Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC)

Background: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. Patients and Methods: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test (TM)). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Results: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received >= 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (>= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). Conclusions: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression

Submillimetric GPS distance measurement over short baselines: noise mitigation by global robust estimation

The potential use of GPS technology for precise length determination is currently a topic of extensive research. A prior work was dedicated to submillimetric length determination over short baselines and under ideal conditions of data availability and a clear environment. This paper presents a new computation method suited to the less favourable working conditions that are usually encountered in practice. It is based on both robust estimation theory and the use of an ambiguity-free estimation method. As the experimental comparisons with the standard procedure based on least-squares ambiguity determination show, it provides more stable values and permits results to be obtained significant to the submillimetre level with time spans of a few hours.This research is funded by the Spanish Ministry of Science and Innovation (AYA2011-23232).Baselga Moreno, S.; García-Asenjo Villamayor, L.; Garrigues Talens, P. (2014). Submillimetric GPS distance measurement over short baselines: noise mitigation by global robust estimation. Measurement Science and Technology. 25(10):1-6. https://doi.org/10.1088/0957-0233/25/10/105004S162510Altamimi, Z., Collilieux, X., & Métivier, L. (2011). ITRF2008: an improved solution of the international terrestrial reference frame. Journal of Geodesy, 85(8), 457-473. doi:10.1007/s00190-011-0444-4Amiri-Simkooei, A. R., & Tiberius, C. C. J. M. (2006). Assessing receiver noise using GPS short baseline time series. GPS Solutions, 11(1), 21-35. doi:10.1007/s10291-006-0026-8Baire, Q., Bruyninx, C., Legrand, J., Pottiaux, E., Aerts, W., Defraigne, P., … Chevalier, J. M. (2013). Influence of different GPS receiver antenna calibration models on geodetic positioning. GPS Solutions, 18(4), 529-539. doi:10.1007/s10291-013-0349-1Baselga, S. (2007). Global Optimization Solution of Robust Estimation. Journal of Surveying Engineering, 133(3), 123-128. doi:10.1061/(asce)0733-9453(2007)133:3(123)Baselga, S. (2010). Global optimization applied to GPS positioning by ambiguity functions. Measurement Science and Technology, 21(12), 125102. doi:10.1088/0957-0233/21/12/125102Baselga, S. (2014). Ambiguity-Free Method for Fast and Precise GNSS Differential Positioning. Journal of Surveying Engineering, 140(1), 22-27. doi:10.1061/(asce)su.1943-5428.0000111Baselga, S., & García-Asenjo, L. (2008). GNSS Differential Positioning by Robust Estimation. Journal of Surveying Engineering, 134(1), 21-25. doi:10.1061/(asce)0733-9453(2008)134:1(21)Baselga, S., & García-Asenjo, L. (2008). Multipath Mitigation by Global Robust Estimation. Journal of Navigation, 61(3), 385-392. doi:10.1017/s0373463308004803Baselga, S., García-Asenjo, L., & Garrigues, P. (2013). Submillimetric GPS distance measurement over short baselines: case study in inner consistency. Measurement Science and Technology, 24(7), 075001. doi:10.1088/0957-0233/24/7/075001Dow, J. M., Neilan, R. E., & Rizos, C. (2009). The International GNSS Service in a changing landscape of Global Navigation Satellite Systems. Journal of Geodesy, 83(3-4), 191-198. doi:10.1007/s00190-008-0300-3Griffiths, J., & Ray, J. R. (2012). Sub-daily alias and draconitic errors in the IGS orbits. GPS Solutions, 17(3), 413-422. doi:10.1007/s10291-012-0289-1Huber, P. J. (1981). Robust Statistics. Wiley Series in Probability and Statistics. doi:10.1002/0471725250Koivula, H., Häkli, P., Jokela, J., Buga, A., & Putrimas, R. (2011). GPS Metrology: Bringing Traceable Scale to a Local Crustal Deformation GPS Network. International Association of Geodesy Symposia, 105-112. doi:10.1007/978-3-642-20338-1_13Niu, X., Chen, Q., Zhang, Q., Zhang, H., Niu, J., Chen, K., … Liu, J. (2013). Using Allan variance to analyze the error characteristics of GNSS positioning. GPS Solutions, 18(2), 231-242. doi:10.1007/s10291-013-0324-xRay, J., Altamimi, Z., Collilieux, X., & van Dam, T. (2007). Anomalous harmonics in the spectra of GPS position estimates. GPS Solutions, 12(1), 55-64. doi:10.1007/s10291-007-0067-7Snay, R. A., & Soler, T. (2008). Continuously Operating Reference Station (CORS): History, Applications, and Future Enhancements. Journal of Surveying Engineering, 134(4), 95-104. doi:10.1061/(asce)0733-9453(2008)134:4(95)Wieser, A., & Brunner, F. K. (2002). Short Static GPS Sessions: Robust Estimation Results. GPS Solutions, 5(3), 70-79. doi:10.1007/pl00012901Yang, Y. (1999). Robust estimation of geodetic datum transformation. Journal of Geodesy, 73(5), 268-274. doi:10.1007/s001900050243Yang, Y., Song, L., & Xu, T. (2002). Robust estimator for correlated observations based on bifactor equivalent weights. Journal of Geodesy, 76(6-7), 353-358. doi:10.1007/s00190-002-0256-

