ABSTRACT

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.

METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10<20<1·32·67; NFS: <-1·4550·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.

FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001

INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.

FUNDING: Innovative Medicines Initiative 2.

PMID:37290471 | DOI:10.1016/S2468-1253(23)00141-3

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PubMed articles on: Cardio-Oncology

The Efficacy of Multi-Leaf Collimator in the Reduction of Cardiac and Coronary Artery Dose in Left-Sided Breast Cancer Radiotherapy

Adv Biomed Res. 2023 Apr 25;12:89. doi: 10.4103/abr.abr_342_21. eCollection 2023.

ABSTRACT

BACKGROUND: Multi-leaf collimator (MLC) is one of the efficient and cost-effective methods for protecting sensitive tissues around the target. This study aimed to evaluate the protective effect of MLC on the protection of sensitive organs in patients with left breast cancer.

MATERIALS AND METHODS: This study was performed on computed tomography (CT) scans of 45 patients with left breast cancer. Two treatment plans were completed for each patient. Only the heart and left lung were considered organs at risk in the first treatment plan, and in the second treatment plan, the left anterior descending artery (LAD) was also considered the organ at risk. It was covered as much as possible by the MLC. Dosimetric results of tumor and organ at risk (OARs) were extracted from the dose-volume histogram and compared.

RESULTS: The results showed that more LAD coverage by MLC leads to a significant reduction in the mean dose of OARs (P-value <0.05).5 (volume received the dose of 5 Gy) and V20 for the lung, V10, V25, and V30 for LAD, and V5, V20, V25, and V30 for the heart also decreased significantly (P-value

CONCLUSIONS: In general, better protection of LAD, heart, and lungs can be achieved by maximal shielding organs at risk by MLC in radiation therapy for patients with left breast cancer.

PMID:37288034 | PMC:PMC10241641 | DOI:10.4103/abr.abr_342_21

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PubMed articles on: Cardio-Oncology

Feasibility of Aerobic Exercise Training to Mitigate Cardiotoxicity of Breast Cancer Therapy: A Systematic Review and Meta-Analysis

Clin Breast Cancer. 2023 May 3:S1526-8209(23)00094-0. doi: 10.1016/j.clbc.2023.04.010. Online ahead of print.

ABSTRACT

BACKGROUND: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy.

MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO2peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive.

RESULTS: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO2peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO2peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO2peak.

CONCLUSION: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy.

PMID:37286435 | DOI:10.1016/j.clbc.2023.04.010

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PubMed articles on: Cardio-Oncology

Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design

J Cardiovasc Med (Hagerstown). 2023 Jul 1;24(7):469-474. doi: 10.2459/JCM.0000000000001491.

ABSTRACT

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme.

METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up.

CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines.

CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

PMID:37285278 | DOI:10.2459/JCM.0000000000001491

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PubMed articles on: Cardio-Oncology

Investigation of cardioprotective effect of lercanidipine on doxorubicin-induced cardiotoxicity

Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun 7. doi: 10.1007/s00210-023-02566-7. Online ahead of print.

ABSTRACT

Although doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5 mg/kg LRD), LRD 1 (DOX + 1 mg/kg LRD), and LRD 2 (DOX + 2 mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.

PMID:37284897 | DOI:10.1007/s00210-023-02566-7

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PubMed articles on: Cardio-Oncology

Impact of Volumetric Dosimetry on the Projected Cost of Radiation-Related Late Effects Screening After Childhood Cancer: A Real-World Cohort Analysis

Oncologist. 2023 Jun 7:oyad136. doi: 10.1093/oncolo/oyad136. Online ahead of print.

ABSTRACT

BACKGROUND: Screening guidelines for childhood cancer survivors treated with radiation currently rely on broad anatomic irradiated regions (IR) to determine risk for late effects. However, contemporary radiotherapy techniques use volumetric dosimetry (VD) to define organ-specific exposure, which supports more specific screening recommendations that could be less costly.

PATIENTS AND METHODS: This was a cross-sectional study of 132 patients treated with irradiation at Children's Hospital Los Angeles from 2000 to 2016. For 5 key organs (cochlea, breast, heart, lung, and colon), radiation exposure was determined retrospectively using both IR and VD methods. Under each method, Children's Oncology Group Long-Term Follow-Up Guidelines were used to identify organs flagged for screening and recommended screening tests. Projected screening costs incurred under each method were computed through age 65 using insurance claims data.

RESULTS: Median age at the end of treatment was 10.6 years (range, 1.4-20.4). Brain tumor was the most common diagnosis (45%) and head/brain the most common irradiated region (61%). For all 5 organs, use of VD rather than IR resulted in fewer recommended screening tests. This led to average cumulative estimated savings of $3769 (P = .099), with significant savings in patients with CNS tumors (P = .012). Among patients with savings, average savings were $9620 per patient (P = .016) and significantly more likely for females than males (P = .027).

CONCLUSION: Use of VD to enhance precision of guideline-based screening for radiation-related late effects permits fewer recommended screening tests and generates cost-savings.

PMID:37284853 | DOI:10.1093/oncolo/oyad136

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PubMed articles on: Cardio-Oncology

CAR-T Therapy in Lymphoma Patients With Coexisting Cardiomyopathy or Cardiac Lymphomatous Involvement

JACC Case Rep. 2023 Apr 21;15:101840. doi: 10.1016/j.jaccas.2023.101840. eCollection 2023 Jun 7.

