all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain

 

ABSTRACT

Cardiotoxicity is a growing concern in the oncology population. Transthoracic echocardiography and multigated acquisition scans have been used for surveillance but are relatively insensitive and resource intensive. Innovative imaging techniques are constrained by cost and availability. More sensitive, cost-effective cardiotoxicity surveillance strategies are needed. Circulating cardiovascular biomarkers could provide a sensitive, low-cost solution. Biomarkers such as troponins, natriuretic peptides (NPs), novel upstream signals of oxidative stress, inflammation, and fibrosis as well as panomic technologies have shown substantial promise, and guidelines recommend baseline measurement of troponins and NPs in all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain to be examined in depth. This review provides comprehensive assessment of critical challenges and solutions in this field, with focus on analytical issues relating to biomarker measurement and interpretation. Examination of evidence pertaining to common and serious forms of cardiotoxicity reveals that improved study designs incorporating larger, more diverse populations, registry-based approaches, and refinement of current definitions are key. Further efforts to harmonize biomarker methodologies including centralized biobanking and analyses, novel decision limits, and head-to-head comparisons are needed. Multimarker algorithms incorporating machine learning may allow rapid, personalized risk assessment. These improvements will not only augment the predictive value of circulating biomarkers in cardiotoxicity but may elucidate both direct and indirect relationships between cardiovascular disease and cancer, allowing biomarkers a greater role in the development and success of novel anticancer therapies.

PMID:37889193 | DOI:10.1161/JAHA.123.029574

19:05

PubMed articles on: Cardio-Oncology

Detection of Early Myocardial Dysfunction by Imaging Biomarkers in Cancer Patients Undergoing Photon Beam vs. Proton Beam Radiotherapy: A Prospective Study

J Cardiovasc Dev Dis. 2023 Oct 4;10(10):418. doi: 10.3390/jcdd10100418.

survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology.

 

ABSTRACT

Cardiovascular disease (CVD) caused by anti-cancer drug-induced cardiotoxicity is now the second leading cause of mortality among cancer survivors. It is necessary to establish efficient in vitro models for early predicting the potential cardiotoxicity of anti-cancer drugs, as well as for screening drugs that would alleviate cardiotoxicity during and post treatment. Human induced pluripotent stem cells (hiPSCs) have opened up new avenues in cardio-oncology. With the breakthrough of tissue engineering technology, a variety of hiPSC-derived cardiac microtissues or organoids have been recently reported, which have shown enormous potential in studying cardiotoxicity. Moreover, using hiPSC-derived heart-on-chip for studying cardiotoxicity has provided novel insights into the underlying mechanisms. Herein, we summarize different types of anti-cancer drug-induced cardiotoxicities and present an extensive overview on the applications of hiPSC-derived cardiac microtissues, cardiac organoids, and heart-on-chips in cardiotoxicity. Finally, we highlight clinical and translational challenges around hiPSC-derived cardiac microtissues/organoids/heart-on chips and their applications in anti-cancer drug-induced cardiotoxicity. • Anti-cancer drug-induced cardiotoxicities represent pressing challenges for cancer treatments, and cardiovascular disease is the second leading cause of mortality among cancer survivors. • Newly reported in vitro models such as hiPSC-derived cardiac microtissues/organoids/chips show enormous potential for studying cardio-oncology. • Emerging evidence supports that hiPSC-derived cardiac organoids and heart-on-chip are promising in vitro platforms for predicting and minimizing anti-cancer drug-induced cardiotoxicity.

PMID:37889357 | DOI:10.1007/s10565-023-09835-4

19:05

PubMed articles on: Cardio-Oncology

Circulating Cardiovascular Biomarkers in Cancer Therapeutics-Related Cardiotoxicity: Review of Critical Challenges, Solutions, and Future Directions

J Am Heart Assoc. 2023 Oct 27:e029574. doi: 10.1161/JAHA.123.029574. Online ahead of print.

serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial

 

ABSTRACT

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and two CCTA scans during the two-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026-2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

PMID:37890547 | DOI:10.1016/j.ahj.2023.10.007

19:05

PubMed articles on: Cardio-Oncology

Recent advances in pluripotent stem cell-derived cardiac organoids and heart-on-chip applications for studying anti-cancer drug-induced cardiotoxicity

Cell Biol Toxicol. 2023 Oct 27. doi: 10.1007/s10565-023-09835-4. Online ahead of print.

developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. T

 

ABSTRACT

Cancer survivors who have received thoracic radiation as part of their primary treatment are at risk for developing radiation-induced cardiotoxicity (RICT) due to incidental radiation delivered to the heart. In recent decades, advancements in radiation delivery have dramatically improved the therapeutic ratio of radiation therapy (RT)-efficiently targeting malignancies while sparing the heart; yet, in many patients, incidental radiation to the heart cannot be fully avoided. Cardiac radiation exposure can cause long-term morbidity and contribute to poorer survival in cancer patients. Severe cardiac effects can occur within 2years of treatment. Currently, there is no way to predict who is at higher or lower risk of developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. The overarching aim of this chapter is to provide researchers with foundational and technical knowledge in the use of mice and rats for RICT investigations. After a brief overview of RICT pathophysiology and clinical manifestations, we discuss important considerations of RICT study design, including animal selection and radiation planning. We then provide example protocols for murine tissue harvesting and processing that can support use in downstream applications of the reader's choosing.

PMID:37890926 | DOI:10.1016/bs.mcb.2023.02.014

19:05

PubMed articles on: Cardio-Oncology

Cardiovascular Impact of Near Complete Estrogen Deprivation in Premenopausal Women with Breast Cancer: The CROWN Study

Am Heart J. 2023 Oct 25:S0002-8703(23)00300-9. doi: 10.1016/j.ahj.2023.10.007. Online ahead of print.

recommendations over recent years. Extensive formulae were employed to translate the recommendations of 7 selected guidelines into rules and proposed action measures. Patient suitability and care suggestions were assessed for several use case examples.

 

ABSTRACT

BACKGROUND: Millions of cancer survivors are at risk of cardiovascular diseases, a leading cause of morbidity and mortality. Tools to potentially facilitate implementation of cardiology guidelines, consensus recommendations, and scientific statements to prevent atherosclerotic cardiovascular disease (ASCVD) and other cardiovascular diseases are limited. Thus, inadequate utilization of cardiovascular medications and imaging is widespread, including significantly lower rates of statin use among cancer survivors for whom statin therapy is indicated.

METHODS: In this methodological study, we leveraged published guidelines documents to create a rules-based tool to include guidelines, expert consensus, and medical society scientific statements relevant to point of care cardiovascular disease prevention in the cardiovascular care of cancer survivors. Any overlap, redundancy, or ambiguous recommendations were identified and eliminated across all converted sources of knowledge. The integrity of the tool was assessed with use case examples and review of subsequent care suggestions.

RESULTS: An initial selection of 10 guidelines, expert consensus, and medical society scientific statements was made for this study. Then 7 were kept owing to overlap and revisions in society recommendations over recent years. Extensive formulae were employed to translate the recommendations of 7 selected guidelines into rules and proposed action measures. Patient suitability and care suggestions were assessed for several use case examples.

CONCLUSION: A simple rules-based application was designed to provide a potential format to deliver critical cardiovascular disease best-practice prevention recommendations at the point of care for cancer survivors. A version of this tool may potentially facilitate implementing these guidelines across clinics, payers, and health systems for preventing cardiovascular diseases in cancer survivors.

TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05377320.

PMID:37891699 | DOI:10.1186/s40959-023-00179-w

19:05

PubMed articles on: Cardio-Oncology

Methods to assess radiation-induced cardiotoxicity in rodent models

Methods Cell Biol. 2023;180:127-146. doi: 10.1016/bs.mcb.2023.02.014. Epub 2023 Apr 24.

 

ABSTRACT

The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.

PMID:37892201 | PMC:PMC10604821 | DOI:10.3390/biom13101519

19:05

PubMed articles on: Cardio-Oncology

Simplified rules-based tool to facilitate the application of up-to-date management recommendations in cardio-oncology

Cardiooncology. 2023 Oct 27;9(1):37. doi: 10.1186/s40959-023-00179-w.

applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF)

 

ABSTRACT

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

PMID:37892623 | PMC:PMC10607346 | DOI:10.3390/jcm12206486

19:05

PubMed articles on: Cardio-Oncology

Exploring the Multifaceted Nexus of Uric Acid and Health: A Review of Recent Studies on Diverse Diseases

Biomolecules. 2023 Oct 13;13(10):1519. doi: 10.3390/biom13101519.

drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX

 

ABSTRACT

Citronellol has been reported to have anti-inflammatory, anti-cancer, and antihypertensive activities, but its effect on myocardial ischemia is still unclear. The aim of this study was to investigate the therapeutic effects and pharmacological mechanisms of citronellol on ischemia. Therefore, a rat model of myocardial ischemia was established using the doxorubicin (DOX) model. To induce cardiotoxicity, the rats were given DOX (2.5 mg/kg) intraperitoneally over a 14-day period. Group I served as the control and received tween 80 (0.2%), group II received the vehicle and DOX, group III received the standard drug dexrazoxane and DOX, whereas groups IV, V, and VI were treated orally with citronellol (25, 50, and 100 mg/kg) and DOX, respectively. After treatment, the rats were euthanized, and blood samples were collected to assess the levels of serum cardiac markers, lipid profiles, and tissue antioxidant enzymes. The gene expressions of eNOS, PPAR-g, IL-10, VEGF, and NFkB-1 were also determined using real-time polymerase chain reactions. Simultaneous treatment with DOX and citronellol reduced cardiac antioxidant enzymes and lipid biomarkers in a dose-dependent manner. Citronellol also increased the expression of anti-inflammatory cytokines while reducing the expression of pro-inflammatory cytokines. Therefore, it can be concluded that citronellol may have potential cardioprotective effects in preventing DOX-induced cardiotoxicity.

