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Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m ), trauma history, renal insufficiency and bevacizumab use. Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.

Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM) in Greece. Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid), participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A) and vildagliptin metformin free-dose combination (group B). Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR) 18.9 (95% CI: 6.2, 57.7; P < 0.001 ). In group A mean HbA1c decreased from 8.1% at baseline to 6.9% ( P < 0.001 ) at the study end and from 7.9% to 6.8% ( P < 0.001 ) in group B. Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment.

Introduction Several studies show that mutational profiles could influence treatment decisions in patients with metastatic CRC (mCRC). KRAS mutational status was the first step in biomarkers development in the era of molecular targeted therapies. Recently, NRAS mutational status was identified as an independent prognostic factor for the response to treatment with anti-EGFR moAbs. The aim of this observational study was to assess the feasibility of the KRAS/NRAS mutational analysis in patients with metastatic colorectal cancer in Greece and to identify any correlations with known clinical characteristics and histopathologic features. Methods From January 2014 until September 2014 all patients registered to the GIC-SG database with newly diagnosed metastatic disease from colon or rectal cancer were included and tumor samples were analyzed for kras/nras mutations in 9 different certified laboratories in Greece. Results Samples from 510 patients were analyzed. Mutations’ distribution was as follows: 173 (33,9%) KRAS exon 2, 10 (2%) KRAS exon 3, 25 (4,9%) KRAS exon 4, 22 (4,3%) NRAS exon 2, 11 (2,2%) NRAS exon 3 and 3 (0,6%) NRAS exon 4. The only factor significantly associated with RAS mutational status was primary tumor location, with right sided tumors exhibiting higher rates of mutations. Discussion The incidence and distribution of KRAS or NRAS exon 2-4 mutations are in accordance with those reported in the literature. The most significant clinical or pathological parameter revealed from the analysis is the location of the primary tumor.

This study aimed to provide real-world safety and effectiveness data of everolimus (EVE) plus exemestane (EXE) in estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER /HER2 ) advanced breast cancer (aBC). This prospective observational study was conducted by 19 hospital-based oncologists in Greece. Eligible patients were treated with EVE+EXE in the first-line setting; EVE was initiated according to the approved label. Overall, 75 eligible patients (mean age: 66.9 years; visceral metastases: 49.3%; bone-only metastases: 37.3%) were included in the effectiveness analyses. Over a median (interquartile range) of 12.1 months (range=4.2-20.5 months) of EVE treatment, the median progression-free survival was 18.0 months and the overall response rate was 22.7%. Among patients that received ≥1 EVE dose (n=80), the incidence of EVE-related adverse events was 72.5% (serious: 55.0%); stomatitis (22.5%), fatigue (22.5%), pneumonitis (18.8%); and cough (18.8%) were the most common. In the routine care in Greece, EVE demonstrates clinical benefit and a predictable safety profile.

Purpose Greece has legislated health decentralization several times since the 1920s, but none had been implemented until 2001. Even so, the decentralized system was subsequently modified several times, curtailing the powers that were initially delegated to the health regions, while the whole process has been criticized as limited in scope. The purpose of this paper is to explore the reasons that the decentralization process did not fulfil its initial aims. Design/methodology/approach Elite interviews were conducted with 37 of the 50 directors of health regions who served between 2001 and 2009. Interview transcripts were divided into four themes and analyzed using thematic analysis. Findings The participants agreed that health decentralization in Greece was only administrative rather than political and did not include fiscal decentralization. They described problematic and competitive relations with party officials and civil servants. They blamed their short tenure for the inability to fulfil their plans. Findings indicate that decentralization in Greece did not achieve its objectives because of the dominant mentality of centralized control, the lack of political support, the discontinuity in health policies and opposition from vested interests. Originality/value The value of the present study lies in the fact that it examines in depth the issue of health decentralization drawing on the experiences of the former directors of the Greek health regions, i.e. the persons who were called on to put into practice the process of regional decentralization.

Two new species of the genus Leptophytum Adey are recognized, endemic to NW Spitsbergen respectively East Novaja Zemlya: L. jenneborgii herein described from sublittoral collections around Vasahalvøya, growing on rocks and thalli of Lithothamnion glaciale, and L. arcticum known from a similar habitat at its type locality (Uddebay, East N. Zemlya). Both species exhibit a foliose and relatively large thallus, up to 10 cm in diameter, which develops several layers in an unattached-superimposed pattern, so that thickness reaches at least 1.5 cm. They differ in conceptacle morphology (convex vs rimmed multiporate roofs), including chamber and pore plate size. Their restricted distribution, on the periphery of the presumed northernmost ice limits during the latest glaciation, indicates that they are glacial survivals. Their characteristic habit sets them apart not only from Arctic congeners, but from Arctic corallines in general, and unites them with distantly related taxa from warmer waters, suggesting that they evolved before the beginning of the cooling period (mid-Tertiary) in the Arctic Ocean.

