University Clinic of Tuebingen

Tübingen, Germany

University Clinic of Tuebingen

Tübingen, Germany

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Rudolph V.,University of Cologne | Huntgeburth M.,University of Cologne | Von Bardeleben R.S.,Johannes Gutenberg University Mainz | Boekstegers P.,Helios Heart Center Siegburg | And 12 more authors.
European Journal of Heart Failure | Year: 2014

Aims As periprocedural risk is low, MitraClip implantation is often performed in critically ill, not fully recompensated patients, who are in NYHA functional class IV at the time of the procedure, to accelerate convalescence. We herein sought to evaluate the procedural and 30-day outcome of this patient group.Methods and results A total of 803 patients undergoing MitraClip implantation were included in the German Mitral Valve Registry, and 30-day outcomes were prospectively assessed. Patients were separated based on NYHA functional class [(NYHA IV (n = 143), III (n = 572), and I/II (n = 88)]. No difference was noted in co-morbities and echocardiographic parameters of LV function between groups. However, parameters of severity of mitral regurgitation (MR) were higher in NYHA IV patients. High procedural success rates and low residual MR grades at discharge were observed throughout all groups. In-hospital major adverse cardiac events were similar between groups. Importantly, 30-day mortality (8.0% vs. 3.2% vs. 4.8%; P < 0.05) was significantly higher in NYHA IV patients, whereas rehospitalization did not differ between groups. At 30 days, 47.6% of NYHA IV patients were still in NYHA class III or IV compared with 32.5% and 14.8% in the other groups (P < 0.05), although NYHA functional class decreased in 69% of patients. Quality of life, which was very poor at baseline, showed an overall improvement in NYHA IV patients after 30 days, with, for example, a reduction of bed-ridden patients from 19.6% to 3.3%.Conclusion MitraClip therapy is feasible and safe even in critically ill, not fully recompensated patients and leads to symptomatic improvement in over two-thirds of these patients; however, it is associated with an elevated 30-day mortality. © 2014 The Authors European Journal of Heart Failure.


PubMed | University Clinic of Tuebingen, University of Pennsylvania, Sahlgrenska University Hospital and Loyola Medical Center
Type: Comparative Study | Journal: BMJ open | Year: 2016

To determine whether kidney transplants performed during a weekend had worse outcomes than those performed during weekdays.Retrospective national database study.United Network for Organ Sharing database of the USA.136,715 adult recipients of deceased donor single organ kidney transplants in the USA between 4/1994 and 9/2010.The primary outcomes were patient survival and death-censored and overall allograft survival. Secondary outcomes included initial length of hospital stay after transplantation, delayed allograft function, acute rejection within the first year of transplant, and patient and allograft survival at 1month and at 1year after transplantation. Cox proportional hazards models were used to evaluate the impact of weekend kidney transplant surgery on primary and secondary outcomes, adjusting for multiple covariates.Among the 136,715 kidney recipients, 72.5% underwent transplantation during a regular weekday (Monday-Friday) and 27.5% during a weekend (Saturday-Sunday). No significant association was noted between weekend transplant status and patient survival, death-censored allograft survival or overall allograft survival in the adjusted analyses (HR 1.01 (95% CI 0.92 to 1.04), 1.012 (95% CI 0.99 to 1.034), 1.012 (95% CI 0.984 to 1.04), respectively). In addition, no significant association was noted between weekend transplant status and the secondary outcomes of patient and graft survival at 1month and 1year, delayed allograft function or acute rejection within the first year. Results remained consistent across all definitions of weekend status.The outcomes for deceased donor kidney transplantation in the USA are not affected by the day of surgery. The operationalisation of deceased donor kidney transplantation may provide a model for other surgeries or emergency procedures that occur over the weekend, and may help reduce length of hospital stay and improve outcomes.


Elsenbruch S.,University of Duisburg - Essen | Rosenberger C.,University of Duisburg - Essen | Enck P.,University Clinic of Tuebingen | Forsting M.,University of Duisburg - Essen | And 2 more authors.
Gut | Year: 2010

Objective: To address the role of anxiety and depression symptoms in altered pain processing in irritable bowel syndrome (IBS). Design: In this functional magnetic resonance imaging study, the blood oxygen level-dependent (BOLD) response to rectal distensions delivered at previously determined individual discomfort thresholds was assessed. Patients: 15 female patients with irritable bowel syndrome (IBS) and with normal rectal pain thresholds, and 12 healthy women. Measures: The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences in pain-induced brain activation with and without controlling for HADS scores were evaluated. Results: Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively, as confounding variables led to a loss of significant group differences. Conclusions: Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affectiveemotivational aspects of the pain response.