PMID:37893193 | PMC:PMC10604204 | DOI:10.3390/biomedicines11102820

19:05

PubMed articles on: Cardio-Oncology

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF

J Clin Med. 2023 Oct 12;12(20):6486. doi: 10.3390/jcm12206486.

foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD.

 

ABSTRACT

Doxorubicin is a widely used anticancer agent as a first-line treatment for various tumor types, including sarcomas. Its use is hampered by adverse events, among which is the risk of dose dependence. The potential cardiotoxicity, which increases with higher doses, poses a significant challenge to its safe and effective application. To try to overcome these undesired effects, encapsulation of doxorubicin in liposomes has been proposed. Caelyx and Myocet are different formulations of pegylated (PLD) and non-pegylated liposomal doxorubicin (NPLD), respectively. Both PLD and NPLD have shown similar activity compared with free drugs but with reduced cardiotoxicity. While the hand-foot syndrome exhibits a high occurrence among patients treated with PLD, its frequency is notably reduced in those receiving NPLD. In this prospective, multicenter, one-stage, single-arm phase II trial, we assessed the combination of NPLD and ifosfamide as first-line treatment for advanced/metastatic soft tissue sarcoma (STS). Patients received six cycles of NPLD (50 mg/m2) on day 1 along with ifosfamide (3000 mg/m2 on days 1, 2, and 3 with equidose MESNA) administered every 3 weeks. The overall response rate, yielding 40% (95% CI: 0.29-0.51), resulted in statistical significance; the disease control rate stood at 81% (95% CI: 0.73-0.90), while only 16% (95% CI: 0.08-0.24) of patients experienced a progressive disease. These findings indicate that the combination of NPLD and ifosfamide yields a statistically significant response rate in advanced/metastatic STS with limited toxicity.

PMID:37894403 | PMC:PMC10605752 | DOI:10.3390/cancers15205036

19:05

PubMed articles on: Cardio-Oncology

The Protective Effect of Citronellol against Doxorubicin-Induced Cardiotoxicity in Rats

Biomedicines. 2023 Oct 18;11(10):2820. doi: 10.3390/biomedicines11102820.

carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot)

 

ABSTRACT

Platinum-based anticancer agents have revolutionized oncological treatments globally. However, their therapeutic efficacy is often accompanied by systemic toxicity. Carboplatin, recognized for its relatively lower toxicity profile than cisplatin, still presents off-target toxicities, including dose-dependent cardiotoxicity, neurotoxicity, and myelosuppression. In this study, we demonstrate a delivery strategy of carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot) exhibits rapid drug release kinetics and notable accumulation in proximity to tumor sites, indicative of amplified tumor targeting precision. Intriguingly, the Car/H-dot shows remarkable efficacy in eliminating tumors across insulinoma animal models. Encouragingly, concerns linked to carboplatin-induced cardiotoxicity are effectively alleviated by adopting the Car/H-dot nanotherapeutic approach. This pioneering investigation not only underscores the viability of H-dot as an organic nanocarrier for platinum drugs but also emphasizes its pivotal role in ameliorating associated toxicities. Thus, this study heralds a promising advancement in refining the therapeutic landscape of platinum-based chemotherapy.

PMID:37895146 | PMC:PMC10607179 | DOI:10.3390/ijms242015466

19:05

PubMed articles on: Cardio-Oncology

Prospective, Multicenter Phase II Trial of Non-Pegylated Liposomal Doxorubicin Combined with Ifosfamide in First-Line Treatment of Advanced/Metastatic Soft Tissue Sarcomas

Cancers (Basel). 2023 Oct 18;15(20):5036. doi: 10.3390/cancers15205036.

 

ABSTRACT

Cancer therapies have revolutionized patient survival rates, yet they come with the risk of cardiotoxicity, necessitating effective monitoring and management. The existing guidelines offer a limited empirical basis for practical approaches in various clinical scenarios. This article explores the intricate relationship between cancer therapy and the cardiovascular system, highlighting the role of advanced multimodality imaging in monitoring patients before, during, and after cancer treatment. This review outlines the cardiovascular effects of different cancer therapy classes, offering a comprehensive understanding of their dose- and time-dependent impacts. This paper delves into diverse imaging modalities such as echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, and nuclear imaging, detailing their strengths and limitations in various conditions due to cancer treatment, such as cardiac dysfunction, myocarditis, coronary artery disease, Takotsubo cardiomyopathy, pulmonary hypertension, arterial hypertension, valvular heart diseases, and heart failure with preserved ejection fraction. Moreover, it underscores the significance of long-term follow-up for cancer survivors and discusses future directions.

PMID:37895484 | PMC:PMC10608651 | DOI:10.3390/life13102103

19:05

PubMed articles on: Cardio-Oncology

H-Dot Mediated Nanotherapeutics Mitigate Systemic Toxicity of Platinum-Based Anticancer Drugs

Int J Mol Sci. 2023 Oct 23;24(20):15466. doi: 10.3390/ijms242015466.

both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5

 

ABSTRACT

Cardiotoxicity is a well-known adverse effect of cancer-related therapy that has a significant influence on patient outcomes and quality of life. The use of antineoplastic drugs to treat colorectal cancers (CRCs) is associated with a number of undesirable side effects including cardiac complications. For both sexes, CRC ranks second and accounts for four out of every ten cancer deaths. According to the reports, almost 39% of patients with colorectal cancer who underwent first-line chemotherapy suffered cardiovascular impairment. Although 5-fluorouracil is still the backbone of chemotherapy regimen for colorectal, gastric, and breast cancers, cardiotoxicity caused by 5-fluorouracil might affect anywhere from 1.5% to 18% of patients. The precise mechanisms underlying cardiotoxicity associated with CRC treatment are complex and may involve the modulation of various signaling pathways crucial for maintaining cardiac health including TKI ErbB2 or NRG-1, VEGF, PDGF, BRAF/Ras/Raf/MEK/ERK, and the PI3/ERK/AMPK/mTOR pathway, resulting in oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis, ultimately damaging cardiac tissue. Thus, the identification and management of cardiotoxicity associated with CRC drug therapy while minimizing the negative impact have become increasingly important. The purpose of this review is to catalog the potential cardiotoxicities caused by anticancer drugs and targeted therapy used to treat colorectal cancer as well as strategies focused on early diagnosing, prevention, and treatment of cardiotoxicity associated with anticancer drugs used in CRC therapy.

PMID:37895912 | PMC:PMC10610064 | DOI:10.3390/ph16101441

19:05

PubMed articles on: Cardio-Oncology

Multimodality Cardiovascular Imaging of Cardiotoxicity Due to Cancer Therapy

Life (Basel). 2023 Oct 23;13(10):2103. doi: 10.3390/life13102103.

therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period.

 

ABSTRACT

BACKGROUND: Certain antineoplastic therapies are associated with an increased risk of cardiomyopathy and heart failure (HF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with HF.

OBJECTIVES: This study aims to examine the efficacy of SGLT2 inhibitors in patients with cancer therapy-related cardiac dysfunction (CTRCD) or HF.

METHODS: The authors conducted a retrospective cohort analysis of deidentified, aggregate patient data from the TriNetX research network. Patients aged ≥18 years with a history of type 2 diabetes mellitus, cancer, and exposure to potentially cardiotoxic antineoplastic therapies, with a subsequent diagnosis of cardiomyopathy or HF between January 1, 2013, and April 30, 2020, were identified. Patients with ischemic heart disease were excluded. Patients receiving guideline-directed medical therapy were divided into 2 groups based on SGLT2 inhibitor use. After propensity score matching, odds ratios (ORs) and Cox proportional HRs were used to compare outcomes over a 2-year follow-up period.

RESULTS: The study cohort included 1,280 patients with CTRCD/HF (n = 640 per group; mean age: 67.6 years; 41.6% female; 68% White). Patients on SGLT2 inhibitors in addition to conventional guideline-directed medical therapy had a lower risk of acute HF exacerbation (OR: 0.483 [95% CI: 0.36-0.65]; P < 0.001) and all-cause mortality (OR: 0.296 [95% CI: 0.22-0.40]; P = 0.001). All-cause hospitalizations or emergency department visits (OR: 0.479; 95% CI: 0.383-0.599; P < 0.001), atrial fibrillation/flutter (OR: 0.397 [95% CI: 0.213-0.737]; P = 0.003), acute kidney injury (OR: 0.486 [95% CI: 0.382-0.619]; P < 0.001), and need for renal replacement therapy (OR: 0.398 [95% CI: 0.189-0.839]; P = 0.012) were also less frequent in patients on SGLT2 inhibitors.

CONCLUSIONS: SGLT2 inhibitor use is associated with improved outcomes in patients with CTRCD/HF.

