III. Medizinische Klinik

Augsburg, Germany

III. Medizinische Klinik

Augsburg, Germany
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Ekberg H.,Lund University | Bernasconi C.,Hoffmann-La Roche | Noldeke J.,Hoffmann-La Roche | Yussim A.,Rabin Medical Center | And 4 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Background. Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens.Methods. Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels.Results. The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels.Conclusions. Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs. © 2010 The Author.

Braun G.,III. Medizinische Klinik | Messmann H.,III. Medizinische Klinik
Medizinische Klinik - Intensivmedizin und Notfallmedizin | Year: 2013

Oral anticoagulation and antiplatelet therapy are risk factors for gastrointestinal (GI) bleeding. GI bleeding-especially lower GI bleeding-seems to be associated with a poorer outcome. With the introduction of dabigatrane and rivaroxaban, difficulties in the management of bleeding complications arose. Thus, the goal of the authors was to establish a standard operating procedure (SOP) for the treatment of severe GI bleeding associated with rivaroxaban, dabigatrane, and antiplatelet therapy. Bleeding complications during phenprocoumon treatment should be treated with prothrombin complex concentrates and vitamin K1. Dabigatrane elimination is highly dependent to the renal function. The measurement of drug concentrations of dabigatrane and rivaroxaban is useful to indicate an increased risk of bleeding complications. Severe bleeding associated with dabigatrane or rivaroxaban therapy should trigger prothrombin complex therapy, whereby in cases with severe bleeding associated with antiplatelet therapy platelet transfusion should be initiated. Low-dose aspirin should be continued after 24 h. © 2013 Springer-Verlag Berlin Heidelberg.

Lindauer M.,III. Medizinische Klinik | Hochhaus A.,Universitatsklinikum Jena
Recent Results in Cancer Research | Year: 2015

Dasatinib is an orally available short-acting dual ABL/SRC tyrosine kinase inhibitor (TKI). It potently inhibits BCR-ABL and SRC family kinases (SRC, LCK, YES, FYN), but also c-KIT, PDGFR-a and PDGFR-b, and ephrin receptor kinase. Dasatinib is an effective treatment for chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Both diseases are characterized by a constitutively active tyrosine kinase; BCRABL. Dasatinib inhibits BCR-ABL with greater potency compared with other BCR-ABL inhibitors and is active in CML resistant or intolerant to imatinib. Dasatinib is approved for the treatment of CML (all phases) and for the treatment of Ph+ ALL, resistant or intolerant to prior imatinib treatment. Randomized trial data in CML show that first-line dasatinib provides superior responses compared with imatinib and enables patients to achieve early, deep responses, correlated with improved longer-term outcomes. A once-daily dose of 100 mg in chronic phase CML results in high hematologic and molecular remission rates and prolongation of survival. In accelerated and blastic phase of CML, as well as in Ph+ ALL, complete hematologic and cytogenetic remissions frequently occur. Remissions however are very short. In these patients, once-daily 140 mg is the recommended dose. The effect of dasatinib in other malignancies including solid tumors is subject of clinical studies. Regardless of many clinical trials in different tumor types and in different combinations of dasatinib with other agents, the role of dasatinib in the treatment of solid tumors has not yet been defined. Side effects of dasatinib are frequent but mostly moderate and manageable and include cytopenias and pleural effusions. The review presents the preclinical and clinical activity of dasatinib with a focus on clinical studies in CML. © Springer-Verlag Berlin Heidelberg 2014.

