ABSTRACT

Recently, cancer-related venous thromboembolism (VTE) has been termed "cancer-associated thrombosis (CAT)" and is the focus of current research. We retrospectively investigated the efficacy of a single-drug approach with edoxaban for the treatment of non-acute CAT. Thirty-two non-acute CAT patients who received edoxaban were analyzed. The primary endpoint of this analysis was the thrombus disappearance rate at the first evaluation. Secondary endpoints included progression/recurrence of VTE, major bleeding, and D-dimer levels. The thrombus disappearance rate was 62.5%. Therefore, the null hypothesis for the primary endpoint (thrombus disappearance rate of ≤32.0%) was rejected (p = 0.00038) based on the rate of the previous study as the historical control. Recurrent VTE and major bleeding occurred in two patients each. After the start of treatment with edoxaban, a significant difference in D-dimer levels was observed (p = 0.00655). We demonstrated that a single-drug approach with edoxaban is a potential treatment option for non-acute CAT.

PMID:32605234 | DOI:10.3390/cancers12071711

20:05

PubMed articles on: Cardio-Oncology

Remote Ischemic Preconditioning Ameliorates Anthracycline-induced Cardiotoxicity and Preserves Mitochondrial Integrity

Galán-Arriola C, et al. Cardiovasc Res 2020.

ABSTRACT

AIMS: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC.

METHODS AND RESULTS: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischemic pre-conditioning (RIPC, 3 cycles of 5 min leg ischemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at weeks 6, 8, 12, and 16, being sacrifice after that. In study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6.In Study 1, LVEF depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5±9.1% vs 32.5±8.7%, p = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs.

CONCLUSION: In a translatable large animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.

TRANSLATIONAL PERSPECTIVE: Serial cardiac magnetic resonance (CMR) evaluation of a highly translatable large animal model of anthracycline-induced cardiotoxicity (AIC) shows that cumulative exposure to doxorubicin results in significantly reduced LVEF and extensive mitochondrial fragmentation. Remote ischemic preconditioning (RIPC) applied before each doxorubicin cycle preserved cardiac contractility and LVEF in long-term CMR exams. RIPC prevented doxorubicin-induced irreversible mitochondrial fragmentation and dysregulated autophagy. RIPC is as an attractive strategy for testing in clinical trials in AIC.

PMID:32597960 | DOI:10.1093/cvr/cvaa181

20:06

PubMed articles on: Cancer & VTE/PE

Practice patterns for extended venous thromboembolism chemoprophylaxis among urologic oncologists after radical cystectomy

Dall CP, et al. Urol Oncol 2020.

ABSTRACT

INTRODUCTION: Extended outpatient chemoprophylaxis (ECP) following radical cystectomy (RC) for bladder cancer is proven to reduce rates of venous thromboembolism (VTE). While ECP is commonly performed with enoxaparin, its cost-effectiveness and adherence rate has been called into question. Data from orthopedic literature suggest that ECP with direct oral anticoagulants (DOACs) may be as effective in VTE prevention as enoxaparin in patients undergoing joint surgery. Our goal is to determine how urologic oncologists employ ECP following RC.

METHODS: Members of the Society of Urologic Oncology were surveyed on practice patterns for the use of ECP after RC. Specific questions were asked regarding the use of inpatient and outpatient VTE prophylaxis, as well as perceived barriers to DOACs and enoxaparin.

RESULTS: There were 121 of 878 (13.8%) respondents and the majority were in academic practices (83%). Most respondents had at least 5 years of experience and performed greater than 10 cystectomies annually. Almost all participants utilized inpatient (97%) and extended (80%) chemoprophylaxis for VTE prevention. Of those who elected for ECP, almost all (96%) used enoxaparin. Only 3 respondents (3%) prescribed oral agents such as rivaroxaban (2) or warfarin (1). Among those using enoxaparin, financial-specific barriers to treatment such as lack of insurance coverage (38%), inability to afford the medication (51%), and need for additional insurance authorization (44%) were reported. Poor patient adherence and refusal to perform injections were reported by 20% and 18% of respondents, respectively. Among the 23 physicians who did not use ECP, cost (39%) and delivery method (26%) were cited as barriers to treatment.

CONCLUSIONS: The majority of surveyed urologic oncologists are prescribing subcutaneous enoxaparin ECP following RC. Poor patient adherence due to self-injections and financial barriers were frequently reported and represent a possible opportunity for the use of oral anticoagulants in the post-operative setting. These data will be used in the development of a proposed clinical trial of a DOAC in the post-RC setting.

PMID:32616422 | DOI:10.1016/j.urolonc.2020.05.030

20:06

PubMed articles on: Cardio-Oncology

Cardio-toxicity among patients with sarcoma: a cardio-oncology registry

Shamai S, et al. BMC Cancer 2020.

ABSTRACT

BACKGROUND: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population.

METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group.

RESULTS: Among 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group.

CONCLUSIONS: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.

PMID:32605637 | PMC:PMC7325299 | DOI:10.1186/s12885-020-07104-9

20:06

PubMed articles on: Cardio-Oncology

Real-time three-dimensional echocardiography predicts cardiotoxicity induced by postoperative chemotherapy in breast cancer patients

Zhou F, et al. World J Clin Cases 2020.

ABSTRACT

BACKGROUND: The anthracycline chemotherapeutic drugs are cardiotoxic. Studies have found some indicators related to cardiotoxicity. However, there is currently no accurate indicator that can predict cardiac toxicity early.

AIM: To explore the diagnostic value of real-time three-dimensional echocardiography (RT3DE) in predicting cardiac toxicity in breast cancer patients undergoing chemotherapy.

METHODS: Female breast cancer patients who underwent radical mastectomy and postoperative chemotherapy at the Affiliated Hanzhou First People's Hospital, Zhejiang University School of Medicine were recruited. All patients were routinely administered with chemotherapy for four cycles (T1-T4) after surgery. Two-dimensional (2D) echocardiography, RT3DE, and serological examinations were performed after each cycle of chemotherapy. Patients were divided into a toxic group and a non-toxic group based on whether patients had Δ left ventricular ejection fraction > 10% after one year of chemotherapy. Repeated measurement analysis of variance was used to compare the changes in 2D echocardiographic indicators, serological indicators, and RT3DE indicators before and after chemotherapy. Multivariate logistic regression was used to identify independent predictive indicators for cardiac toxicity in postoperative chemotherapy patients. Receiver operating characteristics (ROC) curve analysis was performed to analyze the diagnostic value of potential indicators in the diagnosis of cardiotoxicity.

RESULTS: A total of 107 female breast cancer patients were included in the study. T4 maximum peak velocity in early diastole (E peak)/mitral annulus lateral tissue Doppler (e' peak) (E/e'), serological indicators [T4 cardiac troponin I (cTnI) and T4 pro-brain natriuretic peptide (Pro-BNP)], T3 minimum left atrial volume (LAV), T4 LAVmin, T3 LAV before the start of the P wave (LAVprep), and T4 LAVprep in the toxicity group were significantly higher than those in the non-toxic group. Multivariate logistic regression found that T4 cTnI, T4 Pro-BNP, T3 LAVmin, T4 LAVmin, T3 LAVprep, and T4 LAVprep had potential predictive value for cardiac toxicity (P 0.05). ROC results showed that T4 LAVmin had the highest accuracy for diagnosing cardiac toxicity [area under the curve (AUC) =0.947; sensitivity =78.57%; specificity =94.62%], followed by T4 LAVprep (AUC =0.899; sensitivity =100%; specificity =66.67%). The accuracies of LAVprep and LAVprep in predicting cardiac toxicity were higher than those of T3 LAVmin and T3 LAVprep.

CONCLUSION: RT3DE of left atrial volume can be used to predict the cardiotoxicity caused by chemotherapy, and it is expected to guide the clinical adjustment of dose and schedule in time.

PMID:32607331 | PMC:PMC7322441 | DOI:10.12998/wjcc.v8.i12.2542

20:06

PubMed articles on: Cancer & VTE/PE

Resection of recurrent hepatocellular carcinoma with thrombi in the inferior vena cava, right atrium, and phrenic vein: a report of three cases

Tomita K, et al. World J Surg Oncol 2020.

