyzed, 79 were associated with future risk of CD (p Conclusion Changes in stool metabolite profiles may predict future risk of CD. A subset of these metabolites has significant correlation with the MRS with consistent direction of effect. This may suggest that these particular stool metabolites mediate the putative effects of the gut microbiome on CD risk. Further validation in the entire GEM cohort is warranted.

Background The gut microbiome may play a role in gut barrier homeostasis including epithelial barrier integrity and function. However, data are scarce and limited to animal studies. We aimed to assess if alterations in the gut microbiome are associated with altered intestinal permeability. Methods We utilized the Genetic Environmental Microbial (CCC GEM) cohort of healthy first-degree relatives of patients with Crohn’s disease. Gut barrier function was assessed using the ratio of urinary fractional excretion of lactulose to mannitol (LMR). Stool bacterial DNA was extracted and sequenced for the V4 hypervariable region of the 16S rDNA gene using MiSeq and processed using QIIME2. PICRUSt2 was used to impute Microbial functions. In order to identify robust associations, the overall cohort was divided based on geographic region into a North American discovery cohort (n=2,472) and non-North American external validation cohort (n=655). LMR>0.025 was defined as abnormal. LMR-microbiome associations were assessed using generalized estimating equation multivariable regression model and Random Forest (RF) classifier algorithm. q Results The median age of the entire cohort was 17.0 years [IQR 12.0; 24.0], 52.6% were females and 25.4% had LMR>0.025. In the discovery cohort, subjects with LMR>0.025 had markedly reduced alpha diversity (Chao1 index, estimate= -0.0037, p=4.0e-04) and altered beta diversity (Bray-Curtis dissimilarity index, PERMANOVA: pseudo-F statistic = 2.99, p=1.0e-03). Eight bacterial genera and 52 microbial pathways were identified to be associated with LMR>0.025 (q Conclusion Gut microbiome community composition and microbial pathways are associated with gut barrier function. These findings may identify microbial targets that enhance barrier function.

Background Cannabis use in inflammatory bowel disease (IBD) may lead to improvement in pain and general health perception. However, its use during pregnancy may result in adverse outcomes such as preterm birth and altered fetal brain development. It remains unknown how women with IBD perceive Cannabis use during pregnancy and whether they discuss its use with their health-care providers. We aimed to determine practices in, and perceptions of, cannabis use during pregnancy in women with IBD of reproductive age. Methods Women with IBD (age 18–45) were recruited at Mount Sinai Hospital and via social media platforms. Participants anonymously completed surveys on baseline demographics and IBD characteristics. They also completed a Cannabis questionnaire which asked about current use, perceived risks during pregnancy, and discussions with health-care providers. Categorical variables were reported as frequencies and compared using the chi-square test. Continuous variables were reported as medians and compared using the Mann-Whitney U test. Results Sixty-four women were included, 26 (40.6%) with ulcerative colitis, 37 (57.8%) with Crohn’s disease, and 1 (1.6%) with indeterminate colitis. Nineteen (29.7%) were preconception, 40 (62.5%) were pregnant, and 5 (7.8%) were post-partum. Eleven (18.0%) patients reported current Cannabis use, 4 (6.3%) during pregnancy. Cannabis users were more likely to have discussed its use with a health-care provider compared to non-users (45.5% vs. 5.7%, p Conclusion Many women with IBD report being unsure of risks of Cannabis use during pregnancy. With the legalization of Cannabis in Canada, it is imperative patients and health-care providers discuss the risks and benefits of its use, particularly during vulnerable times such as pregnancy.

Background Patients diagnosed with inflammatory bowel disease (IBD) during childhood require transfer to an adult gastroenterologist, in Ontario usually just before their 18th birthday. Pediatric onset IBD is a complex phenotype with demonstrated noncompliance risk that may require targeted measures to optimize health care outcomes in the adult care setting. Purpose The purpose of this study was to determine the impact of posttransfer health care setting (academic versus community gastroenterologist) on emergent health resource utilization. Methods This was a population-based retrospective cohort study using health care administrative data from Ontario, Canada. A cohort of patients with Pediatric onset IBD was identified and health resource utilization during a 2-year pretransfer period, transfer of care period and 2-year posttransfer period was analyzed. Posttransfer health care setting was defined as academic (i.e., gastroenterologists providing care in a university affiliated tertiary care center) versus community. A third comparator group, loss to follow-up, was also identified. The primary outcome of this study comprised emergency department utilization. Secondary outcomes included hospitalizations, surgeries, ambulatory visits, endoscopic investigations, and radiological investigations. Results Overall, there were no significant differences found in emergency department use, ambulatory care visits (aside from the expected drop in the lost to follow-up group), hospitalizations, endoscopic procedures, or radiological procedures between exposure groups. Conclusions Posttransfer health care setting does not seem to significantly impact emergent health resource utilization in the posttransfer period.

