PubMed | Gesundheitszentrum St. Marien, Haematology and Oncology, Ludwig Maximilians University of Munich, Johannes Gutenberg University Mainz and 5 more.
Type: | Journal: International journal of cancer | Year: 2016
We explored the association of early tumor shrinkage (ETS) and non-ETS with efficacy of first-line and consecutive second-line treatment in patients with KRAS wild-type metastatic colorectal cancer treated in FIRE-3. Assessment of tumor shrinkage was based on the sum of longest diameters of target lesions, evaluated after six weeks of treatment. Shrinkage was classified as ETS (shrinkage by20%), mETS (shrinkage by 0% - <20%), mPD (minor progression >0% - <20%) and PD (progression 20%). Overall survival (OS) was 33.2 (95% CI 28.0-38.4) months in ETS patients, while non-ETS was associated with less favourable outcome (mETS 24.0 (95% CI 21.2-26.9) months, mPD 19.0 (95% CI 13.0-25.0) months, PD 12.8 (95% CI 11.1-14.5) months). Differences in PFS of first-line therapy were less pronounced. ETS subgroups defined in 1st-line therapy also correlated with efficacy of 2nd-line therapy. Progression-free survival in 2nd-line (PFS2nd) was 6.5 months (5.8-7.2) for ETS, and was 5.6 (95% CI 4.7-6.5) months for mETS, 4.9 (95% CI 3.7-6.1) months for mPD and 3.3 (95% CI 2.3-4.3) months for PD. PFS of first-line and PFS2nd showed a linear correlation (Bravais-Pearson coefficient: 0.16, P=0.006). While ETS is associated with the most favourable outcome, non-ETS represents a heterogeneous subgroup with distinct characteristics of less favourable initial tumor response to treatment. This is the first analysis to demonstrate that early tumor response observed during 1st-line FOLFIRI-based therapy may also relate to efficacy of 2
PubMed | Klinik fur Kardiologie II, Universitatsklinikum Kiel, Klinik III fur Innere Medizin, Universitares Herzzentrum Hamburg and 12 more.
Type: Journal Article | Journal: Herzschrittmachertherapie & Elektrophysiologie | Year: 2015
The AV nodal reentrant tachycardia (AVNRT) is one of the most common arrhythmias encountered in clinical practice. It is characterized by a constant heart rate and an on/off phenomenon. The clinical symptoms may include palpitations, anxiety, polyuria, and dyspnea. Typically, tachycardia may be disrupted by vagal maneuvers in many patients. First-line treatment of symptomatic AVNRT is radiofrequency ablation. The present article deals with the characteristics, differential diagnosis and treatment of AVNRT in the EP lab. It is the second part of a series of manuscripts which may facilitate further education in the specific field of electrophysiology.
Luik A.,Medizinische Klinik IV |
Radzewitz A.,Medizinische Klinik IV |
Kieser M.,University of Heidelberg |
Walter M.,Medizinische Klinik IV |
And 10 more authors.
Circulation | Year: 2015
Background - There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency (RF) and cryoballoon catheter (CB) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation. Methods and Results - In a prospective, noninferiority study, 315 patients were randomly assigned to RF (n=159) or CB (n=156) ablation. The primary end point was freedom from atrial arrhythmia with absence of persistent complications. Patients were largely comparable between groups with more vascular disease in the RF group (8.2% versus 2.6% for CB; P=0.028). The primary end point at 12 months was achieved by 70.7% with RF and 73.6% with CB (multiple procedure success), including 31 redo procedures in each group (19.5% of RF versus 19.9% of CB; P=0.933). For the intention-to-treat population, noninferiority of CB was revealed for the predefined inferiority margin (risk difference, 0.029; 95% confidence interval, -0.074 to 0.132; P<0.001). Rates at 6 months were 63.1% and 64.1% for the RF and CB groups (single procedure success), and noninferiority was confirmed (risk difference, 0.010; 95% confidence interval, -0.097 to 0.116; P=0.002). Periprocedural complications for the index procedure were more frequent in the CB group (5.0% RF, 12.2% CB; P=0.022) with a significant difference in phrenic nerve palsies (0% RF, 5.8% CB; P=0.002). Conclusion - This large, prospective, randomized, controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation. © 2015 The Authors. © 2015 The Authors.
