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4/24/26

ABSTRACT

Cardiorenal syndrome (CRS) is a condition characterized by the intricate two-way relationship between the heart and kidneys, which can lead to acute or chronic dysfunction in these organs. The interplay between cardiorenal connectors and both hemodynamic and non-hemodynamic factors is crucial to understanding this syndrome. The clinical importance of these interactions is evident in the changes observed in hemodynamic factors, neurohormonal markers, and inflammatory processes. Identifying and understanding biomarkers associated with CRS is valuable for early detection and enabling intervention before significant organ dysfunction occurs. This comprehensive review focuses on the clinical significance of biomarkers in the diagnosis, prognosis, and management of CRS. Finally, it highlights the necessity for further advancements in managing this condition.

PMID:37529809 | PMC:PMC10389294 | DOI:10.7759/cureus.41252

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PubMed articles on: Cardio-Oncology

Late-onset cardiotoxicity in patients with HER2-positive metastatic breast cancer receiving trastuzumab-based therapy

J Oncol Pharm Pract. 2023 Aug 1:10781552231193149. doi: 10.1177/10781552231193149. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) typically receive long-term trastuzumab treatment for several years. The aim of our study is to identify the incidence and characterize late-onset cardiotoxicity in patients with HER2-positive MBC receiving trastuzumab-based therapy.

METHODS: We retrospectively reviewed charts of HER2-positive MBC patients who received >1 year of trastuzumab-based therapy at the Massachusetts General Hospital Cancer Center over three-year period. The primary endpoint was development of trastuzumab-induced cardiotoxicity (TIC). Secondary endpoints included time to TIC development, incidence/duration of trastuzumab interruption due to TIC, incidence of permanent discontinuation of trastuzumab due to TIC, clinic visit, or hospitalization due to TIC.

RESULTS: Thirty-seven patients were included. Mean age was 56 years (range: 33-78 years, SD 9.5). Seven patients received prior doxorubicin and 14 patients received previous or concurrent breast irradiation. Mean duration of trastuzumab-based therapy was 57 months (range: 14-140 months, SD 39.3). Seven patients (18.9%) experienced TIC resulting in treatment interruption for two patients (28 and 78 days). The median time from starting trastuzumab therapy to TIC was 14 months (interquartile range: 11-29.5 months). The mean number of left ventricular ejection fraction (LVEF) assessment completed per year was 2.7 (range: 1.2-6.6, SD 1.1).

CONCLUSION: Cardiotoxicity occurred in a minority of patients with HER2-positive MBC receiving trastuzumab-based therapy for more than one year. LVEF reductions to below the institutional lower limit of normal and therapy modifications were uncommon.

PMID:37528623 | DOI:10.1177/10781552231193149

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PubMed articles on: Cardio-Oncology

Statins as preventive therapy for anthracycline cardiotoxicity: A meta-analysis of randomized controlled trials

Int J Cardiol. 2023 Jul 30:131219. doi: 10.1016/j.ijcard.2023.131219. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiotoxicity occurs in 5-20% of cancer patients who receive anthracyclines. The aim of this study was to pool all the randomized controlled trials (RCTs) investigating the cardio-protective role of statins in patients treated with anthracyclines.

METHODS: PubMed and Scopus electronic databases were scanned for eligible studies up to May 3rd, 2023. A total of 5 RCTs with 808 patients were included. Efficacy endpoints were the rate of anthracycline-mediated cardiotoxicity, the incidence of hospitalization for heart failure (HF), left ventricular ejection fraction (LVEF) value after anthracycline treatment, and ∆LVEF calculated as the difference in LVEF before and after anthracycline therapy. Safety endpoints [i.e., the incidence of muscle pain and serious adverse events (SAE)] were also assessed.

RESULTS: On pooled analysis, the statin-treated group had a lower incidence of cardiotoxicity compared to the placebo group [risk ratio (RR) 0.52, 95% confidence Interval (CI) 0.33-0.83, P = 0.01; I2 = 0%], as well as higher mean LVEF [Mean difference (MD) 1.88, 95% CI 0.66-3.1, P < 0.01; I2 = 57.3%)] and a more favorable ∆LVEF during follow-up (MD 2.38, 95% CI -0.03 - +4.79, P = 0.05; I2 = 99%), despite no significant difference in terms of hospitalization for HF and rate of adverse events. Of note, severe heterogeneity affected the analyses for both LVEF and ΔLVEF.

CONCLUSIONS: The current meta-analysis of all RCTs conducted so far shows an overall beneficial effect of statins on the risk of anthracyclines induced cardiotoxicity and LVEF preservation. No difference was observed in the rate of HF hospitalization. . More powered RCTs are needed to fully investigate the impact of statins on prognosis in patients receiving anthracyclines therapy.

PMID:37527752 | DOI:10.1016/j.ijcard.2023.131219

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PubMed articles on: Cardio-Oncology

Role of hypoxia inducible factor/vascular endothelial growth factor/endothelial nitric oxide synthase signaling pathway in mediating the cardioprotective effect of dapagliflozin in cyclophosphamide-induced cardiotoxicity

Hum Exp Toxicol. 2023 Jan-Dec;42:9603271231193392. doi: 10.1177/09603271231193392.

ABSTRACT

BACKGROUND: Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive alkylating agent. However, cardiac adverse effects of CP interfere with its clinical benefit. Cardio-oncology research is currently an important issue and finding effective cardiopreserving agents is a critical need. For the first time, we aimed to detect if dapagliflozin (DAP) could ameliorate CP-induced cardiac injury and investigated the role of hypoxia inducible factor α (HIF1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) pathway.

METHODS: Forty male Wistar albino rats were included in the current model. Studied groups are: control group; CP-induced cardiotoxicity group; CP group treated with DAP; CP group treated with DAP and administered a nitric oxide synthase inhibitor; nitro-ω-L-arginine (L-NNA) before DAP to explore the role of eNOS.