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. The current article describes the Acceptance and Commitment Therapy (ACT) in Daily Life (ACT-DL) training, a new mobile health treatment protocol for ACT applied in a randomized controlled trial in early psychosis individuals. Between weekly ACT therapy sessions, patients fill out brief questionnaires on an app about their mood, symptoms, activity, and current context, thus promoting awareness - a crucial component of ACT. The app also provides them with visual cues and exercises specifically related to the ACT sessions, to help them implement the techniques previously learned in therapy into their daily lives. Here we assess the feasibility of this protocol in 16 early psychosis individuals, as part of an ongoing randomized controlled trial. Specifically, we investigate the experienced usefulness of the ACT therapy and app, and burden of the protocol. Results indicate that participants find both the therapy sessions and the app useful, and that ACT-DL guides them in putting ACT into everyday practice, although the protocol may be moderately burdensome. These findings indicate that ACT-DL may help early psychosis patients applying ACT skills to diverse contexts of everyday life. Since ACT is not symptom-specific, ACT-DL may also be suited for different target populations. Limitations and future directions are discussed. ispartof: PSYCHOSIS-PSYCHOLOGICAL SOCIAL AND INTEGRATIVE APPROACHES vol:11 issue:2 pages:93-104 status: published

Background Commonly used endoscopic indices in IBD lack ability to provide overall disease burden and severity, generate low inter-observer agreement, and demonstrate incomplete validation of some scores. We developed an endoscopic reporting tool, the Toronto IBD Global Endoscopic Reporting (TIGER) score for Crohn’s disease (CD) and ulcerative colitis (UC) patients. The aim of our study was to compare the usability and validity of the TIGER score against fecal calprotectin (FC), C-reactive protein (CRP) and IBD DISK score in CD patients. Methods A cohort of 60 CD patients participated in the study. Blinded IBD experts reviewed and graded ileocolonoscopy videos. In the validation phase, the TIGER score was compared to: (1) the Simple endoscopic Score for Crohn’s disease (SES-CD) as a reference standard and: (2) inflammatory biomarkers FC and CRP and (3) IBD Disk score. Results Inter-observer reliability per segment between reviewers was excellent: Interclass Correlation Coefficient (ICC)=0.94; [95%CI: 0.92–0.96]. For categorized TIGER score, lowest overall agreement was 96.6% [95%CI: 93.5–98.6] and lowest kappa 0.91 [95%CI: 0.84–0.98], reflecting excellent agreement. Overall agreement per segment between SES-CD and TIGER was 91% [95%CI: 84–95] with kappa coefficient 0.77 [95%CI: 0.63–0.91]. Per subject analysis for CD yielded overall agreement of 80% [95%CI: 64–91] and kappa coefficient 0.44 [95%CI: 0.14–0.75]. There was a significant correlation between TIGER and CRP (r s = .689, p < .0083), and TIGER and FC (r s = .687, p < .0001). In addition, there was significant correlation between TIGER and IBD Disk (r s = .613, p < .0001). Conclusion The TIGER score demonstrates significant correlation with FC, CRP and IBD disk score in Crohn’s disease patients and thus can be used as a reliable and simple endoscopic score for CD patients to capture overall endoscopic disease burden.

Background Commonly used endoscopic indices in IBD lack ability to provide overall disease burden and severity, generate low inter-observer agreement, and demonstrate incomplete validation of some scores. We developed a new endoscopic reporting tool, the Toronto IBD Global Endoscopic Reporting (TIGER) score for Crohn’s disease (CD) and ulcerative colitis (UC) patients. The aim of our study was to compare the usability and validity of the TIGER score against fecal calprotectin (FC), C-reactive protein (CRP) and IBD DISK score in UC patients. Methods A cohort of 53 UC patients participated in the study. Blinded IBD experts reviewed and graded ileocolonoscopy videos. In the validation phase, the TIGER score was compared to (1) the Mayo endoscopic score serving as a reference standard and; (2) inflammatory biomarkers FC, CRP and; (3) IBD Disk. Results Inter-observer reliability of the TIGER score per segment between reviewers was excellent, Interclass Correlation Coefficient (ICC)=0.94; [95%CI: 0.92–0.96]. For categorized TIGER score, lowest overall agreement was 96.6% [95%CI: 93.5–98.6] and lowest kappa 0.91 [95%CI: 0.84–0.98], reflecting excellent agreement. Overall agreement per segment between Mayo endoscopic score and TIGER was 84% [95%CI:74%-90%] and kappa coefficient 0.60 [95%CI: 0.42–0.808]. Per subject analysis for UC yielded overall agreement of 80% [95%CI: 64–91] and kappa coefficient 0.44 [95%CI: 0.14–0.75]. There was a significant correlation between TIGER and FC (r s = .794, p < .0001). There was a significant correlation between TIGER and IBD Disk (r s = .613, p < .0001). As expected, there was a lower correlation between TIGER score and CRP (r s = .309, p < .0850) in UC patients. Conclusion The TIGER endoscopic score demonstrates significant correlation with FC and IBD disk score in ulcerative colitis patients and thus can be used as a reliable and simple endoscopic score for UC patients to capture overall endoscopic disease burden.