 

A new class of 3-substituted isocoumarin/3-alkylidenephthalide based novel small molecules derived from rosuvastatin were designed and synthesized via the ultrasound assisted Cu-mediated coupling-cyclization in a single pot with remarkable regioselectivity. The phthalides were generally obtained at lower temperature whereas the use of elevated temperature afforded isocoumarins. Two compounds e.g. 3n and 4d showed promising cytotoxic effects when tested against HCT 116, HepG2 and PA-1 cell lines at 10 μM. Indeed, 4d was found to be a potent cytotoxic agent (IC50 ∼ 0.76-4.51 μM). Both 3n and 4d were tested for their effects on PANC-1 cells. Considerable decrease in p-Akt substrates shown by 4d and 3n at 50 μM (western blot analysis) indicated their ability to inhibit p-Akt signal transduction pathway and arresting growth of PANC-1 cells in vitro. This was further supported by the cytotoxic effect of 4d on PANC-1 cells (MTT assay) that was better than rosuvastatin. While none of 3n and 4d showed any significant effect on non-cancerous HEK cell line (indicating their potential selectivity towards cancer cells) these compounds were further evaluated for their toxicities in Zebrafish embryo. The NOAEL (No Observed Adverse Effect Level) for teratogenicity, hepatotoxicity and cardiotoxicity was found to be 100 μM for both compound. Thus, 4d as a novel and potent but safer cytotoxic agent with potential to treat colorectal/ovarian and pancreatic cancer is of further medicinal interest.

PMID:32599323 | DOI:10.1016/j.ejmech.2020.112335

20:05

PubMed articles on: Cardio-Oncology

Curcumin in cancer therapy: A novel adjunct for combination chemotherapy with paclitaxel and alleviation of its adverse effects

Ashrafizadeh M, et al. Life Sci 2020 - Review.

ABSTRACT

Dealing with cancer is of importance due to enhanced incidence rate of this life-threatening disorder. Chemotherapy is an ideal candidate in overcoming and eradication of cancer. To date, various chemotherapeutic agents have been applied in cancer therapy and paclitaxel (PTX) is one of them. PTX is a key member of taxane family with potential anti-tumor activity against different cancers. Notably, PTX has demonstrated excellent proficiency in elimination of cancer in clinical trials. This chemotherapeutic agent is isolated from Taxus brevifolia, and is a tricyclic diterpenoid. However, resistance of cancer cells into PTX chemotherapy has endangered its efficacy. Besides, administration of PTX is associated with a number of side effects such as neurotoxicity, hepatotoxicity, cardiotoxicity and so on, demanding novel strategies in obviating PTX issues. Curcumin is a pharmacological compound with diverse therapeutic effects including anti-tumor, anti-oxidant, anti-inflammatory, anti-diabetic and so on. In the current review, we demonstrate that curcumin, a naturally occurring nutraceutical compound is able to enhance anti-tumor activity of PTX against different cancers. Besides, curcumin administration reduces adverse effects of PTX due to its excellent pharmacological activities. These topics are discussed with an emphasis on molecular pathways to provide direction for further studies in revealing other signaling networks.

PMID:32593707 | DOI:10.1016/j.lfs.2020.117984

20:05

PubMed articles on: Cancer & VTE/PE

Deep Venous Thrombosis in a Patient with a Moderate Pretest Probability and a Negative D-Dimer Test: A Review of the Diagnostic Algorithms

Al-Khafaji RA and Schierbeck L. J Blood Med 2020 - Review.

ABSTRACT

Modern diagnostic strategies of venous thromboembolism (VTE) have been developed. In this review, the diagnostic algorithms for deep-vein thrombosis (DVT) and their parameters are discussed individually in the context of reporting a case of DVT in a 43-year-old Caucasian female with a moderate pretest probability stratified by Wells' score and a negative high quality D-dimer test. The patient was on treatment with Xarelto (rivaroxaban), 20 mg PO daily at the time of presentation. The diagnosis was verified through a complete lower limb ultrasound (US). This case highlights the diagnostic challenges and pitfalls of the current algorithms, especially those seen in a subgroup of patients such as patients with cancer, pregnancy, recurrent VTE or are on anticoagulation therapy at the time of presentation. The diagnosis of DVT is less plausible in a patient who is on anticoagulation therapy, but physicians should be aware of such a possibility. Physicians should also know in advance the numerous clinically relevant limitations of D-dimer testing before interpreting the results. Unifying the current diagnostic strategies, modifying the current Wells' score and using the protocol of a whole-leg compression US instead of the limited US protocol are among the several cautious suggestions that have been proposed based on this review to possibly decrease the incidence of missed DVT.

PMID:32581617 | PMC:PMC7266946 | DOI:10.2147/JBM.S244773

20:05

PubMed articles on: Cardio-Oncology

Incidence and Onset of Severe Cardiac Events After Radiotherapy for Esophageal Cancer

Wang X, et al. J Thorac Oncol 2020.

ABSTRACT

PURPOSE: Late cardiotoxicity related to radiotherapy (RT) in breast cancer and Hodgkin lymphoma has been well reported. However, the relatively higher cardiac dose exposure for esophageal cancer (EC) may result in earlier onset of cardiac diseases. In this report, we examined the incidence, onset, and long-term survival outcomes of high-grade cardiac events after RT in a large cohort of EC patients.

PATIENTS AND METHODS: Between March 2005 and August 2017, 479 patients with EC from a prospectively maintained institutional database at The University of Texas MD Anderson Cancer Center were analyzed. All patients were treated with either intensity modulated RT (IMRT) or proton beam therapy (PBT), either pre-operatively or definitively. We focused on any grade 3 or higher (G3+) cardiac events according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

RESULTS: G3+ cardiac events occurred in 18% of patients at a median of 7 months with a median follow-up time of 76 months. Pre-existing cardiac disease (P=0.001) and radiation modality (IMRT vs PBT) (P=0.027) were significantly associated with G3+ cardiac events. Under multivariable analysis, mean heart dose, particularly < 15 Gy, was associated with reduced G3+ events. Furthermore, G3+ cardiac events were associated with worse overall survival (P=0.041).

CONCLUSION: Severe cardiac events were relatively common with early onset in EC patients after radiotherapy, especially those with pre-existing cardiac disease and higher radiation doses to the heart. Optimal treatment approaches should be taken to reduce cumulative doses to the heart, especially for patients with pre-existing cardiac disease.

PMID:32599073 | DOI:10.1016/j.jtho.2020.06.014

20:05

PubMed articles on: Cancer & VTE/PE

Safety and Efficacy of Apixaban vs Enoxaparin for Preventing Postoperative Venous Thromboembolism in Women Undergoing Surgery for Gynecologic Malignant Neoplasm: A Randomized Clinical Trial

20:05

PubMed articles on: Cancer & VTE/PE

Urosepsis Increases the Risk of Pulmonary Embolism in Patients Affected by SARS-CoV-2

Cai T, et al. J Urol 2020.

NO ABSTRACT

PMID:32609571 | DOI:10.1097/JU.0000000000001228

20:05

PubMed articles on: Cardio-Oncology

Involvement of ROS/NLRP3 Inflammasome Signaling Pathway in Doxorubicin-Induced Cardiotoxicity

Wei S, et al. Cardiovasc Toxicol 2020.

ABSTRACT

Doxorubicin (Dox) is widely used in cancer therapy, but the clinical application is limited by its cardiotoxicity. The underlying mechanism of Dox-induced cardiotoxicity remains unclear. Present study aimed to evaluate the role of NLRP3 inflammasome in Dox-induced cardiotoxicity. The NLRP3 inflammasome was activated in the myocardium of Dox-treating (5 mg/kg, once every other day, cumulative dosage to 15 mg/kg and sacrificed after 2 days of last Dox injection) C57BL/6 mice as shown by the up-regulation of NLRP3 and Caspase-1 p20. Dox (1 μM for 48 h) induced the apoptosis of H9c2 cells and primary cardiomyocytes concomitantly with up-regulation of NLRP3, ASC and Caspase-1 p20 expressions, as well as the increased IL-1β secretion, suggesting the activation of NLRP3 inflammasome. These effects of Dox on H9c2 cells and primary cardiomyocytes can be reversed by MCC950, a specific inhibitor of NLRP3. In view of the key role of ROS on the Dox-induced cardiotoxicity, the relationship between ROS and NLRP3 was further investigated. The ROS level was increased in myocardium, H9c2 cells and primary cardiomyocytes after treating with Dox. Decreasing ROS level by NAC can inhibit the NLRP3 inflammasome activation, secretion of IL-1β and apoptosis in Dox-treating H9c2 cells and primary cardiomyocytes. Collectively, this study reveals a crucial role of ROS/NLRP3-associated inflammasome activation in Dox-induced cardiotoxicity, and NLRP3 inflammasome may represent a new therapeutic target for Dox-induced cardiotoxicity.