Probst A.,III. Medizinische Klinik | Messmann H.,III. Medizinische Klinik
Viszeralmedizin: Gastrointestinal Medicine and Surgery | Year: 2012

Background: Endoscopic submucosal dissection (ESD) is a technique which allows en-bloc resection of gastrointestinal lesions regardless of their size. Advantages are an improved histopathological assessment, an increase in R0 resections, and a reduced risk of recurrence. ESD is technically difficult and requires a learning curve. Regardless of the resection technique, oncologic criteria need to be strictly adhered to in the resection of early gastrointestinal malignancies. Method: Literature review. Results: Large studies from Asia have been published on ESD while first European data recently reported promising R0 resection rates. For early gastric cancer, ESD is the endoscopic resection method of choice also in Europe. At present, the German guideline allows endoscopic resection in early gastric cancer for selected small lesions only (according to the Japanese 'guideline resection criteria'). In contrast to gastric lesions, ESD in the colorectum and the esophagus is more difficult and the complication risk is higher. Currently, colorectal and eso phageal ESD should be restricted to centers experienced in gastric ESD. Conclusion: In order to answer the question if resection criteria for early gastric cancers can be expanded at least partially also in Europe (according to the Japanese 'expanded resection criteria'), prospective studies are needed. Furthermore, the role of colorectal ESD (especially outside of the rectum) has to be defined in the next years. © 2012 S. Karger GmbH, Freiburg.

Perianayagam M.C.,Tufts University | Tighiouart H.,Biostatistics Research Center | Liangos O.,III Medizinische Klinik | Kouznetsov D.,University of Massachusetts Medical School | And 4 more authors.
Kidney International | Year: 2012

Myeloperoxidase (MPO) is a lysosomal enzyme that may be involved in oxidative stressmediated kidney injury. Using a two-step approach, we measured the association of four polymorphisms across the length of the MPO gene with systemic markers of oxidative stress: plasma MPO and urinary 15-F 2t-isoprostane levels. Adverse outcomes were measured in a primary cohort of 262 adults hospitalized with acute kidney injury, and a secondary cohort of 277 adults undergoing cardiac surgery with cardiopulmonary bypass and at risk for postoperative acute kidney injury. Dominant and haplotype multivariable logistic regression analyses found a genotypephenotype association in the primary cohort between rs2243828, rs7208693, rs2071409, and rs2759 MPO polymorphisms and both markers of oxidative stress. In adjusted analyses, all four polymorphic allele groups had 23-fold higher odds for composite outcomes of dialysis or in-hospital death or a composite of dialysis, assisted mechanical ventilation, or in-hospital death. The MPO T-G-A-T haplotype copy-number was associated with lower plasma MPO levels and lower adjusted odds for the composite outcomes. Significant but less consistent associations were found in the secondary cohort. In summary, our two-step genetic association study identified several polymorphisms spanning the entire MPO gene locus and a common haplotype marker for patients at risk for acute kidney injury. © 2012 International Society of Nephrology.

Background: Systemic chemotherapy has become established as the standard treatment for advanced incurable gastric cancer. In the metastatic setting, systemic chemotherapy can prolong the survival time, improve symptom control and help to maintain a better quality of life. Material and methods: Testing the human epidermal growth factor receptor 2 (HER2) expression status of the primary tumor and/or metastases is warranted before initiation of first-line treatment. Results: In cases of HER2 overexpression or amplified tumors, trastuzumab in combination with cisplatin and 5‑fluorouracil (5-FU) or capecitabine are the standard forms of treatment. Tumors that are HER2 negative or weakly positive are treated with a platinum-fluoropyrimidine combination as doublet or as a triplet with docetaxel in younger patients who can tolerate more intensive treatment. Taxane derivatives, such as docetaxel and paclitaxel as well as irinotecan are accepted treatment options for patients who show progress during or after first-line chemotherapy. The anti-vascular endothelial growth factor receptor 2 (anti-VEGFR2) antibody ramucirumab demonstrated efficacy with prolongation of survival both as monotherapy and in combination with paclitaxel. Objective: This review article outlines the indications and clinical data for pharmaceutical treatment of advanced gastric cancer. © 2016, Springer-Verlag Berlin Heidelberg.

