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2/8/26

ABSTRACT

BACKGROUND: Tissue factor (TF) is the principal activator of the coagulation system, but an increased concentration in the blood in cancer and inflammatory diseases has been suggested to play a role increasing the risk of venous thromboembolism. However, measurement of the TF concentration is difficult, and quantitation of activity is the most valid estimation. The objective of this study was to establish a sensitive method to measure TF activity based on thrombin generation.

METHODS: The assay is based on thrombin generation (TG) measured on the Calibrated Automated Thrombogram (CAT). Various low concentrations of TF were prepared from reagents containing 1 pM TF and 4 μM phospholipid (PPL), and no TF and 4 μM PPL, and a calibration curve was produced from Lagtime vs TF concentration. TF in blood samples was measured after isolation and resuspension of extracellular vesicles (EVs) in a standard plasma from which EVs had been removed. The same standard plasma was used for the calibrators.

RESULTS: Contact activation of the coagulation system was avoided using CTI plasma samples in Monovette tubes. EVs contain procoagulant phospholipids but addition of PPL only reduced lagtime slightly at very low concentrations of TF resulting in overestimation to a lesser extent at 10 fM but no interference at 30 fM or higher. Addition of EVs to the TG analysis induced a small unspecific TF-independent activity (i.e., an activity not inhibited by antibodies against TF) which also may result in a smaller error in estimation of TF activity at very low levels but the effect was negligible at higher concentrations. It was possible to measure TF activity in healthy controls which was found to be 1-6 fM (EVs were concentrated, i.e. solubilized in a lower volume than the original volume plasma). Coefficient of variation (CV) was below 20% at the low level, and below 10% at a level around 100 fM TF. However, the step with isolation of EVs have a higher inherent CV.

CONCLUSION: A sensitive and rather precise one-stage TG-based method to measure TF activity has been established.

PMID:37467256 | PMC:PMC10355404 | DOI:10.1371/journal.pone.0288918

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PubMed articles on: Cancer & VTE/PE

Comment on: Silent Pulmonary Thromboembolism in Patients Undergoing Craniotomy for Brain Tumor

Turk Neurosurg. 2023;33(4):711. doi: 10.5137/1019-5149.JTN.44181-23.0.

NO ABSTRACT

PMID:37470514 | DOI:10.5137/1019-5149.JTN.44181-23.0

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PubMed articles on: Cancer & VTE/PE

Does the Use of Negative Pressure Wound Therapy and Postoperative Drains Impact the Development of Surgical Site Infections?: A PARITY Trial Secondary Analysis

J Bone Joint Surg Am. 2023 Jul 19;105(Suppl 1):34-40. doi: 10.2106/JBJS.22.01185. Epub 2023 Jul 19.

ABSTRACT

BACKGROUND: Surgical site infections (SSIs) represent a major complication following oncologic reconstructions. Our objectives were (1) to assess whether the use of postoperative drains and/or negative pressure wound therapy (NPWT) were associated with SSIs following lower-extremity oncologic reconstruction and (2) to identify factors associated with the duration of postoperative drains and with the duration of NPWT.

METHODS: This is a secondary analysis of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial, a multi-institution randomized controlled trial of lower-extremity oncologic reconstructions. Data were recorded regarding the use of drains alone, NPWT alone, or both NPWT and drains, including the total duration of each postoperatively. We analyzed postoperative drain duration and associations with tourniquet use, intraoperative thromboprophylaxis or antifibrinolytic use, incision length, resection length, and total operative time, through use of a linear regression model. A Cox proportional hazards model was used to evaluate the independent predictors of SSI.

RESULTS: Overall, 604 patients were included and the incidence of SSI was 15.9%. Postoperative drains alone were used in 409 patients (67.7%), NPWT alone was used in 15 patients (2.5%), and both postoperative drains and NPWT were used in 68 patients (11.3%). The median (and interquartile range [IQR]) duration of drains and of NPWT was 3 days (IQR, 2 to 5 days) and 6 days (IQR, 4 to 8 days), respectively. The use of postoperative drains alone, NPWT alone, or both drains and NPWT was not associated with SSI (p = 0.14). Increased postoperative drain duration was associated with longer operative times and no intraoperative tourniquet use, as shown on linear regression analysis (p < 0.001 and p = 0.03, respectively). A postoperative drain duration of ≥14 days (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.3 to 9.6; p = 0.01) and an operative time of ≥8 hours (HR, 4.5; 95% CI, 1.7 to 11.9; p = 0.002) were independent predictors of SSI following lower-extremity oncologic reconstruction.