The incretin concept - From physiology to innovative diabetes therapy with GLP-1 anagoges and DPPIV inhibitors [Das inkretinkonzept - Von der physiologie zur innovativen diabetestherapie mit GLP-1-analoga und DPPIV-inhibitoren]
Gallwitz B.,Medizinische Klinik IV
Medizinische Welt | Year: 2010
With incretin based therapies (DPPIV inhibitors and GLP-1 analogues) novel antidiabetic drugs are available since 2007. In contrast to other insulinotropic compounds, they stimulate insulin secretion in a glucose-dependent manner during hyperglycemia and they do not have an intrinsic risk for causing hypoglycaemia. Additionally, they inhibit glucagon secretion and have a favourable effect on body weight. DPPIV inhibitors (sitagliptin, saxagliptin and vildagliptin) can be used for combination therapy with metformin, glitazones and sulfonylureas according to the guidelines. Their effectiveness is comparable to other oral antidiabetics. DPPIV inhibitors are weight neutral. Their tolerability is good, specific side effects are not known. GLP-1 analogues (exenatide and liraglutide) are injectable medications with similar indications according to the guidelines. They are more effective than DPPIV inhibitors and additionally allow weight loss. Further incretin based substances are in the approval process or in clinical development. © Schattauer 2010.
Gallwitz B.,Medizinische Klinik IV
Pediatric Nephrology | Year: 2010
Treatment options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were first introduced in 2005. These comprise the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In adult medicine, both treatment options are attractive and more commonly used because of their action and safety profile. The incretinbased therapies stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner and carry no intrinsic risk of hypoglycaemia. GLP-1 receptor agonists allow weight loss, whereas DPP-4 inhibitors are weight neutral. This review gives an overview of the mechanism of action and the substances and clinical data available. © IPNA 2010.
He H.,Chongqing Medical University |
Yang D.,Chongqing Medical University |
Ma L.,Chongqing Medical University |
Luo Z.,Chongqing Medical University |
And 7 more authors.
Hypertension | Year: 2010
Telmisartan shows antihypertensive and several pleiotropic effects that interact with metabolic pathways. In the present study we tested the hypothesis that telmisartan prevents adipogenesis in vitro and weight gain in vivo through activation of peroxisome proliferator-activated receptor (PPAR)-δ- dependent pathways in several tissues. In vitro, telmisartan significantly upregulated PPAR-δ expression in 3T3-L1 preadipocytes in a time-and dose-dependent manner. Other than enhancing PPAR-δ expression by 68.2±17.3% and PPAR-δ activity by 102.0±9.0%, telmisartan also upregulated PPAR-γ expression, whereas neither candesartan nor losartan affected PPAR-δ expression. In vivo, long-term administration of telmisartan significantly reduced visceral fat and prevented high-fat diet-induced obesity in wild-type mice and hypertensive rats but not in PPAR-δ knockout mice. Administration of telmisartan did not influence food intake in mice. Telmisartan influenced several lipolytic and energy uncoupling related proteins (UCPs) and enhanced phosphorylated protein kinase A and hormone sensitive lipase but reduced perilipin expression and finally inhibited adipogenesis in 3T3-L1 preadipocytes. Telmisartan-associated reduction of adipogenesis in preadipocytes was significantly blocked after PPAR-δ gene knockout. Chronic telmisartan treatment upregulated the expressions of protein kinase A, hormone-sensitive lipase, and uncoupling protein 1 but reduced perilipin expression in adipose tissue and increased uncoupling protein 2 and 3 expression in skeletal muscle in wild-type mice but not in PPAR-δ knockout mice. We conclude that telmisartan prevents adipogenesis and weight gain through activation of PPAR-δ-dependent lipolytic pathways and energy uncoupling in several tissues. © 2010 American Heart Association, Inc.
Gallwitz B.,University Hospital of Tuebingen |
Hamann A.,Medizinische Klinik IV
Diabetes Aktuell | Year: 2013
Treatment of type 2 diabetes remains a challenge in spite of new treatment options and modern types of insulin, in particular for obese subjects. It is frequently difficult to achieve strict HbA1c targets, and even in case of success this frequently happens at the expense of weight gain and an increased risk of hypoglycemia. Therefore, new treatment strategies are needed in particular for the high risk patient population with obesity, insulin resistance and inadequately high HbA1c. From a pathophysiological perspective, it is reasonable to combine insulin and glucagon-like peptide 1 (GLP 1) receptor agonists, although hard clinical data regarding the reduction of micro- and macrovascular complications are still missing. This review summarizes the clinical data available and illustrates that combined treatment with insulin plus GLP-1 receptor agonist will frequently achieve improved glycemic control and results in weight loss, with only a slightly increased risk of hypoglycemia, but associated with the known gastrointestinal side effect profile of GLP-1 receptor agonists. Additionally, this review explains why short-acting GLP-1 receptor agonists that are associated with a marked decrease of postprandial blood glucose levels may be particularly suitable for a combination with basal insulin, whereas long-acting GLP-1 receptor agonists that primarily aim at fasting blood glucose control may be more suitable for a combination with more complex insulin regimens such as the intensified conventional insulin therapy, although comparative clinical data are also missing here. © Georg Thieme Verlag KG Stuttgart New York.