RESULTS: Our data revealed that CP could induce cardiac damage as manifested by significant increases in cardiac enzymes, blood pressure, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), HIF1α, sodium glucose co-transporter 2 (SGLT2) and cleaved caspase-3 levels with toxic histopathological changes. However, there are significant decreases in reduced glutathione (GSH), total antioxidant capacity (TAC), VEGF, and eNOS. On the opposite side, co-administration of DAP showed marked improvement of CP-induced cardiac damage that may be due to its ability to inhibit SGLT2, antioxidant, anti-inflammatory and anti-apoptotic properties. Results showed decreasing the cardioprotective effect of DAP on administration of L-NNA, reflecting the critical effect of eNOS in mediating such protection.

CONCLUSION: DAP could reduce CP cardiotoxicity based upon its ability to modulate SGLT2 and HIF1α/VEGF/eNOS signaling pathway.

PMID:37526264 | DOI:10.1177/09603271231193392

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PubMed articles on: Cardio-Oncology

Neopetroside-B alleviates doxorubicin-induced cardiotoxicity via mitochondrial protection

Biomed Pharmacother. 2023 Jul 29;165:115232. doi: 10.1016/j.biopha.2023.115232. Online ahead of print.

ABSTRACT

Doxorubicin, a member of the anthracycline family, is a widely prescribed anticancer chemotherapy drug. Unfortunately, cumulative doses of doxorubicin can cause mitochondrial dysfunction, leading to acute or chronic cardiotoxicity. This study demonstrated that Neopetroside-B (NPS-B) protects cardiomyocytes in the presence of doxorubicin. NPS-B improved mitochondrial function in cardiomyocytes by increasing ATP production and oxygen consumption rates. On the other hand, NPS-B negatively influenced cancer cell lines by increasing reactive oxygen species. We analyzed NPS-B-influenced metabolites (VIP > 1.0; AUC>0.7; p < 0.05) and proteins (FC > 2.0) and constructed metabolite-protein enrichment, which showed that NPS-B affected uracil metabolism and NAD-binding proteins (e.g., aldehyde dehydrogenase and glutathione reductase) in cardiomyocytes. However, for the cancer cells, NPS-B decreased the NAD+/NADH balance, impairing cell viability. In a xenograft mouse model treated with doxorubicin, NPS-B reduced cardiac fibrosis and improved cardiac function. NPS-B may be a beneficial intervention to reducing doxorubicin-induced cardiotoxicity with anticancer effects.

PMID:37523986 | DOI:10.1016/j.biopha.2023.115232

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PubMed articles on: Cardio-Oncology

Cardio-oncology today: digest of the first European clinical guidelines (2022)

Kardiologiia. 2023 Jul 28;63(7):3-15. doi: 10.18087/cardio.2023.7.n2445.

ABSTRACT

Over the past few decades, due to the extensive implementation of cancer screening programs, up-to-date early diagnostic methods, and effective combinations of antitumor therapy, it has become possible to significantly improve survival of cancer patients. At the same time, despite the effective treatment of malignancies, most patient face adverse and often life-threatening effects of specific treatment on the heart and blood vessels. All this resulted in active development of a new field in cardiology, cardio-oncology. In recent years, based on the experience of leading experts, data from large studies, and meta-analyses, both international and Russian Consensuses, conciliation documents, have been formed and published. These documents regulate principal methodological approaches to management and control of the cardiovascular conditions in cancer patients. Finally, 2022 was marked by issuing the first official European Guidelines on Cardio-Oncology in the history of medicine. This article highlights the most relevant, in our opinion, positions of these guidelines as well as controversial and unresolved issues.

PMID:37522822 | DOI:10.18087/cardio.2023.7.n2445

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PubMed articles on: Cardio-Oncology

Editorial: Case reports in cardio-oncology: 2022

Front Cardiovasc Med. 2023 Jul 13;10:1235015. doi: 10.3389/fcvm.2023.1235015. eCollection 2023.

NO ABSTRACT

PMID:37522080 | PMC:PMC10374430 | DOI:10.3389/fcvm.2023.1235015

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PubMed articles on: Cardio-Oncology

Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe

Front Immunol. 2023 Jul 13;14:1203425. doi: 10.3389/fimmu.2023.1203425. eCollection 2023.

ABSTRACT

The adaptive immune system of jawed vertebrates generates a highly diverse repertoire of antibodies to meet the antigenic challenges of a constantly evolving biological ecosystem. Most of the diversity is generated by two mechanisms: V(D)J gene recombination and somatic hypermutation (SHM). SHM introduces changes in the variable domain of antibodies, mostly in the regions that form the paratope, yielding antibodies with higher antigen binding affinity. However, antigen recognition is only possible if the antibody folds into a stable functional conformation. Therefore, a key force determining the survival of B cell clones undergoing somatic hypermutation is the ability of the mutated heavy and light chains to efficiently fold and assemble into a functional antibody. The antibody is the structural context where the selection of the somatic mutations occurs, and where both the heavy and light chains benefit from protective mechanisms that counteract the potentially deleterious impact of the changes. However, in patients with monoclonal gammopathies, the proliferating plasma cell clone may overproduce the light chain, which is then secreted into the bloodstream. This places the light chain out of the protective context provided by the quaternary structure of the antibody, increasing the risk of misfolding and aggregation due to destabilizing somatic mutations. Light chain-derived (AL) amyloidosis, light chain deposition disease (LCDD), Fanconi syndrome, and myeloma (cast) nephropathy are a diverse group of diseases derived from the pathologic aggregation of light chains, in which somatic mutations are recognized to play a role. In this review, we address the mechanisms by which somatic mutations promote the misfolding and pathological aggregation of the light chains, with an emphasis on AL amyloidosis. We also analyze the contribution of the variable domain (VL) gene segments and somatic mutations on light chain cytotoxicity, organ tropism, and structure of the AL fibrils. Finally, we analyze the most recent advances in the development of computational algorithms to predict the role of somatic mutations in the cardiotoxicity of amyloidogenic light chains and discuss the challenges and perspectives that this approach faces.

