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Berlin, Germany

Seifarth C.,Charite - Medical University of Berlin | Ritz J.-P.,Helios Kliniken | Kroesen A.,Medical Center Porz am Rhein | Buhr H.J.,Charite - Medical University of Berlin | Groene J.,Charite - Medical University of Berlin
Surgical Endoscopy | Year: 2014

Background Laparoscopic interventions to minimize access trauma are increasingly gaining importance for both cosmetic reasons and lower postoperative morbidity. The aim of this study was to compare the clinical outcomes for different laparoscopic colectomy and proctocolectomy accesses considering IBD. A comparison was made between total laparoscopic (LR)-without an extra incision for sample -and laparoscopic-assisted resection using a small incision for retrieval of the specimen (LAR) Patients and methods From 2006 to 2012, 109 IBD patients underwent minimal invasive total colectomy or proctocolectomy. Patients were subdivided according to access into LR and LAR. Perioperative outcomes were evaluated. Results 86 patients with Ulcerative Colitis (UC) and 23 with Crohn's disease (CD) were included (LR: 64 UC/13 CD, LAR: 22 UC/10 CD). Among them, there were no differences in age, BMI, sex, ASA score or pre-existing immunosuppression. Patients with LR and UC had a higher disease activity score (Truelove III LR: 42 %, LAR: 5 %; p = 0.005). The Crohn's Disease Activity Index did not differ. Patients with LR had a shorter operating time (LR: 211.5, LAR: 240 min; p = 0.002). There was no significant difference in hospital stay (LR: 11, LAR: 12.5 days; p ≥ 0.05), length of stay at the ICU (both 1 days; p ≥ 0.05), duration of required analgesia (LR: 7 days, LAR: 8 days; p ≥ 0.05), and nutritional build-up (both 5 days; p ≥ 0.05). Groups had the same overall complication rate, but surgical site infection rates tended to be higher in patients with LAR (LR: 9.1 %, LAR: 21.9 %, p = 0.07). Discussion Laparoscopic procedures for colectomy and proctocolectomy are safe and effective techniques for patients with colon involvement and IBD. Minimizing the access trauma in laparoscopic colectomy offers a potential advantage of reduced surgical site infections, especially for frequently immunosuppressed IBD patients. © 2014 Springer Science+Business Media New York.

Langhans B.,University of Bonn | Kramer B.,University of Bonn | Louis M.,University of Bonn | Nischalke H.D.,University of Bonn | And 9 more authors.
Journal of Hepatology | Year: 2013

Background & Aims Regulatory CD4+ T cells (Tregs) are considered to affect outcomes of HCV infection, because they increase in number during chronic hepatitis C and can suppress T-cell functions. Methods Using microarray analysis, in situ immunofluorescence, ELISA, and flowcytometry, we characterised functional differentiation and localisation of adaptive Tregs in patients with chronic hepatitis C. Results We found substantial upregulation of IL-8 in Foxp3+CD4+ Tregs from chronic hepatitis C. Activated GARP-positive IL-8+ Tregs were particularly enriched in livers of patients with chronic hepatitis C in close proximity to areas of fibrosis and their numbers were correlated with the stage of fibrosis. Moreover, Tregs induced upregulation of profibrogenic markers TIMP1, MMP2, TGF-beta1, alpha-SMA, collagen, and CCL2 in primary human hepatic stellate cells (HSC). HSC activation, but not Treg suppressor function, was blocked by adding a neutralizing IL-8 antibody. Conclusions Our studies identified Foxp3 +CD4+ Tregs as an additional intrahepatic source of IL-8 in chronic hepatitis C acting on HSC. Thus, Foxp3+CD4+ Tregs in chronic hepatitis C have acquired differentiation as regulators of fibrogenesis in addition to suppressing local immune responses. © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Wedekind D.,University of Gottingen | Broocks A.,Helios Kliniken | Weiss N.,University of Gottingen | Engel K.,University of Gottingen | And 2 more authors.
World Journal of Biological Psychiatry | Year: 2010

Objectives. Regular aerobic exercise (running) has been shown to be superior to a pill placebo in the treatment of panic disorder. Combined drug and exercise treatment has not been investigated in randomized controlled studies to date. Methods. This is a randomized, 10-week, controlled, parallel group, pilot study. A total of 75 outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10) received either (1) exercise plus paroxetine 40 mg/day (n=21), (2) relaxation plus paroxetine (n=17), (3) exercise plus pill placebo (n=20), or (4) relaxation plus pill placebo (n=17). Changes in the Panic and Agoraphobia Scale (P&A), and the Clinical Global Impression Scale (CGI) underwent repeated measure analysis. Results. Effects sizes were large for all groups (d1.533.87), however not significantly different. Paroxetine-treated patients were significantly more improved than placebo-treated patients. On the CGI, patients in the exercise groups (plus paroxetine or placebo) had a trend toward better improvement compared to relaxation (P0.06). Response and remission rates were higher in the paroxetine compared to pill placebo groups. Conclusions. While paroxetine was superior to placebo, aerobic exercise did not differ from relaxation training in most efficacy measures. © 2010 Informa Healthcare.

