Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor-positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials.

BACKGROUND: Randomised trials comparing the efficacy of standard endocrine therapy (ET) versus experimental ET + bevacizumab (Bev) in 1st line hormone receptor-positive patients with metastatic breast cancer have thus far shown conflicting results. PATIENTS AND METHODS: We pooled data from two similar phase III randomised trials of ET ± Bev (LEA and Cancer and Leukemia Group B 40503) to increase precision in estimating treatment effect. Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Exploratory analyses were performed within subgroups defined by patients with recurrent disease, de novo disease, prior endocrine sensitivity or resistance and reported grades III-IV hypertension and proteinuria. RESULTS: The pooled sample consisted of 749 patients randomised to ET or ET + Bev. Median PFS was 14.3 months for ET versus 19 months for ET + Bev (unadjusted hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.66-0.91; p < 0.01). ORR and CBR with ET and ET + Bev were 40 versus 61% (p < 0.01) and 64 versus 77% (p < 0.01), respectively. There was no difference in OS (HR 0.96; 95% CI 0.77-1.18; p = 0.68). PFS was superior for ET + Bev for endocrine-sensitive patients (HR 0.68; 95% CI 0.53-0.89; p = 0.004). Grade III-IV hypertension (2.2 versus 20.1%), proteinuria (0 versus 9.3%), cardiovascular (0.5 versus 4.2%) and liver events (0 versus 2.9%) were significantly higher for ET + Bev (all p < 0.01). Hypertension and proteinuria were not predictors of efficacy (interaction test p = 0.33). CONCLUSION: The addition of Bev to ET increased PFS overall and in endocrine-sensitive patients but not OS at the expense of significant additional toxicity. TRIALS REGISTRATION: ClinicalTrial.Gov NCT00545077 and NCT00601900.

Induction of proliferation of basal epidermal keratinocytes by cold atmospheric-pressure plasma.

BACKGROUND: Over the past few decades, new cold plasma sources have been developed that have the great advantage of operating at atmospheric pressure and at temperatures tolerable by biological material. New applications for these have emerged, especially in the field of dermatology. Recently it was demonstrated that cold atmospheric-pressure plasma positively influences healing of chronic wounds. The potential of cold plasma lies in its capacity to reduce bacterial load in the wound while at the same time stimulating skin cells and therefore promoting wound closure. In recent years, there have been great advances in the understanding of the molecular mechanisms triggered by cold plasma involving signalling pathways and gene regulation in cell culture. AIM: To investigate cold plasma-induced effects in ex vivo treated human skin biopsies. METHODS: Human skin tissue was exposed to cold plasma for different lengths of time, and analysed by immunofluorescence with respect to DNA damage, apoptosis, proliferation and differentiation markers. RESULTS: After cold plasma treatment, the epidermal integrity and keratin expression pattern remained unchanged. As expected, the results revealed an increase in apoptotic cells after 3 and 5 min of treatment. Strikingly, an induction of proliferating basal keratinocytes was detected after cold plasma exposure for 1 and 3 min. As these are the cells that regenerate the epidermis, this could indeed be beneficial for wound closure. CONCLUSION: We investigated the effect of cold plasma on human skin by detecting molecules for growth and apoptosis, and found that both processes are dependent on treatment time. Therefore, this approach offers promising results for further applications of cold plasma in clinical dermatology.

A Novel Approach to Visualizing Dark Matter Simulations.

In the last decades cosmological N-body dark matter simulations have enabled ab initio studies of the formation of structure in the Universe. Gravity amplified small density fluctuations generated shortly after the Big Bang, leading to the formation of galaxies in the cosmic web. These calculations have led to a growing demand for methods to analyze time-dependent particle based simulations. Rendering methods for such N-body simulation data usually employ some kind of splatting approach via point based rendering primitives and approximate the spatial distributions of physical quantities using kernel interpolation techniques, common in SPH (Smoothed Particle Hydrodynamics)-codes. This paper proposes three GPU-assisted rendering approaches, based on a new, more accurate method to compute the physical densities of dark matter simulation data. It uses full phase-space information to generate a tetrahedral tessellation of the computational domain, with mesh vertices defined by the simulation's dark matter particle positions. Over time the mesh is deformed by gravitational forces, causing the tetrahedral cells to warp and overlap. The new methods are well suited to visualize the cosmic web. In particular they preserve caustics, regions of high density that emerge, when several streams of dark matter particles share the same location in space, indicating the formation of structures like sheets, filaments and halos. We demonstrate the superior image quality of the new approaches in a comparison with three standard rendering techniques for N-body simulation data.

Post-duty psychomotor performance in young and senior anaesthetists.

