ABSTRACT


There is limited data on the effect of sacubitril-valsartan on the echocardiographic parameters in acute decompensated heart failure (ADHF). We prospectively enrolled 68 consecutive patients with ADHF who received sacubitril-valsartan (N = 34, S/V group) or angiotensin inhibition-based therapy (N = 34, ACEi/ARB group). Two-dimensional echocardiography with speckle tracking (2D-STE) was performed at baseline and after 3 months of treatment. Changes in 2D-STE parameters, including global longitudinal strain (GLS), were compared between the groups by t test and ANCOVA. Baseline characteristics were similar between the groups. Following 3 months of treatment, LVEF and GLS significantly improved in the S/V group (mean LVEF from 27 to 34.5% and GLS from - 6.6 to - 9.4%) but not in ACEi/ARB group. The improvement in LVEF and GLS was more prominent in patients with non-ischemic cardiomyopathy. In patients with ADHF 3-month treatment with sacubitril-valsartan, compared to guideline directed medical therapy without sacubitril, improves LVEF and GLS. Graphical Abstract A typical change in GLS in a patient with acute decompensated heart failure after 3 months of sacubitril-valsartan.


PMID:32557158 | DOI:10.1007/s12265-020-10041-4

15:56

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

15:56

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

15:57

PubMed articles on: Cancer & VTE/PE

Dissolution of metastatic thymic carcinoma-associated right atrial thrombus with rivaroxaban


Nimblette C, et al. SAGE Open Med Case Rep 2020.


ABSTRACT


Thymic carcinoma typically exhibits more clinically aggressive behavior and portends a worse prognosis as compared to thymoma. Venous thromboembolism is a significant cause of morbidity and mortality in oncologic patients. Traditionally, the standard-of-care management of cancer-associated venous thromboembolism has been therapeutic anticoagulation with low molecular weight heparins; however, with the advent of direct oral anticoagulants, there is an ongoing paradigm shift to transition to these novel agents in an attempt to attenuate cancer-associated venous thromboembolism events. We describe an exceedingly rare case of metastatic thymic carcinoma-associated right atrial thrombus with high-risk embolic features, which subsequently underwent near-complete dissolution with rivaroxaban after 3 months.


PMID:32551115 | PMC:PMC7278298 | DOI:10.1177/2050313X20927596

15:57

PubMed articles on: Cardio-Oncology

Cardiac MRI Myocardial Functional and Tissue Characterization Detects Early Cardiac Dysfunction in a Mouse Model of Chemotherapy-Induced Cardiotoxicity


Naresh NK, et al. NMR Biomed 2020.


ABSTRACT


BACKGROUND: Doxorubicin and doxorubicin-trastuzumab combination chemotherapy have been associated with cardiotoxicity that eventually leads to heart failure and may limit dose-effective cancer treatment. Current diagnostic strategies rely on decreased ejection fraction (EF) to diagnose cardiotoxicity.


PURPOSE: The aim of this study is to explore the potential of cardiac MR (CMR) imaging to identify imaging biomarkers in a mouse model of chemotherapy-induced cardiotoxicity.


METHODS: A cumulative dose of 25 mg/kg doxorubicin was administered over three weeks using subcutaneous pellets (n = 9, Dox). Another group (n = 9) received same dose of Dox and a total of 10 mg/kg trastuzumab (DT). Mice were imaged at baseline, 5/6 weeks and 10 weeks post-treatment on a 7T MRI system. The protocol included short-axis cine MRI covering the left ventricle (LV) and mid-ventricular short-axis tissue phase mapping (TPM), pre- and post-contrast T1 mapping, T2 mapping and Displacement Encoding with Stimulated Echoes (DENSE) strain encoded MRI. EF, peak myocardial velocities, native T1, T2, extracellular volume (ECV), and myocardial strain were quantified. N = 7 mice were sacrificed for histopathologic assessment of apoptosis at 5/6 weeks.


RESULTS: Global peak systolic longitudinal velocity was reduced at 5/6 weeks in Dox (0.6 ± 0.3 vs 0.9 ± 0.3, p = 0.02). In the Dox group, native T1 was reduced at 5/6 weeks (1.3 ± 0.2 ms vs 1.6 ± 0.2 ms, p = 0.02), and relatively normalized at week 10 (1.4 ± 0.1 ms vs 1.6 ± 0.2 ms, p > 0.99). There was no change in EF and other MRI parameters and histopathologic results demonstrated minimal apoptosis in all mice (~1-2 apoptotic cell/high power field), suggesting early-stage cardiotoxicity.