PMID:37897456 | DOI:10.1016/j.jchf.2023.08.026

19:05

PubMed articles on: Cardio-Oncology

Recent Perspectives on Cardiovascular Toxicity Associated with Colorectal Cancer Drug Therapy

Pharmaceuticals (Basel). 2023 Oct 11;16(10):1441. doi: 10.3390/ph16101441.

 

ABSTRACT

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety. On this basis, drug targeting factor XI emerged as an option. In particular, cancer patients might be one of the populations that will most benefit from this technical advance. In this review, after a brief presentation of the different factor IX inhibitors, we explore the potential benefit of this new treatment for cancer patients.

PMID:37833881 | PMC:PMC10572808 | DOI:10.3390/ijms241914433

19:05

Cardiotoxicity News

PubMed articles on: Cardio-Oncology

SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Cancer Therapy-Related Cardiac Dysfunction

JACC Heart Fail. 2023 Oct 12:S2213-1779(23)00596-6. doi: 10.1016/j.jchf.2023.08.026. Online ahead of print.

CVADs in this clinical setting. (2) Methods: A systematic review and meta-analysis were conducted to identify publications from PubMed/MEDLINE,

 

ABSTRACT

(1) Background: Central venous access devices (CVADs) have been commonly employed during various courses of anticancer treatment. Currently, there are a few types of clinically available CVADs, which are associated with short-term and long-term complications. However, little is known about the complication rates when CVADs are used only in palliative care settings. We therefore performed a systematic review and meta-analysis of all the published literature to evaluate the complication rates of CVADs in this clinical setting. (2) Methods: A systematic review and meta-analysis were conducted to identify publications from PubMed/MEDLINE, Embase (Ovid), Scopus, Cochrane Library, CINAHL, Google Scholar, and trial registries. Publications reporting the complication rates of PICCs, central lines, and PORTs in palliative settings for terminally ill cancer patients were included, while those on the use of systemic anticancer therapy and peripheral venous catheters were excluded. The outcome measures included overall complication rate, rate of catheter-related bloodstream infection (CRBSI), and rate of thromboembolism (TE). This systematic review was registered with PROSPERO (CRD42023404489). (3) Results: Five publications with 327 patients were analyzed, including four studies on PICCs and one study on central lines. No studies on PORTs were eligible for analysis. The overall complication rate for PICCs (pooled estimate 7.02%, 95% CI 0.27-19.10) was higher than that for central lines (1.44%, 95% CI 0.30-4.14, p = 0.002). The risk of CRBSI with PICCs (2.03%, 95% CI 0.00-9.62) was also higher than that with central lines (0.96%, 95% CI 0.12-3.41, p = 0.046). PICCs also had a trend of a higher risk of TE (2.10%, 95% CI 0.00-12.22) compared to central lines (0.48%, 95% CI 0.01-2.64, p = 0.061). (4) Conclusions: PICCs for palliative cancer care were found to have greater complications than central lines. This might aid in the formulation of future recommendation guidelines on the choice of CVAD in this setting.

PMID:37835406 | PMC:PMC10571956 | DOI:10.3390/cancers15194712

15:08

PubMed articles on: Cancer & VTE/PE

Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

Int J Mol Sci. 2023 Sep 22;24(19):14433. doi: 10.3390/ijms241914433.

framework, to map the relationships among barriers and facilitators, feasible and effective implementation strategies, and implementation and clinical outcomes that will be used to evaluate the implementation strategies.

 

ABSTRACT

BACKGROUND: Evidenced-based interventions have been developed to prevent venous thromboembolism (VTE) in ambulatory patients with cancer, including VTE-risk assessment for all patients and targeted primary thromboprophylaxis for high-risk patients. Despite supportive evidence and recommendations, oncologists rarely assess VTE risk or provide primary prophylaxis. Our previous work identified barriers and facilitators to using VTE prevention interventions in oncology practice.

OBJECTIVES: To identify potential strategies that address the identified barriers and leverage facilitators to achieve successful implementation of evidence-based interventions for VTE prevention in oncology practice.

METHODS: We used the Implementation Research Logic Model, an implementation science framework, to map the relationships among barriers and facilitators, feasible and effective implementation strategies, and implementation and clinical outcomes that will be used to evaluate the implementation strategies.

RESULTS: We identified 12 discrete implementation strategies (eg, conducting clinician education and training and staged implementation scale-up) that address barriers and leverage facilitators through their mechanisms of action (eg, increased clinician awareness of evidence and targeting the highest effectiveness). We identified key implementation (eg, penetration, adoption, acceptability, fidelity, appropriateness, and sustainability), system (eg, integration of VTE-risk assessment into clinical workflow), and clinical (eg, lower VTE rates) outcomes targeted by the selected strategies.

CONCLUSION: Using the Implementation Research Logic Model framework and building on our knowledge of barriers and facilitators, we identified implementation strategies and important outcomes to evaluate these strategies. We will use these results to test and measure the strategies to improve the uptake of evidence-based recommendations for VTE prevention in oncology practice.

PMID:37822563 | PMC:PMC10562910 | DOI:10.1016/j.rpth.2023.102173

15:08

PubMed articles on: Cancer & VTE/PE

Complications of Central Venous Access Devices Used in Palliative Care Settings for Terminally Ill Cancer Patients: A Systematic Review and Meta-Analysis

Cancers (Basel). 2023 Sep 25;15(19):4712. doi: 10.3390/cancers15194712.

entered into the calculator. The accuracy of the calculator was evaluated using Pearson's chi-squared test, C-statistic, Brier score, and Hosmer-Lemeshow test.

 

ABSTRACT

INTRODUCTION: The prediction of complications before gastric surgery is of utmost importance in shared decision making and proper counseling of the patient in order to minimize postoperative complications. Our aim was to evaluate the predictive validity of American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk calculator in gastric cancer patients who underwent gastrectomy.

METHODS: Preoperative assessment data of 432 patients were retrospectively reviewed and manually entered into the calculator. The accuracy of the calculator was evaluated using Pearson's chi-squared test, C-statistic, Brier score, and Hosmer-Lemeshow test.

RESULTS: The lowest Brier scores were observed in urinary tract infection, renal failure, venous thromboembolism, pneumonia, and cardiac complications. Best results were obtained for predicting sepsis, discharge to rehabilitation facility, and death (low Brier scores, C-statistic >.7, and Hosmer-Lemeshow P > .05).

CONCLUSION: The calculator had a strong performance in predicting sepsis, discharge to the rehabilitation facility, and death. However, it performed poor in predicting the most commonly observed events (any or serious complication and surgical site infection).

PMID:37823864 | DOI:10.1177/00031348231206581

15:08

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prevention in cancer care: implementation strategies to address underuse

Res Pract Thromb Haemost. 2023 Aug 20;7(7):102173. doi: 10.1016/j.rpth.2023.102173. eCollection 2023 Oct.

points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk.

 

.

ABSTRACT

Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100 K/μL at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia. Cumulative incidences at 180 days were calculated with death as a competing risk. The primary outcome was major bleeding; secondary outcomes were clinically relevant non-major bleeding (CRNMB), recurrent thrombosis, and survival. The analysis included 1,045 patients with primarily solid tumor malignancies (89%), median age 65 years, and 52% male. The thrombocytopenia group comprised 9.6% (N=101) of the cohort and relative to the non-thrombocytopenia cohort (N=944), experienced significantly higher major bleeding (9.0% vs. 4.0%, sub-distribution hazard ratio (SHR) 2.4, P=0.02) and CRNMB (17.9% vs. 9.6%, SHR 2.0, P=0.01). Thrombocytopenia did not impact recurrent VTE (9.8% vs. 7.4%, SHR 1.3, P=0.37) nor overall mortality (21.8% vs. 26.0%, HR 0.9, P=0.48). Major bleeding was higher in patients with thrombocytopenia and gastrointestinal malignancies receiving edoxaban versus dalteparin (16.8% vs 0, p.

PMID:37855029 | DOI:10.3324/haematol.2023.284192

15:08

PubMed articles on: Cancer & VTE/PE

Accuracy of the ACS NSQIP Surgical Risk Calculator for Predicting Postoperative Complications in Gastric Cancer Following Open Gastrectomy

Am Surg. 2023 Oct 12:31348231206581. doi: 10.1177/00031348231206581. Online ahead of print

rivaroxaban and apixaban dose adjustment. Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5),

 

ABSTRACT

Background: Almonertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is commonly used as a first-line treatment for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutations. Rivaroxaban and apixaban are a selective, direct factor Xa inhibitor used to treat venous thromboembolism (VTE), which is a frequent complication of NSCLC. Rivaroxaban and apixaban are substrates of CYP3A4, P-gp and BCRP, whereas almonertinib is an inhibitor of P-gp and BCRP. Rivaroxaban or apixaban are often prescribed together with almonertinib in NSCLC patients, but clear information on pharmacokinetic drug interaction is lacking. Therefore, this study aimed to unravel the extent of interactions between almonertinib-rivaroxaban and almonertinib apixaban in rats, and whether the pharmacokinetic interaction can be mitigated by rivaroxaban and apixaban dose adjustment. Methods: Rats were divided into ten groups (n = 6) that received rivaroxaban (2 mg/kg) (group 1), apixaban (0.5 mg/kg) (group 2), almonertinib (15 mg/kg) (group 3, group 4), almonertinib with rivaroxaban (2 mg/kg) (group 5), almonertinib with rivaroxaban (1 mg/kg) (group 6), almonertinib with apixaban (0.5 mg/kg) (group 7), almonertinib with apixaban (0.25 mg/kg) (group 8), rivaroxaban (2 mg/kg) with almonertinib (group 9), apixaban (0.5 mg/kg) with almonertinib (group 10). The concentrations of drugs were determined by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The levels of messenger RNA were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results and Discussion: The results indicate that almonertinib increased the Cmax and AUC0-t of 2 mg/kg rivaroxaban by 3.30 and 3.60-fold, 1 mg/kg rivaroxaban by 1.28 and 1.90-fold. Almonertinib increased the Cmax and AUC0-t of 0.5 mg/kg apixaban by 2.69 and 2.87-fold, 0.25 mg/kg apixaban by 2.19 and 2.06-fold. In addition, rivaroxaban also increased systemic exposure to almonertinib. The results of qRT-PCR showed that almonertinib reduced the expression of Cyp3a1 in liver and intestine, and Abcb1a, Abcg2 in intestine and kidney. The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

PMID:37860116 | PMC:PMC10582335 | DOI:10.3389/fphar.2023.1263975

15:08

PubMed articles on: Cancer & VTE/PE

Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer

Haematologica. 2023 Oct 19:0. doi: 10.3324/haematol.2023.284192. Online ahead of print.

dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB).

