Wendler J.,Rheumatologische Schwerpunktpraxis |
Burmester G.R.,Humboldt University of Berlin |
Sorensen H.,Rheumaprojekt Berlin Brandenburg |
Krause A.,Immanuel Krankenhaus |
And 7 more authors.
Arthritis Research and Therapy | Year: 2014
Introduction: The aim of this study was to evaluate the safety and efficacy of rituximab (RTX) in a large cohort of patients with rheumatoid arthritis in routine care, and to monitor changes in daily practice since the introduction of RTX therapy.Methods: This was a multicentre, prospective, non-interventional study conducted under routine practice conditions in Germany. Efficacy was evaluated using Disease Activity Score in 28 joints (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed by recording adverse drug reactions (ADRs). Physician and patient global efficacy and tolerability assessments were also evaluated.Results: Overall, 2,484 patients (76.7% female, mean age 56.4 years, mean disease duration 11.7 years) received RTX treatment (22.7% monotherapy). The total observation period was approximately six-years (median follow-up 14.7 months). RTX treatment led to improvements in DAS28 and HAQ-DI that were sustained over multiple courses. DAS28 improvements positively correlated with higher rheumatoid factor levels up to 50 IU/ml. Response and tolerability were rated good/very good by the majority of physicians and patients. Mean treatment intervals were 10.5 and 6.8 months for the first and last 400 enrolled patients, respectively. Infections were the most frequently reported ADRs (9.1%; 11.39/100 patient-years); approximately 1% of patients per course discontinued therapy due to ADRs.Conclusions: Prolonged RTX treatment in routine care is associated with good efficacy and tolerability, as measured by conventional parameters and by physicians' and patients' global assessments. Rheumatoid factor status served as a distinct and quantitative biomarker of RTX responsiveness. With growing experience, physicians repeated treatments earlier in patients with less severe disease activity. © 2014 Wendler et al.; licensee BioMed Central Ltd.
Current therapy of hepatocellular carcinoma with special consideration of new and multimodal treatment concepts [Aktuelle Therapie des hepatozellulären Karzinoms unter besonderer Berücksichtigung neuer und multimodaler Therapiekonzepte]
Gobel T.,Klinik fur Innere Medizin II Gastroenterologie |
Blondin D.,Heinrich Heine University Düsseldorf |
Kolligs F.,Medizinische Klinik und Poliklinik II |
Bolke E.,Heinrich Heine University Düsseldorf |
Erhardt A.,Klinik fur Innere Medizin II Gastroenterologie
Deutsche Medizinische Wochenschrift | Year: 2013
The incidence of hepatocellular carcinoma (HCC) is increasing worldwide due to the growing number of hepatitis C related HCCs. In more than 80 % of the patients, HCC arises in a cirrhotic liver. Furthermore, more than half of the patients have an advanced Child-Pugh score or an inoperable tumor stage at the initial diagnosis. Recommendations for the treatment of HCC by national and international guidelines rely on the BCLC ("Barcelona Clinic for Liver Cancer") algorithm. Depending on the stage of liver function and tumor disease it recommends resection, liver transplantation, radiofrequency thermal ablation (RFA), transarterial chemoembolisation (TACE), systemic therapy with sorafenib or best supportive care, but does neither take into consideration combination of therapies nor new therapy modalities. However, there is increasing evidence that combinations i. e. sorafenib with TACE or combination of locoregional techniques enhance effectivity and tumor control compared to monotherapies. TACE with drug-eluting beads, selective internal radiotherapy (SIRT) and new locoregional therapy procedures like microwave ablation (MWA) are further promising therapeutic approaches. Patients with HCC should be discussed in a local tumor board in order to provide the optimal and most individual way of treatment. © Georg Thieme Verlag KG · Stuttgart · New York.
Lux M.P.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Maass N.,RWTH Aachen |
Schutz F.,Universitatsklinikum Heidelberg |
Schwidde I.,Klinik fur Senologie |
And 6 more authors.
Geburtshilfe und Frauenheilkunde | Year: 2013
The treatment options and characteristics for therapeutic decisions for patients with primary and advanced breast cancer are becoming more and more numerous. New targeted therapies in combination with established chemotherapy regimens are expending the spectrum but potentially promising combinations do not also give a better result. The latest data from pharmacogenomics point to prognosis and predictive factors that take not only the properties of the tumour but also the hereditary genetic features of the patient into account. Current therapy decisions are thus based on a combination of classical clinical and modern molecular biomarkers. Health-economic aspects are also being taken into account more often, so that health-political considerations may also play a part. The present review article summarises parts of the results presented at the 2012 San Antonio Breast Cancer Symposia (SABCS), ESMO 2012 and St. Gallen 2013 together with new and important publications on the prevention of and therapy for breast cancer. © Georg Thieme Verlag KG · Stuttgart · New York.