 

ABSTRACT

Background:As a new drug delivery and embolization system, drug-eluted bronchial artery chemoembolization (DEB-BACE) can not only embolize the tumor blood supply artery but also load chemotherapy drugs and slowly release them into the local environment. Bevacizumab (BEV) combined with chemotherapy drugs has attained significant achievements in the first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC). The role of BEV-loaded DEB-BACE combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma (LUAD) is unclear. This study was designed to evaluate the efficacy and safety of bevacizumab-loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy in patients with lung adenocarcinoma. Methods:Nine patients with LUAD who received BEV-loaded CalliSpheres® BACE combined with immunotherapy and targeted therapy from 1 Jan 2021 to Dec 2021 were included in this study. The primary endpoint was the disease control rate (DCR) and the objective response rate (ORR). The secondary endpoints were the overall survival rates (OS) at 6 months and 12 months. The tumor response was evaluated according to the mRECIST standard. Safety was assessed by the occurrences of adverse events and the severity of the adverse events. Results:All patients received CalliSpheres® BACE loaded with BEV (200 mg) in combination with immunotherapy and targeted therapy. A total of nine patients received the BACE procedures 20 times, four of them received a third session of BACE, three underwent a second session of DEB-BACE, and two underwent one cycle of DEB-BACE. Partial response and stable disease were found in seven (77.8%), and two (22.2%) patients, respectively, 1 month after the last multimodal treatment. The ORR at 1, 3, 6, and 12 months was 77.8%, 66.7%, 44.4%, and 33.3%, respectively, while the DCR was 100%, 77.8%, 44.4%, and 33.3%, respectively. The OS rates at 6-and 12-month were 77.8% and 66.7%, respectively. There were no serious adverse events. Conclusion:BEV-loaded CalliSpheres® transcatheter bronchial arterial chemoembolization combined with immunotherapy and targeted therapy is a promising and well-tolerated treatment for patients with lung adenocarcinoma.

PMID:37284322 | PMC:PMC10239861 | DOI:10.3389/fphar.2023.1170344

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PubMed articles on: Cancer & VTE/PE

Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism

Curr Oncol Rep. 2023 Jun 6. doi: 10.1007/s11912-023-01428-y. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).

RECENT FINDINGS: In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.

PMID:37278934 | DOI:10.1007/s11912-023-01428-y

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PubMed articles on: Cancer & VTE/PE

Pulmonary vein stenosis with pulmonary infarction secondary to primary mediastinal seminoma: a case report

Zhonghua Jie He He Hu Xi Za Zhi. 2023 Jun 12;46(6):592-594. doi: 10.3760/cma.j.cn112147-20221026-00847.

ABSTRACT

Pulmonary vein stenosis is a rare condition that is often underdiagnosed and misdiagnosed. The clinical and radiologic manifestations are unspecific such as cough, hemoptysis and pulmonary lesions and are therefore difficult to distinguished with pneumonia and tuberculosis. The present study is a successful case report of pulmonary vein stenosis and pulmonary infraction secondary to mediastinal seminoma. This case suggested that pulmonary vein stenosis should be considered when a mediastinal mass is accompanied by pulmonary opacites that cannot be explained by common causes such as infection.

PMID:37278174 | DOI:10.3760/cma.j.cn112147-20221026-00847

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PubMed articles on: Cancer & VTE/PE

Risk of Venous Thromboembolism in Multiple Myeloma Patients During the Immediate Peri-Autologous Hematopoietic Cell Transplantation Phase

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231177678. doi: 10.1177/10760296231177678.

ABSTRACT

Venous thromboembolism (VTE) is a serious complication commonly experienced in cancer patients. Incidence of VTE typically brings poor prognosis as it represents the second most common cause of mortality in cancer patients just after the malignancy itself. Studies suggest that multiple myeloma (MM) is among the malignancies with further enhanced risk of VTE, especially in patients undergoing autologous hematopoietic cell transplantation (AHCT). However, risk factors and preventative approaches remain poorly explored. Here, we explore the incidence of VTE in MM patients undergoing AHCT, while also highlighting risk factors and preventions that may aid in preventing VTE in patients who are at higher risk.

PMID:37277999 | DOI:10.1177/10760296231177678

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PubMed articles on: Cancer & VTE/PE

Cerebral infarction and in-hospital mortality for patients admitted to hospital with intracardiac thrombus: insights from the National Inpatient Sample

J Thromb Thrombolysis. 2023 Jun 5. doi: 10.1007/s11239-023-02824-8. Online ahead of print.

ABSTRACT

The factors associated with cerebral infarction and mortality in patients hospitalized with intracardiac thrombus are unknown. A retrospective cohort study was undertaken of nationally representative hospital admissions in the National Inpatient Sample with a diagnosis of intracardiac thrombus between 2016 to 2019. Multiple logistic regressions were used to define factors associated with cerebral infarction and in-hospital mortality. There were a total of 175,370 admissions for patients with intracardiac thrombus and 10.1% patients had cerebral infarction (n = 17,675). Intracardiac thrombus represented 4.4% of primary diagnosis for admissions while circulatory conditions (65.4%), infection (5.9%), gastrointestinal conditions (4.4%), respiratory conditions (4.4%) and cancer (2.2%) were the other prevalent primary diagnoses. All-cause mortality was higher for patients with cerebral infarction (8.5% vs 4.8%). The five factors most associated with cerebral infarction were nephrotic syndrome (OR 2.67 95%CI 1.05-6.78), other thrombophilia (OR 2.12 95%CI 1.52-2.95), primary thrombophilia (OR 1.99 95%CI 1.52-2.53), previous stroke (OR 1.61 95%CI 1.47-1.75) and hypertension (OR 1.41 95%CI 1.27-1.56). The strongest independent predictors of death were heparin induced thrombocytopenia (OR 2.45 95%CI 150-4.00), acute venous thromboembolism (OR 2.03 95%CI 1.78-2.33, p < 0.001) acute myocardial infarction (OR 1.95 95%CI 1.72-2.22), arterial thrombosis (OR 1.75 95%CI 1.39-2.20) and cancer (OR 1.57 95%CI 1.36-1.81). Patients with intracardiac thrombus are at risk of cerebral infarction and in-hospital mortality. Nephrotic syndrome, thrombophilia, previous stroke, hypertension, and heparin induced thrombocytopenia were associated with cerebral infarction, while acute venous thromboembolism, acute myocardial infarction, and cancer were predictors of mortality.

PMID:37277607 | DOI:10.1007/s11239-023-02824-8

C

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Cardiotoxicity News

PubMed articles on: Cardio-Oncology

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue

bioRxiv. 2023 May 25:2023.05.24.542198. doi: 10.1101/2023.05.24.542198. Preprint.

ABSTRACT

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart's energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

SIGNIFICANCE STATEMENT: This study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.