Reinmuth N.,Member of the German Center for Lung Research | Meyer A.,Kliniken Maria Hilf | Hartwigsen D.,Malteser Krankenhaus St. Franziskus | Schaeper C.,Universitaetsklinikum | And 6 more authors.
Lung Cancer | Year: 2014

Objectives: Adding nitroglycerin to the combination of vinorelbine plus cisplatin has been reported to improve the overall survival (OS) of Asian patients with stage IIIB/IV non-small cell lung cancer (NSCLC) probably due to better drug delivery based on changed vascular tonus. The main objective of our study was to evaluate the effect of adding nitroglycerin to vinorelbine and cisplatin in a Caucasian population. Methods: 66 chemonaïve patients with stage IIIB/IV NSCLC received oral vinorelbine (first cycle 60mg/m2, subsequent cycles: 80mg/m2 in the absence of any hematological toxicity ≥grade 3 in cycle 1) once daily on days 1 and 8 of each cycle and cisplatin (80mg/m2 i.v.) on day 1 of each cycle (q3w). Nitroglycerin (arm A, n=34) or placebo patches (arm B, n=32) were administered once daily from day -3 to day 2 of each cycle and were removed about 12h after administration. One nitroglycerin patch contained 25mg nitroglycerin. Results: Median age was 62.5 (33-82) years. In the overall population (n= 66), the objective response rate (ORR) was 27.3% (all PR; 95%CI: 17.0-39.6), with a disease control rate (DCR) of 57.6% (95%CI: 44.8-69.7), a median time to progression (TTP) of 4.8 months (n= 58; 95%CI: 3.4-5.9) and a median overall survival (OS) of 11.5 months (95%CI: 7.9-13.6). ORR and DCR were numerically higher in arm A than in arm B (35.3% vs. 18.8% and 61.8% vs. 53.1%, respectively), whereas TTP and OS were comparable. The main hematological and non-hematological toxicities grade ≥3 were moderate with no significant differences between the two treatment arms. Conclusions: Overall, oral vinorelbine plus cisplatin showed a high level of efficacy and adequate tolerability in first line treatment of NSCLC. Despite the low sample size per group the results seem to confirm the previous results reported in Asian patients. © 2014 Elsevier Ireland Ltd.

Huber M.B.,University of Rochester | Nagarajan M.B.,University of Rochester | Leinsinger G.,Ludwig Maximilians University of Munich | Eibel R.,Helios Kliniken | And 3 more authors.
Medical Physics | Year: 2011

Purpose: Topological texture features were compared in their ability to classify "honeycombing," a morphological pattern that is considered indicative for the presence of fibrotic interstitial lung disease in high-resolution computed tomography (HRCT) images. Methods: For 14 patients with known occurrence of honeycombing, a stack of 70 axial, lung kernel reconstructed images was acquired from HRCT chest exams. A set of 964 regions of interest of both healthy and pathological (356) lung tissue was identified by an experienced radiologist. Texture features were extracted using statistical features (Stat), six properties calculated from gray-level co-occurrence matrices (GLCMs), Minkowski dimensions (MDs), and three Minkowski functionals (MFs) (e.g., MF.Euler). A naïve Bayes (NB) and k -nearest-neighbor (k -NN) classifier, a multilayer radial basis functions network (RBFN), and a support vector machine with a radial basis function (SVMrbf) kernel were optimized in a tenfold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction. Results: The best classification results were obtained by the MF features, which performed significantly better than all the standard Stat, GLCM, and MD features (p<0.001) for both classifiers. The highest accuracies were found for MF.Euler (93.6%, 94.9%, 94.2%, and 95.0% for NB, k -NN, RBFN, and SVMrbf, respectively). The best groups of standard texture features were a Stat and GLCM ("homogeneity") feature set (up to 91.8%). Conclusions: The results indicate that advanced topological texture features derived from MFs can provide superior classification performance in computer-assisted diagnosis of fibrotic interstitial lung disease patterns when compared to standard texture analysis methods. © 2011 American Association of Physicists in Medicine.

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