Scheurlen M.,Medizinische Klinik und Poliklinik II
Medizinische Klinik - Intensivmedizin und Notfallmedizin | Year: 2015
Background: Acute vascular occlusion within the mesenteric circulation leads to ischemic damage of the corresponding bowel segment, which starts on the mucosal level and progresses transmurally. Objectives: Report on pathogenesis, clinical picture and treatment of various forms of intestinal ischemia. Materials and methods: Analysis of the available literature taking into consideration our own experience. Results: Frequently, predisposing diseases and risk factors are present (e.g., cardiac diseases, hypercoagulability, status post cardiac surgery, circulatory failure, or administration of vasoconstrictive drugs). Acute small bowel ischemia—caused by either mesenteric embolism, mesenteric artery thrombosis, nonocclusive mesenteric ischemia (NOMI) or mesenteric venous thrombosis—represents an acute emergency. If this condition is suspected clinically, the diagnosis must be established immediately by computed tomography of the abdomen with intravenous administration of contrast medium in order to prevent irreversible damage to the small bowel. Medical treatment is supportive. If possible, occluded vessels may be re-opened either by radiologic intervention or surgically. Irreversibly damaged bowel segments must be surgically removed. Ischemic colitis has a benign course in most cases if limited to reversible mucosal damage. The diagnosis is based mainly on colonoscopy and computed tomography findings, and treatment is symptom oriented. Rarely, severe manifestations with a worse prognosis due to considerable comorbidities occur. In such cases, surgical removal of the ischemic bowel is frequently required. Conclusion: Even today, acute mesenteric ischemia is associated with a poor prognosis. To improve survival and to reduce long-term morbidity, a rapid and systematic diagnostic workup is mandatory. © 2015, Springer-Verlag Berlin Heidelberg.
Knop S.,Medizinische Klinik und Poliklinik II
Medizinische Monatsschrift fur Pharmazeuten | Year: 2014
The multiple myeloma (MM) is still an incurable malignant plasma cell disease. Therapy is necessary, once symptoms of end organ damage occur. Numerous "new substances" (proteasome inhibitors, immunomodulatory substances) were introduced in the past decade, resulting in improved treatment results. Polychemotherapy, alternating drug applications and the principle of "continuous therapy" are used to achieve a high response rate (with the aim of a long-lasting disease control). Among all patients those with extramedullary disease (EMD) are currently the most difficult treatable patients. It remains to be seen whether and when genomic analyses by next generation sequencing will yield to an understanding of the ups and downs of various tumor subclones. Maybe such technologies result in the development of real targeted therapies for myeloma in the future. To date, such therapies are not available. © Deutscher Apotheker Verlag.
Scheurlen M.,Medizinische Klinik und Poliklinik II
Internist | Year: 2013
Proton pump inhibitors (PPI) are among the most frequently prescribed drugs worldwide. Recently, several side effects of chronic PPI therapy have been identified. Reduced intestinal absorption of vitamin B12 or calcium, an increased rate of bone fractures, an interference with the metabolism of other drugs (e.g., clopidogrel), and an increased incidence of Clostridium difficile-associated colitis are discussed. So far, data on such side effects of PPI are mainly supported by retrospective and/or uncontrolled studies. Therefore, a definitive estimation of the real risk of long-term PPI medication is not yet possible. However, since chronic treatment with PPI may lead to severe side effects, it is necessary to keep the established indications for these drugs (peptic ulcer therapy, gastro-esophageal reflux disease, prophylaxis of mucosal lesions by potentially ulcerogenic drugs) in mind. PPI therapy as stress ulcer prophylaxis should be confined to risk groups and risk situations. Long-term treatment with PPI requires repeated confirmation of a persisting indication, choice of the lowest effective dose, and - if applicable - an interval or "on demand" treatment. © 2013 Springer-Verlag Berlin Heidelberg.
Knop S.,Medizinische Klinik und Poliklinik II
Arzneimitteltherapie | Year: 2014
The multiple myeloma (MM) is still an incurable malignant plasma cell disease. Therapy is necessary, once symptoms of end organ damage occur. Numerous "new substances" (proteasome inhibitors, immunomodulatory substances) were introduced in the past decade, resulting in improved treatment results. Polychemotherapy, alternating drug applications and the principle of "continuous therapy" are used to achieve a high response rate (with the aim of a long-lasting disease control). Among all patients those with extramedullary disease (EMD) are currently the most difficult treatable patients. It remains to be seen whether and when genomic analyses by next generation sequencing will yield to an understanding of the ups and downs of various tumor subclones. Maybe such technologies result in the development of real targeted therapies for myeloma in the future. To date, such therapies are not available.