PMID:37292714 | PMC:PMC10245950 | DOI:10.1101/2023.05.24.542198

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PubMed articles on: Cardio-Oncology

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Lancet Gastroenterol Hepatol. 2023 Jun 5:S2468-1253(23)00141-3. doi: 10.1016/S2468-1253(23)00141-3. Online ahead of print.

 

ABSTRACT

BACKGROUND: More than half of patients with embolic stroke of undetermined source (ESUS) suffer from recurrent ischaemic stroke, despite the absence of atrial fibrillation (AF) on invasive cardiac monitoring (ICM). This study investigated the predictors and prognosis of recurrent stroke in ESUS without AF on ICM.

METHOD: This prospective study included patients with ESUS at two tertiary hospitals from 2015 to 2021 who underwent comprehensive neurological imaging, transthoracic echocardiography, and inpatient continuous electrographic monitoring for ≥48 hours prior to ICM for definitive exclusion of AF. Recurrent ischaemic stroke, all-cause mortality, and functional outcome by the modified Rankin scale (mRS) at 3 months were evaluated in patients without AF.

RESULTS: Of 185 consecutive patients with ESUS, AF was not detected in 163 (88%) patients (age 62±12 years, 76% men, 25% prior stroke, median time to ICM insertion 26 [7, 123] days), and stroke recurred in 24 (15%) patients. Stroke recurrences were predominantly ESUS (88%), within the first 2 years (75%), and involved a different vascular territory from qualifying ESUS (58%). Pre-existing cancer was the only independent predictor of recurrent stroke (adjusted hazard ratio [AHR] 5.43, 95% CI 1.43-20.64), recurrent ESUS (AHR 5.67, 95% CI 1.15-21.21), and higher mRS score at 3 months (ß 1.27, 95% CI 0.23-2.42). All-cause mortality occurred in 17 (10%) patients. Adjusting for age, cancer, and mRS category (≥3 vs <3),

CONCLUSIONS: Patients with recurrent ESUS are a high-risk subgroup. Studies elucidating optimal diagnostic and treatment strategies in non-AF-related ESUS are urgently required.

PMID:37291002 | DOI:10.1016/j.hlc.2023.05.010

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PubMed articles on: Cancer & VTE/PE

Congenital hepatic hemangioma: an unusual case report of pulmonary hypertension

BMC Pediatr. 2023 Jun 7;23(1):284. doi: 10.1186/s12887-023-04096-w.

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) in newborns is a rare but serious condition that often requires immediate intervention and quick diagnosis of the correct etiology to prevent mortality. Congenital hepatic hemangioma (CHH) is an example of an extrathoracic etiology of PH.

CASE PRESENTATION: Herein, we report the case of a newborn with a giant liver hemangioma, who presented with an early onset of PH and was successfully treated with intra-arterial embolization.

CONCLUSIONS: This case illustrates the importance of suspicion and prompt evaluation of CHH and related systemic arteriovenous shunts among infants with unexplained PH.

PMID:37286954 | DOI:10.1186/s12887-023-04096-w

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PubMed articles on: Cancer & VTE/PE

Dynamic Patterns and Persistence of Anticoagulation Therapy in Patients with Venous Thromboembolism in South Korea: A Nationwide Cohort Study

Thromb Haemost. 2023 Jun 7. doi: 10.1055/a-2107-0815. Online ahead of print.

ABSTRACT

Background Venous thromboembolism (VTE) is associated with increased morbidity, mortality, and healthcare expenditure. However, the comprehensive utilization of anticoagulation therapy in patients with VTE, especially regarding active cancer, in real-world practice remains unclear. Objective To describe the prescription, persistence, and patterns of anticoagulation therapy among patients with VTE stratified according to active cancer. Methods Using Korean nationwide claims data, we identified an incident, treatment-naïve cohort of patients with VTE from 2013 to 2019 and classified them according to the presence/absence of active cancer. We explored the secular trends, treatment patterns (e.g., discontinuation, interruption, and switch), and persistence of anticoagulation therapy. Results There were 48,504 and 7,255 patients without and with active cancer, respectively. NOACs were the most common anticoagulant in both groups (65.1% and 57.9%, respectively). The prescription of non-vitamin K antagonist oral anticoagulants (NOACs) increased steeply over time, regardless of active cancer, whereas parenteral anticoagulants (PACs) plateaued and warfarin decreased sharply. A heterogeneous pattern was observed between the groups without and with active cancer (3-month persistence was 60.8%, 62.9%, 57.2%, and 3.4%, respectively; 6-month persistence was 42.3%, 33.5%, 25.9%, and 1.2% vs. 9.9%). Median duration of continuous anticoagulant therapy for warfarin, NOAC, and PAC were 183, 147, and 3 days in non-active cancer patients, and 121, 117, and 44 days in active cancer patients. Conclusion Our findings suggest that there were substantial differences in persistence, patterns, and patient characteristics of anticoagulant therapy based on index anticoagulant and active cancer.

PMID:37285903 | DOI:10.1055/a-2107-0815

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PubMed articles on: Cancer & VTE/PE

Prognosis of incidental pulmonary embolism vs. symptomatic pulmonary embolism in cancer patients: a single-center retrospective cohort study in China

Thromb J. 2023 Jun 6;21(1):64. doi: 10.1186/s12959-023-00502-6.

ABSTRACT

BACKGROUND: The incidence of incidental pulmonary embolism (IPE) has greatly increased, but its clinical characteristics and outcomes are still controversial. This study aimed to compare the clinical characteristics and outcomes between cancer patients with IPE and patients with symptomatic pulmonary embolism (SPE).

PATIENTS/METHODS: Clinical data of 180 consecutive patients with cancer complicated with pulmonary embolism admitted to Beijing Cancer Hospital from July 2011 to December 2019 were retrospectively collected and analysed. General characteristics, diagnosis time of pulmonary embolism (PE), location of PE, concurrent deep venous thrombosis, anticoagulant treatment, impact of PE on anti-tumor treatment, recurrent venous thromboembolism, rate of bleeding after anticoagulation therapy, survival and risk factors of IPE were compared with SPE.

