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ABSTRACT

The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J Mir34a-/-mice. Finally, a positive correlation was observed between circulating miR-34a and IL6 in healthy subjects of 20-90 years. Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC.

PMID:32585876 | DOI:10.3390/ijms21124454

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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

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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

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

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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

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PubMed articles on: Cancer & VTE/PE

Evaluation of Biomarkers for the Prediction of Venous Thromboembolism in Ambulatory Cancer Patients

Schorling RM, et al. Oncol Res Treat 2020.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common complication of cancer. This study aimed to evaluate immature platelet fraction (IPF), mean platelet volume (MPV), P-selectin, D-dimer, and thrombin generation (TG) as predictive biomarkers for VTE and further the improvement of existing risk assessment models (RAMs).

METHODS: A prospective, observational, exploratory study was conducted on ambulatory cancer patients with indication for systemic chemotherapy. Baseline RAMs included the Khorana-, Vienna Cancer, Thrombosis-, Protecht-, ONKOTEV-, and Catscore. IPF, MPV, P-selectin, D-dimer, and TG were analysed at baseline and 3-month follow-up.

RESULTS: We enrolled 100 patients, of whom 89 completed the follow-up. Frequent tumour types were breast (30%), gastric (14%), gynaecological (14%), and colorectal (14%) cancer. Ten of the 89 patients (11.2%) developed VTE. The highest VTE rate was observed in patients with cholangiocarcinoma (3/5; 60%). Baseline D-dimer levels but not IPF, MPV, or P-selectin were associated with the risk of developing VTE (HR 6.9; p = 0.021). None of the RAMs showed statistical significance in predicting VTE. Peak thrombin and endogenous thrombin potential were lower in patients who developed VTE. Biomarker changes between baseline and follow-up were not associated with VTE risk.

CONCLUSIONS: VTE risk was well predicted by baseline D-dimer levels. Adding D-dimer could improve existing RAMs to better identify patients who may benefit from primary VTE prophylaxis. The VTE risk among patients with cholangiocarcinoma should be further evaluated.

PMID:32580190 | DOI:10.1159/000508271

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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 | DOI:10.1186/s12885-020-07104-9

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PubMed articles on: Cancer & VTE/PE

Quality Improvement at an Academic Cancer Center: Venous Thromboembolism Prophylaxis in Patients With Multiple Myeloma

Baz R, et al. Cancer Control 2020.

ABSTRACT

Patients with multiple myeloma are at elevated risk of venous thromboembolism (VTE), the second leading cause of death in patients with cancer, but physician adherence to VTE prevention guidelines is low. Several organizations partnered in designing and implementing a 2-year quality improvement (QI) program in a tertiary care/academic cancer center, to increase awareness of VTE prophylaxis for patients with multiple myeloma and thus improve adherence to prophylaxis guidelines and protocols. The QI arm included 2 chart audits, conducted 2 years apart, of unmatched cohorts of 100 patients with multiple myeloma. An Education arm included 2 grand rounds presentations, 3 web-based case discussions, and a patient education module. Twenty providers took part in the continuous QI arm. More than 1100 learners participated in the online cases; the patient education curriculum reached 112 multiple myeloma patients. The initiative proved helpful in defining barriers to guideline adherence and identifying data-driven practice improvement strategies for VTE prophylaxis. It also increased learner awareness of VTE guidelines, patient risk stratification, and optimal thromboprophylaxis strategies. There was a reduction in VTE events (primary clinical outcome) from 10% at baseline to 4% in the follow-up cohort, although this was not statistically significant. Higher rates of guideline-based prophylaxis were observed in low-risk patients, and a lower incidence of VTE was observed in multiple myeloma patients with a prior history of VTE. Additional research is needed to refine prophylaxis guidelines. With appropriate institutional support, this type of QI program can be readily adopted by other organizations to address practice improvement needs.

PMID:32551873 | PMC:PMC7303783 | DOI:10.1177/1073274820930204

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PubMed articles on: Cancer & VTE/PE

Pulmonary embolism and acro-ischemia in a lung cancer patient with COVID-19

González Del Portillo E and Pérez-Romasanta LA. Med Clin (Barc) 2020.