BACKGROUND AND OBJECTIVE: The level of performance in junior and senior anaesthetists was investigated after 24-h shift working and on-call duties. METHODS: Pre- and post-duty psychomotor function, influence on response time, cognitive function and well-being in 23 individuals (13 junior and 12 senior anaesthetists) was assessed before and after 24-h in-house on-call duty. Subjective perception of tiredness and concentration abilities was estimated by applying a visual analogue scale. RESULTS: The self-assessed tiredness prior to duty was high in both age groups and significantly increased in senior anaesthetists after night duty (P = 0.01). Post-duty impairment of concentration abilities was reported in both groups. Comparing results from pre- and post-duty psychometric testing showed a comparable decline in junior and senior anaesthetists as well. Assessment of burnout showed a significant lack of personal accomplishment in junior anaesthetists as compared to their older colleagues (P = 0.038). Senior anaesthetists judged their contribution to patient well-being significantly higher than did their younger colleagues (P = 0.035). CONCLUSIONS: Although tiredness and subjective impairment of concentration abilities was high in senior anaesthetists after 24-h in-house on-call duty, performance assessed by psychometric testing does not support the hypothesis that senior colleague's performance cannot keep up with routine hospital shift work.

Economic evaluation of the societal costs of hepatitis B in South Korea.

BACKGROUND AND AIMS: Hepatitis B (HBV) infection remains a major public health problem in South Korea, and accounts for considerable morbidity and mortality. At present, very little is known about the cost of HBV to the South Korean health-care system and society. The present study was therefore conducted to estimate the total annual cost of HBV infection in South Korea for a given year (1997). METHODS: The study was conducted from the South Korean societal perspective, taking into account the direct and indirect costs of HBV vaccination programs (prevention costs), and those related to the treatment of acute and chronic hepatitis, cirrhosis and liver cancer (disease costs). Several assumptions were made in arriving to actual cost estimates. RESULTS: The total societal cost of HBV in 1997 was 1078.3 billion Won ($US 959.7 million), 142.3 billion Won or 13.2% being attributable to prevention costs and 225.4 billion Won or 20.9% being attributable to indirect costs of HBV-related diseases. The total cost (direct plus indirect) associated with HBV-related diseases to the South Korean society was 936.1 billion Won ($US 833.1 million), of which 45.3% was attributable to cirrhosis-related costs. In terms of disease-related direct costs alone (710.5 billion Won or $US 632.3 million), the estimated annual spending per patient was 1.37 million Won ($US 1219). The direct costs of the HBV disease (prevention and disease treatment, amounting to 782.2 billion Won or $US 696.2 million) is equivalent to 3.2% of the national health-care expenditure for 1997. CONCLUSIONS: This study confirms that HBV is a significant cost burden to the South Korean society, and in the absence of an effective cure reinforces the importance of continued disease prevention via vaccination.

Risk for tuberculosis infection among internally displaced persons in the Republic of Georgia.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection and disease among internally displaced persons residing in Tbilisi, Republic of Georgia. DESIGN: Residents of eight refugee hostels were screened for TB infection using a tuberculin skin test (TST) and a symptom questionnaire. Participation was voluntary. TST-positive individuals were referred for chest radiography. Subjects with cough, fever, or night sweats of > 2 weeks duration provided sputum for acid-fast bacilli (AFB) microscopy and culture. RESULTS: Of approximately 4000 potential subjects (internally displaced persons), 988 (24.7%) participated in the screening program. Of these 988, 931 (94.2%) who had a TST placed returned at 48-72 hours to have the skin test examined; 447 (48.0%) were TST-positive (> or = 10 mm induration). In multivariate analysis, risk factors for a positive TST included male sex, ever having received BCG, history of close contact with a case of active tuberculosis, and living in one specific refugee hostel. Risk for a positive TST was greater among subjects > 20 years old, but there was no difference between age groups over the age of 20 years. Five patients with active TB were identified through the screening program, giving a case rate of 537 per 100,000 population. CONCLUSION: Tuberculosis infection and disease were common in this group of internally displaced persons. Screening was a useful mechanism of case finding among this high prevalence population.

[Simultaneous occurrence of cervicofacial an pleuropulmonary actinomycosis]. / Cervicofacialis és pleuropulmonalis actinomycosis együttes elöfordulása.

Successful treatment of rapidly spread cervicofacial and pleuropulmonary actinomycosis case is reported. Significant law destruction and pathological fractures were observed as well.

[The use of human lyophilized bone matrix gelatin in oral surgery (preliminary report)]. / Humán liofilizált csontmátrix-zselatin alkalmazása a szájsebészeti gyakorlatban (elözetes közlemény).

Clinical application of human freeze-dried bone matrix gelatin (BMG) in the bone-cysts is reported. The BMG is produced at the West Hungarian Regional Tissue Bank in Gyór under principles of the American and European Association of Tissue Banks. BMG was applied to fill bone cysts in maxilla and mandible. The BMG has many advantages in comparison to other materials in the management of maxillofacial cysts. Of 31 cases 28 primary bone-heating have been detected clinically assessed by X-ray and histologically in three cases there was secondary restoration. In the favourable courses very fast and effective restorations have been found. The authors possess very favorable experience on the field of implantation of human bone matrix gelatin and recommend its clinical application at the maxillofacial surgery.