Dysphagia in Patients with Acute Ischemic Stroke: Early Dysphagia Screening May Reduce Stroke-Related Pneumonia and Improve Stroke Outcomes

Background Dysphagia is associated with poor outcome in stroke patients. Studies investigating the association of dysphagia and early dysphagia screening (EDS) with outcomes in patients with acute ischemic stroke (AIS) are rare. The aims of our study are to investigate the association of dysphagia and EDS within 24 h with stroke-related pneumonia and outcomes. Methods Over a 4.5-year period (starting November 2007), all consecutive AIS patients from 15 hospitals in Schleswig-Holstein, Germany, were prospectively evaluated. The primary outcomes were stroke-related pneumonia during hospitalization, mortality, and disability measured on the modified Rankin Scale ≥2-5, in which 2 indicates an independence/slight disability to 5 severe disability. Results Of 12,276 patients (mean age 73 ± 13; 49% women), 9,164 patients (74%) underwent dysphagia screening; of these patients, 55, 39, 4.7, and 1.5% of patients had been screened for dysphagia within 3, 3 to 72 h following admission. Patients who underwent dysphagia screening were likely to be older, more affected on the National Institutes of Health Stroke Scale score, and to have higher rates of neurological symptoms and risk factors than patients who were not screened. A total of 3,083 patients (25.1%; 95% CI 24.4-25.8) had dysphagia. The frequency of dysphagia was higher in patients who had undergone dysphagia screening than in those who had not (30 vs. 11.1%; p < 0.001). During hospitalization (mean 9 days), 1,271 patients (10.2%; 95% CI 9.7-10.8) suffered from stroke-related pneumonia. Patients with dysphagia had a higher rate of pneumonia than those without dysphagia (29.7 vs. 3.7%; p < 0.001). Logistic regression revealed that dysphagia was associated with increased risk of stroke-related pneumonia (OR 3.4; 95% CI 2.8-4.2; p < 0.001), case fatality during hospitalization (OR 2.8; 95% CI 2.1-3.7; p < 0.001) and disability at discharge (OR 2.0; 95% CI 1.6-2.3; p < 0.001). EDS within 24 h of admission appeared to be associated with decreased risk of stroke-related pneumonia (OR 0.68; 95% CI 0.52-0.89; p = 0.006) and disability at discharge (OR 0.60; 95% CI 0.46-0.77; p < 0.001). Furthermore, dysphagia was independently correlated with an increase in mortality (OR 3.2; 95% CI 2.4-4.2; p < 0.001) and disability (OR 2.3; 95% CI 1.8-3.0; p < 0.001) at 3 months after stroke. The rate of 3-month disability was lower in patients who had received EDS (52 vs. 40.7%; p = 0.003), albeit an association in the logistic regression was not found (OR 0.78; 95% CI 0.51-1.2; p = 0.2). Conclusions Dysphagia exposes stroke patients to a higher risk of pneumonia, disability, and death, whereas an EDS seems to be associated with reduced risk of stroke-related pneumonia and disability

The role of signal transducers and activators of transcription in T inflammatory bowel diseases

Signal transducers and activators of transcription (STAT) proteins are intracellular effector molecules of cytokine-modulated signaling. On the one hand, they play an important role in hematopoiesis and the development of the human immune system. STAT transcription factors are necessary for embryogenesis and the maintenance of the mammalian immune response. In the adult, STAT signaling is responsible for T-cell polarization toward interferon gamma-secreting Th1 T cells or interleukin 4-producing Th2 cells. On the other hand, these proteins are involved in the regulation of T-cell survival. STAT activation is strongly associated with tyrosine phosphorylation by tyrosine kinases, namely Jak1, Jak2, Jak3, and Tyk2. Counterregulatory mechanisms protecting from overwhelming STAT activation are represented by protein inhibitors of activated STATs and the SOCS family proteins. Because STAT proteins are key response elements of cytokine-induced T-cell activation, the characterization of STAT proteins is one step to elucidate disturbed T-cell function in inflammatory bowel disease. In particular, an activation of STAT-4 and STAT-3 in T cells seems to play a key pathogenic role in Crohn's disease

Mucosal T cells : mediators or guardians of inflammatory bowel disease?