NO ABSTRACT

PMID:32586671 | PMC:PMC7274584 | DOI:10.1016/j.medcli.2020.05.023

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PubMed articles on: Cardio-Oncology

Downregulation of miR-125b-5p and Its Prospective Molecular Mechanism in Lung Squamous Cell Carcinoma

Huang SP, et al. Cancer Biother Radiopharm 2020.

ABSTRACT

Background:To explore the clinical significance of miR-125b-5p and its potential mechanisms in lung squamous cell carcinoma (LUSC). Materials and Methods:An integrated analysis of data from in-house quantitative real-time polymerase chain reaction (qRT-PCR), microRNA-sequencing, and microarray assays to appraise the expression level of miR-125b-5p in LUSC tissues compared to adjacent noncancerous controls. The authors identified the candidate targets of miR-125b-5p and conducted functional analysis using computational biology strategies from gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, disease ontology (DO), and protein-protein interaction (PPI) network analyses to investigate the prospective mechanisms. Results:According to qRT-PCR results, the expression level of miR-125b-5p was markedly decreased in LUSC tissues compared to noncancerous control tissues. Receiver operating characteristic and summary receiver operating characteristic analyses showed that miR-125b-5p had good specificity and sensitivity for distinguishing LUSC tissue from noncancerous lung tissue. The standard mean difference revealed that men and women with lower expression levels of miR-125b-5p may have a higher risk for LUSC. KEGG analysis and DO analysis intimated that target genes were evidently enriched in pyrimidine metabolism and pancreatic carcinoma. The PPI network of the top assembled KEGG pathway indicated that RRM2, UMPS, UCK2, and CTPS1were regarded as crucial target genes for miR-125b-5p, and RRM2was eventually deemed a key target. Conclusions:The authors' findings implicate a low expression level of miR-125b-5p in LUSC. A tumor-suppressive role of miR-125b-5p is proposed, based on its effects on LUSC tumor growth, clinical stage progression, and lymph node metastasis.

PMID:32614608 | DOI:10.1089/cbr.2020.3657

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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: Cancer & VTE/PE

Prevention of thromboembolic disease in elderly patients admitted to medical wards

Lopez-Picazo Ferrer JJ, et al. J Healthc Qual Res 2020.

ABSTRACT

OBJECTIVES: To determine the suitability of the prevention of thromboembolic disease in elderly patients admitted to medical departments, as well as some associated factors, such as the measures required in order to improve quality and safety.

PATIENTS AND METHODS: A retrospective study in a tertiary level hospital that included elderly patients that were admitted to medical departments. A simple, non-proportional, randomised sample was used, stratified by department. The risk was measured using the Padua prediction model and the risk assessment model of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) adjusting depending on the number of discharges. A Lot Quality Assurance Sampling (LQAS) plan was used with three levels, good, (standard 95%, threshold 70%), acceptable (standard 95%, threshold 50%), and not acceptable.

RESULTS: A total of 72 cases from 8 departments were evaluated. Just over half (51.4%) of patients had a high risk of thromboembolic disease (Padua≥4), and 23.6% of bleeding (IMPROVE≥7). Besides the advanced age, the adjusted scores were particularly due to cancer (22%) and reduced mobility (19%) for Padua, and male gender (13%) and renal failure (12%) for IMPROVE. The adjusted overall suitability was 57.5% (95%CI: ±19.0%). The OR for suitable conduct on not starting medication, 1.56 (95%CI: 1.07-2.26). The suitability by department was not uniform: all the lots were acceptable, in 3 with level "good" and in 5 with "acceptable".

CONCLUSIONS: The suitability of thromboembolic prophylaxis in the study hospital maintains acceptable levels, although not homogeneous. There is an opportunity for improvement that must be taken. The data obtained may help in deciding interventions, with LQAS being useful to optimise the evaluation effort.

PMID:32593592 | DOI:10.1016/j.jhqr.2019.11.006

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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

INSPIRE: A European training network to Foster research and training in cardiovascular safety pharmacology

Guns PD, et al. J Pharmacol Toxicol Methods 2020.