Schonberger T.,University Clinic of Tuebingen | Jurgens T.,University Clinic of Tuebingen | Muller J.,Heinrich Heine University Düsseldorf | Armbruster N.,University Clinic of Tuebingen | And 10 more authors.
American Journal of Pathology | Year: 2014

Myocardial inflammation is critical for ventricular remodeling after ischemia. Phospholipid mediators play an important role in inflammatory processes. In the plasma membrane they are degraded by phospholipase D1 (PLD1). PLD1 was shown to be critically involved in ischemic cardiovascular events. Moreover, PLD1 is coupled to tumor necrosis factor-α signaling and inflammatory processes. However, the impact of PLD1 in inflammatory cardiovascular disease remains elusive. Here, we analyzed the impact of PLD1 in tumor necrosis factor-α-mediated activation of monocytes after myocardial ischemia and reperfusion using a mouse model of myocardial infarction. PLD1 expression was highly up-regulated in the myocardium after ischemia/reperfusion. Genetic ablation of PLD1 led to defective cell adhesion and migration of inflammatory cells into the infarct border zone 24 hours after ischemia/reperfusion injury, likely owing to reduced tumor necrosis factor-α expression and release, followed by impaired nuclear factor-κB activation and interleukin-1 release. Moreover, PLD1 was found to be important for transforming growth factor-β secretion and smooth muscle α-actin expression of cardiac fibroblasts because myofibroblast differentiation and interstitial collagen deposition were altered in Pld1 -/- mice. Consequently, infarct size was increased and left ventricular function was impaired 28 days after myocardial infarction in Pld1-/- mice. Our results indicate that PLD1 is crucial for tumor necrosis factor-α-mediated inflammation and transforming growth factor-β-mediated collagen scar formation, thereby augmenting cardiac left ventricular function after ischemia/reperfusion. © 2014 American Society for Investigative Pathology.


Wiegand G.,University Hospital of Tuebingen | Sieverding L.,University Hospital of Tuebingen | Bocksch W.,University Clinic of Tuebingen | Hofbeck M.,University Hospital of Tuebingen
Pediatric Cardiology | Year: 2013

Although vascular plugs allow the interventional closure of medium-sized to large abnormal vessels, their application is limited by the need for long sheaths or large guiding catheters. The authors report their experience with the new Amplatzer vascular plug 4 (AVP 4), a self-expanding spindle-shaped occluder made of Nitinol wire mash, which can be placed through 4-Fr catheters with an internal diameter of 0.038 in. or larger. From October 2009 until June 2012, 14 AVP 4 devices were deployed in 12 patients (ages, 0.3-48.8 years). Nine patients had venovenous or arteriovenous collaterals in functional univentricular hearts. One patient had pulmonary atresia with a ventricular septal defect and major aortopulmonary collateral arteries, and one patient had a pulmonary arteriovenous fistula. One child had a large coronary artery fistula to the right atrium. The authors used AVP 4 devices with diameters of 4-8 mm. In all the patients, the AVP 4 was implanted successfully. No occluder dislocations and no complications related to the procedure occurred. Complete vessel occlusion was achieved in seven cases. In seven additional cases, a residual shunt was present at the end of the procedure while the patients were still fully heparinized. In 2 of 14 vessels, the decision was made to place additional devices to abolish residual shunting. According to the authors' experience, the AVP 4 allows safe and effective occlusion of medium-size and large abnormal vessels. It is also well suited for tortuous high-flow vessels such as coronary or pulmonary arteriovenous fistulas. In case of a suboptimal position, it is possible to reposition the occluder with ease. Further studies are needed to determine whether initial residual shunting in heparinized patients disappears during follow-up care. The AVP 4 represents a valuable new device for the interventional treatment of complex congenital vessel malformations. © 2013 Springer Science+Business Media New York.


