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ABSTRACT

Speckle-tracking echocardiography has enabled clinicians to detect changes in myocardial function with more sensitivity than that afforded by traditional diastolic and systolic functional measurements, including left ventricular ejection fraction. Speckle-tracking echocardiography enables evaluation of myocardial strain in terms of strain (percent change in length of a myocardial segment relative to its length at baseline) and strain rate (strain per unit of time). Both measurements have potential for use in diagnosing and monitoring the cardiovascular side effects of cancer therapy. Regional and global strain measurements can independently predict outcomes not only in patients who experience cardiovascular complications of cancer and cancer therapy, but also in patients with a variety of other clinical conditions. This review and case series examine the clinical applications and overall usefulness of speckle-tracking echocardiography in cardio-oncology and, more broadly, in clinical cardiology.

PMID:32603473 | DOI:10.14503/THIJ-18-6736

07:22

PubMed articles on: Cardio-Oncology

A clinician's guide for developing a prediction model: a case study using real-world data of patients with castration-resistant prostate cancer

Veen KM, et al. J Cancer Res Clin Oncol 2020 - Review.

ABSTRACT

PURPOSE: With the increasing interest in treatment decision-making based on risk prediction models, it is essential for clinicians to understand the steps in developing and interpreting such models.

METHODS: A retrospective registry of 20 Dutch hospitals with data on patients treated for castration-resistant prostate cancer was used to guide clinicians through the steps of developing a prediction model. The model of choice was the Cox proportional hazard model.

RESULTS: Using the exemplary dataset several essential steps in prediction modelling are discussed including: coding of predictors, missing values, interaction, model specification and performance. An advanced method for appropriate selection of main effects, e.g. Least Absolute Shrinkage and Selection Operator (LASSO) regression, is described. Furthermore, the assumptions of Cox proportional hazard model are discussed, and how to handle violations of the proportional hazard assumption using time-varying coefficients.

CONCLUSION: This study provides a comprehensive detailed guide to bridge the gap between the statistician and clinician, based on a large dataset of real-world patients treated for castration-resistant prostate cancer.

PMID:32556680 | DOI:10.1007/s00432-020-03286-8

07:22

PubMed articles on: Cancer & VTE/PE

microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors

Oto J, et al. Cancers (Basel) 2020.

ABSTRACT

Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.

PMID:32545233 | DOI:10.3390/cancers12061536

07:22

PubMed articles on: Cardio-Oncology

Gender differences in quality of life in coronary artery disease patients with comorbidities undergoing coronary revascularization

Oreel TH, et al. PLoS One 2020.

ABSTRACT

In comparison to male patients with coronary artery disease, female patients suffer from more comorbidities, experience symptoms of coronary artery disease differently and report poorer health-related quality of life (HRQoL) after coronary revascularization. However, there is limited data on the impact of comorbidity burden on the recovery in HRQoL in female and male patients. We investigated the impact of comorbidity burden on the change in HRQoL following coronary revascularization in female patients versus male patients. 230 patients (60 female) with coronary artery disease were assessed before, and two weeks, three months and six months after coronary revascularization. Disease-specific HRQoL was measured with the Short-Form Seattle Angina Questionnaire. Physical and mental health was measured with the Short-Form Health Survey. Comorbidity burden was assessed by the total number of identified comorbidity conditions and by the Charlson comorbidity score. Linear mixed models were used to estimate the effects of time, gender and comorbidity burden on HRQoL. Whereas HRQoL improved after coronary revascularization in all patients, female patients reported poorer physical health and disease-specific HRQoL and their physical health improved more slowly than male patients. A higher comorbidity burden was related with poorer physical health and disease-specific HRQoL in male patients, but not in female patients. A higher comorbidity burden was associated with slower improvement in HRQoL for both female and male patients. Female patients reported poorer HRQoL and their physical health improved more slowly after coronary revascularization, irrespective of comorbidity burden. Higher comorbidity burden was associated with poorer physical health and disease-specific HRQoL in male patients only. Our results indicate that female and male patients recover differently after coronary revascularization. These findings highlight the importance of comorbidity- and gender-specific approaches for evaluating coronary artery disease and coronary revascularization procedures.