In this paper, a self-adaptive resonance frequency tracking method is presented. The resonance frequency tracking is used in a LCL-filter-based active power filter to adapt the frequency of the notch filter applied for active resonance damping. By determining the resonance frequency of the LCL-filter and adapting the notch filter frequency, the bandwidth of the notch filter can be decreased, whereby the dynamic performance of the current control loop is increased. The notch filter frequency is adapted to the resonance frequency by a PI controller using the frequency depending difference in the attenuation of two band-pass filters which are kept equidistant below and above the notch filter frequency. At this, the symmetrical attenuation of both band-pass filters in the frequency range between them is used.

BACKGROUND: Ectopic varices (EV) account for 5% of variceal bleeding. Anastomotic varices (AV) are a rare form of EV that have been predominantly described in small bowel. To our knowledge colorectal AV have not been described. We describe a case of colorectal AV hemorrhage in a patient with portal hypertension (PH) treated with endoscopic band ligation (EBL). AIMS: To gain insight into the incidence, location and optimal treatment of AV. METHODS: Case report and literature review. RESULTS: CASE REPORT: A 63 year old woman with alcoholic cirrhosis presented with recurrent lower GI bleeding (LGIB) 2 years following sigmoid resection and primary colorectal anastomosis for colorectal cancer. Colonoscopy demonstrated anastomotic neovascularization with prominent submucosal vessels suggestive of varices, without high risk stigmata. Her symptoms resolved without intervention. She returned 5 weeks later with recurrent LGIB; sigmoidoscopy revealed AV with stigmata of recent hemorrhage successfully managed with single EBL. The next episode of LGIB occurred over 2 years later; colonoscopy revealed AV with visible erosions treated with EBL. She attended subsequent EBL sessions until variceal extinction. After several months, she presented on 3 occasions over a 2-month period for LGIB in the context of alcohol binges. AV with erosions were visualized at each episode, however there was no active bleeding or endoscopic intervention. LITERATURE REVIEW: A PubMed and Cochrane Database of Systematic Reviews search produced publications describing varices at surgical sites, most of which were peristomal. There were 4 cases of esophagojejunal AV, 13 cases of gastroduodenal AV, and 3 cases of jejunal varices after hepatico- or choledochojejunostomy. The most distal anastomosis reported was a case series of 10 patients with PH who underwent ileal pouch-anal anastomosis; none developed pouch variceal bleeding. The lack of colonic variceal involvement, particularly of the descending and sigmoid colon, may relate to their anatomical distance from, and indirect drainage to, the portal vein, resulting in indirect transmission of venous pressure. Management of AV is controversial. Endoscopic intervention with N-butyl-2-cyanoacrylate is efficacious in small bowel AV. Transjugular intrahepatic portosystemic shunt and percutaneous transhepatic obliteration is beneficial in EV. Surgical resection or transcatheter embolization can be effective, however perioperative morbidity and mortality is high. To our knowledge, EBL for colorectal AV has not been described. This treatment modality appears to be useful for temporary hemostasis but rebleeding rates appear to be high. CONCLUSIONS: A case report of colorectal AV is presented. EBL achieved temporary hemostasis but rebleeding rates were high. FUNDING AGENCIES: None

In this paper, a model based predictive current control scheme for active power filters is presented. The proposed method is based on common control schemes, but is only related with a low computational effort. For the predictive control, an inverse model of the voltage source inverter is used. For calculating the inverse model, a future value of the reference current is needed. In the steady state, the load current and thereby the reference current are periodic with the fundamental period, meaning that a future value is equal to a corresponding past value. Thus, this past value can be used. The proposed method is applied to a three-phase four-wire system with control in natural frame and to a three-phase three-wire system with control in the synchronous dq frame. With focus on the predictive control, the general advantages and disadvantages of the different setups are discussed. Simulation and measurement results compensating the distortion current of a non-linear load are presented and the performance of both setups is compared.

Summary Background Clostridium difficile colitis (CDC) is associated with an increased short-term mortality risk in hospitalised ulcerative colitis (UC) patients. We sought to determine whether CDC also impacts long-term risks of adverse health events in this population. Aim To determine whether CDC also impacts long-term risks of adverse health events in this population. Methods A population-based retrospective cohort study was conducted of UC patients hospitalised in Ontario, Canada between 2002 and 2008. Patients with and without CDC were compared on the rates of adverse health events. The primary outcomes were the 5-year adjusted risks of colectomy and death. Results Among 181 patients with CDC and 1835 patients without CDC, the 5-year cumulative colectomy rates were 44% and 33% (P = 0.0052) and the 5-year cumulative mortality rates were 27% and 14% (P

Antibodies to infliximab reduce serum infliximab with loss of clinical benefit, but undetectable trough serum concentrations of infliximab may occur without antibody formation. The relationship between trough serum infliximab and clinical outcomes was evaluated in acute ulcerative colitis.In a cohort of 115 patients with ulcerative colitis treated with three-dose induction followed by scheduled maintenance infliximab, rates of clinical remission, colectomy, antibodies to infliximab and trough serum infliximab were determined.Rates of remission were 32% at week 10 and 37% at week 54. Colectomy occurred in 40% of patients, at a median of 5.3 (IQR 1.9-12.1) months. Detectable trough serum infliximab was present in 39% of patients and, among patients with undetectable infliximab, 41% were antibody positive and 20% were antibody negative. For antibody-positive and antibody-negative patients, rates of remission (18% vs 14%), endoscopic improvement (25% vs 35%) and colectomy (52% vs 59%) were not different. A detectable serum infliximab was associated with higher rates of remission (69% vs 15%; p0.001) and endoscopic improvement (76% vs 28%, p0.001). An undetectable serum infliximab predicted an increased risk for colectomy (55% vs 7%, OR 9.3; 95% CI 2.9 to 29.9; p0.001). Concurrent immunosuppression was not associated with clinical outcomes.For patients with ulcerative colitis treated with infliximab, a detectable trough serum infliximab predicts clinical remission, endoscopic improvement and a lower risk for colectomy. An undetectable trough serum infliximab, irrespective of antibody status, is associated with less favourable outcomes.