Thromboprophylaxis, as a preventive measure for cancer-associated thrombosis (CAT), may be beneficial for patients with active cancer and high-risk for thrombosis. The present post hoc analysis include a total of 407 patients enrolled in the Greek Management of Thrombosis study, who received thromboprophylaxis with tinzaparin. The objectives of the present analysis were: i) To obtain sufficient evidence for the administration of prophylaxis in patients with active cancer, irrespective of Khorana risk assessment model score; ii) to identify the selection criteria for both dose and duration of tinzaparin; and iii) to evaluate the efficacy and safety of tinzaparin administered for CAT prophylaxis. The main tumor types for the patients included in the present study were as follows: Lung (25.1%), pancreatic (14.3%), breast (9.1%), stomach (8.4%), colorectal (7.9%) and ovarian (7.6%). Furthermore, metastatic disease was observed in 69.5% of the patients. High thrombotic burden agents (HTBAs) were administered to 66.3% of the patients, and 17.4% received erythropoietin. A total of 43.7% of the patients exhibited a Khorana score <2. The results of the present study demonstrated that both the presence of metastatic disease and the use of HTBAs seemed to influence oncologists' decisions for the use of thromboprophylaxis in patients with active cancer, regardless of Khorana score. Tinzaparin, in dose expressed in the standard notation for heparins, i.e., anti-Xa factor international units (Anti-Xa IU), was administered at an intermediate dose (InterD; 8,000-12,000 Anti-Xa IU; once daily) to 52.4% of patients, while the remaining patients received a prophylactic dose (ProD; ≤4,500 Anti-Xa IU; once daily). The average duration of thromoprophylaxis was 5 months. Furthermore, a total of 14 (3.4%) thrombotic events and 6 (1.5%) minor bleeding events were recorded. A total of four thrombotic events were observed following an InterD treatment of tinzaparin, while 10 thrombotic events were observed following ProD treatment. The present study also demonstrated that an InterD of tinzaparin was administered more frequently to patients with a body mass index >30 kg/m2, a history of smoking and a history of metastatic disease, along with administration of erythropoietin. InterD tinzaparin treatment was found to be potentially more efficacious and without safety concerns. The present study is a registered clinical trial (ClinicalTrials.gov code, NCT03292107; registration date, September 25, 2017).

Viscosity can be the major factor governing a system's bulk mechanical properties and internal processes on the microscale such as molecular diffusion. Mechanical and rheological properties measured on the microscale may differ widely from the macroscopic properties of a physical system. While they are of extreme interest in biology, chemistry and in natural sciences, these microscopic properties are often very challenging to measure due to small dimensions of the system under study. Lifetime-based molecular rotors, fluorescent molecules whose fluorescence lifetime decay profile is sensitive to the microviscosity of their environment, can be used in Fluorescence Lifetime Imaging (FLIM) to acquire lifetime/viscosity images of high spatial and temporal resolution. In our study we used molecular rotors to overcome the inherent limitations of current mechanical and spectroscopic methods and to measure and image microviscosity in: i) cells during oxidative stress from singlet oxygen during Photodynamic Therapy (PDT) and ii) organic aerosol particles during chemical ageing and hydration. Organic aerosols (OA) play a prominent role in many atmospheric processes, climate change and can affect human health. Their physical and chemical properties control their lifetime, reaction rates and optical properties. In our study, we utilised a rare combination of optical trapping and FLIM to measure OA viscosity changes, in their true aerosol phase, during atmospherically-relevant oxidation with ozone and hydroxyl radicals. The results were compared with oxidation experiments of OA deposited on the flat surface of a coverslip. The well established lifetime-based rotor Bodipy-C10 was used as a hydrophobic rotor during oxidation of model OA squalene particles. Our results showed a fast viscosity increase to the point of solidification and revealed the development of spatial viscosity heterogeneities during oxidation. A new hydrophilic molecular rotor, thiazole orange (TO), was characterized and used to measure secondary organic aerosol (SOA) viscosity under different relative humidity (RH) conditions, along with the already well characterised lifetime-based hydrophilic rotor Cy3. TO fluorescence quantum yield and lifetime profile showed a marked sensitivity in the high range of viscosities, unlike any other known rotor, rendering TO an ideal viscosity sensor for the highly viscous SOA particles. Atmospherically relevant SOA particles derived from three different volatile compounds (VOCs) were measured and their viscosity was found to vary from hundreds to millions centipoise. The dynamic changes in viscosity of SOA were also measured during a sudden RH change. Intracellular viscosity was measured in the hydrophobic areas of live monolayers of cells using Bodipy-C10 during PDT with two different photosensitisers. Such measurement where the photosensitiser that induced the treatment and the rotor were separate molecules was performed for the first time. Consequently, we were able to use the same rotor (Bodipy-C10) and two different photosensitisers (PSs) with different intracellular localisation: verteporfin (VP) and porphycene (PO1). Their different localisation in cells was confirmed by confocal microscopy. Our results showed a marked viscosity increase over irradiation with both PSs, which resulted in singlet oxygen production and cell death as a result of PDT. This viscosity increase was observed both in the irradiated intracellular areas but also at distant non irradiated locations, believed to result from the formation and diffusion of long lived peroxides. The highest viscosity values measured were different for VP and PO1, as was the distance of remote damage. Overall, the potential of molecular rotors as viscosity sensors was demonstrated in biological and physical systems, providing unprecedented insight on the mechanical properties, with the emphasis on monitoring dynamic changes in viscosity. Our results revealed additional levels of complexity in the systems under study, which was not possible to observe using any other currently available techniques for monitoring viscosity.