RESULTS: Of 180 patients, 88 (49%) had IPEs and 92 (51%) had SPEs. Patients with IPE and SPE did not differ in age, sex, tumor type, or tumor stage. Median diagnosis times of IPE and SPE after cancer were 108 (45, 432) days and 90 (7, 383) days, respectively. Compared to SPE, IPE tended to be central (44% versus 26%; P < 0.001), isolated (31.8% versus 0.0%; P < 0.001), and unilateral (67.1% versus 12.8%; P < 0.00). The rate of bleeding after anticoagulation therapy did not differ between IPE and SPE. Patients with IPE had a better prognosis than patients with SPE in terms of 30-, and 90-day mortality, as well as overall survival after diagnosis of PE (median: 314.5 vs. 192.0 days, log-rank P = 0.004) and cancer (median: 630.0 vs. 450.5 days, log-rank P = 0.018). SPE (compared to IPE) was an independent risk factor for poor survival after diagnosis of PE in multivariate analysis (hazard ratio [HR] = 1.564, 95% confidence interval [CI]: 1.008-2.425, p = 0.046).

CONCLUSIONS: IPE accounts for nearly one half of PE cases among Chinese cancer patients. With active anticoagulation treatment, IPE is expected to achieve better survival rates than SPE.

PMID:37280671 | PMC:PMC10245445 | DOI:10.1186/s12959-023-00502-6

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PubMed articles on: Cancer & VTE/PE

Tissue factor (coagulation factor III): a potential double-edge molecule to be targeted and re-targeted toward cancer

Biomark Res. 2023 Jun 6;11(1):60. doi: 10.1186/s40364-023-00504-6.

ABSTRACT

Tissue factor (TF) is a protein that plays a critical role in blood clotting, but recent research has also shown its involvement in cancer development and progression. Herein, we provide an overview of the structure of TF and its involvement in signaling pathways that promote cancer cell proliferation and survival, such as the PI3K/AKT and MAPK pathways. TF overexpression is associated with increased tumor aggressiveness and poor prognosis in various cancers. The review also explores TF's role in promoting cancer cell metastasis, angiogenesis, and venous thromboembolism (VTE). Of note, various TF-targeted therapies, including monoclonal antibodies, small molecule inhibitors, and immunotherapies have been developed, and preclinical and clinical studies demonstrating the efficacy of these therapies in various cancer types are now being evaluated. The potential for re-targeting TF toward cancer cells using TF-conjugated nanoparticles, which have shown promising results in preclinical studies is another intriguing approach in the path of cancer treatment. Although there are still many challenges, TF could possibly be a potential molecule to be used for further cancer therapy as some TF-targeted therapies like Seagen and Genmab's tisotumab vedotin have gained FDA approval for treatment of cervical cancer. Overall, based on the overviewed studies, this review article provides an in-depth overview of the crucial role that TF plays in cancer development and progression, and emphasizes the potential of TF-targeted and re-targeted therapies as potential approaches for the treatment of cancer.

PMID:37280670 | PMC:PMC10242999 | DOI:10.1186/s40364-023-00504-6

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PubMed articles on: Cancer & VTE/PE

Bevacizumab loaded CalliSpheres® bronchial arterial chemoembolization combined with immunotherapy and targeted therapy for advanced lung adenocarcinoma

Front Pharmacol. 2023 May 22;14:1170344. doi: 10.3389/fphar.2023.1170344. eCollection 2023.

 

ABSTRACT

PURPOSE: Breast cancer survivors may experience a variety of disabilities that could potentially compromise their independent functioning. This study aimed to examine their perspectives and experts on their functioning and interpret concepts with the International Classification of Functioning, Disability, and Health (ICF) and the Item-Perspective Classification Framework (IPF).

METHODS: Interpretive descriptive methods were used with in-depth interviewing with 16 breast cancer survivors and 22 experts using a semi-structured interview guide. The interviews were recorded, transcribed, and qualitatively analyzed using thematic analysis. The extracted data were linked to the ICF Core Set for Breast cancer and were interpreted by the IPF.

RESULTS: Four main themes emerged to define the functioning of breast cancer survivors: body functioning, physical functioning, social functioning, and mental functioning. Three other factors were also categorized as modifiers of functioning personal, emotional, and environmental. The 592 extracted meaningful concepts were linked to 38 (47%) categories from the ICF: 16 Body Functions, 14 Activities and Participation, and 8 Environmental Factors. The IPF classified all the extracted concepts, and most rational appraisals fell in the biological (B) domain. The concepts that required emotional appraisal were classified in Psychology (P).

CONCLUSION: Psychological and emotional factors were pivotal in defining functioning in patients with BC.

PMID:37237439 | DOI:10.1080/09638288.2023.2212915

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PubMed articles on: Cancer & VTE/PE

COVID-19 related acute necrotizing encephalopathy presenting in the early postoperative period

Arch Clin Cases. 2023 Jun 7;10(2):78-85. doi: 10.22551/2023.39.1002.10246. eCollection 2023.

ABSTRACT

Besides respiratory and gastrointestinal symptoms, SARS-CoV-2 also has potential neurotropic effects. Acute hemorrhagic necrotizing encephalopathy is a rare complication of Covid-19. This article presents a case of an 81-year-old female, fully vaccinated, who underwent laparoscopic transhiatal esophagectomy due to gastroesophageal junction cancer. In the early postoperative period, the patient developed persistent fever accompanied by acute quadriplegia, impaired consciousness, and no signs of respiratory distress. Imaging with Computed Tomography and Magnetic Resonance revealed multiple bilateral lesions both in gray and white matter, as well as pulmonary embolism. Covid-19 infection was added to the differential diagnosis three weeks later, after other possible causes were excluded. The molecular test obtained at that time for coronavirus was negative. However, the high clinical suspicion index led to Covid-19 antibody testing (IgG and IgA), which confirmed the diagnosis. The patient was treated with corticosteroids with noticeable clinical improvement. She was discharged to a rehabilitation center. Six months later, the patient was in good general condition, although a neurological deficit was still present. This case indicates the significance of a high clinical suspicion index, based on a combination of clinical manifestations and neuroimaging, and the confirmation of the diagnosis with molecular and antibody testing. Constant awareness of a possible Covid-19 infection among hospitalized patients is mandatory.