Colorectal cancer is one of the most common cancers in the western world. Its early detection has been found to improve the prognosis of the patient, providing a wide window of opportunity for successful therapeutic interventions. However, current diagnostic techniques all have some limitations; there is a need to develop a better technique for routine screening purposes. We present a new methodology based on magnetic resonance spectroscopy of fecal extracts for the non-invasive detection of colorectal cancer. Five hundred twenty-three human subjects (412 with no colonic neoplasia and 111 with colorectal cancer, who were scheduled for colonoscopy or surgery) were recruited to donate a single sample of stool. One-dimensional (1)H magnetic resonance spectroscopy (MRS) experiments were performed on the supernatant of aqueous dispersions of the stool samples. Using a statistical classification strategy, several multivariate classifiers were developed. Applying the preprocessing, feature selection and classifier development stages of the Statistical Classification Strategy led to approximately 87% average balanced sensitivity and specificity for both training and monitoring sets, improving to approximately 92% when only crisp results, i.e. class assignment probabilities > or =75%, are considered. These results indicate that (1)H magnetic resonance spectroscopy of human fecal extracts, combined with appropriate data analysis methodology, has the potential to detect colorectal neoplasia accurately and reliably, and could be a useful addition to the current screening tools.

The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors (TLR), are critical to the host/pathogen interaction and have been implicated in IBD pathophysiology. To explore the association of genetic variation in TLR pathways with susceptibility to IBD, we performed a replication study and pooled analyses of the putative IBD risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for association to IBD in the TLR genes and a selection of their adaptor and signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of 4805 cases of IBD validates the published association of a TLR4 allele with risk of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15 - 1.48; P = 0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16 - 1.54; P = 0.000035) but not ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR: 1.16, 95% CI: 1.04 - 1.30; P = 0.007) has a modest effect on risk of IBD. Our analysis, therefore, offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to IBD. ispartof: Genes and immunity vol:8 issue:5 pages:387-397 ispartof: location:England status: published

Summary Aim To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release mesalazines in maintaining medically and surgically induced Crohn’s disease remission. Methods A systematic search identified 13 randomized controlled trials (RCTs). The rate of symptomatic relapse (Crohn’s disease activity index >150, or an increase in baseline by at least 60–100 points) was extracted from each randomized controlled trial. Pooled odds ratios (OR), the number needed to treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were calculated. Results Treatment with pH 7-dependent mesalazine significantly reduced the risk of relapse in patients with either surgically [OR 0.28; 95% confidence interval (CI) 0.12–0.65; P = 0.0032] or medically induced remission (OR 0.38; 95% CI 0.17–0.85; P = 0.0113). However, treatment with controlled-release mesalazine and pH 6-dependent mesalazine failed to show any significant advantage over placebo. The NNT to maintain surgically or medically induced remission was lowest for pH 7-dependent mesalazine (NNT = 4 and 5, respectively; NNT = 15 and 16 for controlled-release mesalazine and NNT = 11 and 23 for pH 6-dependent mesalazine). Therapeutic benefit was highest for pH 7-dependent mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9% (surgical) and 6.4% (medical) for controlled-release mesalazine, and 9.8% and 4.4%, respectively, for pH 6-dependent mesalazine. Conclusion Further trials of pH 7-dependent mesalazine formulations are warranted in the maintenance of remission in Crohn’s disease.

In recent years computer-navigation systems have been commonly used in the field of otorhinolaryngology. Taking its limitations and possible failures into account, this technology is considered reasonable and helpful in routine paranasal sinus surgery, particularly in revision cases and complex approaches to the lateral skull base. We report on a patient with a large recurrent craniopharyngioma, and show that the use of intraoperative navigation might even be necessary to accomplish the desired postoperative outcome in certain cases. Future developments will demonstrate whether computer assisted surgery can extend the indications for operative procedures in complex anatomical regions.

Schwere Komplikationen der endoskopischen Chirurgie der Nasennebenhohlen (NNH) haben haufig fatale Folgen fur die Patienten. Verletzungen des N. opticus oder der A. carotis interna treten v. a.bei Perforationen der Keilbeinhohlenvorderwand auf. Das Robotersystem „A 73“ wurde mit einem 4-Kanal-Mikroendoskop und speziellen Instrumenten nach vorheriger Programmierung vollautomatisiert zur Eroffnung der Keilbeinhohlenvorderwand bei 5 anatomischen Praparaten eingesetzt. In allen Fallen konnte die Keilbeinhohlenvorderwand ohne Verletzung benachbarter Strukturen durch den Roboter vollautomatisiert eroffnet werden. Der Zugang wurde anschliesend uber den Telemanipulationsmodus endoskopisch kontrolliert auf den gewunschten Durchmesser erweitert. Die Analyse des Transformationsfehlers und der intraoperativen Genauigkeit ergab Werte im Submillimeterbereich. Mit einem neu entwickelten Robotersystem gelingt die vollautomatisierte Eroffung der Keilbeinhohle prazise und reproduzierbar. Der geschaffene Zugang lasst sich uber einen Telemanipulationsmodus erweitern.