CONCLUSIONS: A postoperative drain duration of ≥14 days and an operative time of ≥8 hours were independent predictors of SSI following lower-extremity oncologic reconstruction. Neither the use of postoperative drains nor the use of NPWT was a predictor of SSI. Future research is required to delineate the association of the combined use of postoperative drains and NPWT with SSI.

LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

PMID:37466578 | DOI:10.2106/JBJS.22.01185

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PubMed articles on: Cancer & VTE/PE

Inferior Vena Cava Filters: Adherence to Clinical Practice Guidelines Recommendations, Retrieval Rates, and Filter Complications in a Tertiary Hospital

Angiology. 2023 Jul 20:33197231190184. doi: 10.1177/00033197231190184. Online ahead of print.

ABSTRACT

The present study evaluated the adherence to guideline recommendations regarding the indication for inferior vena cava filter (IVCF) placement, retrieval rates, complications, thrombotic recurrences, and mortality. Patients in whom an IVCF was placed between 2015 and 2020 in a tertiary hospital were retrospectively included. We considered absolute indication of IVCF placement if all the guidelines evaluated agreed on the indication, relative indication if only some guidelines recommended it and without indication if none of the evaluated guidelines recommended it. From the 185 patients included; 47% had an absolute indication, 15% a relative indication, and 38% had no indication. Filter-associated complications and non-removal rates were 12.4% and 41%, respectively. Venous thromboembolism recurrence rate was 17.8%, being filter-associated complications (24.2 vs 9.8%, P = .02) and thrombosis of the inferior cava or iliac veins (12.1 vs 2.6%, P = .03) more frequent in this group. The mortality rate was 40%, with higher mortality risk in patients with co-existing cancer. Previous major bleeding, filter-associated complications, and mortality were associated with a major risk of non-removal. In conclusion, the adherence to guidelines regarding the indication of IVCF placement is still low and IVCF complications are not negligible. This fact is of special concern in the elderly, comorbid, and cancer patients.

PMID:37470426 | DOI:10.1177/00033197231190184

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PubMed articles on: Cancer & VTE/PE

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PubMed articles on: Cancer & VTE/PE

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis

Eur Heart J. 2023 Jul 15:ehad417. doi: 10.1093/eurheartj/ehad417. Online ahead of print.

ABSTRACT

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations.

METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10.

CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study.

REGISTRATION: PROSPERO ID 89366.

PMID:37452732 | DOI:10.1093/eurheartj/ehad417

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PubMed articles on: Cancer & VTE/PE

PREDICTORS OF RETRIEVAL AND LONG-TERM MORTALITY IN PATIENTS TREATED WITH INFERIOR VENA CAVA FILTERS

J Vasc Surg Venous Lymphat Disord. 2023 Jul 13:S2213-333X(23)00251-2. doi: 10.1016/j.jvsv.2023.07.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Inferior vena cava filters are a therapeutic resource for the treatment of patients with thromboembolic disease who have a contraindication to full-dose anticoagulation.

OBJECTIVE: To report the retrieval rate and long-term mortality of patients receiving optional inferior vena cava filters. To identify predictors of retrieval and all-cause mortality during follow-up.

METHODS: We conducted a retrospective cohort study including 739 consecutive recipients of optional vena cava filters from January 2002 to December 2021 in two hospitals. Different clinical characteristics and procedure-related variables were included for this analysis. All-cause mortality rate, retrieval rate and its predictors were evaluated in a multivariate analysis.

RESULTS: Fifty three percent of the patients were female. The mean age was 69 ± 15 years. Sixty seven percent presented pulmonary thromboembolism and 43% deep vein thrombosis. A contraindication to anticoagulation was present in nearly 90% of the patients, mainly (47%) related to a surgical procedure. Forty four percent of the patients had active cancer. Follow-up was performed in 94% of the patients, for an average time of 6.08 ± 5.83 years. Long-term mortality was 53%. Cancer [OR 3.60 (95% CI 2.22-5.83)], age [OR 1.03 (95% CI 1.08-1.42)] and deep vein thrombosis [OR 2.01 (95% CI 1.08-1.42)] were identified as independent predictors of mortality. The retrieval rate at follow-up was 33%. As predictors of retrieval, we identified the indication of the filter related to a surgical procedure [OR 4.85 (95% CI 2.54-9.59)], the absence of cancer [OR 2.89 (95% CI 1.45-5.75)] and age [OR 0.98 (95% CI 0.97-0.99)].

CONCLUSIONS: A high long-term mortality was observed. Predictors of death were cancer, age and deep vein thrombosis. One third of the filters implanted were retrieved. Predictors of retrieval were contraindication to surgical-related anticoagulation, absence of cancer, and younger age.

