Sparse kernel methods for high-dimensional survival data
Abstract Sparse kernel methods like support vector machines (SVM) have been applied with great success to classification and (standard) regression settings. Existing support vector classification and regression techniques however are not suitable for partly censored survival data, which are typically analysed using Cox's proportional hazards model. As the partial likelihood of the proportional hazards model only depends on the covariates through inner products, it can be ‘kernelized’. The kernelized proportional hazards model however yields a solution that is dense, i.e. the solution depends on all observations. One of the key features of an SVM is that it yields a sparse solution, dependin…
Different calculations of ankle-brachial index and their impact on cardiovascular risk prediction.
Background— An ankle-brachial index (ABI; ratio of ankle and brachial systolic blood pressure) <0.9 indicates peripheral arterial disease (PAD) and is a strong predictor of cardiovascular events. The aim of the present study was to address the prognostic value of different methods of ABI calculation. Methods and Results— In 831 patients admitted with chest pain for diagnostic heart catheterization, blood pressure of both anterior and posterior tibial arteries was measured. ABI was calculated for each leg with the higher of the 2 ankle pressures (current definition of the American Heart Association) or with the lower of the 2 ankle pressures (modified definition) in relation to the highe…
Neue Perspektiven der laparoskopischen Simulation: Vom Studententrainingslabor bis zur Stressevaluation
Hintergrund: Die Anwendung eines LapSim®-Trainingsmodells im Studententrainingslabor sowie die objektive Evaluation von Stress in einem virtuellen Operations-Szenario bieten neue Perspektiven der laparoskopischen Simulation. Methodik: Im Studententrainingslabor erfolgte bei 28 Probanden am LapSim® Virtual-Reality (VR)-Simulator in einem Trainingscurriculum, bestehend aus 9 Einheiten, die Erfassung von Lernkurven laparoskopischer Basisfertigkeiten sowie komplexer Prozesse. In einem virtuellen Operations-Szenario wurde des Weiteren bei 18 Chirurgen eine Stressevaluation mittels eines Sympathikografen vorgenommen und dabei die laparoskopische Fehler- und Komplikationsrate erfasst. Hierbei konn…
Resistin, acute coronary syndrome and prognosis results from the AtheroGene study
Resistin, an adipocyte and macrophage derived cytokine, causes insulin resistance and glucose intolerance. We investigated the impact of resistin as a diagnostic marker in patients with acute coronary syndrome and its prognostic value for future cardiovascular events.Resistin levels were determined in 1153 patients with stable angina (SAP), 380 patients with unstable angina, 278 patients with non-ST-elevation myocardial infarction (NSTEMI) and 111 patients with ST-elevation myocardial infarction (STEMI). All patients have been followed up for a median follow-up of 2.6 years. During follow-up, 70 patients died from cardiovascular causes.Compared to SAP, resistin levels (5.1 ng/mL in SAP) wer…
Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study
Aims Chronic kidney disease is associated with increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably mirror renal function. The role of cystatin C in patients with coronary artery disease (CAD) and normal or mildly reduced kidney function is the subject of current investigation. Methods and results In 2162 patients, over the whole spectrum of CAD, baseline cystatin C concentrations were measured. Patients with an estimated glomerular filtration rate of ≤60 mL/min per 1.73 m2 ( n = 295) were excluded. In patients with complete follow-up information ( n = 1827), 66 cardiovascular deaths were registered during a median follow-up of 3.65 years. Logarithmically t…
B-type natriuretic peptide as a marker for sepsis-induced myocardial depression in intensive care patients.
In early stages of septic shock, impaired myocardial function plays an important prognostic role. In this context, B-type natriuretic peptide (BNP) has been shown to be a neurohumoral marker for left ventricular dysfunction, because myocardial strain and ischemia both increase BNP concentration. The present study was designed to test if BNP allows for identification of patients at risk for developing sepsis-induced myocardial depression and if an increased concentration of BNP is associated with an adverse outcome in patients with septic shock.In a prospective study, 93 patients with septic shock were divided into one group with normal ventricular function (left ventricular ejection fractio…
Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the AtheroGene study.