Background: Cancer patients are at high risk for cancer-associated thrombosis (CAT). CAT is the second leading cause of death in these patients but it can be preventable with thromboprophylaxis. Patients and Methods: An observational, prospective, multicenter study aiming to record CAT management in clinical practice was conducted by the Hellenic Society of Medical Oncology (HeSMO). Results: A total of 426 active cancer patients (mean age 65.3 years, mean BMI: 26.1 kg/m2) who received thromboprophylaxis, were included from 18 oncology units. Tumor types were lung 25.1%, pancreas 13.9%, breast 8.7%, stomach 8.5%, ovarian 7.8%, and others 36%, while 69% had metastases. A total of 71% had a Khorana score ≤2 and 61% received High Thrombotic Risk Chemotherapy Agents (HTRCAs, e.g., platinum). For thromboprophylaxis patients received mainly Low Molecular Weight Heparins (LMWHs), on higher than prophylactic doses in 50% of cases. Overall, 16 (3.8%) thrombotic events and 6 (1.4%) bleeding events were recorded. Notably, patients on higher doses of LMWHs compared to patients who received standard prophylactic doses had 70% lower odds to develop thrombotic events (OR: 0.3, 95% CI: 0.10–1.0, p = 0.04). Conclusion: CAT is an important issue in oncology. Along with the Khorana score, factors as metastases and use of HTRCAs should also be taken into consideration. Thromboprophylaxis for active cancer patients with LMWHs, even on higher doses is safe and efficient.

Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive early breast cancer. However, which is the preferable taxane in a dose-dense regimen remains unknown. We conducted a randomized study to compare the efficacy of dose-dense paclitaxel versus docetaxel following 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) as adjuvant chemotherapy in women with node-positive early breast cancer. Following surgery women with HER2-negative breast cancer and at least one infiltrated axillary lymph node were randomized to receive four cycles of FEC (700/75/700 mg/m 2 ) followed by four cycles of either paclitaxel (175 mg/m 2 ) or docetaxel (75 mg/m 2 ). All cycles were administered every 14 days with G-CSF support. The primary endpoint was disease-free survival (DFS) at 3 years. Between 2004 and 2007, 481 women were randomized to paclitaxel ( n  = 241) and docetaxel ( n  = 240). After a median follow-up of 6 years, 51 (21 %) and 48 (20 %) women experienced disease relapse ( p  = 0.753) and there was no significant difference in DFS between the paclitaxel- and docetaxel-treated groups (3-year DFS 87.4 vs. 88.3 %, respectively; median DFS not reached; p  = 0.633). Toxicities were manageable, with grade 2–4 neutropenia in 21 versus 31 % ( p  = 0.01), thrombocytopenia 0.8 versus 3.4 % ( p  = 0.06), any grade neurotoxicity 17 versus 7.5 % ( p  = 0.35) and onycholysis 4.9 versus 12.1 % ( p  = 0.03) for patients receiving paclitaxel and docetaxel, respectively. There were no toxic deaths. Dose-dense paclitaxel versus docetaxel after FEC as adjuvant chemotherapy results in a similar 3-year DFS rate in women with axillary node-positive early breast cancer. Due to its more favorable toxicity profile, paclitaxel is the taxane of choice in this setting.