PMID:37293685 | PMC:PMC10246599 | DOI:10.22551/2023.39.1002.10246

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PubMed articles on: Cancer & VTE/PE

Incidence and risk factors for venous thromboembolism in patients with ovarian cancer during neoadjuvant chemotherapy: a meta-analysis

Am J Cancer Res. 2023 May 15;13(5):2126-2134. eCollection 2023.

ABSTRACT

In recent years, there has been increasing recognition of the relationship between neoadjuvant chemotherapy (NACT) in ovarian cancer and the incidence rate of venous thromboembolism (VTE). Some studies have suggested that NACT may be associated with a high risk of VTE in patients with ovarian cancer. To investigate this, we conducted a systematic review and meta-analysis of the incidence of VTE during NACT and its associated risk factors. We searched PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN) from their inception to September 15, 2022. We calculated the incidence of VTE as the event rate (%) and used logistic regression analysis to investigate pooled VTE rates. Risk factors for VTE were presented as odds ratios (ORs), and pooled ORs was estimated using the inverse variance method. We reported pooled effect estimates with 95% confidence intervals (CIs). Our review included 7 cohort studies with 1244 participants. Meta-analysis of these studies revealed a pooled VTE rate of 13% during NACT (1224 participants; 95% CI, 9%-17%), with body mass index identified as a risk factor for VTE during NACT in 3 of the included studies (633 participants; OR, 1.76; 95% CI, 1.13-2.76).

PMID:37293158 | PMC:PMC10244120

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PubMed articles on: Cancer & VTE/PE

Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomisation analysis

medRxiv. 2023 May 18:2023.05.16.23289792. doi: 10.1101/2023.05.16.23289792. Preprint.

ABSTRACT

Background:People with cancer experience high rates of venous thromboembolism (VTE). Additionally, risk of subsequent cancer is increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer. Methods:We used data from large genome-wide association study meta-analyses to perform bi-directional Mendelian randomisation analyses to estimate causal associations between genetically-proxied lifetime risk of VTE and risk of 18 different cancers. Results:We found no conclusive evidence that genetically-proxied lifetime risk of VTE was causally associated with an increased incidence of cancer, or vice-versa. We observed an association between VTE and pancreatic cancer risk (odds ratio for pancreatic cancer 1.23 (95% confidence interval 1.08 - 1.40) per log-odds increase in risk of VTE, P =0.002). However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence from Mendelian randomisation to suggest a causal relationship. Conclusions:These findings do not support the hypothesis that genetically-proxied lifetime risk of VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesise evidence for these mechanisms.

KEY MESSAGES: 1) There is strong observational evidence that active cancer is associated with venous thromboembolism.2) It is currently unknown whether venous thromboembolism is a risk factor for cancer.3) We applied a bi-directional Mendelian randomisation framework to appraise the causal relationships between genetically-proxied risk of venous thromboembolism and 18 different cancers.4) Overall, there was no clear evidence from Mendelian randomisation that lifetime-elevated risk of venous thromboembolism is causally associated with an increased risk of cancer, or visa versa.

PMID:37292802 | PMC:PMC10246038 | DOI:10.1101/2023.05.16.23289792

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PubMed articles on: Cancer & VTE/PE

Stroke Recurrence in Embolic Stroke of Undetermined Source Without Atrial Fibrillation on Invasive Cardiac Monitoring

Heart Lung Circ. 2023 Jun 6:S1443-9506(23)00514-0. doi: 10.1016/j.hlc.2023.05.010. Online ahead of print.

 

ABSTRACT

Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter-Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of -17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m2, and the right ventricular free wall longitudinal strain (LS) was impaired in some patients but not in all. There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group (32% vs. 62.5%, p= 0.04). In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy (-19.1 ± 3.1% vs. -16.5 ± 5.1%, p= 0.04). DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter-Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment.

PMID:37240533 | PMC:PMC10219019 | DOI:10.3390/jcm12103427

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PubMed articles on: Cardio-Oncology

Primary Cardiac Schwannoma: A Meta-Analysis of Individual Case Reports

J Clin Med. 2023 May 9;12(10):3356. doi: 10.3390/jcm12103356.

ABSTRACT

Primary cardiac schwannoma (PCS) is a neurogenic tumor that arises from Schwann cells. Malignant schwannoma (MSh) is an aggressive cancer comprising 2% of all sarcomas. Information on the proper management of these tumors is limited. Four databases were searched for case reports/series of PCS. The primary outcome was overall survival (OS). Secondary outcomes included therapeutic strategies and the corresponding outcomes. Among 439 potentially eligible studies, 53 met the inclusion criteria. The patients included had 43.72 ± 17.76 years and 28.3% were males. Over 50% of patients had MSh, with 9.4% also demonstrating metastases. Schwannoma commonly occurs in the atria (66.0%). Left-sided PCS were more common than right-sided ones. Surgery was performed in almost 90% of the cases; chemotherapy and radiotherapy were used in 16.9% and 15.1% of cases, respectively. Compared to benign cases, MSh occurs at a younger age and is commonly located on the left side. OS of the entire cohort at 1 and 3 years were 60.7%, and 54.0%, respectively. Females and males OS were similar up to 2 years follow-up. Surgery was associated with higher OS (p < 0.01). Surgery is the primary treatment option for both benign and malignant cases and was the only factor associated with a relative improvement in survival.

PMID:37240461 | PMC:PMC10219427 | DOI:10.3390/jcm12103356

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PubMed articles on: Cardio-Oncology

Inflammasome Activity in the Skeletal Muscle and Heart of Rodent Models for Duchenne Muscular Dystrophy

Int J Mol Sci. 2023 May 9;24(10):8497. doi: 10.3390/ijms24108497.