Aims Metalloproteinases are proteolytic enzymes, which decompose the extracellular matrix, influence cardiac remodelling, and are inhibited by tissue inhibitor of metalloproteinases (TIMPs). Little is known about the prognostic impact of the TIMP-1/matrix metalloproteinase complex in patients with future cardiovascular death. Methods and results In 1979 patients with suspected coronary artery disease (CAD), TIMP-1 has been determined at baseline. Among 1945 (98.4%) patients with a mean follow-up period of 2.6±1.2 years, 75 patients died because of cardiovascular causes. Mean concentrations of TIMP-1 were higher among patients who experienced a fatal cardiovascular event than among those who…
Safety and Efficacy of Sorafenib in Patients With Advanced Hepatocellular Carcinoma in Consideration of Concomitant Stage of Liver Cirrhosis
GOALS AND BACKGROUND: The multikinase inhibitor sorafenib provides survival benefit for patients with advanced hepatocellular carcinoma (HCC) and liver cirrhosis (LCI) Child-Pugh A. We report our experiences with sorafenib in advanced HCC, particularly in patients with LCI Child-Pugh B/C, where only limited data are available in regard to safety and efficacy of sorafenib. METHODS: Thirty-four patients with advanced HCC were treated with sorafenib regardless of liver function and prior anticancer therapy. Adverse events (AEs) were graded using Common Toxicity Criteria version 3.0, tumor response was assessed according to Response Evaluation Criteria in Solid Tumors. RESULTS: Fifteen patients…
Femoropopliteal prosthetic bypass with glutaraldehyde stabilized human umbilical vein (HUV).
Objective Femoropopliteal bypass still is the standard surgical therapy for disabling claudication and critical ischemia. When autologous vein is not suitable synthetic or biological prostheses may be considered. Second generation glutaraldehyde tanned human umbilical vein (HUV) graft was chosen for above and below knee femoropopliteal bypass when autologous vein was not available. A single center experience regarding long-term graft function, secondary reinterventions, and potential biodegeneration of the HUV is presented. Methods Between January 1994 and January 2005, 211 consecutive femoropopliteal bypass operations with HUV (65 above knee and 146 below knee) were performed in 197 patien…
Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease
Background Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease (CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial. Methods Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-…
Searching for Gene Expression Differences in Primary Fibroblasts Between Patients with One and Two Neoplasms in Childhood
Genetic factors are important for developing primary and subsequent malignancies in children. This study investigated the role of genetic factors involved in DNA-repair. Designed as a feasibility study, it addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. Testing feasibility was as important as the biological question itself. We analyzed the expression of DNA-repair genes in untreated primary fibroblasts of 20 individuals with a second neoplasm compared to 20 matched single neoplasm cases using customized cDNA microarrays (1344 gene sequences, about 800 genes). Matching was by first neoplasm, age, and year …
Impact of C-reactive protein and fibrinogen on cardiovascular prognosis in patients with stable angina pectoris: the AtheroGene study.
Aims C-reactive protein and fibrinogen have been extensively studied and shown to be predictive for a first cardiovascular event in healthy individuals. We evaluated the potential clinical use of C-reactive protein and fibrinogen in patients already suffering from coronary artery disease (CAD). Methods and results In a substudy of the prospective Athero Gene registry, we assessed in 1806 patients with documented CAD and stable angina pectoris, the risk of cardiovascular death and non-fatal myocardial infarction ( n =183) over a median follow-up of 3.5 (maximum 7.7) years according to baseline levels of C-reactive protein and fibrinogen. C-reactive protein and fibrinogen were associated with…
Abstract 5504: Second neoplasms after childhood cancer and gene expression differences in primary fibroblasts
Abstract Treatment of the primary neoplasm with radiotherapy or chemotherapy is an established risk factor for second neoplasms (SNs) after childhood cancer. As only a small percentage of the treated children suffer from SN, other shared risk factors must be involved. A predisposition for the occurrence of a SN might be a pre-existing somatic genetic defect associated with DNA repair. We investigated the association between gene expression involved in DNA-repair and the development of SNs after childhood cancer. Designed as a feasibility study this project addressed the possibility of obtaining samples for genetic analyses from former patients through the German Childhood Cancer Registry. W…