Biochemical markers and assessment of cardiotoxicity during preparative regimen and hematopoietic cell transplantation in acute leukemia

Introduction: Cardiotoxicity is a relatively frequent and potentially serious complication of antitumor treatment. Anthracyclines and other high-dose chemotherapy represent the greatest risk. The aim of the study was to assess cardiotoxicity during preparative regimen (PR) and hematopoietic cell transplantation (HCT) in acute leukemia (AL) with biochemical markers — “N-terminal pro brain natriuretic peptide” (NT-proBNP), cardiac troponin T (cTnT) and creatine kinase MB (CK-MB mass). Methods: Nineteen adult AL patients previously treated with anthracyclines — idarubicine, daunorubicine, mitoxantrone with standard doses for a cycle as 3 х 12 mg/m2, 3 х 50 mg/m2, 3 х 10 mg/m2 accordingly were studied. PR consisted of high-dose cyclophosphamide (HD-C) in combination with busulphan or total body irradiation (TBI). Plasma NT-proBNP, cTnT and CK-MB mass concentrations were measured the day before PR, the day after PR, the day after HCT and 14 days after HCT. Results: Before PR, mean plasma NT-proBNP value was 106.3 ± 55.7 ng/l. After PR, it increased to 426.1 ± 391.5 ng/l. After HCT, a further increase to 847.6 ± 780.6 ng/l was observed. Fourteen days after HCT, the mean NT-proBNP was 330.8±236.8 ng/l. The differences were statistically significant in comparison with the baseline values (p < 0.01). The NT-proBNP elevations were more pronounced in patients with cumulative doses (CD) of anthracyclines above 450 mg/m2 (p < 0.05), in patients with PR containing HD-C and TBI (p < 0.05). In all patients, plasma cTnT and CK-MB mass concentrations remained unchangable during PR and HCT. Conclusion: Our results suggest that administration of PR and HCT is in most AL patients associated with acute neurohumoral activation (significant rise in NT-proBNP). Persistent NT-proBNP elevations, in our study in 12 (63.2 %) patients, indicate subclinical cardiotoxicity (risk for development of heart failure) and require further follow-up. More pronounced NT-proBNP elevations in patients with higher CD of anthracyclines and in patients with PR containing combination of HD-C and TBI confirm that these therapeutic procedures seem to be more cardiotoxic and not very appropriate for patients with cumulation of risk factors for cardiotoxicity. Negative plasma cTnT and CK-MB mass concentrations show no detectable damage of cardiomyocyte structure during PR and HCT.Введение: кардиотоксические осложнения — это относительно частые и потенциально опасные последствия противоопухолевой терапии. Наибольшую кардиотоксичность отмечают при применении высоких доз химиопрепаратов, в частности антибиотиков антрациклинового ряда. Целью данного исследования была оценка кардиотоксичности при лекарственной подготовке пациентов с острым лейкозом (ОЛ) и проведении им трансплантации гематопоэтических стволовых клеток (ГСК), а также определение следующих биохимических маркеров – N-терминального промозгового натрийуретического пептида (NT-proBNP), сердечного тропонина T (cTnT) и креатинкиназы MB (CK-MB). Методы: обследованы 19 взрослых пациентов с ОЛ, прошедших предварительное лечение (ПЛ) с применением антрациклиновых антибиотиков (АА) – идарубицина, даунорубицина, митотриксантрона в дозах 3 х 12 мг/м2 , 3 х 50 мг/м2 , 3 х 10 мг/м2 соответственно. Кроме применения АА, ПЛ включало высокие дозы циклофосфамида (ВД-Ц) в сочетании с бусульфаном или радиолучевой терапией (РЛТ). Концентрацию NT-proBNP, cTnT и CK-MB определяли в плазме крови за день до и через день после проведения ПЛ, а также за день до и через 14 дней после трансплантации ГСК. Результаты: уровень NT-proBNP перед проведением ПЛ составил 106,3 ± 55,7 нг/л, а после повышался до 426,1 ± 391,5 нг/л. После трансплантации ГСК отмечали дальнейшее возрастание исследуемого показателя до 847,6 ± 780,6 нг/л. Через 14 дней после трансплантации ГСК концентрация NT-proBNP достигла 330,8 ± 236,8 нг/л, при этом разница была статистически достоверна по сравнению с исходными значениями (p < 0,01). Повышение уровня NT-proBNP в плазме крови более выражено у пациентов, получавших АА в суммарной дозе (СД) выше 450 мг/м2 (p < 0,05), а также у больных, получавших ВД-Ц и РЛТ (p < 0,05). Концентрация cTnT и CK-MB при проведении ПЛ и трансплантации ГСК не изменялась по отношению к исходному уровню. Выводы: показано, что применение ПЛ и трансплантация ГСК у большинства пациентов с ОЛ сопровождается острой нейрогуморальной активацией, что проявлялось в существенном повышении уровня NT-proBNP. Постоянно высокий уровень NTproBNP, отмеченный у 12 (63,2%) пациентов, свидетельствует о бессимптомной кардиотоксичности (риске развития сердечной недостаточности) и требует последующего врачебного наблюдения больных. Более выраженное повышение уровня NT-proBNP у пациентов с более высокой СД АА и у больных, получавших ВД-Ц и РЛТ, свидетельствует о том, что такое лечение является более кардиотоксичным и не рекомендовано для применения в случае наличия факторов риска проявления кардиотоксичности

