Charles University in Prague

About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial.

Abstract: Summary Background Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab. Methods Treatment-naive fit patients with chronic lymphocytic leukaemia (aged 33–81 years) without del(17p) were enrolled after undergoing a central screening process. Patients were randomly assigned (1:1) with a computer-generated randomisation list using randomly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage. Patients were allocated to receive six cycles of intravenous fludarabine (25 mg/m 2 per day) and cyclophosphamide (250 mg/m 2 per day) for the first 3 days or to intravenous bendamustine (90 mg/m 2 per day) for the first 2 days of each cycle. Rituximab 375 mg/m 2 was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m 2 during the next five cycles on day 1. The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the standard therapy. We aimed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67·5% or less with a corresponding non-inferiority margin of 1·388 for the hazard ratio (HR) based on the 90·4% CI. The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. Findings 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included in the intention-to-treat population: 282 patients in the fludarabine, cyclophosphamide, and rituximab group and 279 in the bendamustine and rituximab group. After a median observation time of 37·1 months (IQR 31·0–45·5) median progression-free survival was 41·7 months (95% CI 34·9–45·3) with bendamustine and rituximab and 55·2 months (95% CI not evaluable) with fludarabine, cyclophosphamide, and rituximab (HR 1·643, 90·4% CI 1·308–2·064). As the upper limit of the 90·4% CI was greater than 1·388 the null hypothesis for the corresponding non-inferiority hypothesis was not rejected. Severe neutropenia and infections were more frequently observed with fludarabine, cyclophosphamide, and rituximab (235 [84%] of 279 vs 164 [59%] of 278, and 109 [39%] vs 69 [25%], respectively) during the study. The increased frequency of infectious complications with fludarabine, cyclophosphamide, and rituximab was more pronounced in patients older than 65 years. Interpretation The combination of fludarabine, cyclophosphamide, and rituximab remains the standard front-line therapy in fit patients with chronic lymphocytic leukaemia, but bendamustine and rituximab is associated with less toxic effects. Funding Roche Pharma AG, Mundipharma, German Federal Ministry of Education and Research.

Serum Thyrotropin Concentration as a Novel Predictor of Malignancy in Thyroid Nodules Investigated by Fine-Needle Aspiration

Abstract: Context: Thyroid nodules and goiter are common, and fine-needle aspiration biopsy (FNAB) is the first investigation of choice in distinguishing benign from malignant disease. Objective: The objective of the study was to assess whether simple clinical and biochemical parameters can predict the likelihood of thyroid malignancy in subjects undergoing FNAB. Design: The design was a prospective cohort. Setting: The study was conducted at a single secondary/tertiary care clinic. Participants: One thousand five hundred consecutive patients without overt thyroid dysfunction (1304 females and 196 males, mean age 47.8 yr) presenting with palpable thyroid enlargement between 1984 and 2002 were evaluated by FNAB of the thyroid. Intervention(s): There were no interventions. Main Outcome Measures: Goiter type was assessed clinically and classified as diffuse in 183, multinodular in 456, or solitary nodule in 861 cases. Serum TSH concentration at presentation was measured in a sensitive assay in patients presenting afte...

Cometary origin of the zodiacal cloud and carbonaceous micrometeorites. implications for hot debris disks

Abstract: The zodiacal cloud is a thick circumsolar disk of small debris particles produced by asteroid collisions and comets. Their relative contribution and how particles of different sizes dynamically evolve to produce the observed phenomena of light scattering, thermal emission, and meteoroid impacts are unknown. Until now, zodiacal cloud models have been phenomenological in nature, composed of ad hoc components with properties not understood from basic physical processes. Here, we present a zodiacal cloud model based on the orbital properties and lifetimes of comets and asteroids, and on the dynamical evolution of dust after ejection. The model is quantitatively constrained by Infrared Astronomical Satellite (IRAS) observations of thermal emission, but also qualitatively consistent with other zodiacal cloud observations, with meteor observations, with spacecraft impact experiments, and with properties of recovered micrometeorites (MMs). We find that particles produced by Jupiterfamily comets (JFCs) are scattered by Jupiter before they are able to orbitally decouple from the planet and drift down to 1 AU. Therefore, the inclination distribution of JFC particles is broader than that of their source comets and leads to good fits to the broad latitudinal distribution of fluxes observed by IRAS. We find that 85%–95% of the observed mid-infrared emission is produced by particles from JFCs and 100 μm undergo a further collisional cascade with smaller fragments being progressively more affected by Poynting–Robertson (PR) drag. Upon reaching D 10 4 times brighter during the Late Heavy Bombardment (LHB) epoch ≈3.8 Gyr ago, when the outer planets scattered numerous comets into the inner solar system. The bright debris disks with a large 24 μm excess observed around mature stars may be an indication of massive cometary populations existing in those systems. We estimate that at least ∼10 22 , ∼2 × 10 21 , and ∼2 × 10 20 go f