The applicability of a robotic system for fully automated surgical procedures approaching the sphenoid sinus is evaluated. An integrated robotic system, A73, for computer navigation-guided, fully automated, and telemanipulation robotic performance is described. Details of the system comprising newly designed surgical instruments for robotic operations and preoperative planning protocols are provided. Experiments with an operational accuracy of less than 1 mm were followed by surgical tests, in which the results of fully automated and telemanipulation performances on 5 cadaveric heads are seen. The A73 system has been successfully used for a reproducible and accurate resection of the anterior wall of the sphenoid sinus. Therefore, we conclude that this system is suited for further testing toward approaching fully automated and more complex procedures of paranasal surgery.

Schwannome des N. facialis im inneren Gehorgang sind seltene Tumoren. Anhand einer retrospektiven Studie sollte die Klinik dieser gutartigen Tumoren analysiert werden. Von 1975 bis 2001 wurde 17-mal ein Schwannom des N. facialis im inneren Gehorgang diagnostiziert. Der Zugang erfolgte in 16 Fallen uber die mittlere Schadelgrube, einmal translabyrinthar. Bei 11 Patienten blieb die Kontinuitat des N. facialis erhalten; in 6 Fallen war ein Nervinterponat erforderlich. In zehn Fallen resultierte eine zufriedenstellende postoperative Funktion. Zu Beginn des Analysezeitraumes uberwogen periphere Fazialisparesen, spater Horstorungen und Tinnitus. Die Kernspintomographie ermoglicht es im Einzelfall, Schwannome des N. facialis von anderen Tumoren des inneren Gehorganges zu differenzieren. Auch die elektrophysiologische Diagnostik kann Hinweise auf ein Schwannom des N. facialis geben. Dadurch kann die Therapie mit den Patienten differenziert besprochen werden.

The objective of the present study is to assess the potential of color Doppler sonography in imaging tumors of the parotid gland enhanced by application of ultrasound contrast agents. To this end 26 patients with tumors of the parotid gland were investigated. The color Doppler signal areas before and after administration of Doppler signal-enhancing agent (Levovist, Schering, Germany) were determined by means of computer-assisted analysis, and the relevant parameters were evaluated. The tumors can be classified as follows: 11 pleomorphic adenomas, 8 adenolymphomas and two squamous cell carcinomas of the parotid gland, two lymph nodes, one adenoma, one neurinoma of the facial nerve and one non-Hodgkin's lymphoma. Before the administration of Doppler signal-enhancing agent, the adenolymphomas showed a significantly stronger Doppler signal area as compared to the pleomorphic adenomas. The maximum color Doppler signal area after administration of Doppler signal-enhancing agent showed no difference within both groups. If one considers the relative change in the Doppler signal area before and after applying enhancing agent, however, a significantly stronger enhancement of perfusion (increase in Doppler signal area) is noted within pleomorphic adenomas. The changes in the Doppler signal area after administration of signal-enhancing agent show a different course depending on the histology of the investigated tumors.

A novel integrated robotic system for computer navigation guided fully automated as well as telemanipulation robotic surgery is introduced. Furthermore, the clinical applicability of the robot system regarding fully automated surgical procedures approaching the sphenoid sinus is evaluated. Details of the system comprising newly designed surgical instruments for robotic operations and preoperative planning protocols are provided. Preliminary trials describing the operational accuracy were followed by preclinical test, in which the results of fully automated and telemanipulation performances on anatomical heads are shown. The robot system has been successfully used for a reproducible and accurate resection of the sphenoid sinus' anterior wall. Therefore, we conclude that this system seems suited for a further clinical use in paranasal surgery.

This paper examines the safety and feasibility of providing short-term, in-home total parenteral nutrition (TPN) for patients with inflammatory bowel disease (IBD) for whom the alternative is prolonged hospitalization or early surgery. The records of all patients with IBD who were receiving temporary home TPN between June 1996 and July 2000 were reviewed. A quality-of-life phone interview was conducted at the time of review. Fifteen patients (11 men and 4 women) were identified whose average age was 35 years. The underlying diagnosis was Crohn's disease in 10 and ulcerative colitis in five. The indications for home TPN were complex internal fistulas and resolving sepsis in two, postoperative septic complications (anastomotic leak/enterocutaneous fistula) in five, high-output proximal stomas in four, prolonged ileus/partial obstruction in three, and spontaneous enterocutaneous fistula in one. The average duration of home TPN was 75 days (range 7 to 240 days). Two patients (13%) failed home TPN (1 with uncontrolled sepsis; 1 with dehydration) and were readmitted to the hospital. Home TPN was discontinued in one patient whose enterocutaneous fistula failed to heal with nonoperative treatment. Home TPN was successful in 12 patients (80%): eight (53%) who underwent planned definitive surgery and four (27%) whose conditions resolved without surgery. Complications of home TPN were line sepsis and pulmonary aspergillosis in one patient. All patients preferred home TPN to further hospitalization and reported good or excellent quality of life at home. Home TPN is a safe alternative to prolonged hospitalization or early surgery in patients with complicated IBD.