PMID:37520549 | PMC:PMC10374031 | DOI:10.3389/fimmu.2023.1203425

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Cardiotoxicity News

PubMed articles on: Cancer & VTE/PE

Thrombotic risk of platinum combination chemotherapy with and without immune checkpoint inhibitors for advanced non-small cell lung cancer: a nationwide inpatient database study

Cancer Immunol Immunother. 2023 Aug 4. doi: 10.1007/s00262-023-03508-1. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the associated thromboembolism risk with adding immune checkpoint inhibitors (ICI) to platinum combination chemotherapy compared with platinum combination chemotherapy alone in patients with advanced non-small cell lung cancer.

MATERIALS AND METHODS: This study identified 75,807 patients with advanced non-small cell lung cancer from the Japanese Diagnosis Procedure Combination database who started platinum combination chemotherapy between July 2010 and March 2021. The incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and all-cause mortality within 6 months after commencing platinum combination chemotherapy was compared between patients receiving chemotherapy with ICI (ICI group, n = 7,177) and without ICI (non-ICI group, n = 37,903). Survival time analysis was performed using the overlap weighting method with propensity scores to adjust for background factors. The subdistribution hazard ratio for developing thromboembolism was calculated using the Fine-Gray model with death as a competing risk. The hazard ratio for all-cause mortality was also calculated using the Cox proportional hazards model.

RESULTS: Overall, VTE and ATE occurred in 761 (1.0%) and 389 (0.51%) patients, respectively; mortality was 11.7%. Propensity score overlap weighting demonstrated that the subdistribution hazard ratio (95% confidence interval) for VTE and ATE in the ICI group was 1.27 (1.01-1.60) and 0.96 (0.67-1.36), respectively, compared with the non-ICI group. The mortality hazard ratio in the ICI group was 0.68 (0.62-0.74).

CONCLUSION: The addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable.

PMID:37540262 | DOI:10.1007/s00262-023-03508-1

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PubMed articles on: Cancer & VTE/PE

Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress

Res Pract Thromb Haemost. 2023 Jun 21;7(4):100193. doi: 10.1016/j.rpth.2023.100193. eCollection 2023 May.

ABSTRACT

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) took place in person in Montréal, Canada, from June 24-28, 2023. The conference, held annually, highlighted cutting-edge advances in basic, translational, population and clinical sciences relevant to the Society. As for all ISTH congresses, we offered a special, congress-specific scientific theme; this year, the special theme was immunothrombosis. Certainly, over the last few years, COVID-19 infection and its related thrombotic and other complications have renewed interest in the concepts of thromboinflammation and immunothrombosis; namely, the relationship between inflammation, infection and clotting. Other main scientific themes of the Congress included Arterial Thromboembolism, Coagulation and Natural Anticoagulants, Diagnostics and Omics, Fibrinolysis and Proteolysis, Hemophilia and Rare Bleeding Disorders, Hemostatic System in Cancer, Inflammation and Immunity, Pediatrics, Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies, Platelets and Megakaryocytes, Vascular Biology, Venous Thromboembolism and Women's Health. Among other sessions, the program included 28 State-of-the-Art (SOA) sessions with a total of 84 talks given by internationally recognized leaders in the field. SOA speakers were invited to prepare brief illustrated reviews of their talks that were peer reviewed and are included in this article. These illustrated capsules highlight the major scientific advances with potential to impact clinical practice. Readers are invited to take advantage of the excellent educational resource provided by these illustrated capsules. They are also encouraged to use the image in social media to draw attention to the high quality and impact of the science presented at the Congress.

PMID:37538494 | PMC:PMC10394567 | DOI:10.1016/j.rpth.2023.100193

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PubMed articles on: Cancer & VTE/PE

Thrombophilia Gene Mutations Predict Venous Thromboembolism in Ambulatory Cancer Patients Receiving Chemotherapy

J Thromb Haemost. 2023 Aug 1:S1538-7836(23)00580-9. doi: 10.1016/j.jtha.2023.07.017. Online ahead of print.

ABSTRACT

BACKGROUND: Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear.

OBJECTIVES: Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-high risk ambulatory cancer patients receiving chemotherapy.

METHODS: We conducted a post-hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (Prothrombin FII G20210A, Factor XI, Fibrinogen Gamma, Serpin Family A Member 10, Factor V K858R, Factor XIII, Factor V Leiden (FVL), and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used comparing heterozygous and homozygous mutations (combined) to wild type. VTE rates, bleeding rates and risk differences for mutations stratified by prophylactic anticoagulation use were calculated.

RESULTS: Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type [OR: 5.2 (95%CI:1.9-14.7) and 2.7 (95%CI:1.2-6.1), respectively]. The use of anticoagulation prophylaxis resulted in complete protection in FVL patients whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding.

CONCLUSIONS: Our results indicate FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

PMID:37536569 | DOI:10.1016/j.jtha.2023.07.017

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PubMed articles on: Cancer & VTE/PE

Low-Molecular-Weight Heparin Versus Warfarin in Adult Cancer Patients as a Precision Medicine for Thrombosis: A Systematic Review and Meta-Analysis

Cureus. 2023 Jul 1;15(7):e41268. doi: 10.7759/cureus.41268. eCollection 2023 Jul.