 

ABSTRACT

BACKGROUND: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study.

METHODS: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB).

RESULTS: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1).

CONCLUSIONS: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

PMID:37835070 | PMC:PMC10573527 | DOI:10.3390/jcm12196427

15:08

PubMed articles on: Cancer & VTE/PE

In vivo evaluation of the pharmacokinetic interactions between almonertinib and rivaroxaban, almonertinib and apixaban

Front Pharmacol. 2023 Oct 4;14:1263975. doi: 10.3389/fphar.2023.1263975. eCollection 2023.

 

ABSTRACT

BACKGROUND: Clinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking.

OBJECTIVES: We aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment.

PATIENTS/METHODS: Consecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3-6 months. PTS was diagnosed using the Villalta score after 6-24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study.

RESULTS: In total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15-2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14-9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04-4.58]).

CONCLUSIONS: Patients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.

PMID:37852838 | DOI:10.1016/j.ejim.2023.10.014

15:08

PubMed articles on: Cancer & VTE/PE

Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients

J Clin Med. 2023 Oct 9;12(19):6427. doi: 10.3390/jcm12196427.

 

#الكانيولات

انواع ومقاسات واستخدام كل نوع حسب اللون ......

1-اللون الاصفر💛 ذات مقاس 24 .وتستخدم للاطفال وحديثي الولادة اي تستخدم للاوردة الصغيرة

2-اللون الازرق💙 ذات مقاس 22. وتستخدم لكبار السن والاشخاص الي اوردتهم ضعيفه ولنقل المحاليل ببطء

3-اللون الوردي💜ذات مقاس20. وتستخدم في اغلب الحالات وتعد الاكثر شيوعا في الاستخدام وتفضل في حالات نقل الدم غير الطارئة

4-اللون الاخضر💚ذات مقاس 18. وتستخدم في اثناء العمليات لسهولة اعطاء الادوية المخدرة ونقل الدم بصورة سريعة اثناء العمليات

5-اللون الرصاصي♡ذات مقاس 16.وتستخدم للجرحى الذين يحتاجون نقل دم بصورة سريعه

6-اللون الاحمر❤ذات مقاس 14. وتستخدم للقسطرة الوريديه المركزيه cvs وتتطلب اوردة كبيرة الحجم .......

بالنهاية يبقى الاستعمال العملي حسب وريد المريض .احيانا بارز او عميق ..كبير او صغير ...لاتحديد بالعمر ،

بحر

25 December 2018

ع

13:48

علم التحاليل المخبرية

🎯معلومة في ب قصة👈🏿👍🏽👇👇👇

أعجبتني الطريقة في الشرح ✌😂

تلخيص #جديد عن ال Brucella

كان يا مكان كان في بنت قصيرة short و ناصحه ' cocobacilli ' اسمها Brucella .. كانت طالعه مع أهلها بيوم من الأيام و عملو حادث و ماتو كل أهلها فكروها الناس ميته بس عرفوا بعدين إنها بتتفس aerobic و ضلت هيه لحالها .. و بهاد الحادث انكسرت رجلها 😞 ' non motile ' و بهاد الحادث كمان فقدت حيويتها و نشاطها 😪 inactive metabolically بس الناس ما تركوها اتعيش لحالها .. اخدها زلمه من كبار الناس لحتى اتعيش جواااات البيت مع بناته located inside the macrophages و طعماها أشياء مفيده فيها بروتينات 🍗 و املاح لحتى تتشافى من الكسر💪

" some strains have been cultivated on defined media containing amino acids, vitamins, salts and glucose "

بس هالبنت لما فقدت أهلها صار عندها حاله نفسيه و صارت اتفكر بطريقه سلبية (-) G حتى الدكتور قال انها كتيير حساسة لل" heat and acid "

و صارت تكره كل الناس و بتحب أذيتهم "obligate parasites " ... و مرة مرضت بمرض اسمه brucellosis و صارت اتعاني " Malaise , fever , weakness , aches and sweats"،، بس اكتر شي بميز مرضتها انه مرات كتيييير بشتد و مرات بكون طبيعي "characterized by an acute bacterimia phase followed by a chronic stage that may extend over many years and may involve many tissue " ،، حتى لما كانت ترتفع درجه حرارتها كانت بنفس الطريقه بالنهار تشتد كتير أما بالليل عاادي

"the fever usually rises in the afternoon and fall during the night "

و استمرت هادي الحالة معها لمده 4 أسابيع

" the incubation period from 1-4 weeks "

و لأنه مرضها كتير خطير قرروا الناس يعزلوها في بيت لحالها و سجلوه باسمها Brucella agar و بسبب هاد المرض الي بخلي الواحد يعصب nervousness ارتكبت 4 جرائم 😱

الجريمه الأولى (+) catalase

أما الجريمه التانية (+) oxidase

و التالتة Hydrogen sulfide production

أما الرابعه reduce nitrate to nitrite

و لأنه كل هادي جرائم خطيرة 😰 كان لااازم من ال FBI انه يتحرك 😂 اخدوا كل احتياطاتهم و كل اجراءاتهم الأمنية لحتى يمسكوها و يتعاملو معها

" all further work on such a culture should be done in a biologic safety cabinet "

طبعا ال Brucella لما سمعت الخبر قررت تهرب لمدينه تانية 😎 .. و لحتى توصل المدينه الي بدها ياها لازم تنقل بالأول بين البيوت الي حواليها اول بيت راحت ع ال skin و بعدين راحت ع ال mucous membrane و بعدين راحت ع ال intestinal tract و بعدين صارت تمشي بالطرق الفرعية lymphatic channels لحتى وصلت للشارع الرئيسي blood stream الي من خلاله رح توصل للمدينه الجديده new organ طبعا ال FBI ما قدروا يمسكوها إلا بعد 3 أسابيع observed for 3 weeks after incubation و يا حرام حطوها بالسجن

" incubated in 8-10% CO2 at 35-37 °C"

و خلصت القصه 😂.🎯

بحر

28 December 2018

ع

14:50

علم التحاليل المخبرية

 

.

🔴 النزلات المعوية عند الأطفال

⛔️ من أهم الأعراض

👦– الإسهال، وهو زياده في الميه وعدد المرات عن المعدل الطبيعي للطفل.

👦– القيء، وارتفاع في درجه الحرارة، وأحيانا دم مع البراز.

👀 هناك ثلاث أنواع من النزلات المعوية

&فيروسيه مثل فيروس الروتا.

&بكتيرية مثل السالمونيلا والشجيلا والاكولاي.

&من أهم هذه الأنواع وهو فيروس الروتا، ويكون مصاحب بإسهال شديد وفقدان كميه كبيره من السوائل مما يودي الي الجفاف واحتياج الطفل لدخول المستشفى وتعويض بالتحاليل الوريد.

📌 الوقاية:

وبما أن الوقاية خير من العلاج ينصح بإعطاء المواليد عند عمر ثلاث وسبع شهور تطعيم الروتا.

👶 العلاج

تأتي الوقاية من الجفاف في أولويات العلاج بإعطاء الطفل محلول الجفاف والذي أنقذ هذا الدواء العديد من الحالات ومن إخطار الجفاف ويجب تحضر وحفظه بالثلاثة وإعطائها بالطفل بالتدريج حتي نتجنب القيء.

👈 نصائح عامه يجب اتباعها

^– تجنب منتجات الألبان واللبن الصناعي أثناء العلاج.

^– لا ينصح بوقف الرضاعة الطبيعة.

^– استخدام السوائل والأكلات سهله الهضم

✔ضرورة الانتباه لأغراض الجفاف مثل جفاف الحلق وسقوط الايفون ودخول حقه العين ونقص البول والتوجه به لأقرب طبيب

بحر

18:43

 

ABSTRACT

OBJECTIVE: To provide procedure-specific estimates of the risk of symptomatic venous thromboembolism (VTE) and major bleeding, in the absence of thromboprophylaxis, following gynecologic cancer surgery.

DATA SOURCES: We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice.

STUDY ELIGIBILITY CRITERIA: Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least one of the following: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic VTE, bleeding requiring reintervention (including re-exploration and angioembolization), bleeding leading to transfusion or post-operative hemoglobin <70

STUDY APPRAISAL AND SYNTHESIS METHODS: Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks post-surgery stratified by patient VTE risk factors, and used the GRADE approach to rate evidence certainty.