BACKGROUND Sporadic vestibular schwannoma show a wide variability of their growth rate. Some tumors might remain quiescent for a long time without symptoms and other tumors might suddenly enlarge. Sometimes during surgical removal of tumors, it is useful to have a parameter for the prediction of the further growth potential of the schwannoma, especially if tumor resection results in functional impairment of the facial nerve. An often used histological parameter for growth rate of tumor cells is the proliferation index. METHODS AND PATIENTS In our study we observed a series of 50 patients with neurinoma of the vestibular nerve by "wait and scan". After the first magnetic resonance imaging (MRI) all patients were controlled by a second MRI. The time between the MRIs ranged between 3 and 26 months (median 9). In 45 of 50 patients a surgical removal of the tumor by transtemporal approach followed. RESULTS The proliferation index (Ki-67) was identified in the histological tumor specimens. The next step was the correlation of proliferation index and "tumor doubling time" (TDT). The volume of the tumors was provided by measuring three diameters of the tumors in MRI and calculating the volume with a formula. The volume of the tumors were used to calculate tumor growth and TDT. 10 patients showed no tumor growth during follow up. The average TDT in 40 cases was 22 months (SD 16). In 33 cases we were able to determine a proliferation index, which showed an average score of 1.99 %. Statistical analysis showed a correlation between proliferation index and TDT with a coefficient of - 0.42 (s: 0.014). In two cases with relevant clinical tumor growth (TDT: 12 months), the MIB-1 index was nearly 0 % in different areas of the tumor specimen. May be in these cases, the cell proliferation declined just before operation. On the other hand we found one patient with a high proliferation index of 3.3 % and a rather long TDT of 19 months. CONCLUSIONS The determination of proliferation can serve as a further decision guidance during surgery of vestibular schwannoma.

The excision of tumors of the pituitary gland is usually achieved via a transsphenoidal transnasal approach. In the past, alternative approaches were described for macroadenomas. Especially in tumors surrounding the internal carotid artery (ICA) and the optic nerve, the selection of the appropriate approach is of importance. We demonstrate the case of a second extensive relapse of a macroadenoma after primary transsphenoidal resection and radiation therapy. As the tumor enclosed both the ICA and left optic nerve, a median external approach via the upper midface was chosen. After the median skin incision and translocation of the upper parts of the nasal structure, the papyraceous lamina was removed bilaterally. The orbital tissue was laterally exposed with retractors, achieving a wide access to both carotids and optic nerves. The functional and aesthetic results were satisfactory. Compared with other approaches, this one provides a good exposure of both the ICA and optic nerve.

Purpose : To address the value of neck dissection (ND) in patients with advanced head and neck cancer following primary radiochemotherapy and to specifically analyse its impact on locoregional tumour control, survival and toxicity. Patients and methods : Between 1987 and 1997 (9335), a total of 142 patients (pts) were treated by primary radiochemotherapy (RCT) according to prospective protocols. There were 64 pts with involvement of the hypopharynx, 57 pts with oropharyngeal and 21 with oral cavity carcinoma. UICC (1997) stages included: 16 pts in stage III, 113 pts in stage IV A, 13 pts in stage IV B. All pts received platin-based RCT up to a median total dose of 70Gy (range, 60–72Gy). Six weeks after RCT, pts with complete response of the primary tumour ( N =97) were offered a uni- or bilateral ND depending on the initially diagnosed nodal disease as part of a strict institutional policy. Fifty-six pts consented to ND and 41 refused. These two groups were analysed in terms of characteristics, local and regional tumour control, survival and long-term side effects. Median follow-up was 37 months (range, 22–124 months). Results : Among the 56 pts receiving ND, a total of 13 (23%) was found to have residual tumour in the neck specimen. The rates of positive histology according to clinical N category after RCT were: yN0 (2/22[9%]), yN1 (2/10[20%]), yN2a-b (2/10[20%), yN2c-3 (7/14[54%]). Five-year overall survival and disease-specific survival rates for pts with ND were 44 and 55%, for pts without ND 42 and 47%, respectively ( P =0.9). No difference was seen for long-term local and regional control between the two patient groups. Comparing the group of patients with and without ND, a trend towards higher subjective morbidity of grade 3 and 4 (LENT-SOMA), i.e. pain recording (24% vs. 17%), dysphagia (48% vs. 35%) and hoarseness (20% vs. 9%) was evident in patients with ND. Conclusion : No clear evidence for routine clinical use of ND after RCT in advanced head and neck tumours can be derived from these data. ND may be contemplated in selected cases with multiple residual nodes only.