ABSTRACT

Venous thromboembolism (VTE) is a condition often seen in patients diagnosed with cancer and is recognized as a predictor of poor outcomes in these patients. The probability of VTE recurring is generally higher in people with cancer than in those without; hence, addressing this issue is essential when making healthcare decisions. Therefore, our systematic review was primarily designed to compare low-weight- molecular heparin (LMWH) to warfarin in reducing recurrent VTE among cancer patients. However, other outcomes were also evaluated, such as mortality and bleeding events observed more in cancer patients. The selection of relevant articles was carried out using a database search and a manual search, which involved reviewing reference lists of articles eligible for inclusion in the current review. The methodological quality of each included study was then assessed using Cochrane's risk of bias tool in the Review Manager software (RevMan 5.4.1). Additionally, pooled results were examined using the Review Manager software and presented as forest plots. Our search of electronic databases elicited a total of 2163 articles, of which only six were deemed eligible for inclusion and analysis. Data pooled from the six studies demonstrated the effectiveness of LMWH in minimizing the reoccurrence of VTE over warfarin [risk ratio (RR): 0.67; 95% CI: 0.47 - 0.95; p = 0.03]. However, LMWH had a similar effect statistically as warfarin on the major bleeding events (RR: 1.05; 95% CI: 0.62 - 1.77; p = 0.85), minor bleeding events (RR: 0.80; 95% CI: 0.54 - 1.20; p = 0.28), and all-cause mortality (RR: 1.00; 95% CI: 0.88 - 1.13; p = 0.99). While LMWH demonstrated its effectiveness in minimizing the incidence of VTE recurrence over warfarin in cancer patients, it had no statistical difference in terms of mortality or bleeding events when compared to warfarin. Based on our findings, we recommend that LMWH continues to be used as a first-line treatment regimen to mitigate recurrent VTE in cancer patients.

PMID:37533609 | PMC:PMC10390756 | DOI:10.7759/cureus.41268

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PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis

Br J Haematol. 2023 Aug 2. doi: 10.1111/bjh.19017. Online ahead of print.

ABSTRACT

Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.

PMID:37533165 | DOI:10.1111/bjh.19017

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PubMed articles on: Cancer & VTE/PE

Genetic insights into resting heart rate and its role in cardiovascular disease

Nat Commun. 2023 Aug 2;14(1):4646. doi: 10.1038/s41467-023-39521-2.

ABSTRACT

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

PMID:37532724 | PMC:PMC10397318 | DOI:10.1038/s41467-023-39521-2

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PubMed articles on: Cancer & VTE/PE

Prevalence of and Eligibility for Surveillance Without Anticoagulation Among Adults With Lower-Risk Acute Subsegmental Pulmonary Embolism

JAMA Netw Open. 2023 Aug 1;6(8):e2326898. doi: 10.1001/jamanetworkopen.2023.26898.

ABSTRACT

IMPORTANCE: Approximately 8% of acute pulmonary emboli are confined to the subsegmental arteries. The 2016 and 2021 American College of Chest Physicians (CHEST) guidelines and expert panel reports suggest the use of structured surveillance without anticoagulation for select ambulatory patients with subsegmental pulmonary embolism who do not have active cancer, deep vein thrombosis, impaired cardiopulmonary reserve, marked symptoms, or increased risk of recurrent venous thromboembolism; however, guideline uptake in community practice is unknown, as is the proportion of outpatients eligible for surveillance.

OBJECTIVE: To describe the prevalence of surveillance among outpatients with acute subsegmental pulmonary embolism and to estimate the proportion of patients eligible for structured surveillance using modified CHEST criteria.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted across 21 US community hospitals in the Kaiser Permanente Northern California integrated health system from January 1, 2017, to December 31, 2021. Adult outpatients with acute subsegmental pulmonary embolism were included. Patients with the following higher-risk characteristics were excluded: codiagnoses requiring hospitalization, non-low-risk vital signs (ie, systolic blood pressure <90

MAIN OUTCOMES AND MEASURES: The main outcomes were the (1) prevalence of surveillance and (2) eligibility for surveillance using 2 sets of criteria: the CHEST criteria modified by excluding patients with higher-risk characteristics or right ventricular dysfunction and a stricter set of criteria requiring age younger than 65 years and no more than 1 embolus. The prevalence of structured surveillance was calculated and the proportion of patients eligible for surveillance was estimated.

RESULTS: Of the 666 outpatients with acute subsegmental pulmonary embolism included in this study, 229 with lower-risk characteristics were examined. Their median age was 58 (IQR, 42-68) years; more than half were men (120 [52.4%]) and self-identified as non-Hispanic White (128 [55.9%]). Six patients (2.6%) were initially not treated with anticoagulants. Among the lower-risk cohort, only 1 patient (0.4% [95% CI, 0.01%-2.4%]) underwent structured surveillance, without 90-day sequelae. Thirty-five patients (15.3% of the lower-risk group and 5.3% of the full cohort) were surveillance eligible using modified CHEST criteria. Fifteen patients (6.6% of the lower-risk group and 2.3% of the full cohort) were surveillance eligible using stricter criteria.

CONCLUSIONS AND RELEVANCE: In this cohort study of lower-risk outpatients with subsegmental pulmonary embolism, few were eligible for structured surveillance, and only a small proportion of eligible patients underwent surveillance despite the CHEST guideline. If forthcoming trials find surveillance safe and effective, substantial uptake into clinical practice may require more than passive diffusion.

PMID:37531107 | PMC:PMC10398409 | DOI:10.1001/jamanetworkopen.2023.26898

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PubMed articles on: Cancer & VTE/PE

A novel risk prediction score for clinically significant bleeding in patients anticoagulated for venous thromboembolism with active cancer

Thromb Haemost. 2023 Aug 1. doi: 10.1055/a-2145-7238. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide accurate bleeding risk prediction.

METHODS: UK Clinical Practice Research Datalink data (2008-2020) was used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE. Patients were observed up to 180 days for significant bleeding including major bleeding, and clinically relevant non-major bleeding requiring hospitalisation (CRNMB-H). A scoring scheme was developed from subdistribution hazard ratios, and its discrimination (expressed by the C-statistic) estimated from cross-validation.

RESULTS: 15,749 patients with Ca-VTE and anticoagulant treatment were included. In total, 537 significant bleeding events, 161 major bleeds and 376 CRNMB-H were identified after adjudicated review in 4914 person-years of observation. Incidence rates of 3.3 and 7.7 per 100 person-years were noted for major bleeding and CRNMB-H. Independent predictors of significant bleeding were cancer of the bladder, central nervous system, cervix, kidney, melanoma, prostate and upper gastrointestinal tract. Overall C-statistic for significant bleeding was 0.70, and 0.76 and 0.67 for major bleeding and for CRNMB-H, respectively.