RESULTS: We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic VTE risk (in the absence of prophylaxis) was <1%2.0% in 13 of 37 (35%). The risks of VTE varied from 0.1% in low VTE risk patients undergoing cervical conization to 33.5% in high VTE risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1%<1%

CONCLUSIONS: VTE reduction with thromboprophylaxis likely outweighs increase in bleeding requiring reintervention in many gynecologic cancer procedures (e.g., open surgery for ovarian cancer and pelvic exenteration). In some procedures (e.g., laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

PMID:37827272 | DOI:10.1016/j.ajog.2023.10.006

15:08

PubMed articles on: Cancer & VTE/PE

Chronic inflammatory diseases increase the risk of post-thrombotic syndrome: A prospective cohort study

Eur J Intern Med. 2023 Oct 16:S0953-6205(23)00369-2. doi: 10.1016/j.ejim.2023.10.014. Online ahead of print.

INTERPRETATION: Despite improved cancer treatment, venous thromboembolism in cancer patients is strongly associated with a poor prognosis.

 

ABSTRACT

BACKGROUND: Despite recent improvements in the treatment of cancer, little is known about the long-term survival in patients with cancer and venous thromboembolism. We aimed to examine the five-year mortality of venous thromboembolism in cancer patients in a large population-based cohort study.

METHODS: Using Danish healthcare registries from 1995 to 2020, we obtained data on cancer patients with venous thromboembolism and comparison cohorts of cancer patients without venous thromboembolism, matched in terms of cancer type, age, sex, and year of cancer diagnosis, and adjusted for level of comorbidity and frailty using the Charlson Comorbidity Index Score and Hospital Frailty Risk Score, marital status, use of selected medications, and recent surgery (<90

FINDINGS: During the study period, 886,536 patients were diagnosed with cancer. Of 1882 cancer patients diagnosed at the time of their venous thromboembolism, 44.4% (835/1882) had distant metastases. In this cohort, the one- and five-year mortality cumulative incidences were 68% (1284/1882) and 84% (1578/1882), respectively, in contrast to 38% (2135/5549) and 67% (3653/5549) in the comparison cohort. The mortality rate ratio was 4.34 (95% confidence interval [CI], 3.95-4.78) for the first year of follow-up and 3.44 (95% CI 3.17-3.73) for the five-year follow-up period. Of the 23,366 patients diagnosed with venous thromboembolism after cancer diagnosis, 18% (4183/23,366) had distant metastases at the time of cancer diagnosis. The cumulative incidence of death at one year was 45% (10,465/23,366; mortality rate ratio 3.48, 95% CI 3.37-3.60) and at five years 69% (15,669/23,366; mortality rate ratio 2.57, 95% CI 2.50-2.63).

INTERPRETATION: Despite improved cancer treatment, venous thromboembolism in cancer patients is strongly associated with a poor prognosis.

FUNDING: The study was supported by grants from the Independent Research Fund Denmark (record no. 3101-00102B) and the Karen Elise Jensen Foundation.

PMID:37809052 | PMC:PMC10558815 | DOI:10.1016/j.lanepe.2023.100739

15:08

PubMed articles on: Cancer & VTE/PE

Risk of Thrombosis and Bleeding in Gynecologic Cancer Surgery: Systematic Review and Meta-Analysis

Am J Obstet Gynecol. 2023 Oct 10:S0002-9378(23)00735-4. doi: 10.1016/j.ajog.2023.10.006. Online ahead of print.

 

ABSTRACT

BACKGROUND: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear.

METHODS: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk.

RESULTS: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs.

CONCLUSIONS: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.

PMID:37857226 | DOI:10.1016/j.thromres.2023.10.004

15:08

PubMed articles on: Cancer & VTE/PE

Impact of venous thromboembolism on the mortality in patients with cancer: a population-based cohort study

Lancet Reg Health Eur. 2023 Sep 28;34:100739. doi: 10.1016/j.lanepe.2023.100739. eCollection 2023 Nov.

 

ABSTRACT

Atrial fibrillation (AF) can increase thrombosis, especially arterial thrombosis, and some studies show that AF patients have a higher risk of developing pulmonary embolism (PE). The objective of our study is to investigate whether there is a direct causal effect of AF on PE. A two-sample Mendelian randomization (MR) approach was utilized to determine whether there is a causal relationship between AF and PE. European population-based consortia provided statistical data on the associations between Single Nucleotide Polymorphisms (SNPs) and relevant traits. The AF dataset was obtained from genome-wide association studies (GWAS) comprising 60,620 cases and 970,216 controls, while a GWAS of 1846 cases and 461,164 controls identified genetic variations associated with PE. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran's Q test, "Leave-one-out," and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity. Using 70 SNPs, there was no evidence to suggest an association between genetically predicted AF and risk of PE with multiplicative random-effects IVW MR analysis (odds ratio = 1.0003, 95% confidence interval: 0.9998-1.0008, P = 0.20). A null association was also observed in other methods. MR-Egger regression and MR-PRESSO respectively showed no evidence of directional (intercept, - 2.25; P = 0.94) and horizontal(P-value in the global heterogeneity test = 0.99) pleiotropic effect across the genetic variants. No substantial evidence was found to support the causal role of AF in the development of PE. Causal effect of atrial fibrillation on pulmonary embolism: a Mendelian randomization study. AF atrial fibrillation, PE pulmonary embolism, GWAS genome-wide association studies, SNPs single nucleotide polymorphisms, OR odds ratio, CI confidence interval.

PMID:37839022 | DOI:10.1007/s11239-023-02903-w

15:08

PubMed articles on: Cancer & VTE/PE

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies

Thromb Res. 2023 Oct 11;231:128-134. doi: 10.1016/j.thromres.2023.10.004. Online ahead of print.

 

ABSTRACT

Venous thromboembolism (VTE) is a common complication in patients with cancer. Data on the role of natural inhibitors of coagulation for occurrence of cancerassociated VTE are limited, thus, we investigated the association of tissue factor pathway inhibitor (TFPI) with risk of VTE and all-cause mortality in patients with cancer. Total TFPI antigen levels were measured with a commercially available ELISA in patients included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study with the primary outcome VTE. Competing risk analysis and Cox regression analysis were performed to explore the association of TFPI levels with VTE and all-cause mortality. TFPI was analyzed in 898 patients (median age: 62 years [interquartile range, IQR: 53-68]; 407 [45%] women). Sixtyseven patients developed VTE and 387 died (24-month cumulative risk: 7.5% and 42.1%, respectively). Patients had median TFPI levels at study inclusion of 56.4ng/mL (IQR: 45.7-70.0), with highest levels in tumor types known to have a high risk of VTE (gastroesophageal-, pancreatic and brain-cancer: 62.0ng/mL [IQR: 52.0-75.0]). In multivariable analysis adjusting for age, sex, cancer type and stage, TFPI levels were associated with VTE risk (SHR per doubling: 1.63, 95%CI: 1.03-2.57). When patients with high and intermediate/low VTE risk were analyzed separately, the association remained independently associated in the high risk group only (SHR: 2.63, 95%CI: 1.40-4.94). TFPI levels were independently associated with all-cause mortality (HR: 2.36, 95%CI: 1.85-3.00). In cancer patients increased TFPI levels are associated with VTE risk, specifically in patients with high risk tumor types, and with all-cause mortality.

PMID:37822244 | DOI:10.3324/haematol.2023.283581

15:08

PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Treatment Evolution: A Comparative Analysis of Pulmonary Embolism Response Team Management at a Single Institution

Am J Cardiol. 2023 Oct 14;208:171-172. doi: 10.1016/j.amjcard.2023.09.003. Online ahead of print.

NO ABSTRACT

PMID:37844520 | DOI:10.1016/j.amjcard.2023.09.003

15:08

PubMed articles on: Cancer & VTE/PE

Causal effect of atrial fibrillation on pulmonary embolism: a mendelian randomization study

J Thromb Thrombolysis. 2023 Oct 15. doi: 10.1007/s11239-023-02903-w. Online ahead of print.

 

ABSTRACT

BACKGROUND: Guidelines recommend extended venous thromboembolism (VTE) prophylaxis for high-risk populations undergoing major abdominal cancer operations. Few studies have evaluated extended VTE prophylaxis in the Medicare population who are at higher risk due to age.

METHODS: We performed a retrospective study using a 20% random sample of Medicare claims, 2012-2017. Patients ≥65 years with an abdominal cancer undergoing resection were included. Primary outcome was the proportion of patients receiving new extended VTE prophylaxis prescriptions at discharge. Secondary outcomes included postdischarge VTE and hemorrhagic events.

RESULTS: The study included 72 983 patients with a mean age of 75. Overall, 8.9% of patients received extended VTE prophylaxis. This proportion increased (7.2% in 2012, 10.6% in 2017; p < 0.001). Incidence of postdischarge hemorrhagic events was 1.0% in patients receiving extended VTE prophylaxis and 0.8% in those who did not. The incidence of postdischarge VTE events was 5.2% in patients receiving extended VTE prophylaxis and 2.4% in those who did not.

CONCLUSION: Adherence to guideline-recommended extended VTE prophylaxis in high-risk patients undergoing major abdominal cancer operations is low. The higher rate of VTE in the prophylaxis group may suggest we captured some therapeutic anticoagulation, which would mean the actual rate of thromboprophylaxis is lower than reported herein.