Colorectal cancer (CRC) occurs with an increased incidence in individuals with chronic inflammatory bowel disease (IBD) of the colon. Recent data suggest that a family history of colorectal cancer is an independent risk factor for CRC in IBD, an observation that implies that genetic factors are relevant to the development of CRC in this context. Among the genetic defects associated with CRC, the APC I1307K mutation has been detected nearly exclusively in individuals of Ashkenazi Jewish (AJ) origin, occurring in 6%-7% of the AJ general population and in 10%-28% of AJ with a either a personal or family history of CRC or adenomatous polyps. These findings, together with the increased incidence of IBD in AJ, prompted the current analysis of the contribution of the APC I1307K variant of CRC in AJ IBD patients. APC I1307K carrier frequencies were determined in 306 AJ individuals affected with IBD and 308 of their unaffected relatives ascertained from a family collection obtained for the identification of IBD susceptibility genes. Prevalence of the I1307K variant was not significantly different among individuals with IBD, Crohn's disease, ulcerative colitis, and unaffected relatives (6.9%, 7.6%, 4.7%, and 6.2%, respectively), and the mutation was detected in only one of five IBD-affected individuals with a diagnosis of CRC. These results reveal that IBD patients of AJ origin carry the APC I1307K variant at the same rate as individuals within the general AJ population. Lack of an increased APC I1307K carrier rate suggests that this mutation does not account for the increased CRC susceptibility associated with IBD.

Hintergrund und Fragestellung. Ein kombinierter Ho:YAG-/Nd-YAG-Laser bietet Laserlicht mit schneidenden und koagulierenden Eigenschaften, wie es getrennt von den in der HNO-Heilkunde etablierten CO2- und Nd:YAG-Lasern bereitgestellt wird. Ein solches, theoretisch vielversprechendes System wurde gepruft. Patienten und Methodik. Mit einem Ho:YAG-/Nd:YAG-Kombinationslaser wurden in vitro an Gewebe von Schweinen Schnittversuche durchgefuhrt. Klinisch wurde bei einzelnen enoralen Operationen die praktische Anwendbarkeit des Kombinationsbetriebs uberpruft. Ergebnisse. Beim Einsatz des Ho:YAG-Lasers kam es zum explosionsartigen Aufreisen des Gewebes mit Versprengung von Gewebepartikeln. Durch Zuschalten des Nd:YAG-Lasers wurde die Koagulationszone vergrosert. Klinisch zeigte sich der Laser bei den Operationen den etablierten Techniken unterlegen. Schlussfolgerungen. Im Vergleich zum etablierten CO2-Laser zeigten sich bis auf die Moglichkeit der flexiblen Faserleitung kaum Vorteile des Ho:YAG-Lasers. Das Versprengen von Gewebe und die breite Schnittspur sind besonders onkologisch bedenklich. Soweit ist der klinische Stellenwert im HNO-Fachgebiet als gering einzustufen.

Hintergrund und Fragestellung. Die Vorhersage des Ortes der Obstruktion oder des Weichteilkollapses bei Patienten mit primarem Schnarchen und obstruktivem Schlafapnoesyndrom war in den letzten Jahren haufig Thema von Untersuchungen. Die flexible Nasopharyngolaryngoskopie im Schlaf oder in Sedierung ist in diesem Zusammenhang eine bekannte Untersuchungsmethode, trotz ihrer nichtphysiologischen Basis. Patienten/Methodik. Die Ergebnisse von 324 Patienten, die neben der Routinediagnostik im Schlaflabor mittels einer flexiblen Pharyngolaryngoskopie im Wachzustand und in Propofol-Sedierung untersucht wurden, werden beschrieben. Hierbei werden Vergleiche zum Muller-Manover und zu den jeweiligen Polysomnographieergebnissen angestellt und die therapeutische Konsequenz dieser Zusatzdiagnostik diskutiert. Ergebnisse. In 95% der Falle konnte wahrend des medikamentos induzierten Schlafs Schnarchen registriert werden. Auf Hohe des Zungengrunds fand sich eine signifikant starkere Kollapsneigung bei der Untersuchung im Propofol-Schlaf verglichen mit den Befunden des Muller-Manovers. Die Starke des Zungengrundkollapses korrelierte mit dem in der Polysomnographie ermittelten RDI (respiratory disturbance index). Schlussfolgerungen. Insgesamt fand sich ein deutlicher Unterschied zwischen der Auspragung des Weichteilkollapses beim Muller-Manover und beim Propofol-Schlaf; Schnarchen und Kollapsneigung liesen sich zuverlassig beobachten. Die Pharyngolaryngoskopie erwies sich als einfach und sicher durchfuhrbare, komplikationsarme und aussagekraftige Zusatzdiagnostik im Rahmen der Abklarung des primaren Schnarchens und des obstruktivem Schlafapnoesyndrom.