Ebigbo A.,III. Medizinische Klinik | Messmann H.,III. Medizinische Klinik
Medizinische Klinik - Intensivmedizin und Notfallmedizin | Year: 2013

Clostridium difficile infections remain a problem especially for patients in the intensive care unit. The fact that C. difficile infections are strongly associated with antibiotic therapy calls for more caution in the use of antibiotics, especially in patients with a high risk of developing C. difficle infections. Severe infections and recurrent episodes are usually difficult to manage and therapeutic options are often limited. The method of stool transplantation, though not new, has received more attention in recent years, with studies showing stool transplantation to be a promising and easy method which has high clinical cure rates even for recurrent C. difficile infections. However, more randomised and controlled trials are needed to further study the efficacy of stool transplantation in patients with C. difficile infection. © 2013 Springer-Verlag Berlin Heidelberg.

Kraus M.R.,University of Würzburg | Schafer A.,University of Würzburg | Teuber G.,Goethe University Frankfurt | Porst H.,III. Medizinische Klinik | And 4 more authors.
Hepatology | Year: 2013

Earlier studies have suggested neurocognitive impairment in patients with chronic hepatitis C virus (HCV) infection even before liver cirrhosis has developed. Since these deficits might be reversible after successful antiviral therapy, we analyzed the long-term course of neurocognitive parameters in HCV patients with and without successful virus elimination by an interferon-based antiviral treatment. In a multicenter study including 168 HCV patients receiving antiviral therapy (peginterferon alpha-2b and ribavirin) we performed a long-term follow-up of neurocognitive performance before and after treatment. Neurocognitive function was psychometrically assessed using the computer-aided TAP (Test Battery of Attentional Performance). When tested at least 12 months after termination of antiviral treatment, patients with sustained virologic response (SVR) had improved significantly as compared to their pretreatment performance in three of five TAP subtasks (vigilance, P < 0.001; shared attention: optical task, P < 0.001; working memory, P < 0.001). Patients who failed to eradicate the virus, however, showed no significant long-term changes in neurocognitive performance in all five subtasks assessed (0.194 < P < 0.804). In the posttreatment evaluation, neurocognitive function was significantly better in responders to the antiviral therapy as compared to nonresponders. Conclusion: Successful eradication of HCV leads to a significant improvement of relevant aspects of attentional and neurocognitive performance, indicating that the neurocognitive impairment caused by chronic HCV infection is potentially reversible. This therefore suggests an added therapeutic benefit of antiviral treatment in HCV infection. Improvement of neurocognitive function may be an additional treatment indication in patients with HCV. © 2013 American Association for the Study of Liver Diseases.

Endoscopic treatment is the standard for nonvariceal upper gastrointestinal bleeding. Established are injection, mechanical and thermal hemostatic procedures. Currently new topically applied substances for endoscopic hemostasis become available. By withdrawal of fluid from the blood, the onset of blood clotting is accelerated. First case series could demonstrate successful treatment for oozing bleeding or as additional therapy in combination with other hemostatic procedures. Today larger, rotatable and repositionable clips TTS (Through the Scope) are available for mechanical hemostasis. One model allows the use of three clips without changing the applicator. A technical different method is the Over the Scope Clip OTSC, which could be applied after suction of the bleeding source. Despite the euphoria of endoscopic hemostasis, there are still some limitations to be known. Arterial vessels > 2 mm and the presence of severe hemorrhagic shock should lead the endoscopist to an interdisciplinary case discussion. © Georg Thieme Verlag KG Stuttgart. New York.

Probst A.,III. Medizinische Klinik | Messmann H.,III. Medizinische Klinik
Chirurg | Year: 2011

Colorectal adenomas are frequent and are detected in about 20% of screening colonoscopies. Adenoma resection can be performed endoscopically or surgically. Endoscopic resection techniques include snare polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Endoscopic treatment of colorectal adenomas is highly effective and shows acceptable complication rates. After resection of large adenomas the recurrence rate is substantial. However endoscopic retreatment of recurrent events is mostly successful. Considering the minimally invasive nature of endoscopic resections and concerning logistic and economic aspects, endoscopic resection is the treatment of choice for colorectal adenomas. © 2011 Springer-Verlag.

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