PMID:37800390 | DOI:10.1002/jso.27473

15:08

PubMed articles on: Cancer & VTE/PE

Tissue factor pathway inhibitor is associated with risk of venous thromboembolism and all-cause mortality in patients with cancer

Haematologica. 2023 Oct 12. doi: 10.3324/haematol.2023.283581. Online ahead of print.

 

ABSTRACT

BACKGROUND Cerebral ischemia and hemorrhages were reported to be the main complications of polycythemia vera (PV). The relationship between PV and increased risk of the cerebrovascular events has been established. Some patients with secondary polycythemia have thromboembolic events comparable to those of PV. However, secondary polycythemia that leads to cerebrovascular events is uncommon. CASE REPORT A 35-year-old man without any prior medical history presented with mild clinical acute ischemic stroke and polycythemia. The patient then showed worsening neurological deficits that were later attributed to the concurrent cerebral venous thrombosis, which led to malignant cerebral infarction with hemorrhagic transformation, and subarachnoid hemorrhage. His polycythemia appeared to be secondary to bacterial infection. The treatments for the secondary polycythemia were first phlebotomy and intravenous hydration, followed by intravenous broad-spectrum antibiotics. PV was excluded because the JAK2 V617F mutation was absent, the patient's peripheral blood smear suggested secondary polycythemia due to bacterial infection, and there were improvements in hemoglobin, erythrocyte count, and hematocrit after intravenous antibiotics. At the 1-month follow-up, he was moderately dependent, and hemoglobin, erythrocyte count, and hematocrit were within normal limits, without receiving any further phlebotomy or cytoreductive agents. CONCLUSIONS This case highlights the plausible causation of secondary polycythemia that could lead to concomitant cerebral thrombosis and hemorrhagic events. The diagnosis of cerebral venous thrombosis should be considered in a patient who presents with headache, focal neurological deficits, polycythemia, and normal head computed tomography scan.

PMID:37838828 | PMC:PMC10584197 | DOI:10.12659/AJCR.941507

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PubMed articles on: Cancer & VTE/PE

Persistent underuse of extended venous thromboembolism prophylaxis in patients undergoing major abdominal cancer operations

J Surg Oncol. 2023 Oct 6. doi: 10.1002/jso.27473. Online ahead of print.

 

ABSTRACT

BACKGROUND: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90

METHODS: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE.

RESULTS: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90

CONCLUSIONS: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

PMID:37814983 | DOI:10.1111/jgs.18626

15:08

PubMed articles on: Cancer & VTE/PE

Concomitant Cerebral Venous Thrombosis and Intracranial Hemorrhages in Presentation of a Patient with Secondary Polycythemia: A Case Report

Am J Case Rep. 2023 Oct 15;24:e941507. doi: 10.12659/AJCR.941507.

 

ABSTRACT

INTRODUCTION: Limited data exist on the risk of venous and arterial thromboembolisms (VTE and ATE) in patients receiving cetuximab plus chemotherapy. We aimed to determine the thromboembolic risk of patients with recurrent/metastatic colorectal cancer (CRC) treated with cetuximab plus chemotherapy compared to chemotherapy alone.

METHODS: This population-based study used nationwide claims data from the Health Insurance Review and Assessment Service of South Korea from 2013 to 2020. Patients with recurrent/metastatic CRC treated with first-line oxaliplatin- or irinotecan-based doublets with or without cetuximab and no secondary prevention for VTE and ATE were included. Primary outcomes were the occurrence of any thromboembolic events, VTE, and ATE, which were determined using the cumulative incidence method incorporating death as a competing event.

RESULTS: We identified 19,723 patients (cetuximab plus chemotherapy, N = 7630; chemotherapy alone, N = 12,093). The cumulative incidence of any thromboembolic events in patients with cetuximab plus chemotherapy was significantly higher than in those receiving chemotherapy alone (6-month, 5.62 % vs. 3.58 %, P < 0.0001). The rates of VTE (6-month, 5.11 % vs. 3.28 %, P < 0.0001) and ATE (6-month, 0.53 % vs. 0.32 %, P = 0.0218) were also higher in patients receiving cetuximab plus chemotherapy. In multivariable analysis, cetuximab plus chemotherapy was independently associated with developing any thromboembolic events (hazard ratio [HR], 1.63; 95 % confidence interval [CI], 1.42-1.87), VTE (HR, 1.62; 95 % CI, 1.40-1.87), and ATE (HR, 1.77; 95 % CI, 1.16-2.71).

CONCLUSIONS: Cetuximab with irinotecan- or oxaliplatin-based doublet chemotherapy was associated with an increased risk of any thromboembolic events, VTE, and ATE; further studies are warranted to examine the underlying mechanisms.

PMID:37804738 | DOI:10.1016/j.thromres.2023.10.005

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PubMed articles on: Cancer & VTE/PE

Clinical Care of Pediatric Patients with or At-Risk of Post-Thrombotic Syndrome: Guidance from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Haemostasis

J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00780-8. doi: 10.1016/j.jtha.2023.10.012. Online ahead of print.

NO ABSTRACT

PMID:37866514 | DOI:10.1016/j.jtha.2023.10.012

15:08

PubMed articles on: Cancer & VTE/PE

Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry

J Am Geriatr Soc. 2023 Oct 10. doi: 10.1111/jgs.18626. Online ahead of print.

 

ABSTRACT

Non-bacterial thrombotic endocarditis (NBTE) involves the deposition of fibrin and platelets on heart valves, frequently leading to systemic embolism. The association between NBTE and cancer demands thorough investigation in cases lacking an evident cause. This case report elucidates the clinical course of a nonsmoking woman in her sixties with NBTE linked to pulmonary adenocarcinoma. The patient, who had a history of multiple sclerosis (MS) and was receiving dimethyl fumarate treatment, presented to the emergency department with stroke-like symptoms. Diagnostic challenges arose due to preexisting motor sensory impairment from MS. Initial evaluations revealed hypocapnia and elevated inflammatory markers. Blood cultures were obtained twice, and imaging confirmed pneumonia, left pleural effusion, and chronic pulmonary embolism while excluding acute vascular events or intracranial hemorrhage. The first transthoracic echocardiogram (TTE) indicated no cardiac abnormalities. Treatment encompassed parenteral antibiotics, systemic anticoagulation, and admission to medical floors. Although the initial treatment yielded a positive clinical response, subsequent complications emerged. On the tenth day, the patient required additional interventions, including broad-spectrum antibiotics and supplemental oxygen. A follow-up chest X-ray revealed persistent pneumonia and pleural effusion, and blood cultures upon admission returned negative. A subsequent head MRI confirmed an embolic stroke and displayed evidence of MS progression. Around the twentieth day, empirical treatment for infective endocarditis was initiated, and an 8 mm vegetation on the aortic valve was identified via transesophageal echocardiography (TOE). Acute pulmonary edema prompted a transfer to the intermediate care unit. Further investigations, including left thoracocentesis and CT, unveiled exudate and metastatic lesions in the liver, ilium, and kidney. Unfortunately, on the twenty-fifth day, the patient experienced acute myocardial infarction, right leg ischemia, disseminated intravascular coagulation, and shock. Pleural fluid analysis revealed malignant cells suggestive of lung adenocarcinoma. This case underscores the pivotal role of timely NBTE recognition and the search for malignancy when workup for infective endocarditis and autoimmune panels is negative. Moreover, it emphasizes the significance of vigilant monitoring, particularly in immunocompromised individuals or those with preexisting neurological deficits, especially when new neurological symptoms manifest. These insights significantly contribute to the comprehension of NBTE management and its implications for analogous patient cohorts.

PMID:37846253 | PMC:PMC10576842 | DOI:10.7759/cureus.45271

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PubMed articles on: Cancer & VTE/PE

Increased risk of venous and arterial thromboembolism in patients with colorectal cancer receiving cetuximab-based combination chemotherapy: A population-based study in Korea

Thromb Res. 2023 Oct 4;231:50-57. doi: 10.1016/j.thromres.2023.10.005. Online ahead of print.

 

ABSTRACT

INTRODUCTION AND IMPORTANCE: The thromboembolic complication of kidney's tumor is rare, and they can be the reason for the discovery of those tumor. Also the collision kidney tumor, such as a simultaneous occurrence of different histological types of adjacent neoplasms in the same organ is rare.

CASE PRESENTATION: We report a patient diagnosed with a kidney tumor discovered in the context of an etiological assessment of thrombosis, presenting with pulmonary embolism and deep vein thrombosis of the lower limb. This tumor treated by a cytoreductive nephrectomy. The histologic diagnosis of PRCC (Papillary Renal Cell Carcinoma) associated with a chromophobe cell carcinoma and sarcomatoid component was rendered.

CLINICAL DISCUSSION: The development of the tumor process and its progression to the metastatic stage is largely favored by the hypercoagulable state, and the cancer itself promotes the appearance of thrombo-enmbolic phenomena due to this phenomenon. Two major studies recommend that immediate cytoreductive nephrectomy should be offered to metastatic patients with a good general condition.

CONCLUSION: A renal tumor collision is rare, whereas the risk factors for a renal tumor collision are the same as a renal tumor without collision, just as the management of a metastatic renal tumor is the same. Understanding the thromboembolic physiopathology in the case of kidney cancer has made it possible to optimize management.