Because the mucosal immune system is continuously exposed to a myriad of potentially harmful environmental antigens, it frequently reacts with antiinflammatory/regulatory T cell responses driven by TGF-beta-producing TH3 cells and IL-10-producing regulatory T cells. Intestinal inflammation in patients with inflammatory bowel diseases is thought to result from an overwhelming uncontrolled activation of the mucosal immune system induced by antigens of the normal luminal flora in genetically susceptible individuals. Inflammatory bowel disease appears to be mediated by subsets of CD4 T lymphocytes or NK T cells secreting high levels of proinflammatory cytokines such as TNF-alpha. The increased expression of integrins/addressins in the inflamed gut and the increased expression of adhesion molecules on T cells facilitate migration of these pathogenic T cell subsets into the lamina propria. Additionally, the local activation of antiapoptotic pathways in pathogenic T lymphocytes leads to a further accumulation of these cells in the lamina propria, causing perpetuation and chronicity of inflammatory bowel disease. This concept is underlined by the finding that most potent immunosuppressive drugs used in treatment of inflammatory bowel disease seem to work by inducing T cell apoptosis via inhibition of STAT-3 and NFkappaB-dependent antiapoptotic pathways. Taken together, distinct T cell subsets appear to act as mediators or guardians of inflammatory bowel disease, and thus they play a central role in controlling the delicate balance between proinflammatory and antiinflammatory immune responses in the gut

Recent results of laparoscopic surgery in inflammatory bowel disease

Inflammatory bowel diseases are an ideal indication for the laparoscopic surgical approach as they are basically benign diseases not requiring lymphadenectomy and extended mesenteric excision; well-established surgical procedures are available for the conventional approach. Inflammatory alterations and fragility of the bowel and mesentery, however, may demand a high level of laparoscopic experience. A broad spectrum of operations from the rather easy enterostomy formation for anal Crohn’s disease (CD) to restorative proctocolectomies for ulcerative colitis (UC) may be managed laparoscopically. The current evidence base for the use of laparoscopic techniques in the surgical therapy of inflammatory bowel diseases is presented. CD limited to the terminal ileum has become a common indication for laparoscopic surgical therapy. In severe anal CD, laparoscopic stoma formation is a standard procedure with low morbidity and short operative time. Studies comparing conventional and laparoscopic bowel resections, have found shorter times to first postoperative bowel movements and shorter hospital stays as well as lower complication rates in favour of the laparoscopic approach. Even complicated cases with previous surgery, abscess formation and enteric fistulas may be operated on laparoscopically with a low morbidity. In UC, restorative proctocolectomy is the standard procedure in elective surgery. The demanding laparoscopic approach is increasingly used, however, mainly in major centers; its feasibility has been proven in various studies. An increased body mass index and acute inflammation of the bowel may be relative contraindications. Short and long-term outcomes like quality of life seem to be equivalent for open and laparoscopic surgery. Multiple studies have proven that the laparoscopic approach to CD and UC is a safe and successful alternative for selected patients. The appropriate selection criteria are still under investigation. Technical considerations are playing an important role for the complexity of both diseases

IL-6 signaling in inflammatory bowel disease: Pathophysiological role and clinical relevance

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) occurring in the gut of genetically susceptible individuals independent of a specific pathogen. The interaction between antigen-presenting cells and the local bacterial flora contributes to an uncontrolled activation of mucosal CD4+ T lymphocytes with the consecutive release of proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-6, IL-12, IL-23, IL-27, and also IL-17, which is attributed to a specific, differentiated CD4+ lineace called Th17 (TH-IL17, THi). Recent data suggest that IL-6 contributes to Th17 differentiation. However, to clarify the importance of Th17 cells in IBD further data are needed. So far, CD has been attributed to a Th1-mediated disease, whereas UC exhibits a modified Th2 cytokine response. In both diseases CD4+ T cells at the site of inflammation are critically dependent on antiapoptotic IL-6 signaling. Thereby, IL-6 induces the transcription factor STAT-3 via transsignaling (activation of a cell lacking membrane-bound IL-6 receptor via soluble IL-6 receptor). STAT-3 itself induces the antiapoptotic factors bcl-2 and bcl-xL, thus resulting in T-cell resistance against apoptosis. This vicious circle of T-cell accumulation, mediated by apoptosis resistance, finally leading to chronic inflammation, can be blocked by anti-IL-6 receptor antibodies. This review highlights the role of IL-6 in IBD immunopathogenesis and its clinical relevance in IBD therapy and diagnostics