CONCLUSIONS: This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.

PMID:37527782 | DOI:10.1055/a-2145-7238

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PubMed articles on: Cancer & VTE/PE

Intravascular Tumor Extension and Pulmonary Tumor Embolism in Children With Solid Malignancies: Is There a Role for Inferior Vena Cava Filters?

J Pediatr Hematol Oncol. 2023 Jul 27. doi: 10.1097/MPH.0000000000002731. Online ahead of print.

ABSTRACT

Intravascular tumor extension is an uncommon complication of solid malignancies that, when present in the inferior vena cava (IVC), can result in fatal pulmonary tumor embolism. Currently, neoadjuvant chemotherapy and surgery are the mainstays of treatment; however, there are no consensus guidelines for management. We describe three cases of pediatric solid malignancies with associated IVC extension and pulmonary tumor embolism. We hypothesize that there is scope for IVC filter placement in such cases to mitigate the risk of fatal pulmonary tumor embolism.

PMID:37526419 | DOI:10.1097/MPH.0000000000002731

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Tissue factor positive microparticles as a biomarker for increased risk of breast cancer-associated thrombosis: a mini review

Curr Opin Hematol. 2023 Sep 1;30(5):180-185. doi: 10.1097/MOH.0000000000000774.

ABSTRACT

PURPOSE OF REVIEW: Cancer-associated thrombosis (CAT), such as venous thromboembolism (VTE), is a frequent complication in cancer patients, resulting in poor prognosis. Breast cancer is not highly thrombogenic but is highly prevalent, resulting in increased VTE cases. Many cancers express tissue factor (TF), a glycoprotein that triggers coagulation. The cancer cells were shown to express and release substantial amounts of TF-positive microparticles (MPTF), associated with a prothrombotic state. This narrative review evaluated the current use of the procoagulant MPTF as a biomarker for thrombosis risk in breast cancer.

RECENT FINDINGS: Tumors of epithelial origin with elevated TF expression have been associated with increased VTE incidence. Thus, studies have affirmed the use of MPTF biomarkers for VTE risk in many cancers. Patients with metastatic breast cancer and CAT were found to exhibit elevated procoagulant microparticles in vitro, due to TF expression. The silencing of TF was associated with decreased microparticle release in breast carcinoma cell lines, associated with decreased coagulation.

SUMMARY: CAT is a multifactorial condition, with several various underlying diseases. It is proposed that MPTF may be an effective biomarker for thrombosis risk in breast cancer patients but requires a more systemic evaluation utilizing standardized quantification methods.

PMID:37522480 | DOI:10.1097/MOH.0000000000000774

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PubMed articles on: Cancer & VTE/PE

Incidence and Factors Associated With Pulmonary Embolism After Upper Extremity Trauma: A Tertiary Hospital Experience in Turkey

Cureus. 2023 Jun 28;15(6):e41077. doi: 10.7759/cureus.41077. eCollection 2023 Jun.

ABSTRACT

Introduction Venous thromboembolism (VTE), particularly pulmonary embolism (PE), is the third highest cause of death in trauma patients who survive beyond the first day. Musculoskeletal surgery is associated with several complications, some of which may be life-threatening, including deep vein thrombosis (DVT) and PE. Objective This research aims to describe risk variables for VTE after upper extremity (UE) fracture at a single institution and estimate the incidence of PE following UE fracture. Methods The writers accessed the database via their respective universities using the International Standard Classification (ICD) codes. The medical files of patients aged 18 and older who sought treatment at our emergency department for an injury to their UE and also sought treatment at the orthopedics and traumatology clinic between the years 2013 and 2021 were manually scanned. The patients who applied to the Chest Diseases Clinic within 30 days after the trauma and were diagnosed with PE in the ICD code scan were included in the study. Results UE trauma was the cause of admission to the emergency department for 3,265 patients, and 21 of those patients (0.64%) were found to have PE. Fifteen of the patients were male, and six were female. The median age was 59 years (IQR 17). There were no deaths associated with PE. One of the patients had a scaphoid fracture, seven patients had a humerus fracture, five patients had a distal radius fracture, two patients had an acromioclavicular joint injury, one patient had a shoulder dislocation, one patient had a finger fracture, four patients had wrist crush injury. Three patients had diabetes mellitus. Five patients were active smokers. JAK-2 gene V617F mutation was detected in one patient. One patient was diagnosed with prostate cancer, and one had gastric cancer. One patient had a central venous catheter. Two patients were being treated for hypothyroidism. Two patients had hypertension. Conclusion According to the findings of our research, the probability of developing PE in the days following of an injury to the UE was found to be 0.64%. Patients with UE injuries who are active smokers and who also have diabetes, hypertension, hypothyroidism, cancer, coagulation disorder (JAK2 gene V617F mutation), or a central venous catheter may benefit from anticoagulant prophylaxis. This is because these patients are at a higher risk of developing dangerous blood clots.

PMID:37519534 | PMC:PMC10375827 | DOI:10.7759/cureus.41077

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PubMed articles on: Cancer & VTE/PE

Comparative Efficacy of Direct Oral Anticoagulants and Low-Molecular-Weight Heparin in Cancer-Associated Thromboembolism: A Systematic Review and Meta-Analysis

Cureus. 2023 Jun 28;15(6):e41071. doi: 10.7759/cureus.41071. eCollection 2023 Jun.