PMID:37812961 | PMC:PMC10568267 | DOI:10.1016/j.ijscr.2023.108922

15:08

PubMed articles on: Cancer & VTE/PE

Unveiling Lung Adenocarcinoma: Non-bacterial Thrombotic Endocarditis as the Debut Sign

Cureus. 2023 Sep 14;15(9):e45271. doi: 10.7759/cureus.45271. eCollection 2023 Sep.

 

ABSTRACT

The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.

PMID:37846195 | DOI:10.1002/jrsm.1676

15:07

PubMed articles on: Cancer & VTE/PE

An etiological assessment of a deep vein thrombosis led to the discovery of a renal tumor collision: Case report

Int J Surg Case Rep. 2023 Oct;111:108922. doi: 10.1016/j.ijscr.2023.108922. Epub 2023 Oct 5.

 

ABSTRACT

BACKGROUND: Patients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH).

OBJECTIVES: The aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer.

METHODS: This was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome.

RESULTS: Overall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors.

CONCLUSION: In patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

PMID:37810416 | PMC:PMC10551887 | DOI:10.1016/j.rpth.2023.102172

15:07

PubMed articles on: Cancer & VTE/PE

A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism

Res Synth Methods. 2023 Oct 17. doi: 10.1002/jrsm.1676. Online ahead of print.

OBJECTIVE: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis

 

ABSTRACT

OBJECTIVE: To compare the venous thromboembolism (VTE) rate in patients with ovarian cancer undergoing neoadjuvant chemotherapy before and after implementing routine thromboprophylaxis.

METHODS: This is a quasi-experimental pre-post study evaluating the VTE rate in patients with ovarian cancer who received neoadjuvant chemotherapy following a quality improvement initiative of routine thromboprophylaxis within a single healthcare system that started in January 2017. Patients were excluded if VTE was diagnosed before initiating chemotherapy. Patient factors and perioperative variables of interest were investigated for their association with VTE through univariate and multivariate models.

RESULTS: Of the 136 patients in the pre-implementation group, 3.7% (n = 5) received thromboprophylaxis. Of the 154 patients in the post-implementation group, 65.6% (n = 101) received thromboprophylaxis. Provider compliance varied from 51% in 2019 to 79.3% in 2021. The overall rate of VTE, from the start of chemotherapy to the end of treatment, was 21.3% (n = 29) pre- and 8.4% (n = 13) in the post-implementation group (p < 0.01). There was no difference in major bleeding events between groups (0% vs. 0.68%, p = 0.63). On univariate analysis, thromboprophylaxis (OR 0.19; 95% CI 0.07-0.52) and post-implementation period (OR 0.34; 95% CI 0.17-0.69) were associated with a decreased risk of any VTE during primary treatment. On multivariate analysis, only thromboprophylaxis remained significantly associated with reduced VTE rates (aOR 0.19; 95% CI 0.07-0.53).

CONCLUSION: Routine thromboprophylaxis during neoadjuvant chemotherapy is associated with reduced risk of VTE throughout primary treatment and is not associated with increased bleeding events.

PMID:37832182 | DOI:10.1016/j.ygyno.2023.10.001

15:07

PubMed articles on: Cancer & VTE/PE

Acute venous thromboembolism in patients with brain cancer: clinical course

Res Pract Thromb Haemost. 2023 Aug 20;7(6):102172. doi: 10.1016/j.rpth.2023.102172. eCollection 2023 Aug.

 

ABSTRACT

Low molecular weight heparins (LMWH) and anti-Xa direct oral anti-coagulants (DOACs) are recommended for the long-term treatment of cancer-associated thrombosis (CAT) based on well-documented randomised controlled trials. Anti-Xa DOACs are viewed as a first choice for the treatment of patients with CAT. A large number of drug-drug interactions have been reported between DOACs and chemotherapy drugs, modifying circulating levels of DOAC leading to fears of increased bleeding risks or thrombotic recurrence. Progresses in anti-neoplastic therapies have improved the prognosis and the survival, thus increasing the prevalence of frail patients with cancer. However, since frailties tend to be excluded from large trials due to multiple co-morbidities, current guidelines are not fully applicable to this population. The management of these frail patients with CAT is particularly complex and requires a risk assessment on a case-by-case basis with specific focus on cancer, patient-related risk factors and drug-drug interactions. In this brief review we have identified age, co-morbidities and co-medications as key factors of frailty that require careful attention and we have developed a therapeutic decision algorithm to help clinicians optimising the use of anti-coagulants in patients with cancer with CAT, especially in case of anti-Xa DOACs concomitant medications. With the evaluation of the bleeding risk according to the type of cancer, and anticipating drug-drug interactions intensity, taking into account patient frailties allows the optimisation of the anti-coagulant choice. A systematic collaboration between oncologists, vascular pathology specialists and pharmacists is warranted to ensure an optimal patient management. Clinical studies are needed to determine the real impact of these interactions.

PMID:37824026 | PMC:PMC10582124 | DOI:10.1007/s40262-023-01298-4

15:07

PubMed articles on: Cancer & VTE/PE

Implementation of routine venous thromboembolism prophylaxis during neoadjuvant chemotherapy for patients with ovarian cancer

Gynecol Oncol. 2023 Oct 11;178:89-95. doi: 10.1016/j.ygyno.2023.10.001. Online ahead of print.

 

ABSTRACT

PURPOSE: Pulmonary embolism (PE) is a significant contributor to mortality in patients with cancer. Although anticoagulation serves as the cornerstone of treatment for cancer-associated PE, it has not been emphasized in real-world settings. The aim of this study was to examine the impact of suboptimal anticoagulant treatment on the prognosis of cancer-associated PE.

METHODS: A cohort of 356 individuals newly diagnosed with acute PE were enrolled. The primary outcome of the study was recurrent venous thromboembolism (VTE), and the secondary outcomes were all-cause mortality and major bleeding (consisting of a reduction in the hemoglobin level by at least 20 g/L, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ or fatal bleeding).

FINDINGS: Of the total participants, 156 (43.8%) were diagnosed with cancer. A comparison between the cancer and noncancer groups revealed that patients with cancer were more frequently asymptomatic (41.0% vs 4.5%; P < 0.001), less likely to have right ventricular dysfunction (4.5% vs 14.0%; P = 0.001), received less anticoagulant treatment during hospitalization (85.3% vs 98.5%; P < 0.001), and had a shorter duration of anticoagulation (5.02 [7.40] months vs 14.19 [10.65] months; P < 0.001). In addition, patients with cancer were found to be at a higher risk of recurrent VTE (17.3% vs 4.0%; P < 0.001) and all-cause mortality (23.7% vs 10.5%; P = 0.001). Multiple Cox regression analysis indicated that discontinuation of anticoagulation at 3 months was a significant risk factor for recurrent VTE in the cancer group (HR, 15.815; 95% CI, 3.047-82.079; P = 0.001).

IMPLICATIONS: The brief duration of anticoagulation therapy and elevated likelihood of recurrent VTE serve as cautionary indicators for the need to enhance awareness of standardized anticoagulant treatment for cancer-associated PE. The ultimate goal is to enhance patient prognosis and quality of life.

PMID:37838562 | DOI:10.1016/j.clinthera.2023.09.014

15:07

PubMed articles on: Cancer & VTE/PE

Anti-coagulant Treatment of Cancer-Associated Thrombosis in Frail Patients: Impact of Frailties on the Management of Drug-Drug Interactions

Clin Pharmacokinet. 2023 Nov;62(11):1523-1531. doi: 10.1007/s40262-023-01298-4. Epub 2023 Oct 12.

 

ABSTRACT

Treating cancer patients with deep venous thrombosis/venous thromboembolism (DVT/VTE) can be challenging as patients are frequently unable to receive the standard therapy of anticoagulation due to the increased risk of bleeding complications seen in this population. Similarly, the hesitation of interventionalists to use thrombolytic agents due to bleeding risks limits percutaneous intervention options as well. Further, outcome data and guidelines do not exist for oncologic patients and often treatment is tailored to patient-specific factors after multidisciplinary discussion. This article reviews specific factors to consider when planning percutaneous treatment of cancer patients with DVT/VTE, focusing on the iliocaval system.

PMID:37865450 | DOI:10.1016/j.tvir.2023.100900

15:07

PubMed articles on: Cancer & VTE/PE

Intensify Standardized Anticoagulation for Cancer-Associated Pulmonary Embolism: From Single-Center Real-World Data

Clin Ther. 2023 Oct 12:S0149-2918(23)00378-8. doi: 10.1016/j.clinthera.2023.09.014. Online ahead of print.

 

ABSTRACT

Arterial (ATE) and venous (VTE) thromboembolic complications are common causes of morbidity and mortality in BCR-ABL-negative myeloproliferative neoplasms (MPNs). However, there are few studies that include all MPN subtypes and focus on both MPN-associated ATE and VTE. In our single-center retrospective study of 832 MPN patients, a total of 180 first thromboembolic events occurred during a median follow-up of 6.6 years (range: 0-37.6 years), of which 105 were VTE and 75 were ATE. The probability of a vascular event at the end of the follow-up period was 36.2%, and the incidence rate for all first ATE/VTE was 2.43% patient/year. The most frequent VTE localizations were deep vein thrombosis with or without pulmonary embolism (incidence rate: 0.59% patient/year), while strokes were the most frequent ATE with an incidence rate of 0.32% patient/year. When comparing the group of patients with ATE/VTE (n = 180) and the group without such an event (n = 652) using multivariate Cox regression analyses, patients with polycythemia vera (hazard ratio [HR]: 1.660; [95% confidence interval [CI] 1.206, 2.286]) had a significantly higher risk of a thromboembolic event than the other MPN subtypes. In contrast, patients with a CALR mutation had a significantly lower risk of thromboembolism compared with JAK2-mutated MPN patients (HR: 0.346; [95% CI: 0.172, 0.699]). In summary, a high incidence of MPN-associated VTE and ATE was observed in our retrospective study. While PV patients or generally JAK2-mutated MPN patients had a significantly increased risk of such vascular events, this risk was reduced in CALR-mutated MPN patients.