ABSTRACT

Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that leads to difficulty moving and premature death, mainly from heart failure. Glucocorticoids are applied in the management of the disease, supporting the hypothesis that inflammation may be driver as well as target. However, the inflammatory mechanisms during progression of cardiac and skeletal muscle dysfunction are still not well characterized. Our objective was to characterize the inflammasomes in myocardial and skeletal muscle in rodent models of DMD. Gastrocnemius and heart samples were collected from mdxmice and DMDmdx rats (3 and 9-10 months). Inflammasome sensors and effectors were assessed by immunoblotting. Histology was used to assess leukocyte infiltration and fibrosis. In gastrocnemius, a tendency towards elevation of gasdermin D irrespective of the age of the animal was observed. The adaptor protein was elevated in the mdxmouse skeletal muscle and heart. Increased cleavage of the cytokines was observed in the skeletal muscle of the DMDmdx rats. Sensor or cytokine expression was not changed in the tissue samples of the mdxmice. In conclusion, inflammatory responses are distinct between the skeletal muscle and heart in relevant models of DMD. Inflammation tends to decrease over time, supporting the clinical observations that the efficacy of anti-inflammatory therapies might be more prominent in the early stage.

PMID:37239853 | PMC:PMC10218525 | DOI:10.3390/ijms24108497

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PubMed articles on: Cardio-Oncology

Radiation Therapy-Induced Cardiac Toxicity

2023 May 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–.

ABSTRACT

Radiation therapy is an important component in the treatment of cancer. It may play a role as an adjuvant, neoadjuvant, palliative, or definitive therapy, with or without concurrent chemotherapy. Radiation is most commonly delivered as a local/regional treatment by an external beam consisting of photons, electrons, protons, or heavy particles but may also be delivered via brachytherapy (where a sealed radiation source is placed adjacent to the target) or systemically via unsealed sources. The side effects of radiation therapy are a function of the tissues included in the radiation field. Treatment of diseases within the thoracic region, such as Hodgkin lymphoma, lung, and breast cancer, carries the risk of radiation-induced cardiovascular toxicity (RICT).

Side effects of therapeutic radiation to the heart and coronary vessels include pericarditis, coronary artery disease (CAD), arrhythmias, cardiomyopathy, valvular dysfunction, and heart failure. Pericarditis and pericardial effusions are potential short-term toxicities that may occur during or within the weeks following treatment. Long-term side effects may present in the months to years after radiation therapy, possibly as late as 20 years or more post-treatment. Late toxicities include CAD, valvular heart disease, and heart failure.

Major risk factors that increase the likelihood of RICT include higher radiation doses, adjuvant treatment with cardiotoxic chemotherapy, irradiation of the left side of the thorax, and the presence of pre-existing cardiovascular disease. Studies have correlated the mean dose of radiation received by various heart sub-structures to the incidence of major adverse cardiac events (MACE), such as hospitalization for heart failure, myocardial infarction, and even cardiac death. Given the importance of radiation therapy in treating cancer and the high prevalence of cardiovascular disease in Western populations, numerous preventive measures have been suggested and used in clinical practice, such as dose limitation, proton and particle therapy, conformal radiation therapy, and deep-inspiration breath-hold technique.

PMID:32119340 | Bookshelf:NBK554453

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PubMed articles on: Cardio-Oncology

Characterization of functioning in breast cancer survivors: an interpretive descriptive analysis study based on the International Classification of Functioning, Disability, and Health (ICF) and the Item-Perspective Classification Framework

Disabil Rehabil. 2023 May 26:1-19. doi: 10.1080/09638288.2023.2212915. Online ahead of print.

 

ABSTRACT

INTRODUCTION: Myocardial bridge is a morphological anomaly of the heart characterised by the presence of a myocardial segment above a coronary artery, which results in a higher risk of cardiovascular events. In patients with prostate cancer treated with androgen receptor-targeted agents, a higher risk of cardiotoxicity was observed.

CASE REPORT: An 88 years old man with metastatic castration-resistant prostate cancer in treatment with enzalutamide, denosumab, and triptorelin presented to our attention complaining dyspnoea and angina pectoris.

MANAGEMENT AND OUTCOME: Blood examinations revealed normal Troponin I levels. Transthoracic echocardiography revealed no signs of acute myocardial ischaemia. The treadmill stress test revealed S-T tract under levelling in V4-V6 with a very slow resolution. Coronary angiography identified a myocardial bridge in the medium tract of the interventricular anterior artery. Due to these findings, ranolazine and simvastatin were started and, after multidisciplinary assessment, we decided to continue the treatment with enzalutamide. At the first follow-up visit echocardiography found out the cardiological reports stability and no therapy changes were performed. During follow-up visit cardiological revaluation showed reports stability and no therapy changes were performed.

DISCUSSION: Due to the high prevalence of prostate cancer in elderly patients at high cardiovascular risk and the increasing use of androgen receptor-targeted agent, a multidisciplinary approach is highly recommended to weigh survival benefits on toxicities. This case report may support the use of androgen receptor-targeted agent in elderly patients with controlled cardiovascular diseases, a population that is often excluded from randomised trials.

PMID:37282514 | DOI:10.1177/10781552231180599

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PubMed articles on: Cardio-Oncology

p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

Nutrients. 2023 May 10;15(10):2259. doi: 10.3390/nu15102259.

ABSTRACT

Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.

PMID:37242146 | PMC:PMC10222243 | DOI:10.3390/nu15102259

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PubMed articles on: Cardio-Oncology

Prognostic Impact of Global Longitudinal Strain and NT-proBNP on Early Development of Cardiotoxicity in Breast Cancer Patients Treated with Anthracycline-Based Chemotherapy

Medicina (Kaunas). 2023 May 15;59(5):953. doi: 10.3390/medicina59050953.