ABSTRACT

Patients diagnosed with cancer often experience an abnormal occurrence of venous thromboembolism (VTE) and its related complications. In order to evaluate the safety and effectiveness of both treatment approaches, we conducted a comprehensive systematic review and meta-analysis within the realm of cancer-associated thromboembolism. A thorough search was conducted across PubMed, the Cochrane Library, and Embase databases to find studies comparing direct oral anticoagulants (DOACs) with low molecular weight heparins (LMWHs) for the treatment of VTE in patients with malignancy. The analyses utilized the random-effects model. This meta-analysis included 11 studies. The results showed that DOACs were associated with a significantly reduced risk of VTE recurrence (RR: 0.67; 95% CI: 0.55, 0.81, p<0.0001;<0.0001;

PMID:37519604 | PMC:PMC10375513 | DOI:10.7759/cureus.41071

5 August 2023

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PubMed articles on: Cardio-Oncology

Amygdalar activity measured using FDG-PET/CT at head and neck cancer staging independently predicts survival

PLoS One. 2023 Aug 4;18(8):e0279235. doi: 10.1371/journal.pone.0279235. eCollection 2023.

ABSTRACT

IMPORTANCE: The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood.

OBJECTIVE: To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival.

DESIGN: Retrospective cohort study.

SETTING: Academic Medical Center (Massachusetts General Hospital, Boston).

PARTICIPANTS: 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging.

MEASUREMENTS: 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV).

RESULTS: Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05<0.001).

CONCLUSIONS AND RELEVANCE: AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.

PMID:37540647 | DOI:10.1371/journal.pone.0279235

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PubMed articles on: Cardio-Oncology

From bedside to the bench: patient-specific hiPSC-EC models uncover endothelial dysfunction in genetic cardiomyopathies

Front Physiol. 2023 Jul 19;14:1237101. doi: 10.3389/fphys.2023.1237101. eCollection 2023.

ABSTRACT

Genetic cardiomyopathies are a group of inherited disorders in which myocardial structure and function are damaged. Many of these pathologies are rare and present with heterogenous phenotypes, thus personalized models are required to completely uncover their pathological mechanisms and develop valuable therapeutic strategies. Both cardiomyocytes and fibroblasts, differentiated from patient-specific human induced pluripotent stem cells, represent the most studied human cardiac cell models in the context of genetic cardiomyopathies. While endothelial dysfunction has been recognized as a possible pathogenetic mechanism, human induced pluripotent stem cell-derived endothelial cells are less studied, despite they constitute a suitable model to specifically dissect the role of the dysfunctional endothelium in the development and progression of these pathologies. In this review, we summarize the main studies in which human induced pluripotent stem cell-derived endothelial cells are used to investigate endothelial dysfunction in genetic-based cardiomyopathies to highlight new potential targets exploitable for therapeutic intervention, and we discuss novel perspectives that encourage research in this direction.

PMID:37538375 | PMC:PMC10394630 | DOI:10.3389/fphys.2023.1237101

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Accelerated cystogenesis by dietary protein load is dependent on, but not initiated by kidney macrophages

Front Med (Lausanne). 2023 Jul 19;10:1173674. doi: 10.3389/fmed.2023.1173674. eCollection 2023.

ABSTRACT

BACKGROUND: Disease severity of autosomal dominant polycystic kidney disease (ADPKD) is influenced by diet. Dietary protein, a recognized cyst-accelerating factor, is catabolized into amino acids (AA) and delivered to the kidney leading to renal hypertrophy. Injury-induced hypertrophic signaling in ADPKD results in increased macrophage (MФ) activation and inflammation followed by cyst growth. We hypothesize that the cystogenesis-prompting effects of HP diet are caused by increased delivery of specific AA to the kidney, ultimately stimulating MФs to promote cyst progression.

METHODS: Pkd1flox/flox mice with and without Cre (CAGG-ER) were given tamoxifen to induce global gene deletion (Pkd1KO). Pkd1KO mice were fed either a low (LP; 6%), normal (NP; 18%), or high (HP; 60%) protein diet for 1 week (early) or 6 weeks (chronic). Mice were then euthanized and tissues were used for histology, immunofluorescence and various biochemical assays. One week fed kidney tissue was cell sorted to isolate tubular epithelial cells for RNA sequencing.

RESULTS: Chronic dietary protein load in Pkd1KOmice increased kidney weight, number of kidney infiltrating and resident MФs, chemokines, cytokines and cystic index compared to LP diet fed mice. Accelerated cyst growth induced by chronic HP were attenuated by liposomal clodronate-mediated MФ depletion. Early HP diet fed Pkd1KO mice had larger cystic kidneys compared to NP or LP fed counterparts, but without increases in the number of kidney MФs, cytokines, or markers of tubular injury. RNA sequencing of tubular epithelial cells in HP compared to NP or LP diet group revealed increased expression of sodium-glutamine transporter Snat3, chloride channel Clcnka, and gluconeogenesis marker Pepck1, accompanied by increased excretion of urinary ammonia, a byproduct of glutamine. Early glutamine supplementation in Pkd1KO mice lead to kidney hypertrophy.

CONCLUSION: Chronic dietary protein load-induced renal hypertrophy and accelerated cyst growth in Pkd1KO mice is dependent on both infiltrating and resident MФ recruitment and subsequent inflammatory response. Early cyst expansion by HP diet, however, is relient on increased delivery of glutamine to kidney epithelial cells, driving downstream metabolic changes prior to inflammatory provocation.

PMID:37538309 | PMC:PMC10394241 | DOI:10.3389/fmed.2023.1173674

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PubMed articles on: Cardio-Oncology

Artificial intelligence modelling to assess the risk of cardiovascular disease in oncology patients

Eur Heart J Digit Health. 2023 May 8;4(4):302-315. doi: 10.1093/ehjdh/ztad031. eCollection 2023 Aug.

ABSTRACT

AIMS: There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care.

METHODS AND RESULTS: De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals.

CONCLUSION: Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology.

PMID:37538144 | PMC:PMC10393891 | DOI:10.1093/ehjdh/ztad031

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PubMed articles on: Cardio-Oncology

Modulatory effect of amifostine (WR-1065) against genotoxicity and oxidative stress induced by methotrexate in human umbilical vein endothelial cells (HUVECs)

Toxicol Mech Methods. 2023 Aug 3:1-11. doi: 10.1080/15376516.2023.2238069. Online ahead of print.