PMID:32607760 | DOI:10.1007/s12012-020-09576-4

20:05

PubMed articles on: Cancer & VTE/PE

Apixaban vs Enoxaparin for Postoperative Prophylaxis: Safety of an Oral Alternative for the Prevention of Venous Thromboembolism

Diver E. JAMA Netw Open 2020.

NO ABSTRACT

PMID:32589227 | DOI:10.1001/jamanetworkopen.2020.8019

20:05

PubMed articles on: Cardio-Oncology

Exploring Social Ecological Determinants of Physical Activity Among Adult Survivors of Childhood Cancer

Dugan KF, et al. J Adolesc Young Adult Oncol 2020.

ABSTRACT

Purpose:Adult survivors of childhood cancer (ASCCs) are at high risk for cardiovascular disease from chemotherapy- and radiation therapy-related cardiotoxicity. Physical activity (PA) can reduce this risk, but the majority of ASCCs do not engage in sufficient PA. The purpose of this study was to identify barriers, facilitators, and resources for PA among ASCCs using the ecological model of physical activity (EMPA) as a theoretical framework. Methods:A concept elicitation survey was distributed independently to ASCCs (diagnosed with cancer before the age of 18, and currently 18-39 years old) and parents/legal guardians of an ASCC. The survey consisted of open-ended questions asking about barriers, facilitators, and resources for PA. Content analysis of open-ended questions categorized responses into levels of the EMPA and identified key themes. Results:Seventeen ASCCs and eight parents of ASCCs completed the survey. The majority of barriers, facilitators, and resources reported were at the individual and microsystem level of the EMPA. Six themes emerged, suggesting that ASCC's PA was related to proximity/access, social support, equipment, time/schedule, finances, and health-related barriers. Conclusion:This is the first study to examine barriers, facilitators, and resources of PA among ASCCs using the EMPA. Findings from this study provide a multilevel perspective on the influences of PA among ASCCs, and can be used for future, in-depth qualitative studies and quantitative survey development, and as a foundational step toward supportive efforts in increasing PA among ASCCs.

PMID:32598196 | DOI:10.1089/jayao.2019.0169

20:05

PubMed articles on: Cancer & VTE/PE

Single-Drug Approach with Edoxaban is Effective for Resolving Non-Acute Cancer-Associated Venous Thrombosis: A Single-Arm Retrospective Analysis

Toshima H, et al. Cancers (Basel) 2020.

 

ABSTRACT

Venous thromboembolism (VTE) and major bleeding in primary central nervous system lymphoma (PCNSL) patients are not well described. We identified 992 PCNSL patients using the California Cancer Registry (2005-2014). The cumulative incidence of VTE and major bleeding was determined using California hospitalization data. The 12-month cumulative incidence of VTE was 13.6% (95% confidence interval (CI) 11.5-15.8%); chemotherapy and radiation therapy were associated with increased risk of VTE (hazard ratio (HR) 2.41, CI 1.31-4.46 and HR 1.56, CI 1.08-2.25, respectively). The 12-month cumulative incidence of major bleeding was 12.4% (CI 10.1-14.6%). Pulmonary embolism (PE) and proximal deep vein thrombosis were associated with increased risk of major bleeding, likely due to anticoagulation. PE (HR 1.61, CI 1.11-2.33, p=.011) and major bleeding (HR 2.36, CI 1.82-3.06, p<.0001)

PMID:32573292 | DOI:10.1080/10428194.2020.1780584

20:05

PubMed articles on: Cancer & VTE/PE

Impact of multidisciplinary team meetings on the management of venous thromboembolism. A clinical study of 142 cases

Mauger C, et al. J Med Vasc 2020.

ABSTRACT

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE). However, therapeutic decision-making may prove challenging in routine clinical practice. With this in mind, multidisciplinary team (MDT) meetings have been set up in Rennes University Hospital, France. This study sought to describe the situations discussed during MDT meetings and to assess whether the meetings bring about changes in the management of these patients.

MATERIALS AND METHODS: A retrospective single-center study conducted at the Rennes University Hospital included cases presented from the beginning of the MDT meetings (February 2015) up to May 2017.

RESULTS: In total, 142 cases were presented in 15 MDT meetings, corresponding to a mean of 10±4 cases per meeting. Of these, 129 related to VTE patients: 33 provoked VTEs, 22 unprovoked VTEs, 49 cancer-related VTEs, and 25 unspecified VTEs. MDT meetings led to significant changes in the anticoagulation type (therapeutic, prophylactic, or discontinuation) and duration, but not in the anticoagulant choice (direct oral anticoagulants, vitamin K antagonists, heparins, etc.).

CONCLUSION: Requests for MDT meetings are made for all VTE types, and these meetings have an impact on VTE management.

PMID:32571559 | DOI:10.1016/j.jdmv.2020.04.011

20:05

PubMed articles on: Cardio-Oncology

Cardiac Imaging in Oncology Patients in Europe: a Model for Advancement of CV Safety and Development of Comprehensive CV Care

López-Fernández T. J Cardiovasc Transl Res 2020 - Review.

ABSTRACT

Cancer therapy-related cardiovascular events are widely recognized as a global problem, and cardio-oncology has been proposed as a new approach to coordinate preventive strategies in oncologic patients. Cardiac imaging plays a critical role in this process. This article summarizes current practices and future needs in cardiac imaging to improve the cardiovascular surveillance of cancer patients.

PMID:32583314 | PMC:PMC7314619 | DOI:10.1007/s12265-020-10028-1

20:05

PubMed articles on: Cardio-Oncology

Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis

Ghosh S, et al. Eur J Nutr 2020.

ABSTRACT

PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it.

METHODS: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam.

RESULTS: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression.

CONCLUSIONS: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views.

PMID:32583016 | DOI:10.1007/s00394-020-02301-5

20:05

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

20:05

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

20:05

PubMed articles on: Cancer & VTE/PE

Incidence of venous thromboembolism after robotic-assisted hysterectomy in obese patients with endometrial cancer: do we need extended prophylaxis?

Carbajal-Mamani SL, et al. J Robot Surg 2020.

ABSTRACT

Robotic surgery for gynecologic malignancy is associated with a lower rate of venous thromboembolism (VTE) than laparotomy. Obese patients represent a particularly high-risk group for VTE, but prior studies tend to focus on patients with a much lower BMI and without extended VTE prophylaxis. Our objective was to examine the role of extended thromboprophylaxis in obese patients who underwent robotic-assisted surgery for endometrial cancer. We conducted a retrospective cohort study of obese patients (BMI ≥ 35 kg/m2) who underwent robotic surgery for newly diagnosed endometrial cancer. The primary outcome measured was the occurrence of a VTE event within the 30-day postoperative period. The Farrington-Manning score test was used for equivalence analysis with a 5% margin. Secondary outcomes were perioperative complications. One hundred thirty-two robotic cases for endometrial cancer met our criteria. One hundred twenty-one (92%) received preoperative pharmacologic thromboprophylaxis, and 100% used pneumatic compression devices. Ninety-three percent and 90% received preoperative pharmacologic prophylaxis in the extended and no extended group, respectively (p-value = 0.7). Seventy patients (54%) received 4-week extended prophylaxis. Estimated blood loss was similar in both groups (75 mL vs 60 mL, p-value = 0.6). Perioperative complications and readmissions were similar between the two groups. There were no VTE events during hospital stay. One patient in the group that did not receive extended prophylaxis developed a VTE in the 30-day postoperative period (1.6%), versus 0% in the group that did receive extended prophylaxis (p-value = 0.1). The risk of VTE was low. The absence of extended VTE prophylaxis did not significantly increase the risk for VTE in obese patients with newly diagnosed endometrial cancer who underwent robotic-assisted surgery.

PMID:32592139 | DOI:10.1007/s11701-020-01110-6

20:05

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.