ABSTRACT

Background. The most important anthracycline side effect is cardiotoxicity, resulting in congestive heart failure (HF). Early detection of cardiac dysfunction and appropriate treatment can improve outcomes and reduce the progression of HF. The aim of our study was to evaluate changes in clinical data, echocardiographic parameters, and NT-proBNP, as well as their associations with early anthracycline-induced cardiotoxicity (AIC) in patients treated with anthracycline-based chemotherapy. Methods and Materials. Patients with breast cancer were prospectively assessed with echocardiography, as well as NT-proBNP testing at baseline, (T0), after two cycles (T1) and four cycles (T2) of chemotherapy. AIC was defined as a new decrease in the LVEF of 10 percentage points, to a value below the lower limit of normal. Results.We evaluated 85 patients aged 54.5 ± 9.3 years. After a cumulative dose of 237.9 mg/m2 of doxorubicin, 22 patients (25.9%) met the criteria of AIC after chemotherapy. Patients who subsequently progressed to cardiotoxicity had demonstrated a significantly larger impairment in LV systolic function compared to those who did not develop cardiotoxicity (LVEF: 54.0 ± 1.6% vs. 57.1 ± 1.4% at T1, p< 0.001, and 49.9 ± 2.1% vs. 55.8 ± 1.6% at T2, p< 0.001; GLS: -17.8 ± 0.4% vs. -19.3 ± 0.9% at T1, p< 0.001, and -16.5 ± 11.1% vs. -18.5 ± 0.9% at T2, p< 0.001, respectively). The levels of NT-proBNP increased significantly from 94.8 ± 43.8 ng/L to 154.1 ± 75.6 ng/L, p< 0.001. A relative decrease in GLS ≤ -18.0% (sensitivity: 72.73%; specificity: 92.06%; AUC, 0.94; p< 0.001) and a relative increase in NT-proBNP > 125 ng/L (sensitivity: 90.0%; specificity: 56.9%; AUC, 0.78; p< 0.001) from baseline to T1 predicted subsequent LV cardiotoxicity at T2. Conclusions. Decrease in GLS and elevation in NT-proBNP were significantly associated with AIC, and these could potentially be used to predict subsequent declines in LVEF with anthracycline-based chemotherapy.

PMID:37241185 | PMC:PMC10224214 | DOI:10.3390/medicina59050953

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PubMed articles on: Cardio-Oncology

Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats

J Pers Med. 2023 Apr 27;13(5):750. doi: 10.3390/jpm13050750.

ABSTRACT

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone's cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.

PMID:37240920 | PMC:PMC10221553 | DOI:10.3390/jpm13050750

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PubMed articles on: Cardio-Oncology

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination

J Clin Med. 2023 May 12;12(10):3427. doi: 10.3390/jcm12103427.

 

ABSTRACT

BACKGROUND: Screening guidelines for childhood cancer survivors treated with radiation currently rely on broad anatomic irradiated regions (IR) to determine risk for late effects. However, contemporary radiotherapy techniques use volumetric dosimetry (VD) to define organ-specific exposure, which supports more specific screening recommendations that could be less costly.

PATIENTS AND METHODS: This was a cross-sectional study of 132 patients treated with irradiation at Children's Hospital Los Angeles from 2000 to 2016. For 5 key organs (cochlea, breast, heart, lung, and colon), radiation exposure was determined retrospectively using both IR and VD methods. Under each method, Children's Oncology Group Long-Term Follow-Up Guidelines were used to identify organs flagged for screening and recommended screening tests. Projected screening costs incurred under each method were computed through age 65 using insurance claims data.

RESULTS: Median age at the end of treatment was 10.6 years (range, 1.4-20.4). Brain tumor was the most common diagnosis (45%) and head/brain the most common irradiated region (61%). For all 5 organs, use of VD rather than IR resulted in fewer recommended screening tests. This led to average cumulative estimated savings of $3769 (P = .099), with significant savings in patients with CNS tumors (P = .012). Among patients with savings, average savings were $9620 per patient (P = .016) and significantly more likely for females than males (P = .027).

CONCLUSION: Use of VD to enhance precision of guideline-based screening for radiation-related late effects permits fewer recommended screening tests and generates cost-savings.

PMID:37284853 | DOI:10.1093/oncolo/oyad136

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PubMed articles on: Cardio-Oncology

CAR-T Therapy in Lymphoma Patients With Coexisting Cardiomyopathy or Cardiac Lymphomatous Involvement

JACC Case Rep. 2023 Apr 21;15:101840. doi: 10.1016/j.jaccas.2023.101840. eCollection 2023 Jun 7.

ABSTRACT

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of aggressive hematologic malignancies. However, its role in patients with lymphoma and cardiac metastasis or cardiomyopathy remains undefined due to potentially life-threatening complications such as ventricular rupture, cardiac tamponade, and circulatory failure. We present a case series of patients with lymphoma and cardiomyopathy or cardiac metastasis managed with chimeric antigen receptor T-cell therapy. (Level of Difficulty: Advanced.).

PMID:37283829 | PMC:PMC10240233 | DOI:10.1016/j.jaccas.2023.101840

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PubMed articles on: Cardio-Oncology

Informatics tools to implement late cardiovascular risk prediction modeling for population management of high-risk childhood cancer survivors

Pediatr Blood Cancer. 2023 Jun 7:e30474. doi: 10.1002/pbc.30474. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical informatics tools to integrate data from multiple sources have the potential to catalyze population health management of childhood cancer survivors at high risk for late heart failure through the implementation of previously validated risk calculators.

METHODS: The Oklahoma cohort (n = 365) harnessed data elements from Passport for Care (PFC), and the Duke cohort (n = 274) employed informatics methods to automatically extract chemotherapy exposures from electronic health record (EHR) data for survivors 18 years old and younger at diagnosis. The Childhood Cancer Survivor Study (CCSS) late cardiovascular risk calculator was implemented, and risk groups for heart failure were compared to the Children's Oncology Group (COG) and the International Guidelines Harmonization Group (IGHG) recommendations. Analysis within the Oklahoma cohort assessed disparities in guideline-adherent care.

RESULTS: The Oklahoma and Duke cohorts both observed good overall concordance between the CCSS and COG risk groups for late heart failure, with weighted kappa statistics of .70 and .75, respectively. Low-risk groups showed excellent concordance (kappa > .9). Moderate and high-risk groups showed moderate concordance (kappa .44-.60). In the Oklahoma cohort, adolescents at diagnosis were significantly less likely to receive guideline-adherent echocardiogram surveillance compared with survivors younger than 13 years old at diagnosis (odds ratio [OD] 0.22; 95% confidence interval [CI]: 0.10-0.49).

CONCLUSIONS: Clinical informatics tools represent a feasible approach to leverage discrete treatment-related data elements from PFC or the EHR to successfully implement previously validated late cardiovascular risk prediction models on a population health level. Concordance of CCSS, COG, and IGHG risk groups using real-world data informs current guidelines and identifies inequities in guideline-adherent care.