CONCLUSIONS: In a mouse model of chemotherapy-induced cardiotoxicity using doxorubicin and trastuzumab, advanced CMR shows promise in identifying treatment-related decrease in myocardial velocity and native T1 prior to the onset of cardiomyocyte apoptosis and reduction of EF.


PMID:32567177 | DOI:10.1002/nbm.4327

15:57

PubMed articles on: Cancer & VTE/PE

An International Survey on the Use of Thromboprophylaxis in Urological Surgery


Violette PD, et al. Eur Urol Focus 2020.


ABSTRACT


BACKGROUND: The use of perioperative thromboprophylaxis in urological surgery is common but not standardized.


OBJECTIVE: To characterize international practice variation in thromboprophylaxis use in urological surgery.


DESIGN, SETTING, AND PARTICIPANTS: We conducted a scenario-based survey addressing the use of mechanical and pharmacological thromboprophylaxis in urological cancer procedures (radical cystectomy [RC], radical prostatectomy [RP], and radical nephrectomy [RN]) among practicing urologists in Canada, Finland, and Japan. The survey presented patient profiles reflecting a spectrum of risk for venous thromboembolism; the respondents described their clinical practice.


OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The proportion of respondents who routinely used (1) mechanical, (2) pharmacological, and (3) extended pharmacological prophylaxis was stratified by procedure. A logistic regression identified characteristics associated with thromboprophylaxis use.


RESULTS AND LIMITATIONS: Of 1051 urologists contacted, 570 (54%) participated in the survey. Japanese urologists were less likely to prescribe pharmacological prophylaxis than Canadian or Finnish urologists (p < 0.001 for all procedures). Canadian and Finnish urologists exhibited large variation for extended pharmacological prophylaxis for RP and RN. Finnish urologists were most likely to prescribe extended prophylaxis versus Canadian and Japanese urologists (RC 98%, 84%, and 26%; Open RP 25%, 8%, and 3%; robotic RP 11%, 9%, and 0%; and RN 43%, 7%, and 1%, respectively; p < 0.001 for each procedure). Less variation was found regarding the prescription of mechanical prophylaxis, which was most commonly used until ambulation or discharge. The length of hospital stay was longer in Japan and may bias estimates of extended prophylaxis in Japan.


CONCLUSIONS: We found large variation in clinical practice regarding pharmacological thromboprophylaxis within and between countries. Knowledge translation of evidence-based guidelines may reduce problematic international variation in practice.


PATIENT SUMMARY: Use of medications to decrease blood clots after urological cancer surgery differs within and between countries. Closer adherence to urology guidelines addressing the prevention of blood clots may decrease this variation and improve patient outcomes.


PMID:32561453 | DOI:10.1016/j.euf.2020.05.015

15:57

PubMed articles on: Cancer & VTE/PE

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer


Alyami M, et al. Eur J Surg Oncol 2020.


ABSTRACT


BACKGROUND: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC.


METHODS: A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0.


RESULTS: One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC.


CONCLUSIONS: PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.


PMID:32561204 | DOI:10.1016/j.ejso.2020.05.021

15:57

PubMed articles on: Cancer & VTE/PE

In vivo performance of gold nanoparticle-loaded absorbable inferior vena cava filters in a swine model


Huang SY, et al. Biomater Sci 2020.


ABSTRACT


Absorbable inferior vena cava filters (IVCFs) offer a promising alternative to metallic retrievable filters in providing protection against pulmonary embolism (PE) for patients contraindicated for anticoagulant therapy. However, because absorbable filters are not radiopaque, monitoring of the filter using conventional X-ray imaging modalities (e.g. plain film radiographs, computed tomography [CT] and fluoroscopy) during deployment and follow-up is not possible and represents a potential obstacle to widespread clinical integration of the device. Here, we demonstrate that gold nanoparticles (AuNPs) infused into biodegradable filters made up of poly-p-dioxanone (PPDO) may improve device radiopacity without untoward effects on device efficacy and safety, as assessed in swine models for 12 weeks. The absorbable AuNP-infused filters demonstrated significantly improved visualization using CT without affecting tensile strength, in vitro degradation, in vivo resorption, or thrombus-capturing efficacy, as compared to similar non-AuNPs infused resorbable IVCFs. This study presents a significant advancement to the development of imaging enhancers for absorbable IVCFs.


PMID:32558854 | DOI:10.1039/d0bm00414f

15:57

PubMed articles on: Cancer & VTE/PE

Using big data to retrospectively validate the COMPASS-CAT risk assessment model: considerations on methodology


Nikolakopoulos I, et al. J Thromb Thrombolysis 2020.


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