ABSTRACT

Amifostine is used in chemotherapy and radiotherapy as a cytoprotective adjuvant alongside DNA-binding chemotherapeutic agents. It functions by reducing free radicals and detoxifying harmful metabolites. Methotrexate, as an antimetabolite drug has been considered for treating various cancers and autoimmune diseases. However, the cytotoxic effects of methotrexate extend beyond tumor cells to crucial organs, including the heart. This study applied the HUVEC cell line as a reference in vitromodel for researching the characteristics of vascular endothelium and cardiotoxicity. The current study aimed to assess amifostine's potential cytoprotective properties against methotrexate-induced cellular damage. Cytotoxicity was measured using the MTT assay. Apoptotic rates were evaluated by Annexin V-FITC/PI staining viaflow cytometry. The genoprotective effect of amifostine was determined using the comet assay. Cells were exposed to various amifostine doses (10-200 μg/mL) and methotrexate (2.5 μM) in pretreatment culture condition. Methotrexate at 2.5 μM revealed cytotoxicity, apoptosis, oxidative stress and genotoxicity while highlighting amifostine's cyto/geno protective properties on HUVECs. Amifostine significantly decreased the levels of ROS and LPO while preserving the status of GSH and SOD activity. Furthermore, it inhibited genotoxicity (tail length, %DNA in tail, and tail moment) in the comet assay. Amifostine markedly attenuated methotrexate-induced apoptotic cell death (early and late apoptotic rates). These findings convey that amifostine can operate as a cytoprotectant agent.

PMID:37537746 | DOI:10.1080/15376516.2023.2238069

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PubMed articles on: Cardio-Oncology

Homotypic targeted nanoplatform enable efficient chemoimmunotherapy and reduced DOX cardiotoxicity in chemoresistant cancer via TGF-β1 blockade

J Control Release. 2023 Aug 1:S0168-3659(23)00486-8. doi: 10.1016/j.jconrel.2023.07.063. Online ahead of print.

ABSTRACT

Doxorubicin (DOX) with broad-spectrum antitumor activity has been reported to induce effective immunogenic cell death (ICD) effect. However, the serious cardiotoxicity and chemoresistance severely restrict the widely clinical application of DOX. Herein, for the first time, a bio-inspired nanoplatform via co-assembly of DOX-conjugated polyethyleneimine (PEI-DOX), cancer cell membrane (CCM) and TGF-β1 siRNA (siTGF-β1) was rationally designed, which can not only overcome the drawbacks of DOX but also display high capability to modulate the tumor microenvironment and prevent the tumor progressing and metastasis. Experimental studies confirmed the pH-sensitivity of PEI-DOX and the homotypic-targeting and immuno-escapable ability of CCM, resulting an enhanced accumulation of DOX and siTGF-β1 in tumor sites. In addition to this, the bio-inspired nanoplatform could also improve the stability and facilitate the endosomal escape of siTGF-β1. All these effects ensured the silence efficiency of siTGF-β1 in tumor sites, which could further modulate the chemoresistant and immunosuppressive tumor microenvironment, resulting a synergistic effect with DOX to prevent tumor progressing and metastasis. Additionally, even trapped in cardiac tissues, siTGF-β1 could inhibit the production of TGF-β1 and ROS induced by DOX, resulting a reduced myocardial damage. Therefore, our newly designed bio-inspired nano-delivery system may be a promising nanoplatform with efficient chemoimmunotherapy to ameliorate DOX-induced cardiotoxicity and combat tumor growth and metastasis in chemoresistant cancer.

PMID:37536544 | DOI:10.1016/j.jconrel.2023.07.063

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PubMed articles on: Cardio-Oncology

Patient mortality following new-onset heart failure stratified by cancer type and status

Eur J Heart Fail. 2023 Aug 3. doi: 10.1002/ejhf.2984. Online ahead of print.

ABSTRACT

AIM: Expected 1-year survival is essential to risk stratification of patients with heart failure (HF); however, little is known about the 1-year prognosis of patients with HF and cancer. Thus, the objective was to investigate the 1-year prognosis following new-onset HF stratified by cancer status in patients with breast-, gastrointestinal-, or lung cancer.

METHODS AND RESULTS: All Danish patients with new-onset HF from 2000-2018 were included. Cancer status was categorized as history of cancer (no cancer-related contact within five years of HF diagnosis), non-active cancer (curative intended procedure administered) and active cancer. Standardized 1-year all-cause mortality was reported using G-computation. Age-stratified 1-year all-cause mortality was estimated using the Kaplan-Meier estimator. In total, 193 359 patients with HF were included, 7.3% had either a breast-, gastrointestinal or lung cancer diagnosis. Patients with cancer were older and more comorbid than patients without cancer. Standardized 1-year all-cause mortalities (95% confidence intervals) were 24.6% (23.0%-26.2%), 27.1% (25.5%-28.6%), and 29.9% (25.9%-34.0%) for history of breast-, gastrointestinal-, and lung cancer, which was comparable to patients with non-active cancers. For active breast-, gastrointestinal-, and lung cancer, standardized 1-year all-cause mortalities were 36.2% (33.8%-38.6%), 49.0% (47.2%-50.9%), and 61.6% (59.7%-63.5%), respectively. One-year all-cause mortality increased incrementally with age, except for active lung cancer.

CONCLUSION: Standardized 1-year all-cause mortality were comparable for patients with history of cancer and non-active cancer regardless cancer type, but varied comprehensively for active cancers. Prognostic impact of age was limited for active lung cancer. Thus, granular stratification of cancer is necessary for optimized management of new-onset HF. This article is protected by copyright. All rights reserved.

PMID:37534618 | DOI:10.1002/ejhf.2984

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PubMed articles on: Cardio-Oncology

Cancer Therapy-Related Cardiotoxicity: A Comprehensive Retrospective Analysis at Najran Cancer Center, Saudi Arabia

Cureus. 2023 Jul 2;15(7):e41287. doi: 10.7759/cureus.41287. eCollection 2023 Jul.