SARS-CoV-2 Droplet and Airborne Transmission Heterogeneity

The spread dynamics of the SARS-CoV-2 virus have not yet been fully understood after two years of the pandemic. The virus’s global spread represented a unique scenario for advancing infectious disease research. Consequently, mechanistic epidemiological theories were quickly dismissed, and more attention was paid to other approaches that considered heterogeneity in the spread. One of the most critical advances in aerial pathogens transmission was the global acceptance of the airborne model, where the airway is presented as the epicenter of the spread of the disease. Although the aerodynamics and persistence of the SARS-CoV-2 virus in the air have been extensively studied, the actual probability of contagion is still unknown. In this work, the individual heterogeneity in the transmission of 22 patients infected with COVID-19 was analyzed by close contact (cough samples) and air (environmental samples). Viral RNA was detected in 2/19 cough samples from patient subgroups, with a mean Ct (Cycle Threshold in Quantitative Polymerase Chain Reaction analysis) of 25.7 ± 7.0. Nevertheless, viral RNA was only detected in air samples from 1/8 patients, with an average Ct of 25.0 ± 4.0. Viral load in cough samples ranged from 7.3 × 105 to 8.7 × 108 copies/mL among patients, while concentrations between 1.1–4.8 copies/m3 were found in air, consistent with other reports in the literature. In patients undergoing follow-up, no viral load was found (neither in coughs nor in the air) after the third day of symptoms, which could help define quarantine periods in infected individuals. In addition, it was found that the patient’s Ct should not be considered an indicator of infectiousness, since it could not be correlated with the viral load disseminated. The results of this work are in line with proposed hypotheses of superspreaders, which can attribute part of the heterogeneity of the spread to the oversized emission of a small percentage of infected people

Исследование ресурса работы зондов для электроимпульсной литотрипсии

В данной статье представлена оценка ресурса работы зондов различных конструкций для электроимпульсной литотрипсии, выявлены наиболее часто возникающие дефекты. Сделаны выводы о перспективах применения и дальнейшего усовершенствования конструкций

Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab

Background: Pertuzumab, a human epidermal growth factor receptor (HER) 2 dimerization inhibitor, has demonstrated promising efficacy in combination with trastuzumab in patients with metastatic breast cancer. As HER signaling pathways are not only involved in oncogenesis, but also in myocardial homeostasis, an analysis of cardiac safety data was undertaken in a large group of patients treated with pertuzumab. Patients and methods: A complete database of patients treated with full-dose pertuzumab was used to describe the incidence of asymptomatic left ventricular systolic dysfunction (LVSD) and symptomatic heart failure (HF). Results: Information for 598 unique patients was available for the current analysis. Of the patients treated with pertuzumab alone (n = 331) or pertuzumab in combination with a non-anthracycline-containing cytotoxic (n = 175) or trastuzumab (n = 93), 23 (6.9%), 6 (3.4%), and 6 (6.5%), respectively, developed asymptomatic LVSD and 1 (0.3%), 2 (1.1%), and 1 (1.1%), respectively, displayed symptomatic HF. None of the 15 patients receiving both pertuzumab and erlotinib demonstrated LVSD. Conclusions: Patients treated with pertuzumab experienced relatively low levels of asymptomatic LVSD or symptomatic HF. There was no notable increase in cardiac side-effects when pertuzumab was given in combination with other anticancer agent

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655

Genetic variability of functional longevity in five rabbit lines

The objectives of this study were to analyse the differences in the genetic determination of functional longevity in five Spanish lines of rabbits and to check how different systematic factors might affect this genetic determination. Four of the lines were maternal (lines A, V, H and LP), these lines were established selecting base generation animals according to different criteria, but in the subsequent generations all of them were selected for litter size at weaning. The other is the paternal line R, this line was constituted by selecting animals with an outstanding daily growth rate. The trait analysed, length of productive life, was the time in days between the date of the first positive pregnancy test and the date of culling or death of a doe. Four models extended from the Cox proportional hazard model were used to analyse data of each line separately and jointly. The complete model (Model 1) included the fixed effect of year-season (YS) combination, positive palpation order (OPP), that is, reproductive cycle, physiological status of the doe (PS) at service and number of kits born alive (NBA) in each kindling as time-dependent factors. The inbreeding coefficient was fitted as a continuous covariate and the animal’s additive genetic effect was also fitted to the model (Model 1). The other models were identical to Model 1 but excluding OPP (Model 2) or PS (Model 3) or NBA (Model 4), which were explored to assess the consequence on additive variance estimates of not correcting for these animal-dependent factors. Estimated effective heritabilities of longevity were 0.07 ± 0.03, 0.03 ± 0.02, 0.14 ± 0.09, 0.05 ± 0.04, 0.02 ± 0.01 and 0.04 ± 0.01 for lines A, V, H, LP, R and for the merged data set, respectively. Removing the PS from the model led to an increase in the estimated additive genetic variance in all lines (0.17 ± 0.05, 0.05 ± 0.03, 0.29 ± 0.19, 0.29 ± 0.20, 0.07 ± 0.04 and 0.05 ± 0.02 for lines A, V, H, LP, R and the merged data set, respectively). The highest hazard of death and/or culling was observed during the first two parities and decreased as the order of parity progressed. Does non-pregnant-non-lactating had the highest risk of death or culling. The does that had zero kits born alive incurred the highest risk, and this risk decreased as the NBA increased. In conclusion, the consideration of longevity as selection criterion for the studied rabbit lines is not recommended.info:eu-repo/semantics/acceptedVersio