PMID:32555617 | PMC:PMC7299316 | DOI:10.1371/journal.pone.0234543

07:22

PubMed articles on: Cardio-Oncology

Pharmacogenomics Meets Precision Cardio-Oncology: Is there synergistic potential?

Hockings JK, et al. Hum Mol Genet 2020.

ABSTRACT

An individual's inherited genetic make-up and acquired genomic variants may account for a significant portion of observable variability in therapy efficacy and toxicity. Pharmacogenomics (PGx) is the concept that treatments can be modified to account for these differences to increase chances of therapeutic efficacy while minimizing risk of adverse effects. This is particularly applicable to oncology in which treatment may be multi-modal. As each tumor type has a unique genomic signature that lends to inclusion of targeted therapy but treatment options may be associated with cumulative toxicity, such as cardiotoxicity, that can impact quality of life. A greater understanding of therapeutic agents impacted by PGx and subsequent implementation has the potential to improve outcomes and reduce risk of drug-induced adverse effects.

PMID:32601683 | DOI:10.1093/hmg/ddaa134

07:22

PubMed articles on: Cancer & VTE/PE

Four cases of Trousseau syndrome associated with breast cancer that exhibited central nervous system manifestations

Okazaki M, et al. Int Cancer Conf J 2020.

ABSTRACT

Cancer-associated thrombosis is known as Trousseau syndrome (TS). Here, we report 4 cases of TS associated with advanced breast cancer that caused central nervous system (CNS) vascular events. All 4 patients experienced sudden onset of CNS symptoms. Imaging revealed multiple brain infarctions or intracranial hemorrhage and all 4 patients had leptomeningeal or brain metastasis. Laboratory findings showed hypercoagulability at diagnosis of TS. Of the 4 patients, 2 patients were treated with unfractionated heparin, while 2 patients could not undergo anticoagulant therapy. In all patients, once the TS occurred, the CNS symptoms progressed rapidly and the prognosis was very poor, 3 patients dying within about a month of diagnosis of TS. Therefore, the predictive factors of TS are important and standards and guidelines for administration of anticoagulants are needed.

PMID:32582520 | PMC:PMC7297874 | DOI:10.1007/s13691-020-00411-9

07:22

PubMed articles on: Cancer & VTE/PE

Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol

Marietta M, et al. Trials 2020. ABSTRACTOBJECTIVES: To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: a)more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: 1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either: a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were receiving standard oxygen therapy5.IMV in patients who at randomisation were receiving non-invasive mechanical ventilationb)Similar in terms of major bleeding risk TRIAL DESIGN: Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study.

PARTICIPANTS: Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit.

INCLUSION CRITERIA (ALL REQUIRED): 1. Age > 18 and < 80 years 2. Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) 3. Severe pneumonia defined by the presence of at least one of the following criteria: a.Respiratory Rate ≥25 breaths /minb.Arterial oxygen saturation≤93% at rest on ambient airc.PaO2/FiO2 ≤300 mmHg 4. Coagulopathy, defined by the presence of at least one of the following criteria: a.D-dimer >4 times the upper level of normal reference rangeb.Sepsis-Induced Coagulopathy (SIC) score >4 5. No need of IMV EXCLUSION CRITERIA: 1. Age <1880 years 2. IMV 3. Thrombocytopenia (platelet count < 80.000 mm3) 4. Coagulopathy: INR >1.5, aPTT ratio > 1.4 5. Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min) 6. Known hypersensitivity to enoxaparin 7. History of heparin induced thrombocytopenia 8. Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) 9. Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves) 10. Concomitant double antiplatelet therapy 11. Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed 12. Pregnancy or breastfeeding or positive pregnancy test 13. Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) 14. Lack or withdrawal of informed consent INTERVENTION AND COMPARATOR: Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day). Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table. This dose is commonly used in Italy when a bridging strategy is required for [...]

07:22

PubMed articles on: Cardio-Oncology

Rosuvastatin based novel 3-substituted isocoumarins / 3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents

Kumar JS, et al. Eur J Med Chem 2020.