De Heer J.,Medizinische Klinik und Poliklinik II |
Goke B.,Medizinische Klinik und Poliklinik II
Tagliche Praxis | Year: 2014
In spite of a wide variety of antidiabetic agents available, management of patients with type 2 diabetes mellitus (T2DM) is still challenging. Controlling glucose levels is often compromised by the occurrence of hypoglycaemia and/or weight gain. Incretin-based therapies enhance or mimic the actions of the incretin hormone «glucagon-like peptide-1» (GLP-1), the secretion of which is diminished in T2DM. Since GLP-1 exerts its actions only in the presence of elevated glucose levels, incretin-based agents per se cannot cause hypoglycaemia. In addition, weight gain is not observed. Thus, in recent years incretin-based therapies have become an important therapeutic option. Dipeptidyl peptidase-4 (DPP4) inhibitors, which are taken orally, are approved for monotherapy in patients with an intolerance or contraindication for metformin or those insufficiently controlled on metformin alone in combination with oral antidiabetic drugs as well as insulin. After dosage adjustment they can also be administered to patients with renal impairment. The injectable GLP-1 receptor agonists can be categorised in short-and long-acting compounds. Compared to DPP4 inhibitors, higher levels of GLP-1 activity are achieved leading to a more pronounced reduction in HbAic levels and even weight loss. They are approved for combination therapy with oral antidiabetic drugs and long-acting (basal) insulin. To which extent DPP4 inhibitors and GLP-1 analogues also have beneficial effects on cardiovascular outcomes is subject to ongoing clinical evaluations. Considering the critical benefit assessment by IQWiG and G-BA, in future type 2 diabetic patients in Germany may be deprived of the'several advantages of incretin-based therapies.
Schardt F.W.,Medizinische Klinik und Poliklinik II |
Schmausser B.,University of Würzburg |
Bachmann E.,University of Würzburg
Histology and Histopathology | Year: 2013
The progression of a tumor from benign to malign and localized to invasive and metastatic growth is the major cause of poor outcome of therapy in cancer patients. The deposition of fibrin along with other procoagulant molecules into the extracellular matrix obviously serves as a scaffold to support proliferation, migration and tumor cell growth as well as protection against the immune system. The use of antibodies as agents for the immunodetection of fibrin deposits in vivo has been hampered by anti-fibrin cross-reactivities with fibrinogen. For the immunohistochemical detection of fibrin we used highly specific monoclonal antibodies to a synthetic fibrinunique peptide, because the fibrin molecule shares many epitopes with fibrinogen. The monoclonal antibody was applied to adenocarcinoma of colon, mamma, pancreas, sarcoma and acute myeloic leukemia. In all tissue sections and cytospin preparations fibrin was identified in a direct apposition to the surface membranes of carcinoma and sarcoma cells, predominantly at the host-tumor interface and also in regions directly adjacent to zones of angiogenesis, whereas normal cells and tissue showed no deposits of fibrin. The findings will be supported by investigations that factors and components of the coagulation system could be detected in the tumor stroma and tumor cells. These factors are obviously produced and secreted by the malignant cells and deposited together with fibrinogen into the extracellular matrix. Our results show that basically all malignant cells examined, independently of ectodermal or mesenchymal derivation, themselves are the origin of hypercoagulability and fibrinolytic system inhibition.
PubMed | Friedrich - Alexander - University, Erlangen - Nuremberg, Medizinische Klinik und Poliklinik II and Rheumatologische Schwerpunktpraxis
Type: Journal Article | Journal: Zeitschrift fur Rheumatologie | Year: 2016
Cells of the adaptive immune system are relevant for the anti-tumor immune response; therefore, the basal therapy with disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis patients with a history of gastrointestinal cancer must be carefully considered.This article presents the evidence regarding colorectal cancer (CRC) and rheumatoid arthritis.The article is based on a PubMed search as well as a search in congress abstracts of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Current recommendations regarding screening and follow-up of CRC are summarized for clinically active rheumatologists. The current status of therapy and future therapeutic options are presented. The lower incidence of CRC in rheumatoid arthritis (RA) patients and the incidence under treatment with various DMARDs are described. The treatment options for RA patients in different tumor situations, e.g. during cytostatic therapy, palliative and curative situations are discussed, as well as the available evidence. In spite of the unsatisfactory level of evidence, conclusions and practical considerations for use by rheumatologists in clinical practice are discussed.