PMID:37453550 | DOI:10.1016/j.jvsv.2023.07.005

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Cardiotoxicity News

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PubMed articles on: Cardio-Oncology

Systolic myocardial function measured by echocardiographic speckle-tracking and peak oxygen consumption in pediatric childhood cancer survivors-a PACCS study

Front Cardiovasc Med. 2023 Jul 5;10:1221787. doi: 10.3389/fcvm.2023.1221787. eCollection 2023.

ABSTRACT

BACKGROUND: Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors.

METHODS: In this sub-study of the international study "Physical Activity and fitness in Childhood Cancer Survivors" (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9-18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function.

RESULTS: Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, -19.7% [95% confidence interval (CI) -20.1% to -19.3%] vs. -21.3% (95% CI: -22.2% to -20.3%) (p = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z-score. Mean RV-LS was similar in the childhood cancer survivors and the controls, -23.2% (95% CI: -23.7% to -22.6%) vs. -23.3% (95% CI: -24.6% to -22.0%) (p = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient (r) = -0.3 for LV-GLS]. Higher doses of anthracyclines (r = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment (r = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function.

CONCLUSIONS: Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk.

PMID:37476575 | PMC:PMC10354364 | DOI:10.3389/fcvm.2023.1221787

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PubMed articles on: Cardio-Oncology

Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies

Cardiovasc Toxicol. 2023 Jul 21. doi: 10.1007/s12012-023-09800-x. Online ahead of print.

ABSTRACT

The advent of BCR-ABL tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. Mitochondria are the key organelles for the maintenance of myocardial tissue homeostasis. However, cardiotoxicity associated with BCR-ABL1 TKIs can directly or indirectly cause mitochondrial damage and dysfunction, playing a pivotal role in cardiomyocytes homeostatic system and putting the cancer survivors at higher risk. In this review, we summarize the cardiotoxicity caused by BCR-ABL1 TKIs and the underlying mechanisms, which contribute dominantly to the damage of mitochondrial structure and dysfunction: endoplasmic reticulum (ER) stress, mitochondrial stress, damage of myocardial cell mitochondrial respiratory chain, increased production of mitochondrial reactive oxygen species (ROS), and other kinases and other potential mechanisms of cardiotoxicity induced by BCR-ABL1 TKIs. Furthermore, detection and management of BCR-ABL1 TKIs will promote our rational use, and cardioprotection strategies based on mitochondria will improve our understanding of the cardiotoxicity from a mitochondrial perspective. Ultimately, we hope shed light on clinical decision-making. By integrate and learn from both research and practice, we will endeavor to minimize the mitochondria-mediated cardiotoxicity and reduce the adverse sequelae associated with BCR-ABL1 TKIs.

PMID:37479951 | DOI:10.1007/s12012-023-09800-x

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PubMed articles on: Cardio-Oncology

Severe cardiotoxicity induced by osimertinib in a patient with EGFR-mutated adenocarcinoma of the lung

BMJ Case Rep. 2023 Jul 21;16(7):e255245. doi: 10.1136/bcr-2023-255245.

ABSTRACT

A man in his 70s was detected an infiltrative shadow on the right lung. A bronchoscopy confirmed the diagnosis of adenocarcinoma of the lung, classified as cT2bN2M0 stage IIIA, with a deletion mutation in EGFRexon 19. Weekly carboplatin plus paclitaxel was administered in combination with thoracic radiotherapy, followed by maintenance therapy with durvalumab for 1 year. Four months later, he was diagnosed with a recurrence of adenocarcinoma in the lung. He started treatment with osimertinib. Six months after initiating osimertinib, a chest CT revealed bilateral pleural effusion and expansion of the inferior vena cava. Eleven months later, he entered our emergency department with progressive dyspnoea. A chest CT showed bilateral massive pleural effusion and cardiac enlargement. He was diagnosed with osimertinib-induced cardiac failure. Osimertinib was discontinued, and echocardiology demonstrated a gradual improvement in cardiac function. It is necessary to take care of osimertinib-related cardiotoxicity.

PMID:37479487 | DOI:10.1136/bcr-2023-255245

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PubMed articles on: Cardio-Oncology

Cardiovascular toxicity from therapies for light chain amyloidosis

Front Cardiovasc Med. 2023 Jul 5;10:1212983. doi: 10.3389/fcvm.2023.1212983. eCollection 2023.