Source identification for mobile devices, based on wavelet transforms combined with sensor imperfections

One of the most relevant applications of digital image forensics is to accurately identify the device used for taking a given set of images, a problem called source identification. This paper studies recent developments in the field and proposes the mixture of two techniques (Sensor Imperfections and Wavelet Transforms) to get better source identification of images generated with mobile devices. Our results show that Sensor Imperfections and Wavelet Transforms can jointly serve as good forensic features to help trace the source camera of images produced by mobile phones. Furthermore, the model proposed here can also determine with high precision both the brand and model of the device

Classification of motor imagery tasks for BCI with multiresolution analysis and multiobjective feature selection

Background: Brain-computer interfacing (BCI) applications based on the classification of electroencephalographic (EEG) signals require solving high-dimensional pattern classification problems with such a relatively small number of training patterns that curse of dimensionality problems usually arise. Multiresolution analysis (MRA) has useful properties for signal analysis in both temporal and spectral analysis, and has been broadly used in the BCI field. However, MRA usually increases the dimensionality of the input data. Therefore, some approaches to feature selection or feature dimensionality reduction should be considered for improving the performance of the MRA based BCI. Methods: This paper investigates feature selection in the MRA-based frameworks for BCI. Several wrapper approaches to evolutionary multiobjective feature selection are proposed with different structures of classifiers. They are evaluated by comparing with baseline methods using sparse representation of features or without feature selection. Results and conclusion: The statistical analysis, by applying the Kolmogorov-Smirnoff and Kruskal-Wallis tests to the means of the Kappa values evaluated by using the test patterns in each approach, has demonstrated some advantages of the proposed approaches. In comparison with the baseline MRA approach used in previous studies, the proposed evolutionary multiobjective feature selection approaches provide similar or even better classification performances, with significant reduction in the number of features that need to be computed

European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment.

AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes

European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment.

AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Predicting Quantitative Genetic Interactions by Means of Sequential Matrix Approximation

Despite the emerging experimental techniques for perturbing multiple genes and measuring their quantitative phenotypic effects, genetic interactions have remained extremely difficult to predict on a large scale. Using a recent high-resolution screen of genetic interactions in yeast as a case study, we investigated whether the extraction of pertinent information encoded in the quantitative phenotypic measurements could be improved by computational means. By taking advantage of the observation that most gene pairs in the genetic interaction screens have no significant interactions with each other, we developed a sequential approximation procedure which ranks the mutation pairs in order of evidence for a genetic interaction. The sequential approximations can efficiently remove background variation in the double-mutation screens and give increasingly accurate estimates of the single-mutant fitness measurements. Interestingly, these estimates not only provide predictions for genetic interactions which are consistent with those obtained using the measured fitness, but they can even significantly improve the accuracy with which one can distinguish functionally-related gene pairs from the non-interacting pairs. The computational approach, in general, enables an efficient exploration and classification of genetic interactions in other studies and systems as well