Funk N.,German Center for Neurodegenerative Diseases | Wieghofer P.,German Center for Neurodegenerative Diseases | Grimm S.,Laboratory for Stem Cell Research | Schaefer R.,University Clinic of Tuebingen | And 4 more authors.
Movement Disorders | Year: 2013

Background: Emerging evidence has highlighted the pivotal role of the immune system in neurodegenerative diseases. This study investigated the impact of progressive neurodegeneration on the differentiation and development of hematopoietic stem cells in the peripheral blood of Parkinson's patients. Methods: A colony-forming cell assay was established to study hematopoietic stem cells from venous blood of Parkinson's patients, and flow cytometry was used to analyze the expression of chemokine receptors on monocytes. Results: We demonstrate that there is strong upregulation in the percentage of monocyte precursors in the peripheral blood of Parkinson's patients and asymptomatic high-risk individuals. We identify the receptor CCR2 as undergoing strong upregulation on the surface of classical monocytes in Parkinson's patients. Conclusions: The association between blood cell development and progressive cell death in the brain of Parkinson's patients should be further investigated as a potential dynamic biomarker and indicator of disease progression. © 2013 Movement Disorder Society.


Hartkopf A.D.,University Clinic of Tuebingen | Fehm T.,University Clinic of Tuebingen | Wallwiener D.,University Clinic of Tuebingen | Lauer U.M.,University of Tübingen
Gynecologic Oncology | Year: 2011

The use of replication competent viruses that selectively target and destroy cancer cells has rapidly evolved over the past decade and numerous innovative oncolytic viruses have been created. Many of these promising anti-cancer agents have recently entered into clinical trials (including those on breast cancer) and demonstrated encouraging safety and efficacy. Virotherapeutic strategies are thus of considerable interest to combat breast cancer in both (i) the primary disease situation in which relapse should be avoided as good as possible and (ii) in the metastatic situation which remains incurable to date. Here, we summarize data from preclinical and clinical trials using oncolytic virotherapy to treat breast cancer. This includes strategies to specifically target breast cancer cells, to arm oncolytic viruses with additional therapeutic transgenes and an outlining of future challenges when translating these promising therapeutics "from bench to bedside". © 2011 Elsevier Inc. All rights reserved.


Sauter R.J.,University Clinic of Tuebingen | Steeg M.,University Clinic of Tuebingen | Bocksch W.,University Clinic of Tuebingen | Schreieck J.,University Clinic of Tuebingen | And 2 more authors.
Blood Coagulation and Fibrinolysis | Year: 2012

It is well accepted that drug-eluting stents (DES) are effective in reducing restenosis, although implantation of DES may result in increased occurrence of stent thrombosis. The study describes the case of a patient with very late stent thrombosis (VLST) despite intravascular ultrasound (IVUS) control after implantation of a paclitaxel-eluting stent, an adequate response to antiplatelet therapy, and the lack of distinct risk factors for VLST. Stent thrombosis remains a serious complication after stent implantation even after prolonged time, and studies are urgently needed to optimize diagnosis and treatment of VLST. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | University Clinic of Tuebingen
Type: Case Reports | Journal: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis | Year: 2012

It is well accepted that drug-eluting stents (DES) are effective in reducing restenosis, although implantation of DES may result in increased occurrence of stent thrombosis. The study describes the case of a patient with very late stent thrombosis (VLST) despite intravascular ultrasound (IVUS) control after implantation of a paclitaxel-eluting stent, an adequate response to antiplatelet therapy, and the lack of distinct risk factors for VLST. Stent thrombosis remains a serious complication after stent implantation even after prolonged time, and studies are urgently needed to optimize diagnosis and treatment of VLST.


PubMed | University Clinic of Tuebingen
Type: Journal Article | Journal: Gynecologic oncology | Year: 2011

The use of replication competent viruses that selectively target and destroy cancer cells has rapidly evolved over the past decade and numerous innovative oncolytic viruses have been created. Many of these promising anti-cancer agents have recently entered into clinical trials (including those on breast cancer) and demonstrated encouraging safety and efficacy. Virotherapeutic strategies are thus of considerable interest to combat breast cancer in both (i) the primary disease situation in which relapse should be avoided as good as possible and (ii) in the metastatic situation which remains incurable to date. Here, we summarize data from preclinical and clinical trials using oncolytic virotherapy to treat breast cancer. This includes strategies to specifically target breast cancer cells, to arm oncolytic viruses with additional therapeutic transgenes and an outlining of future challenges when translating these promising therapeutics from bench to bedside.

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