ABSTRACT

 

ABSTRACT

Venous thromboembolism (VTE) and major bleeding in primary central nervous system lymphoma (PCNSL) patients are not well described. We identified 992 PCNSL patients using the California Cancer Registry (2005-2014). The cumulative incidence of VTE and major bleeding was determined using California hospitalization data. The 12-month cumulative incidence of VTE was 13.6% (95% confidence interval (CI) 11.5-15.8%); chemotherapy and radiation therapy were associated with increased risk of VTE (hazard ratio (HR) 2.41, CI 1.31-4.46 and HR 1.56, CI 1.08-2.25, respectively). The 12-month cumulative incidence of major bleeding was 12.4% (CI 10.1-14.6%). Pulmonary embolism (PE) and proximal deep vein thrombosis were associated with increased risk of major bleeding, likely due to anticoagulation. PE (HR 1.61, CI 1.11-2.33, p=.011) and major bleeding (HR 2.36, CI 1.82-3.06, p<.0001)

PMID:32573292 | DOI:10.1080/10428194.2020.1780584

20:05

PubMed articles on: Cancer & VTE/PE

Impact of multidisciplinary team meetings on the management of venous thromboembolism. A clinical study of 142 cases

Mauger C, et al. J Med Vasc 2020.

ABSTRACT

OBJECTIVE: Numerous guidelines have been published on the management of venous thromboembolism (VTE). However, therapeutic decision-making may prove challenging in routine clinical practice. With this in mind, multidisciplinary team (MDT) meetings have been set up in Rennes University Hospital, France. This study sought to describe the situations discussed during MDT meetings and to assess whether the meetings bring about changes in the management of these patients.

MATERIALS AND METHODS: A retrospective single-center study conducted at the Rennes University Hospital included cases presented from the beginning of the MDT meetings (February 2015) up to May 2017.

RESULTS: In total, 142 cases were presented in 15 MDT meetings, corresponding to a mean of 10±4 cases per meeting. Of these, 129 related to VTE patients: 33 provoked VTEs, 22 unprovoked VTEs, 49 cancer-related VTEs, and 25 unspecified VTEs. MDT meetings led to significant changes in the anticoagulation type (therapeutic, prophylactic, or discontinuation) and duration, but not in the anticoagulant choice (direct oral anticoagulants, vitamin K antagonists, heparins, etc.).

CONCLUSION: Requests for MDT meetings are made for all VTE types, and these meetings have an impact on VTE management.

PMID:32571559 | DOI:10.1016/j.jdmv.2020.04.011

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PubMed articles on: Cardio-Oncology

Cardiac Imaging in Oncology Patients in Europe: a Model for Advancement of CV Safety and Development of Comprehensive CV Care

López-Fernández T. J Cardiovasc Transl Res 2020 - Review.

ABSTRACT

Cancer therapy-related cardiovascular events are widely recognized as a global problem, and cardio-oncology has been proposed as a new approach to coordinate preventive strategies in oncologic patients. Cardiac imaging plays a critical role in this process. This article summarizes current practices and future needs in cardiac imaging to improve the cardiovascular surveillance of cancer patients.

PMID:32583314 | PMC:PMC7314619 | DOI:10.1007/s12265-020-10028-1

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PubMed articles on: Cardio-Oncology

Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis

Ghosh S, et al. Eur J Nutr 2020.

ABSTRACT

PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it.

METHODS: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam.

RESULTS: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression.

CONCLUSIONS: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views.

PMID:32583016 | DOI:10.1007/s00394-020-02301-5

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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

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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

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PubMed articles on: Cancer & VTE/PE

Incidence of venous thromboembolism after robotic-assisted hysterectomy in obese patients with endometrial cancer: do we need extended prophylaxis?

Carbajal-Mamani SL, et al. J Robot Surg 2020.

ABSTRACT

Robotic surgery for gynecologic malignancy is associated with a lower rate of venous thromboembolism (VTE) than laparotomy. Obese patients represent a particularly high-risk group for VTE, but prior studies tend to focus on patients with a much lower BMI and without extended VTE prophylaxis. Our objective was to examine the role of extended thromboprophylaxis in obese patients who underwent robotic-assisted surgery for endometrial cancer. We conducted a retrospective cohort study of obese patients (BMI ≥ 35 kg/m2) who underwent robotic surgery for newly diagnosed endometrial cancer. The primary outcome measured was the occurrence of a VTE event within the 30-day postoperative period. The Farrington-Manning score test was used for equivalence analysis with a 5% margin. Secondary outcomes were perioperative complications. One hundred thirty-two robotic cases for endometrial cancer met our criteria. One hundred twenty-one (92%) received preoperative pharmacologic thromboprophylaxis, and 100% used pneumatic compression devices. Ninety-three percent and 90% received preoperative pharmacologic prophylaxis in the extended and no extended group, respectively (p-value = 0.7). Seventy patients (54%) received 4-week extended prophylaxis. Estimated blood loss was similar in both groups (75 mL vs 60 mL, p-value = 0.6). Perioperative complications and readmissions were similar between the two groups. There were no VTE events during hospital stay. One patient in the group that did not receive extended prophylaxis developed a VTE in the 30-day postoperative period (1.6%), versus 0% in the group that did receive extended prophylaxis (p-value = 0.1). The risk of VTE was low. The absence of extended VTE prophylaxis did not significantly increase the risk for VTE in obese patients with newly diagnosed endometrial cancer who underwent robotic-assisted surgery.

PMID:32592139 | DOI:10.1007/s11701-020-01110-6

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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.

ABSTRACT

 

ABSTRACT

OBJECTIVES: To investigate the association of extremes in body weight EBW and outcomes in patients with acute venous thromboembolism (VTE), recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with body weight <60120 kg.

METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview.

RESULTS: Amongst 2577 patients with the weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 - 120 kg, 223 (8.7%) bodyweight <60120 kg. Patients with bodyweight <60kg120kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (p=0.01).

CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60kg.120kg on rivaroxaban.

PMID:32557773 | DOI:10.1111/ejh.13471

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PubMed articles on: Cardio-Oncology

Cardiac effects and toxicity of chloroquine: a short update

Mubagwa K. Int J Antimicrob Agents 2020 - Review.

ABSTRACT

There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions resulting from their inhibition of ion channels, including voltage-dependent Na+ and Ca2+ channels, background and voltage-dependent K+ channels, and pacemaker channels. The drugs also exert a vagolytic effect due at least in part to a muscarinic receptor antagonist action. They also interfere with normal autophagy flux, an effect that could aggravate ischaemia/reperfusion injury or post-infarct remodelling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.

PMID:32565195 | PMC:PMC7303034 | DOI:10.1016/j.ijantimicag.2020.106057

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PubMed articles on: Cancer & VTE/PE

A Case of Trousseau's Syndrome Accompanying Ovarian Cancer with Widespread Thromboembolisms

Kobayashi H, et al. Case Rep Obstet Gynecol 2020.

ABSTRACT

The patient was a 41-year-old woman, gravida 0. She had no notable medical history. Laparoscopic right salpingo-oophorectomy and left cystectomy were performed for bilateral ovarian endometriomas, which were both pathologically diagnosed as benign. Six months later, she presented with left lower abdominal pain and expressive aphasia. Examination revealed multiple cerebral infarctions and pulmonary embolism. The patient was diagnosed with Trousseau's syndrome secondary to ovarian cancer, and anticoagulant therapy was initiated. Despite treatment, she developed visual field loss due to occlusion of the left retinal artery; dizziness due to cerebellar infarction and myocardial infarction; and right hemiplegia due to new cerebral infarction. She received chemotherapy (two courses of paclitaxel and carboplatin), which did not improve her condition, and died two months after onset. An autopsy revealed that her left ovary was enlarged to a size of 12 cm and an endometrioid carcinoma G2 was identified. Ovarian cancer had spread throughout the abdominal cavity, and a large amount of pleural and ascites fluid was present. Multiple thrombi were found in bilateral pulmonary arteries and bilateral common iliac veins. There was a 2.5 cm thrombus in the left ventricle apex, and the anterior descending branch was obstructed by thrombus with recanalization.

PMID:32566336 | PMC:PMC7293738 | DOI:10.1155/2020/3738618

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PubMed articles on: Cancer & VTE/PE

Efficacy and safety of direct oral anticoagulants versus low molecular weight heparin for cancer related venous thromboembolism: A meta-analysis of randomized trials

Elbadawi A, et al. Eur Heart J Cardiovasc Pharmacother 2020.

ABSTRACT

AIMS: To examine the efficacy and safety of direct oral anticoagulants (DOAC) versus low molecular weight heparin (LMWH) in patients with cancer-related venous thrombo-embolism (VTE).