ABSTRACT

Background Cardiotoxicity, produced as an adverse effect of anticancer therapy, is a common issue during cancer treatment. Acute coronary syndrome, myocarditis, arrhythmias, or heart failure can all be symptoms of this issue. Little is known about its occurrence among Saudi Arabian cancer patients. This study aims to investigate factors linked to anticancer therapy-related cardiotoxicity. Methods A retrospective study was conducted from April 2020 to May 2022 at the King Khalid Hospital, Najran, Saudi Arabia. The study included adult cancer patients receiving anticancer therapy, regardless of their cardiovascular disease history. Univariate analysis was used to investigate factors associated with the occurrence of cardiotoxicity related to anticancer therapy. Results Of 78 patients receiving anticancer therapy, cardiotoxicity occurred in 12 (15.4%) patients. The mean age was 56.5 ± 13.4 years, with 33.3% aged over 65 years. Comorbidities included hypertension (44; 56.4%), diabetes (41; 52.6%), dyslipidemia (13; 16.7%), smoking (16; 20.5%), heart disease (6; 7.7%), trastuzumab use (9; 11.5%), and chronic kidney disease (2; 2.6%). The most common cancers were breast cancer and gastrointestinal cancer (27.6% each). Monoclonal anticancer agents 35 (46.1%) and alkylating agents 29 (38.2%) were commonly used chemotherapies. Cardiac protective agents were used in 16 (21.1%) of patients, with angiotensin-converting enzyme (ACE) inhibitors 15 (19.7%) and statins (13; 17.1%) being the most prescribed. Baseline ejection fraction (EF) was normal in 69 (90.8%) of cases. The follow-up duration was 1.93 ± 1.90 years. A drop in EF occurred in five (6.6%) of cases. Dyslipidemia (OR: 0.12; 95% CI: 0.03-0.47, p=0.002), previous heart disease (OR: 0.14; 95% CI: 0.02-0.81, p=0.029), and impaired baseline EF (p=0.029) were associated with increased risk of cardiotoxicity. Statin (OR: 0.22; 95% CI: 0.05 to 0.84, p=0.028) and antiplatelet agents (OR: 0.19; 95% CI: 0.03 to 1.01, p=0.051) were protective agents against cardiac toxicity. Conclusion Effective anti-cancer therapy may be accompanied by an increased risk of cardiotoxicity. In this study, a history of prior heart disease, dyslipidemia, low baseline ejection fraction, and the administration of multiple anticancer therapy agents was associated with cardiotoxicity. Proactive management strategies aimed at mitigating the potential cardiotoxic effects of anti-cancer therapies are crucial.

PMID:37533611 | PMC:PMC10393428 | DOI:10.7759/cureus.41287

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PubMed articles on: Cardio-Oncology

The protective effect of thiolutin on doxorubicin-induced H9c2 cardiomyocyte injury

J Toxicol Sci. 2023;48(8):469-479. doi: 10.2131/jts.48.469.

ABSTRACT

The use of doxorubicin (DOX) may contribute to cardiotoxicity, limiting its clinical application. Thiolutin (THL) has been found to exert protective roles in various biological activities, while its effects on DOX-induced cardiotoxicity are still uncovered. Cell counting kit 8 assay was utilized to detect cell viability and half maximal inhibitory concentration of THL in H9c2 cardiomyocytes. The level of lactate dehydrogenase (LDH), adenosine triphosphate (ATP), interleukin (IL)-18 and IL-1 beta (IL-1β) were measured using the corresponding detection kits, and flow cytometry determined cell apoptosis rate. The reactive oxygen species (ROS) accumulation was evaluated by utilizing immunofluorescence or flow cytometry assay. The protein levels of NLR family Pyrin domain 3 (NLRP3), pro-Caspase1, cleaved-Caspase1, gasdermin D (GSDMD) and cleaved-GSDMD (GSDMD-N) in H9c2 cells were detected by immunoblotting assay. The treatment of THL reduced H9c2 cell viability in a gradient-dependent manner. THL treatment reversed the DOX-induced inhibition of proliferation, decrease of ATP, up-regulation of LDH, IL-18, IL-1β and production of ROS, activation of NLRP3 and inflammasome-mediated pyroptosis in H9c2 cells. Additionally, NLRP3 knockdown abolished the effects of THL in DOX-treated H9c2 cells remarkably. This investigation proved that THL notably ameliorated DOX-induced apoptosis, oxidative stress, and pyroptosis in H9c2 cardiomyocytes. Besides, THL effectively inactivated DOX-induced NLRP3 inflammasome in H9c2 cells. These findings revealed a promising drug to assist DOX in its anti-cancer effects and protect the heart of patients.

PMID:37532580 | DOI:10.2131/jts.48.469

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PubMed articles on: Cardio-Oncology

Late-onset cardiotoxicity in patients with HER2-positive metastatic breast cancer receiving trastuzumab-based therapy

J Oncol Pharm Pract. 2023 Aug 1:10781552231193149. doi: 10.1177/10781552231193149. Online ahead of print.

ABSTRACT

PMID:37528623 | DOI:10.1177/10781552231193149

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PubMed articles on: Cancer & VTE/PE

Thrombotic risk of platinum combination chemotherapy with and without immune checkpoint inhibitors for advanced non-small cell lung cancer: a nationwide inpatient database study

Cancer Immunol Immunother. 2023 Aug 4. doi: 10.1007/s00262-023-03508-1. Online ahead of print.

ABSTRACT

CONCLUSION: The addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable.

PMID:37540262 | DOI:10.1007/s00262-023-03508-1

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PubMed articles on: Cancer & VTE/PE

Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress

Res Pract Thromb Haemost. 2023 Jun 21;7(4):100193. doi: 10.1016/j.rpth.2023.100193. eCollection 2023 May.

ABSTRACT

PMID:37538494 | PMC:PMC10394567 | DOI:10.1016/j.rpth.2023.100193