A new model of chronic colitis in scid mice induced by adoptive transfer of cd62l cd4 t cells: insights into the regulatory role of interleukin-6 on apoptosis

Objective: The proinflammatory cytokine interleukin (IL)6 is involved in various chronic inflammatory processes. IL-6 is a predominant cytokine produced by lamina propria T cells in Crohn's disease and experimental colitis. This study was designed to examine the effect of a neutralizing IL-6-receptor (IL-6R) antibody on the programmed cell death of mucosal T cells in the CD62L+ CD4+ SCID transfer model of chronic experimental colitis in mice and to gain more insight into the pathogenesis of this transfer colitis model. Methods: For adoptive transfer, we isolated CD62L+ CD4+ double-positive T cells from wild-type BALB/c mice followed by intraperitoneal application of 1 million cells in CB17 SCID mice. The purity of the transferred T-cell population was tested by FACS analysis. Cytokine secretion was measured by ELISA. Western blot analysis was performed to detect phospho-STAT-3 in protein extracts of splenic cells. Cryo- and paraffin colon cross-sections were used to perform immunochemical or fluorescence TUNEL stainings. Results: We isolated-CD62L+ CD4+ and CD62L- CD4+ T cells. In vitro studies showed an increased production of IL-4 by CD62L- CD4+ T cells compared to CD62L+ T cells. 8-10 weeks after transfer of CD62L+ CD4+ T cells in SCID mice, reconstituted mice developed wasting disease, anal prolapse and diarrhea, whereas mice reconstituted with CD62L- CD4+ did not, similar to anti-IL-6R-treated CD62L+ CD4+-reconstituted SCID mice. Anti-IL-6R-treated reconstituted SCID mice showed decreased levels of activated STAT-3. The previously described efficacy of anti-IL-6R antibody treatment on colitis activity appeared to be due to the induction of apoptosis, as many TUNEL-positive cells were detected in the lamina propria. Conclusions: These results suggest that the activation of the IL-6/STAT-3-signaling pathway plays a pivotal role in the pathogenesis of CD62L+ CD4+ transfer colitis. Moreover, the application of a neutralizing antibody to IL-6R induces apoptosis in transferred T cells. These data implicate the importance of anti-apoptotic pathways in chronic disease and might contribute to future therapies

Prospective evaluation of the learning curve of confocal laser endomicroscopy in patients with IBD

Background and aims: Confocal laser endomicroscopy (CLE) represents a novel endoscopic imaging technique which enables the in vivo microscopic imaging within the mucosal layer of the gut at subcellular resolution. Currently, there are no data available on the learning curve of CLE, which was therefore the aim of our study. Methods: Twenty-six consecutive patients with inflammatory bowel disease (IBD) underwent total colonoscopy and were examined by fluorescein-aided CLE. Image data were collected and reviewed by two endoscopists in a blinded fashion. CLE images were compared to endoscopical and histological findings. Prospectively, the following performance parameters were documented: total duration of the procedure, confocal imaging time, time to receive a confocal image in focus, number of confocal images, number of confocal images in focus, CLE diagnosis and final histopathological diagnosis. Results: A significance decrease of CLE duration was detected between the first 8 and the subsequent cases (p=0.002). Confocal imaging time and the time to receive an image in focus declined significantly over time (p=0.0001), while number of images in focus significantly increased (p=0.0007). Agreement between CLE and histopathology improved over time with kappa values of 0.81 after twenty-six cases. Conclusions: There was a significant improvement in CLE performance over time, including decreased confocal imaging time, successful CLE diagnosis and decline in procedural time. These parameters improved significantly after the initial three cases. Therefore, CLE represents an easy to learn and apply novel diagnostic method for in vivo analysis and diagnosis in IBD