METHODS AND RESULTS: An electronic search of MEDLINE, SCOPUS and COCHRANE without language restrictions was performed through April 2020 for randomized controlled trials that compared the effects of DOACs versus LMWH on patients with cancer-related VTE. Summary estimates were reported using random effects model. The main efficacy outcome was VTE recurrence while the main safety outcome was major bleeding events. The final analysis included 4 randomized trials with a total of 2,907 patients. The weighted mean follow-up was 6.1 months. Compared with LMWH, DOACs were associated with lower risk of VTE recurrence (5.7% vs. 9.1%, risk ratio [RR] 0.62; 95% confidence interval [CI] 0.44 to 0.87; P = 0.01), driven by lower deep venous thrombosis (P = 0.02). There was no difference between DOACs and LMWH in major bleeding events (4.8% vs. 3.6%, RR 1.33; 95% CI 0.84 to 2.11; P = 0.23). The incidence of all-cause mortality was similar (RR 0.99; 95% CI 0.84 to 1.16; P = 0.91). Subgroup analysis suggested no differences according to the type of DOAC in recurrent VTE or major bleeding (Pinteraction= 0.53 and Pinteraction= 0.11, respectively).

CONCLUSION: Among patients with cancer-related VTE, DOACs were associated with lower risk of VTE recurrence and similar risk of major bleeding compared with LMWH. Future studies examining the subset of cancer patients who drive the most benefit are encouraged.

PMID:32556105 | DOI:10.1093/ehjcvp/pvaa067

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PubMed articles on: Cardio-Oncology

Successful Heart Transplant in a Childhood Cancer Survivor With Chemoradiotherapy-Induced Cardiomyopathy

Sipahi NF, et al. Exp Clin Transplant 2020.

ABSTRACT

Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing population caused by a significant improvement in cancer therapy during the past decades. Although some listing criteria have been defined for these patients, it is still a compelling decision to list patients with a complex cancer anamnesis. We describe herein a childhood cancer survivor after a cancer anamnesis with 2 different malignancies and an end-stage heart failure following chemoradiotherapy who was successfully treated with orthotopic heart transplant.

PMID:32552629 | DOI:10.6002/ect.2020.0062

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PubMed articles on: Cardio-Oncology

High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease

Sparkenbaugh EM, et al. J Thromb Haemost 2020.

ABSTRACT

BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusive crises, chronic inflammation, and activation of coagulation. The clinical complications such as painful crisis, stroke, pulmonary hypertension, nephropathy and venous thromboembolism lead to cumulative organ damage and premature death. High molecular weight kininogen (HK) is a central cofactor for the kallikrein-kinin and intrinsic coagulation pathways, which contributes to both coagulation and inflammation.

OBJECTIVE: We hypothesize that HK contributes to the hypercoagulable and pro-inflammatory state that causes end-organ damage and early mortality in sickle mice.

METHODS: We evaluated the role of HK in the Townes mouse model of SCD.

RESULTS/CONCLUSIONS: We found elevated plasma levels of cleaved HK in sickle patients compared to healthy controls, suggesting ongoing HK activation in SCD. We used bone marrow transplantation to generate wild type and sickle cell mice on a HK-deficient background. We found that short-term HK deficiency attenuated thrombin generation and inflammation in sickle mice at steady state, which was independent of bradykinin signaling. Moreover, long-term HK deficiency attenuates kidney injury, reduces chronic inflammation, and ultimately improves of sickle mice.

PMID:32573897 | DOI:10.1111/jth.14972

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PubMed articles on: Cancer & VTE/PE

High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease

Sparkenbaugh EM, et al. J Thromb Haemost 2020.

ABSTRACT

BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusive crises, chronic inflammation, and activation of coagulation. The clinical complications such as painful crisis, stroke, pulmonary hypertension, nephropathy and venous thromboembolism lead to cumulative organ damage and premature death. High molecular weight kininogen (HK) is a central cofactor for the kallikrein-kinin and intrinsic coagulation pathways, which contributes to both coagulation and inflammation.

OBJECTIVE: We hypothesize that HK contributes to the hypercoagulable and pro-inflammatory state that causes end-organ damage and early mortality in sickle mice.

METHODS: We evaluated the role of HK in the Townes mouse model of SCD.

RESULTS/CONCLUSIONS: We found elevated plasma levels of cleaved HK in sickle patients compared to healthy controls, suggesting ongoing HK activation in SCD. We used bone marrow transplantation to generate wild type and sickle cell mice on a HK-deficient background. We found that short-term HK deficiency attenuated thrombin generation and inflammation in sickle mice at steady state, which was independent of bradykinin signaling. Moreover, long-term HK deficiency attenuates kidney injury, reduces chronic inflammation, and ultimately improves of sickle mice.

PMID:32573897 | DOI:10.1111/jth.14972

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20:05

PubMed articles on: Cancer & VTE/PE

High incidence of venous thromboembolism and major bleeding in patients with primary CNS lymphoma

Mahajan A, et al. Leuk Lymphoma 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

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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

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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

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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.

ABSTRACT

External validation is a prerequisite in order for a prediction model to be introduced into clinical practice. Nonetheless, methodologically intact external validation studies are a scarce finding. Utilization of big datasets can help overcome several causes of methodological failure. However, transparent reporting is needed to standardize the methods, assess the risk of bias and synthesize multiple validation studies in order to infer model generalizability. We describe the methodological challenges faced when using multiple big datasets to perform the first retrospective external validation study of the Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients-Cancer Associated Thrombosis (COMPASS-CAT) Risk Assessment Model for predicting venous thromboembolism in patients with cancer. The challenges included choosing the starting point, defining time sensitive variables that serve both as risk factors and outcome variables and using non-research oriented databases to form validated definitions from administrative codes. We also present the structured plan we used so as to overcome those obstacles and reduce bias with the target of producing an external validation study that successfully complies with prediction model reporting guidelines.

PMID:32564180 | DOI:10.1007/s11239-020-02191-8

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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

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PubMed articles on: Cancer & VTE/PE

Prevention and treatment of venous thromboembolism in cancer patients

Spehlmann ME, et al. Herz 2020 - Review.

ABSTRACT

Deep vein thrombosis and pulmonary artery embolism are common and serious concomitant diseases in patients with cancer. The prophylaxis and therapy of such venous thromboembolic events (VTE) in oncology have so far been achieved with low-molecular-weight heparins. An increasing number of studies show evidence of the use of direct oral anticoagulants. However, since none of the possible options were shown to have a clear advantage in all patients, the individual decision to use a drug should be made depending on its effectiveness in preventing VTE, the risk of bleeding, the nature of the cancer, the interactions with other medications, the route of administration, and finally the cost of treatment.

PMID:32564097 | DOI:10.1007/s00059-020-04961-9

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PubMed articles on: Cardio-Oncology

Cardiac Imaging in Cardio-oncology: An Ongoing Challenging

Citro R and Monte IP. J Cardiovasc Echogr 2020.

NO ABSTRACT

PMID:32566459 | PMC:PMC7293867 | DOI:10.4103/jcecho.jcecho_1_19

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism after adult thymus or thymic tumor resection: A single-center experience

Yang X, et al. Thorac Cancer 2020.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication. Previous studies have shown that the VTE incidence after major thoracic surgery is high. However, there have been no exclusive data after thymectomy thus far. To investigate the incidence of postoperative VTE, we conducted a single-center, prospective cohort study.

METHODS: Patients who underwent thymectomy between December 2017 and January 2020 were enrolled. None of the patients received any prophylaxis perioperatively. Subjects were risk stratified into groups of low risk (0-4), moderate risk (5-8), and high risk (≥9). Occurrence of VTE events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), were identified by imaging.

RESULTS: There were 192 patients who underwent thymectomy enrolled into the study. The overall VTE incidence was 8.9%. All the patients were diagnosed with DVT, and none were diagnosed with PE. The VTE incidence was 4.6% in patients with benign thymic diseases and 14.5% with malignant diseases. The VTE incidence was 4.7% in patients undergoing thoracoscopic surgery and 22.7% undergoing median sternotomy. The VTE incidence increased with Caprini score. Scores in the low, moderate, and high risk groups were associated with a VTE incidence of 0%, 10.3% and 37.5%, respectively. In patients with thymic malignancy, the VTE incidence in the moderate and high risk groups were 8.8% and 31.8%, respectively.

CONCLUSIONS: VTE occurred frequently in patients after thymectomy without VTE prophylaxis. The median sternotomy procedure and malignant tumor may be the major risk factors for the development of VTE. Aggressive VTE screening/treatment protocols should be implemented in patents after thymectomy.