PMID:37813367 | DOI:10.1055/a-2159-8767

15:07

PubMed articles on: Cancer & VTE/PE

Catheter Directed Thrombectomy and Other Deep Venous Interventions in Cancer Patients

Tech Vasc Interv Radiol. 2023 Jun;26(2):100900. doi: 10.1016/j.tvir.2023.100900. Epub 2023 Aug 5.

BACKGROUND: The optimal therapy of venous thromboembolism (VTE) in cancer patients with renal insufficiency (RI) is unknown. Current guidelines recommend to use low-molecular-weight heparin over direct oral anticoagulants to treat VTE in cancer patients at high-risk for bleeding.

 

ABSTRACT

BACKGROUND: The optimal therapy of venous thromboembolism (VTE) in cancer patients with renal insufficiency (RI) is unknown. Current guidelines recommend to use low-molecular-weight heparin over direct oral anticoagulants to treat VTE in cancer patients at high-risk for bleeding.

METHODS: We used the RIETE registry to compare the 6-month incidence rates of: 1) VTE recurrences vs. major bleeding; and 2) fatal pulmonary embolism (PE) vs. fatal bleeding in 3 subgroups (those with mild, moderate, or severe RI) of cancer patients receiving enoxaparin monotherapy.

RESULTS: From January 2009 through June 2022, 2,844 patients with RI received enoxaparin for ≥6 months: 1,432 (50%) had mild, 1,168 (41%) moderate, and 244 (8.6%) had severe RI. Overall, 68%, 62% and 12% respectively, received the recommended doses. Among patients with mild RI, the rates of VTE recurrences vs. major bleeding (4.6% vs. 5.4%) and fatal PE vs. fatal bleeding (1.3% vs. 1.2%) were similar. Among patients with moderate RI, VTE recurrences were half as common as major bleeding (3.1% vs. 6.3%), but fatal PE and fatal bleeding were close (1.8% vs. 1.2%). Among patients with severe RI, VTE recurrences were 3-fold less common than major bleeding (4.1% vs. 13%), but fatal PE was 3-fold more frequent than fatal bleeding (2.5% vs. 0.8%). During the first 10 days, fatal PE was 5-fold more common than fatal bleeding (2.1% vs. 0.4%).

CONCLUSIONS: Among cancer patients with severe RI, fatal PE was 5-fold more common than fatal bleeding. The recommended doses of enoxaparin in these patients should be revisited.

PMID:37832588 | DOI:10.1055/a-2191-7510

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PubMed articles on: Cancer & VTE/PE

Arterial and Venous Thromboembolic Complications in 832 Patients with BCR-ABL-Negative Myeloproliferative Neoplasms

Hamostaseologie. 2023 Oct 9. doi: 10.1055/a-2159-8767. Online ahead of print.

 

ABSTRACT

[This retracts the article DOI: 10.1155/2022/2471039.].

PMID:37810512 | PMC:PMC10551532 | DOI:10.1155/2023/9839816

15:07

PubMed articles on: Cancer & VTE/PE

Enoxaparin for the long-term therapy of venous thromboembolism in patients with cancer and renal insufficiency

Thromb Haemost. 2023 Oct 13. doi: 10.1055/a-2191-7510. Online ahead of print.

BACKGROUND: Incidence of and risk factors for bleeding in cancer patients with venous thromboembolism (VTE) treated with apixaban are poorly described.

 

ABSTRACT

BACKGROUND: Incidence of and risk factors for bleeding in cancer patients with venous thromboembolism (VTE) treated with apixaban are poorly described.

METHODS: We analyzed data from the prospective CAP study where 298 cancer patients with any type of VTE received 5 mg apixaban twice daily for 6 months, and then 2.5 mg apixaban twice daily for 30 months. For most analyses major bleedings and clinically relevant non-major bleedings were merged to "clinically relevant bleedings". Risk factors were estimated by odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: The incidence of clinically relevant bleedings was 38% per person year during the first 6 months of treatment, 21% per person year from 7 to 12 months, and between 4% and 8% per person year from 13 to 36 months. Clinically relevant bleedings were associated with age above 74 years (OR 2.0, 95% CI 1.0-4.1), BMI below 21.7 (OR 2.3, 95% CI 1.1-4.8), and hemoglobin at baseline below 10.5 for females (OR 2.8, 95% CI 1.1-7.3) and 11.1 for males (OR 3.3, 95% CI 1.3-8.4) during the first 6 months. Gastrointestinal (GI) or urogenital cancer were not associated with clinically relevant bleedings compared with other cancers. Among patients with luminal GI-cancer, non-resected cancer had increased risk of bleeding (OR 3.4, 95% CI 1.0-11.6) compared with resected GI-cancer.

CONCLUSION: It was very few bleedings while patients were on low-dose apixaban. Factors associated with bleeding in patients treated with full-dose apixaban were high age, low BMI, and low hemoglobin, and probably non-resected luminal GI-cancer.

PMID:37816388 | DOI:10.1055/a-2188-8773

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PubMed articles on: Cancer & VTE/PE

Retracted: Effect Evaluation of Bronchial Artery Embolization for Hemoptysis of Lung Cancer and Changes in Serum Tumor Markers and miR-34 Levels

Contrast Media Mol Imaging. 2023 Sep 27;2023:9839816. doi: 10.1155/2023/9839816. eCollection 2023.

 

ABSTRACT

INTRODUCTION: Previous studies suggest that quality improvement initiatives focused on hospital-acquired venous thromboembolism have a positive impact on prescribing rates of venous thromboembolism prophylaxis, especially those that incorporate computerized changes.

METHODS: We conducted a quality improvement project to determine whether education and computerized prescriber order entry system changes affect venous thromboembolism prophylaxis compliance rates in hospitalized medical patients at a Comprehensive Cancer Center. Between 1 January 2021 and 31 January 2023, 37,739 non-surgical, adult patient encounters with a length of stay > 48 h were analyzed in our study. From 18 December 2021 to 8 March 2022, provider education was delivered to the three largest admitting services, and computerized prescriber order entry changes were implemented incorporating a mandatory requirement to either order venous thromboembolism prophylaxis or document a contraindication for all patients at moderate venous thromboembolism risk.

RESULTS: Monthly venous thromboembolism prophylaxis compliance rates, as defined by the Centers for Medicare and Medicaid Services VTE-1 metric, increased from a mean of 74% to 93% after the interventions. This change was driven primarily by an increased utilization of mechanical venous thromboembolism prophylaxis from 37% to 53%.

CONCLUSION: Our study demonstrated that a multi-faceted intervention incorporating provider education and computerized prescriber order entry system changes can significantly increase venous thromboembolism prophylaxis compliance rates in cancer patients.

PMID:37801550 | DOI:10.1177/10781552231205779

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PubMed articles on: Cancer & VTE/PE

Risk factors for bleeding in cancer patients treated with conventional dose followed by low dose apixaban for venous thromboembolism

Thromb Haemost. 2023 Oct 10. doi: 10.1055/a-2188-8773. Online ahead of print.

hypothyroidism, chronic kidney disease, diabetes, obstructive sleep apnea, pulmonary embolism, hypotension, COVID-19, and recurrent tachycardia, with inconsistent adherence to treatment recommendations.

 

ABSTRACT

OBJECTIVE: Craniopharyngiomas are extremely rare (incidence rate of 1.34 per million). Due to its proximity to the sellar/suprasellar prefrontal regions region, cognitive impairment, behavioral changes, and adverse endocrinological outcomes are common. Further, surgery and radiotherapy can further impact functioning. Currently, there is no parsimonious cognitive profile of adult patients following interventions. This case highlights the role of neuropsychological evaluations in monitoring global psychological functioning and frontal behavioral syndrome in an adult with recurrent craniopharyngioma.

METHOD: The patient is a 39-year-old Black female first evaluated as an inpatient prior to resection surgery. She was evaluated on four additional times post-surgically. At the most recent evaluation, she and her family reported memory problems, apathy, and gait instability. Complicating factors included hypothyroidism, chronic kidney disease, diabetes, obstructive sleep apnea, pulmonary embolism, hypotension, COVID-19, and recurrent tachycardia, with inconsistent adherence to treatment recommendations.

RESULTS: She displayed global cognitive deficits two years post-surgery, particularly in language and memory. Neurobehaviorally, she exhibited pervasive signs of severe frontal lobe syndrome, including, abulia, hypophonic and dysarthric speech, psychomotor retardation, bradyphrenia, and anosognosia.

CONCLUSION: Neuropsychological evaluations remain critical in monitoring the patient's neurocognitive status and provide valuable insights into treatment planning and need for additional support and care to optimize patients' quality of life in the context of significant cognitive disability.

PMID:37807245 | DOI:10.1093/arclin/acad067.136

15:07

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