Hintergrund und Fragestellung. Der Therapieerfolg einer nCPAP-Therapie (“nasal continuous positive airway pressure”) ist einerseits abhangig von der Linderung der Beschwerden und andererseits von der Langzeitakzeptanz und der hiermit verbundenen Vermeidung von Komplikationen. Nasale Beschwerden sind die haufigsten Nebenwirkungen und neben den Maskenproblemen die wichtigste Ursache, weshalb eine nCPAP-Therapie fruhzeitig unterbrochen wird. Patienten/Methodik. Wir haben bei 12 Patienten mit einem obstruktivem Schlafapnoesyndrom Probeexzisionen aus der Nasenschleimhaut vor und 3–10 Monate nach Anpasssung der nCPAP-Maske entnommen und elektronenmikroskopisch untersucht. Bei all diesen Patienten war die Anpassung der nCPAP-Maske die Ersttherapie. Daruber hinaus wurde vor und nach der Therapie die mukoziliare Clearance mit Hilfe des Saccharintests beurteilt. Ergebnisse. Bei allen Patienten kam es nach der nCPAP-Therapie zur grundlegenden Veranderungen des Nasenepithels mit Veranderung der Epithelzellenform, Verklebungen und Verklumpungen der Mikrovilli und auftreten von immunkompetenten Zellen. In allen Fallen war die mukoziliare Clearance nach Anpassung der nCPAP-Maske deutlich verlangert. Schlussfolgerungen. Ein erfolgreiches Therapiekonzept sollte die Normalisierung der Raumtemperatur und Luftfeuchtigkeit gleich nach der Anpassung der nCPAP-Maske und die regelmasige Beurteilung der Schleimhautverhaltnisse der oberen Atemwege beinhalten. Nur somit konnen nasale Komplikationen aufgehalten oder fruhzeitig therapiert werden.

Eine 36 Jahre alte Patientin stellte sich mit einem ausgedehnten Tumor der rechten Nasenhohle und des rechten Nasenrachens vor. Die histologische Untersuchung ergab ein undifferenziertes Plattenepithelkarzinom. Sowohl mit Hilfe der computertomographischen, als auch der kernspintomographischen Befunde, war keine eindeutige Bestimmung der Primartumorregion moglich. Anhand der bekannten Assoziation zwischen Karzinomen des Nasenrachens und Epstein-Barr Virus (EBV) wurde versucht, die Primarlokalisation des Tumors zu klaren. Immunhistologisch und durch „polymerase chain reaction” war es moglich, eine EBV-Infektion im Tumor nachzuweisen. Die Primarlokalisation des Tumors wurde damit dem Nasenrachen zugeordnet und die entsprechende Therapie fur diese Lokalisation in Form einer simultanen Radiochemotherapie eingeleitet.

Druckveranderungen des Mittelohrs mit vorubergehender Horminderung zahlen zu den Begleiterscheinungen von Ohroperationen, insbesondere im Zusammenhang mit der Verwendung von Lachgas oder positiver Beatmungsdrucke wahrend Maskenbeatmung im Rahmen der Narkose. Ein akuter sensorineuraler Horverlust ist eine bekannte Komplikation nach Spinalanasthesien oder kardiopulmonalen Operationen. Es sind allerdings nur sehr wenige Falle mit einer Innenohrschwerhorigkeit bzw. Taubheit nach nicht otochirurgischen Eingriffen in Intubationsnarkose und bei Patienten ohne otologische Vorerkrankungen beschrieben. Wir berichten von einem Patienten mit postoperativer Surditas und sensorineuraler Schwerhorigkeit in der Folge einer Leistenhernienoperation in balancierter Anasthesie. Nach Durchsicht der Literatur werden mogliche Ursachen und Faktoren dieses postoperativen Horverlusts diskutiert.

Bei der chirurgischen Entfernung von ausgedehnten Karzinomen der hypopharyngealen Rachenhinterwand stellt sich die Frage der Kehlkopfentfernung in erster Linie aus funktionellen Grunden. Zwischen 1994 und 1997 wurde allen Patienten mit einem Rachenhinterwandkarzinom des Hypopharynx und einer geschatzten Tumorausdehnung von mehr als 6 cm ein kehlkopferhaltendes chirurgisches Behandlungskonzept vorgeschlagen. Bei 9 Patienten mit T2 (n=2) und T4 (n=7) Karzinomen erfolgte nach lateraler Pharyngotomie eine Rekonstruktion der Rachenhinterwand mit freien Lappen (8 Unterarmlappen und 1 Dunndarmtransplantat). Die maximalen Tumorausdehnungen reichten von 6,5–12,5 cm. Bei der Praparation wurde versucht, den N. laryngeus superior zu erhalten und bei der Einnaht der freien Lappen fand die exakte Anpassung des Lappens an den Defekt besondere Beachtung. Bei 7 Patienten war innerhalb von 3 Monaten die Schluckfunktion so wiederhergestellt, das die Ernahrung oral erfolgen konnte. Ein Patient benotigte hierzu 4 Monate und ein Patient war 12 Monate postoperativ aufgrund von Aspirationen weiterhin nicht zur ausreichenden oralen Nahrungsaufnahme fahig, 6 Patienten wurden bisher dekanuliert und in keinem Fall war in der Beobachtungszeit eine Laryngektomie aufgrund von Komplikationen oder auf Wunsch des Patienten erforderlich. Die funktionelle Rehabilitation nach der Entfernung ausgedehnter Rachenhinterwandkarzinome gelingt mit Hilfe von freien Lappen bei einem Grosteil der Patienten.