PMID:32558357 | DOI:10.1111/1759-7714.13543

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PubMed articles on: Cardio-Oncology

Vascular Damage - Coronary Artery Disease

Cadeddu Dessalvi C, et al. J Cardiovasc Echogr 2020 - Review.

ABSTRACT

Cardiovascular complications during chemotherapy and radiotherapy are becoming an increasing problem because many patients with cancer are treated with agents that exert significant vascular toxicity. Coronary heart disease in patients with cancer presents particular challenges, which directly impact the management of both the coronary disease and malignancy. Several chemotherapeutic agents have been shown to trigger ischemic heart disease, and as it has happened for myocardial cardiotoxicity, more attention should be dedicated to improving early recognition and prevention of cardiac vascular toxicity. Cardiac imaging could facilitate early detection of vascular toxicity, but a thorough risk stratification should always be performed to identify patients at higher risk of vascular impairment.

PMID:32566461 | PMC:PMC7293870 | DOI:10.4103/jcecho.jcecho_3_19

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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

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PubMed articles on: Cancer & VTE/PE

Effectiveness and Safety of Apixaban and Rivaroxaban for Acute Venous Thromboembolism Therapy in Patients with Extremes in Body Weight (ClinicalTrials.gov: NCT03504007)

Wysokinski WE, et al. Eur J Haematol 2020.

 

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

20:03

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

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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

20:04

PubMed articles on: Cardio-Oncology

Echocardiography and biomarkers for the diagnosis of cardiotoxicity

Berliner D, et al. Herz 2020 - Review.

ABSTRACT

As a result of better treatment options for malignant cancer, the cardiovascular side effects of such therapies have increasingly come into focus in recent years. The new cardiological subspecialty of oncocardiology is developing strategies to prevent and/or detect those effects early in order to treat them in a timely and adequate manner. The diagnosis of cardiotoxic effects is based mainly on imaging and specific biomarkers. Echocardiography has become the main imaging technique due to its wide availability. In addition to quantitative determination of left ventricular function using two-dimensional methods, three-dimensional methods offer better precision and less variability in the detection of cardiac dysfunction. Furthermore, the analysis of the global longitudinal strain (GLS) reveals even subtle changes in left ventricular function and thus detects very early damage before left ventricular ejection fraction drops. Various biomarkers have been tested recently for their potential to detect cardiotoxicity. Cardiac troponins are currently the best investigated biomarkers and certainly have the highest impact. Due to contradicting results, the importance of natriuretic peptides has not yet been conclusively clarified. Results for myeloperoxidase are promising, as are the results for circulating microRNAs, which still mainly derive from experimental data. In this context, further studies still need to show the value of these in everyday clinical practice.

PMID:32564096 | DOI:10.1007/s00059-020-04957-5

20:04

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

INTRODUCTION: We conducted a longitudinal study in patients with pancreatic and colorectal cancer. We determined the effect of chemotherapy on extracellular vesicle tissue factor (EVTF) activity and the association of plasma EVTF activity with venous thromboembolism (VTE) and survival.

MATERIAL AND METHODS: We enrolled 13 patients with pancreatic and 22 patients with colorectal cancer. Plasma samples were collected during the 85-day study period. Patients were followed for 3 months after the study period. We recorded symptomatic VTE during the study period (3 months) or asymptomatic deep vein thrombosis detected by ultrasound at day 85. We measured EVTF activity before and after chemotherapy.

RESULTS AND CONCLUSIONS: In the pancreatic cancer group, 2 patients had elevated levels of EVTF activity. One of these patients developed symptomatic VTE and died, and the second patient did not have a VTE but died. Chemotherapy decreased EVTF activity in 2 pancreatic patients with high levels. In the colorectal cancer group, 4 patients developed VTE, but EVTF activity was not elevated in any patient and no patient died. We observed a borderline significant correlation between EVTF activity and D-dimer in the patients with pancreatic but not colorectal cancer. In this small descriptive study, 2 patients with pancreatic cancer had an elevated level of EVTF activity. Both patients died during the study period, and one had a VTE. Chemotherapy decreased EVTF activity in these patients. In contrast, elevated levels of EVTF activity were not observed in patients with colorectal cancer with or without VTE.

PMID:32548563 | PMC:PMC7292676 | DOI:10.1002/rth2.12317

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PubMed articles on: Cardio-Oncology

Reprogramming of tumor-associated macrophages by targeting β-catenin/FOSL2/ARID5A signaling: A potential treatment of lung cancer

Sarode P, et al. Sci Adv 2020.

ABSTRACT

Tumor-associated macrophages (TAMs) influence lung tumor development by inducing immunosuppression. Transcriptome analysis of TAMs isolated from human lung tumor tissues revealed an up-regulation of the Wnt/β-catenin pathway. These findings were reproduced in a newly developed in vitro "trained" TAM model. Pharmacological and macrophage-specific genetic ablation of β-catenin reprogrammed M2-like TAMs to M1-like TAMs both in vitro and in various in vivo models, which was linked with the suppression of primary and metastatic lung tumor growth. An in-depth analysis of the underlying signaling events revealed that β-catenin-mediated transcriptional activation of FOS-like antigen 2 (FOSL2) and repression of the AT-rich interaction domain 5A (ARID5A) drive gene regulatory switch from M1-like TAMs to M2-like TAMs. Moreover, we found that high expressions of β-catenin and FOSL2 correlated with poor prognosis in patients with lung cancer. In conclusion, β-catenin drives a transcriptional switch in the lung tumor microenvironment, thereby promoting tumor progression and metastasis.

PMID:32548260 | PMC:PMC7274802 | DOI:10.1126/sciadv.aaz6105

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PubMed articles on: Cardio-Oncology

Risk of Prevalent Asthma among Children Affected by Inflammatory Bowel Disease: A Population-Based Birth Cohort Study

Barbiellini Amidei C, et al. Int J Environ Res Public Health 2020.

ABSTRACT

Literature on the risk of asthma among children with inflammatory bowel disease (IBD) is limited and has reported discording results. To the best of our knowledge, no previous study has evaluated the association between asthma and childhood onset IBD, focusing on pediatric IBD with onset between 10 and 17 years, early-onset IBD (EO-IBD) between 0 and 9 years, and very early-onset IBD (VEO-IBD) between 0 and 5 years, all conditions characterized by different clinical progressions. A nested matched case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of asthma among children with IBD compared with controls. We found 162 children with IBD and 1620 controls. Overall, childhood onset IBD was associated with increased risks of being affected by asthma (OR: 1.49 95% CI 1.05-2.12), although a significant risk was only present among males (OR: 1.60 95% CI 1.02-2.51). Children with Crohn's disease and ulcerative colitis had similarly increased risks, although they failed to attain statistical significance. Risks of asthma based on age at IBD onset were inversely related to age, with the lowest non-significant risks for pediatric IBD and EO-IBD, while children affected by VEO-IBD had the highest risk of asthma (OR: 2.75 95% CI 1.26-6.02). Our study suggests the presence of a higher prevalence of asthma among both male children with IBD and children with VEO-IBD. It could be advisable to pay greater attention to possible respiratory symptoms among these categories at higher risk.

PMID:32549223 | DOI:10.3390/ijerph17124255

20:03

PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants compared to low-molecular-weight heparin for the treatment of cancer-associated thrombosis: Updated systematic review and meta-analysis of randomized controlled trials

Moik F, et al. Res Pract Thromb Haemost 2020.

ABSTRACT

BACKGROUND: Low-molecular-weight-heparins (LMWHs) have been established for the treatment of cancer-associated venous thromboembolism (VTE). Recently published randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) with LMWHs. The aim of this systematic review and meta-analysis was to evaluate efficacy and safety of DOACs versus LMWHs and update the evidence for treatment of VTE in cancer.

METHODS: Biomedical databases were screened for RCTs evaluating DOACs for cancer-associated VTE. Primary efficacy and safety outcomes of this meta-analysis were recurrent VTE and major bleeding at 6 months. Secondary outcomes comprised clinically relevant nonmajor bleeding (CRNMB), major gastrointestinal (GI) and genitourinary bleeding, mortality, fatal bleeding/pulmonary embolism, and treatment discontinuation rate. We performed prespecified subgroup analyses. Pooled relative risk (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effect model.