Wolf K.-H.,Hannover Medical School |
Hetzer K.,Medizinische Klinik IV |
zu Schwabedissen H.M.,Medizinische Klinik IV |
Wiese B.,Hannover Medical School |
Marschollek M.,Hannover Medical School
Zeitschrift fur Gerontologie und Geriatrie | Year: 2013
Background: Falls are a major problem in hospitals and nursing homes. The consequences of falls can be severe, both for the individual and for the caring institution. Objective: The aim of the work presented here is to reduce the number of falls on a geriatric ward by monitoring patients more closely. To achieve this goal, a bed-exit alarm that reliably detects an attempt to get up has been constructed. Materials and methods: A requirements analysis revealed the nurses' and physicians' needs and preferences. Based on the gathered information, an incremental design process generated different prototypes. These were tested for the reliability of their ability to detect attempts to get up in both laboratory settings and with geriatric patients. Based on the result of these tests, a scalable technical solution has been developed and proven its reliability in a 1-year, randomized controlled pilot clinical trial on a geriatric ward. Results: The developed system is unobtrusive and easy to deploy. It has been tested in laboratory settings, usability tests and a 1-year randomized clinical trial with 98 patients. This paper focuses on the technical development of the system. We present different prototypes, the experiments and the pilot study used to evaluate their performance. Last but not least, we discuss the lessons learned so far. Conclusion: The developed bed-exit alarm is able to reliably detect patients' attempts to get up. The results of the clinical trial show that the system is able to reduce the number of falls on a geriatric ward. Next steps are the design of a specialized sensor node that is easier to use and can be applied on an even larger scale due to its reduced cost. A multicenter trial with a larger number of patients is required to confirm the results of this pilot study. © 2013 Springer-Verlag Berlin Heidelberg.
Wei W.,Medizinische Klinik IV |
Tolle M.,Medizinische Klinik IV |
Zidek W.,Medizinische Klinik IV |
Van Der Giet M.,Medizinische Klinik IV
Blood Pressure Monitoring | Year: 2010
Objective: Twenty-four-hour blood pressure measurement is of importance not only in the detection of hypertension but also in the detection of blood pressure changes in hypertensive and nonhypertensives over the day to identify, for example, nondipper hypertensives. This study describes the validation of the mobil-O-Graph according to the criteria of the British Hypertension Society (BHS). METHODS: For each patient three readings obtained by the mobil-O-Graph were compared with auscultatory sphygmomanometric readings obtained by two trained clinicians. The sphygmomanometric reference measurements were alternated with the readings obtained by the device. Eighty-five patients (mean age 53.4±18.4 years) were recruited for the BHS protocol. Differences between blood pressure values of the test device and the mercury reading were calculated for each measurement. RESULTS: In the BHS validation procedure the mean differences of the observer readings and the test device were -2.2±6.7 (systolic) and -0.6±5.6mmHg (diastolic) for observer 1 and -2.2±7.3mmHg (systolic) and-0.4±6.1mmHg (diastolic) for observer 2. The device achieved grade A for systolic and diastolic blood pressure for both the observers 1 and 2 leading to a final grade A/A. According to the BHS protocol the measurements of the device have to be considered 'very accurate and with no error of clinical relevance'. CONCLUSION: The device met the accuracy requirements of the BHS standard and can be recommended for clinical use. © Lippincott Williams & Wilkins.
Gallwitz B.,Medizinische Klinik IV
Handbook of Experimental Pharmacology | Year: 2015
Novel therapeutic options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were introduced in 2005. Incretinbased therapies consist of two classes: (1) the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor and (2) dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) as oral medications raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In type 2 diabetes therapy, incretin-based therapies are attractive and more commonly used due to their action and safety profile. Stimulation of insulin secretion and inhibition of glucagon secretion by the above-mentioned agents occur in a glucose-dependent manner. Therefore, incretinbased therapies have no intrinsic risk for hypoglycemias. GLP-1 receptor agonists allow weight loss; DPP-4 inhibitors are weight neutral. This review gives an overview on the mechanism of action and the substances and clinical data available. © Springer-Verlag Berlin Heidelberg 2011.