FOLFIRI Plus Bevacizumab 5 mg/kg Versus 10 mg/kg as Second-line Therapy in Patients with Metastatic Colorectal Cancer Who Have Failed First-line Bevacizumab Plus Oxaliplatin-based Therapy: A Randomized Phase III Study (EAGLE Study)

We planned a multicenter randomized phase III study to evaluate the efficacy of appropriate dose of bevacizumab (5 or 10 mg/kg) with FOLFIRI in patients with advanced/metastatic colorectal cancer who have failed prior bevacizumab plus oxaliplatin-based therapy. The primary endpoint is progression-free survival. The secondary endpoints are the toxicity, response rate, time to treatment failure, overall survival, overall survival from the start of the first-line treatment and second progression-free survival (time duration from the initiation of the first-line treatment until progression after the protocol treatment). A total of 370 patients were considered to be appropriate for this trial

Quality of human-computer interaction - results of a national usability survey of hospital-IT in Germany

<p>Abstract</p> <p>Background</p> <p>Due to the increasing functionality of medical information systems, it is hard to imagine day to day work in hospitals without IT support. Therefore, the design of dialogues between humans and information systems is one of the most important issues to be addressed in health care. This survey presents an analysis of the current quality level of human-computer interaction of healthcare-IT in German hospitals, focused on the users' point of view.</p> <p>Methods</p> <p>To evaluate the usability of clinical-IT according to the design principles of EN ISO 9241-10 the IsoMetrics Inventory, an assessment tool, was used. The focus of this paper has been put on suitability for task, training effort and conformity with user expectations, differentiated by information systems. Effectiveness has been evaluated with the focus on interoperability and functionality of different IT systems.</p> <p>Results</p> <p>4521 persons from 371 hospitals visited the start page of the study, while 1003 persons from 158 hospitals completed the questionnaire. The results show relevant variations between different information systems.</p> <p>Conclusions</p> <p>Specialised information systems with defined functionality received better assessments than clinical information systems in general. This could be attributed to the improved customisation of these specialised systems for specific working environments. The results can be used as reference data for evaluation and benchmarking of human computer engineering in clinical health IT context for future studies.</p

The role of tenascin-C in tissue injury and tumorigenesis

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer

Low-density lipoprotein cholesterol is associated with insulin secretion.

OBJECTIVE: Pharmacological lowering of LDL cholesterol potently reduces cardiovascular risk while concurrently increasing type 2 diabetes risk. The aim of this study was to investigate the relationship between LDL cholesterol concentrations and insulin secretion and glucagon levels. METHODS: 3,039 subjects without cholesterol lowering therapy, but with increased risk for diabetes, underwent routine blood tests and a 5-point oral glucose tolerance test (OGTT). Glucagon concentrations, insulin secretion and insulin clearance indices were derived from the OGTT. RESULTS: There was no association between LDL cholesterol and fasting glucagon (p=0.7, ß=-0.01) or post glucose load glucagon levels (p=0.7, ß=-0.07), but we detected significant positive associations of LDL cholesterol and C-peptide-based indices of insulin secretion (AUCC-Peptide(0-30min)/AUCGlucose(0-30min): p=0.0001, ß=0.06; AUCC-Peptide(0-120min)/AUCGlucose(0-120min): p&lt;0.0001, ß=-0.08). In contrast we found a negative association of insulin-based insulin secretion indices with LDL concentrations (Insulinogenic index: p=0.014, ß=-0.04; disposition index: p=0.0005, ß=-0.06). Though, LDL cholesterol levels were positively associated with insulin clearance assessed from C-peptide and insulin concentrations, both in the fasting state and post glucose load (p&lt;0.0001, ß=0.09 and p&lt;0.0001, ß=0.06, respectively). CONCLUSION: As C-peptide based indices reflect insulin secretion independent of hepatic clearance, our results indicate lower insulin secretion in case of lesser LDL cholesterol. This could explain deteriorating glycemic control in response to cholesterol lowering drugs

Effect of SGLT2 inhibitors on body composition, fluid status and renin-angiotensin-aldosterone system in type 2 diabetes: A prospective study using bioimpedance spectroscopy.

BackgroundSGLT2-inhibitors are potent antihyperglycemic drugs for patients with type 2 diabetes and have been shown to reduce body weight. However, it is unclear which body compartments are reduced and to what extent.MethodsIn this longitudinal observational study, we analyzed the body composition of 27 outpatients with type 2 diabetes mellitus during the first week and up to 6months after initiation of treatment with SGLT2-inhibitors (n=18 empagliflozin, n=9 dapagliflozin) using bioimpedance spectroscopy (BCM, Fresenius). Fluid status of hypertensive patients taking medication with hydrochlorothiazide (n=14) and healthy persons (n=16) were analyzed for comparison.ResultsAt 6months, HbA1c decreased by 0.8% (IQR 2.3; 0.4), body weight and BMI by 2.6kg (1.5; 9.3) and 0.9kg/m(2) (0.4; 3.3), respectively. Bioimpedance spectroscopy revealed significant decrease in adipose tissue mass and fat tissue index while lean tissue parameters remained stable. Overhydration (OH) and extracellular water (ECW) decreased by -0.5L/1.73m(2) (-0.1; -0.9) and -0.4 L/1.73m(2) (-0.1; -0.8) at day 3, respectively, and returned to the initial value after 3 and 6months. Plasma renin activity increased by 2.1-fold (0.5; 3.6) at 1month and returned to the initial level at month 3 and 6. Fluid status of patients with SGLT2 inhibitors after 6months showed no difference from that of hypertensive patients taking hydrochlorothiazide or healthy persons.ConclusionsBody weight reduction under the treatment with SGLT2-inhibitors is caused by reduction of adipose tissue mass and transient loss of extracellular fluid, which is accompanied by upregulation of renin-angiotensin-aldosterone system (RAAS). Permanent loss of extracellular water does not occur under SGLT2 inhibition