RESULTS: We screened 759 articles and included 4 RCTs (n = 2894). DOACs significantly reduced recurrent VTEs compared to LMWHs (5.2% vs 8.2%; RR, 0.62 [95% CI, 0.43-0.91]), but were associated with a nonsignificant increase in major bleedings (4.3% vs 3.3%; RR, 1.31 [95% CI, 0.83-2.08]) and a significant increase in CRNMB (10.4% vs 6.4%; RR, 1.65 [95% CI, 1.19-2.28]). Mortality risks were comparable between groups (RR, 0.99 [95% CI, 0.83-1.18]). Preterm treatment discontinuation was less common with DOACs (RR, 0.88 [95% CI, 0.81-0.96]). Major bleeding was more frequent in patients with GI cancer treated with DOACs (RR, 2.30 [95% CI, 1.08-4.88]).

CONCLUSION: In patients with cancer-associated VTE, DOACs are more effective in preventing recurrent VTE compared to LMWH. However, risk of bleeding is increased with DOACs, especially in patients with GI cancer.

PMID:32548553 | PMC:PMC7292654 | DOI:10.1002/rth2.12359

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20:03

PubMed articles on: Cardio-Oncology

Cardiovascular disease and asymptomatic childhood cancer survivors: Current clinical practice

Bottinor WJ, et al. Cancer Med 2020.

ABSTRACT

BACKGROUND: It is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care.

OBJECTIVES: To describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS.

METHODS: At 50 pediatric academic medical centers, a childhood cancer survivorship clinic director, pediatric cardiologist, and adult cardiologist with a focus on CCS were identified and invited to participate in a survey. Surveys were managed electronically. Categorical data were analyzed using nonparametric methods.

RESULTS: Of the 95 (63%) respondents, 39% were survivorship practitioners, and 61% were cardiologists. Eighty-eight percent of survivorship practitioners reported that greater than half of CCS received cardiovascular screening. CCS followed by adult cardiology were more likely to be seen by a cardio-oncologist. Those followed by pediatric cardiology were more likely to be seen by a heart failure/transplant specialist. Common reasons for referral to cardiology were abnormal cardiovascular imaging or concerns a CCS was at high risk for cardiovascular disease. Ninety-two percent of cardiologists initiated angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy for mild systolic dysfunction. Adult cardiologists initiated beta-blocker therapy for less severe systolic dysfunction compared to pediatric cardiologists (P < .001). Pediatric cardiologists initiated mineralocorticoid therapy for less severe systolic dysfunction compared to adult cardiologists (P = .025). Practitioners (93%) support a multi-institutional collaboration to standardize cardiovascular care for CCS.

CONCLUSIONS: While there is much common ground in the clinical approach to CCS, heterogeneity is evident. This highlights the need for cohesive, multi-institutional, standardized approaches to cardiovascular management in CCS.

PMID:32558321 | DOI:10.1002/cam4.3190

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PubMed articles on: Cancer & VTE/PE

Cancer-associated venous thromboembolism: Treatment and prevention with rivaroxaban

Bauersachs R, et al. Res Pract Thromb Haemost 2020 - Review.

ABSTRACT

Cancer-associated venous thromboembolism (VTE) is a frequent, potentially life-threatening event that complicates cancer management. Anticoagulants are the cornerstone of therapy for the treatment and prevention of cancer-associated thrombosis (CAT); factor Xa-inhibiting direct oral anticoagulants (DOACs; apixaban, edoxaban, and rivaroxaban), which have long been recommended for the treatment of VTE in patients without cancer, have been investigated in this setting. The first randomized comparisons of DOACs against low-molecular-weight heparin for the treatment of CAT indicated that DOACs are efficacious in this setting, with findings reflected in recent updates to published guidance on CAT treatment. However, the higher risk of bleeding events (particularly in the gastrointestinal tract) with DOACs highlights the need for appropriate patient selection. Further insights will be gained from additional studies that are ongoing or awaiting publication. The efficacy and safety of DOAC thromboprophylaxis in ambulatory patients with cancer at a high risk of VTE have also been assessed in placebo-controlled randomized controlled trials of apixaban and rivaroxaban. Both studies showed efficacy benefits with DOACs, but both studies also showed a nonsignificant increase in major bleeding events while on treatment. This review summarizes the evidence base for rivaroxaban use in CAT, the patient profile potentially most suited to DOAC use, and ongoing controversies under investigation. We also describe ongoing studies from the CALLISTO (Cancer Associated thrombosis-expLoring soLutions for patients through Treatment and Prevention with RivarOxaban) program, which comprises several randomized clinical trials and real-world evidence studies, including investigator-initiated research.

PMID:32548552 | PMC:PMC7292665 | DOI:10.1002/rth2.12327

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20:03

PubMed articles on: Cardio-Oncology

Left-Ventricular Function After 3 Months of Sacubitril-Valsartan in Acute Decompensated Heart Failure

Mirić D, et al. J Cardiovasc Transl Res 2020.

 

ABSTRACT

Even if cancer and cardiovascular diseases are considered two distinct diseases, an intricate interconnection between these conditions has been established. Increased risk of malignancy has been identified in patients with cardiovascular disease, as well as a greater propensity to the development of cardiovascular diseases has been observed in patients with cancer. The development of cardiotoxicity following exposure to certain anticancer drugs only partially explains this relationship. Shared risk factors and common pathogenic mechanisms suggest the existence of a common biology and a complex interplay between these two conditions. Due to improving longevity and therapeutic advances, the number of patients affected or potentially at risk of developing these two diseases is constantly increasing and currently, several drugs against cancer from anthracyclines to checkpoint inhibitors, can also cause a wide range of unexpected cardiovascular side effects. Management of these issues in clinical practice is an emerging challenge for cardiologists and oncologists, and led to the development of a new dedicated discipline called cardio-oncology. Surveillance and prevention strategies as well as interventions to reduce cardiovascular risk and prevent cardiotoxicities are the primary objectives of cardio-oncology. In this review, we explore the etiopathogenesis common to cardiovascular disease and cancer and the complex interplay between them. We also report the main characteristics of the drugs responsible for cardiotoxicity, highlighting the available strategies for optimal patient management based on a multidisciplinary approach in the cardio-oncology setting.

PMID:32571000 | DOI:10.4081/monaldi.2020.1348

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PubMed articles on: Cancer & VTE/PE

High incidence of venous thromboembolism and major bleeding in patients with primary CNS lymphoma

Mahajan A, et al. Leuk Lymphoma 2020.

ABSTRACT

Venous thromboembolism (VTE) and major bleeding in primary central nervous system lymphoma (PCNSL) patients are not well described. We identified 992 PCNSL patients using the California Cancer Registry (2005-2014). The cumulative incidence of VTE and major bleeding was determined using California hospitalization data. The 12-month cumulative incidence of VTE was 13.6% (95% confidence interval (CI) 11.5-15.8%); chemotherapy and radiation therapy were associated with increased risk of VTE (hazard ratio (HR) 2.41, CI 1.31-4.46 and HR 1.56, CI 1.08-2.25, respectively). The 12-month cumulative incidence of major bleeding was 12.4% (CI 10.1-14.6%). Pulmonary embolism (PE) and proximal deep vein thrombosis were associated with increased risk of major bleeding, likely due to anticoagulation. PE (HR 1.61, CI 1.11-2.33, p=.011) and major bleeding (HR 2.36, CI 1.82-3.06, p<.0001)

PMID:32573292 | DOI:10.1080/10428194.2020.1780584

15:59

PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants and cancer-associated VTE: good for all, or just some?

Carrier M and Wang TF. Blood 2020.

ABSTRACT

Venous thromboembolism (VTE) is associated with significant mortality and morbidity in patients with cancer. Therefore, tailoring anticoagulation is of utmost importance in order to decrease the risk of recurrent VTE while minimizing the risk of bleeding. Direct oral anticoagulants have been recently compared to low-molecular-weight heparin for the management of acute cancer-associated thrombosis. Although direct oral anticoagulants are a welcome addition, clinicians need to incorporate clinical characteristics, drug-drug interactions and patient preference in decision making.

PMID:32575112 | DOI:10.1182/blood.2019004177

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Cardiotoxicity News

PubMed articles on: Cancer & VTE/PE

Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism

Cambron JC, et al. Mayo Clin Proc Innov Qual Outcomes 2020.

ABSTRACT

OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome.

METHODS: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories.

RESULTS: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category.

CONCLUSION: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03504007.