ABSTRACT

Amyloid light-chain (AL) amyloidosis is a hematological disorder characterized by abnormal proliferation of a plasma cell clone producing monoclonal free light chains that misfold and aggregate into insoluble fibrils in various tissues. Cardiac involvement is a common feature leading to restrictive cardiomyopathy and poor prognosis. Current first-line treatments aim at achieving hematological response by targeting the plasma cell clones, and these have been adapted from multiple myeloma therapy. Patients with AL amyloidosis often exhibit multiorgan involvement, making them susceptible to cancer therapy-related cardiovascular toxicity. Managing AL amyloidosis is a complex issue that requires enhanced knowledge of the cardio-oncological implications of hematological treatments. Future research should focus on implementing and validating primary and secondary prevention strategies and understanding the biochemical basis of oncological therapy-related damage to mitigate cardiovascular toxicity.

PMID:37476571 | PMC:PMC10354454 | DOI:10.3389/fcvm.2023.1212983

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PubMed articles on: Cardio-Oncology

3-Indolepropionic acid mitigates sub-acute toxicity in the cardiomyocytes of epirubicin-treated female rats

Naunyn Schmiedebergs Arch Pharmacol. 2023 Jul 21. doi: 10.1007/s00210-023-02618-y. Online ahead of print.

ABSTRACT

Epirubicin (EPI) is an effective chemotherapeutic against breast cancer, though EPI-related cardiotoxicity limits its usage. Endogenously derived 3-indolepropionic acid (3-IPA) from tryptophan metabolism is of interest due to its antioxidant capabilities which may have cardioprotective effects. Supplementation with 3-IPA may abate EPI's cardiotoxicity, and herein we studied the possibility of lessening EPI-induced cardiotoxicity in Wistar rats. Experimental rats (n = 30; BW 180-200 g) were randomly distributed in five cohorts (A-E; n = 6 each). Group A (control), Group B (EPI 2.5 mg/mL), and group C (3-IPA 40 mg/kg) while Groups D and E were co-treated with EPI (2.5 mg/mL) together with 3-IPA (D: 20 and E: 40 mg/kg). Following sacrifice, oxidative status, lipid profile, transaminases relevant to cardiac function, and inflammatory biomarkers were analysed. Also, 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and cardiac troponin T (cTnT) levels were assessed using an enzyme-linked immunosorbent assay (ELISA). EPI-initiated increases in cardiotoxicity biomarkers were significantly (p < 0.05) reduced by 3-IPA supplementation. Decreased antioxidant and increases in reactive oxygen and nitrogen species (RONS), 8-OHdG and lipid peroxidation were lessened (p < 0.05) in rat hearts co-treated with 3-IPA. EPI-induced increases in nitric oxide and myeloperoxidase were reduced (p < 0.05) by 3-IPA co-treatment. In addition, 3-IPA reversed EPI-mediated alterations in alanine aminotransferase (ALT), aspartate amino transaminases (AST), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and serum lipid profile including total cholesterol and triglycerides. Microscopic examination of the cardiac tissues showed that histopathological lesions severity induced by EPI was lesser in 3-IPA co-treated rats. Our findings demonstrate that supplementing endogenously derived 3-IPA can enhance antioxidant protection in the cardiac tissue susceptible to EPI toxicity in female rats. These findings may benefit breast cancer patients undergoing chemotherapy by further validating these experimental data.

PMID:37477660 | DOI:10.1007/s00210-023-02618-y

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PubMed articles on: Cardio-Oncology

Ferroptosis-induced Cardiotoxicity and Antitumor Drugs

Curr Med Chem. 2023 Jul 19. doi: 10.2174/0929867331666230719124453. Online ahead of print.

ABSTRACT

The induction of regulated cell death ferroptosis in tumors is emerging as an intriguing strategy for cancer treatment. Numerous antitumor drugs (e.g., doxorubicin, etoposide, tyrosine kinase inhibitors, trastuzumab, arsenic trioxide, 5-fluorouracil) induce ferroptosis. Although this mechanism of action is interesting for fighting tumors, the clinical use of drugs that induce ferroptosis is hampered by cardiotoxicity. Besides in cancer cells, ferroptosis induced by chemotherapeutics can occur in cardiomyocytes, and this feature represents an important drawback of antitumor therapy. This inconvenience has been tackled by developing less or no cardiotoxic antitumor drugs or by discovering cardioprotective agents (e.g., berberine, propofol, fisetin, salidroside, melatonin, epigallocatechin-3gallate, resveratrol) to use in combination with conventional chemotherapeutics. This review briefly summarizes the molecular mechanisms of Fer and describes the Fer-dependent mechanisms responsible for cardiac toxicity developed by cancer-suffering patients following the administration of some chemotherapeutics. Additionally, the pharmacological strategies very recently proposed for potentially preventing this inconvenience are considered.

PMID:37469161 | DOI:10.2174/0929867331666230719124453