PMID:32542216 | PMC:PMC7283932 | DOI:10.1016/j.mayocpiqo.2020.02.002

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PubMed articles on: Cancer & VTE/PE

Infantile hepatic hemangioendothelioma associated with pulmonary artery hypertension and cardiac insufficiency successfully treated with transcatheter arterial embolization and propranolol: A case report

Wang L, et al. Medicine (Baltimore) 2020.

ABSTRACT

INTRODUCTION: Infantile hepatic hemangioendothelioma is a type of benign hepatic tumor that occurs in infancy. Many hepatic tumors are diagnosed when screening is done for multiple cutaneous hemangiomas. Hepatic tumors are small multifocal lesions and are mostly asymptomatic. There have been many case reports of asymptomatic infantile hepatic hemangioendothelioma, but few of these have pointed out that hepatic hemangiomas can sometimes be life-threatening due to fatal hepatomegaly complications such as pulmonary artery hypertension or even congestive heart failure. At present, there are no standard protocols for treating infantile hepatic hemangioendothelioma, though most clinicians agree that treatment is unnecessary for multiple small hepatic hemangiomas in asymptomatic patients. Little is known about treatment for cases with life-threatening complications induced by infantile hepatic hemangioendothelioma as there are so few reported cases. Here, we report a special case with hepatomegaly, pulmonary artery hypertension, and cardiac insufficiency induced by infantile hepatic hemangioendothelioma.

PATIENT CONCERNS: We present a case with hepatomegaly, pulmonary artery hypertension, and cardiac insufficiency caused by infantile hepatic hemangioendothelioma.

DIAGNOSIS: Infantile hepatic hemangioendothelioma was diagnosed.

INTERVENTIONS: The patient underwent transcatheter arterial embolization and was given propranolol.

OUTCOMES: The patient responded well to treatment with transcatheter arterial embolization and propranolol. The patient gained weight steadily, liver volume, and mass size have decreased considerably, echocardiography showed normal pulmonary artery pressure and ejection fraction, and we discovered no serious complications after 1 year of follow-up.

CONCLUSION: Transcatheter arterial embolization combined with propranolol is an effective treatment for life-threatening infantile hepatic hemangioendothelioma.

PMID:32541524 | PMC:PMC7302649 | DOI:10.1097/MD.0000000000020728

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PubMed articles on: Cancer & VTE/PE

Real world data regarding the management of cancer-associated thrombosis

Tsoukalas N, et al. Curr Opin Oncol 2020.

ABSTRACT

PURPOSE OF REVIEW: Patients with cancer are at high risk for thrombotic events, mainly deep vein thrombosis and pulmonary embolism. Low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the current treatment options for cancer-associated thrombosis (CAT). We assessed real world data (RWD) regarding treatment patterns of CAT from 1 September 2018 to 31 January 2020.

RECENT FINDINGS: RWD showed that LMWHs were the most common initial anticoagulation treatment for CAT. Based on these data DOACs had a lower risk of recurrent venous thromboembolism compared with LMWHs and warfarin. However, the selection bias and the small number of patients in these studies might explain this difference and these limitations should be taken into consideration. Moreover, there was no statistical difference regarding adverse events during anticoagulant treatment between LMWHs and DOACs with the limitations of RWD. As far as the duration of the treatment is concerned, the adherence ranged from 100% to 67.3% at 6 months.

SUMMARY: The current review of RWD illustrates that LMWHs and DOACs are used for the treatment of CAT. LMWHs are most commonly used for the initial management of CAT. Data regarding recurrence of CAT, adverse events, compliance and duration of anticoagulant treatment should be analyzed with caution as RWD are observational studies with many limitations. Further research is needed to elucidate the best algorithm for the management of CAT.

PMID:32541315 | DOI:10.1097/CCO.0000000000000646

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20:03

PubMed articles on: Cardio-Oncology

Cardio-oncology - More than just cardiac complications of cancer treatment

Ghosh AK. Int J Cardiol 2020.

NO ABSTRACT

PMID:32544476 | DOI:10.1016/j.ijcard.2020.06.003

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PubMed articles on: Cancer & VTE/PE

Anticoagulants for the treatment of venous thromboembolism in patients with cancer: A comprehensive systematic review, pairwise and network meta-analysis

Sidahmed S, et al. Crit Rev Oncol Hematol 2020 - Review.

ABSTRACT

Cancer-associated venous thromboembolism (VTE) is associated with high VTE recurrence and bleeding. We included all randomized clinical trials that evaluated the efficacy and safety of various anticoagulants in cancer-associated VTE. Trial-level data were extracted from 13 trials. Aggregate odds ratios (ORs) were calculated using direct and network meta-analysis. The primary outcome was VTE (pulmonary embolism and/or deep vein thrombosis) recurrence. Secondary outcomes were major bleeding and all-cause mortality. We identified 13 trials with 4869 patient-years of follow-up (6595 total patients; mean age 62.4 ± 12.2; 50.4 % female; 17.7 % hematological malignancies). The most common cancer type was colorectal and 48 % had metastatic cancer at baseline. Compared to vitamin-K-antagonists (VKAs), non-vitamin-K-antagonist-oral-anticoagulants (NOACs) were associated with significantly reduced VTE recurrence (OR, 0.58; 95 % CI, 0.40-0.83) and reduced major bleeding risks (OR, 0.56; 95 % CI, 0.35-0.91). However, no differences were observed in the subgroup analysis of patients with active cancer. Although NOACs were associated with reduced VTE recurrence compared with low-molecular-weight-heparin (LMWHs) (OR, 0.46; 95 % CI, 0.25- 0.85), there was a significant increased major bleeding in high-quality trials. LMWHs were associated with significantly reduced VTE recurrence compared with VKAs (OR, 0.52; 95 % CI, 0.39-0.71) and similar bleeding risks. Conclusions: Among patients with cancer-associated VTE, NOACs were associated with significantly reduced VTE recurrence and bleeding compared with VKAs, however, with similar outcomes in the active cancer population. NOACs were associated with reduced VTE recurrence but higher bleeding risks compared with LMWHs. LMWHs were associated with significantly reduced VTE recurrence and similar bleeding compared with VKAs.

PMID:32540780 | DOI:10.1016/j.critrevonc.2020.103005

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PubMed articles on: Cardio-Oncology

Resiliency and Our Cardio-Oncology Community

Ky B. JACC CardioOncol 2020.

NO ABSTRACT

PMID:32548596 | PMC:PMC7243765 | DOI:10.1016/j.jaccao.2020.05.003

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PubMed articles on: Cancer & VTE/PE

Vascular effects of cancer treatments

Campia U. Vasc Med 2020.

ABSTRACT

Chemotherapy, alone or in association with radiation therapy, has represented the cornerstone of cancer treatment for decades. However, in the last several years, an unprecedented progress in the understanding of cancer biology and the discovery of novel therapeutic targets have led to a paradigm shift in the management of patients with neoplastic diseases. The introduction of tyrosine kinase inhibitors, vascular endothelial growth factor pathway inhibitors, immunomodulatory agents, proteasome inhibitors, immune checkpoint inhibitors, and chimeric antigen receptor T cells, among others, has been associated with prolonged survival in many forms of cancer. A common feature of both chemotherapy and novel cancer treatments is the frequent occurrence of vascular toxicity, mainly mediated by injury to the endothelium. While the mechanisms may vary between agents, the clinical manifestations may overlap and range from hypertension, vasospastic and thrombotic arterial events (myocardial ischemia and infarction, peripheral ischemia, and limb gangrene), venous thromboembolism (deep vein thrombosis and pulmonary embolism) to capillary leak syndrome. Therefore, the effective management of patients with cancer requires a multidisciplinary team approach in which oncologist and cardiovascular medicine specialists work together to prevent, detect, and minimize acute vascular toxicity and long-term consequences of cancer therapy.

PMID:32539632 | DOI:10.1177/1358863X20914978

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PubMed articles on: Cardio-Oncology

Cardio-Oncology in Brazil: The Dimensions of a New Era in the Care of Patients

Hajjar LA and Mathias C. JACC CardioOncol 2020.

NO ABSTRACT

PMID:32548595 | PMC:PMC7243784 | DOI:10.1016/j.jaccao.2020.05.004

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PubMed articles on: Cancer & VTE/PE

Effect of chemotherapy and longitudinal analysis of circulating extracellular vesicle tissue factor activity in patients with pancreatic and colorectal cancer

Kasthuri RS, et al. Res Pract Thromb Haemost 2020.