PMID:37283294 | DOI:10.1002/pbc.30474

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PubMed articles on: Cardio-Oncology

Myocardial bridge in a patient with castration-resistant metastatic prostate cancer treated with enzalutamide

J Oncol Pharm Pract. 2023 Jun 6:10781552231180599. doi: 10.1177/10781552231180599. Online ahead of print.

 

ABSTRACT

BACKGROUND: Multi-leaf collimator (MLC) is one of the efficient and cost-effective methods for protecting sensitive tissues around the target. This study aimed to evaluate the protective effect of MLC on the protection of sensitive organs in patients with left breast cancer.

MATERIALS AND METHODS: This study was performed on computed tomography (CT) scans of 45 patients with left breast cancer. Two treatment plans were completed for each patient. Only the heart and left lung were considered organs at risk in the first treatment plan, and in the second treatment plan, the left anterior descending artery (LAD) was also considered the organ at risk. It was covered as much as possible by the MLC. Dosimetric results of tumor and organ at risk (OARs) were extracted from the dose-volume histogram and compared.

RESULTS: The results showed that more LAD coverage by MLC leads to a significant reduction in the mean dose of OARs (P-value <0.05).5 (volume received the dose of 5 Gy) and V20 for the lung, V10, V25, and V30 for LAD, and V5, V20, V25, and V30 for the heart also decreased significantly (P-value

CONCLUSIONS: In general, better protection of LAD, heart, and lungs can be achieved by maximal shielding organs at risk by MLC in radiation therapy for patients with left breast cancer.

PMID:37288034 | PMC:PMC10241641 | DOI:10.4103/abr.abr_342_21

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PubMed articles on: Cardio-Oncology

Feasibility of Aerobic Exercise Training to Mitigate Cardiotoxicity of Breast Cancer Therapy: A Systematic Review and Meta-Analysis

Clin Breast Cancer. 2023 May 3:S1526-8209(23)00094-0. doi: 10.1016/j.clbc.2023.04.010. Online ahead of print.

ABSTRACT

BACKGROUND: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy.

MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO2peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive.

RESULTS: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO2peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO2peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO2peak.

CONCLUSION: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy.

PMID:37286435 | DOI:10.1016/j.clbc.2023.04.010

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Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design

J Cardiovasc Med (Hagerstown). 2023 Jul 1;24(7):469-474. doi: 10.2459/JCM.0000000000001491.

ABSTRACT

AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme.

METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up.

CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines.

CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).

PMID:37285278 | DOI:10.2459/JCM.0000000000001491

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PubMed articles on: Cardio-Oncology

Investigation of cardioprotective effect of lercanidipine on doxorubicin-induced cardiotoxicity

Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun 7. doi: 10.1007/s00210-023-02566-7. Online ahead of print.

ABSTRACT

Although doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5 mg/kg LRD), LRD 1 (DOX + 1 mg/kg LRD), and LRD 2 (DOX + 2 mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.

PMID:37284897 | DOI:10.1007/s00210-023-02566-7

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PubMed articles on: Cardio-Oncology

Impact of Volumetric Dosimetry on the Projected Cost of Radiation-Related Late Effects Screening After Childhood Cancer: A Real-World Cohort Analysis

Oncologist. 2023 Jun 7:oyad136. doi: 10.1093/oncolo/oyad136. Online ahead of print.

 

ABSTRACT

Pulmonary arteriovenous malformations (PAVMs), particularly where feeding artery/arteries to PAVMs ≥ 3 mm can be treated with embolization. The treatment for hypoxemia resulting from multiple small or diffuse PAVMs remains unclear.We report a girl aged 5 years and 10 months presented with cyanosis and decreased activity after exercise (83-85% of pulse oxygen saturation, SpO2). She had 1 skin lesion on her face and 1 suspected hemangioma on her left upper extremity at birth and that gradually disappeared spontaneously. Physical examination revealed clubbed fingers, and abundant vascular networks on her back. Contrast-enhanced lung CT (slice thickness:1.25 mm) with vascular three-dimensional reconstruction and abdominal CT revealed increased bronchovascular bundles, increased diameter of the pulmonary artery and ascending aorta, and intrahepatic portosystemic venous shunts due to patent ductus venosus. Echocardiography revealed increased diameter of aortic and pulmonary artery. Transthoracic contrast echocardiography was highly positive (bubble appearing in the left ventricle after 5 cardiac cycles). Abdominal doppler ultrasound revealed hepatic-portal venous shunt. Magnetic resonance imaging, artery and vein of the brain revealed multiple malformations of venous sinuses. The patient received sirolimus for 2 years and 4 months. Her condition improved significantly. SpO2 gradually increased to 98%. Her finger clubbing gradually normalized.Our report implicates sirolimus might be a potential treatment option in persistent hypoxemia mainly due to intrapulmonary right-to-left shunt even small multiple or diffusive PAVMs in pediatric patients with multiple cutaneous and visceral vascular anomalies.

PMID:37226169 | PMC:PMC10206540 | DOI:10.1186/s13023-023-02732-3

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PubMed articles on: Cancer & VTE/PE

Safety of catheter ablation for atrial fibrillation in patients with cancer: a nationwide cohort study

Postgrad Med. 2023 May 29:1-7. doi: 10.1080/00325481.2023.2218188. Online ahead of print.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with cancer, especially breast, gastrointestinal, respiratory, urinary tract, and hematological malignancies. Catheter ablation (CA) is a well-established, safe treatment option in healthy patients; however, literature regarding safety of CA for AF in patients with cancer is limited and confined to single centers.

OBJECTIVE: We aimed to assess the outcomes and peri-procedural safety of CA for AF in patients with certain types of cancer.

METHODS: The NIS database was queried between 2016 and 2019 to identify primary hospitalizations with AF and CA. Hospitalizations with secondary diagnosis of atrial flutter and other arrhythmias were excluded. Propensity score matching was used to balance the covariates between cancer and non-cancer groups. Logistic regression was used to analyze the association.

RESULTS: During this period, 47,765 CA procedures were identified, out of which 750 (1.6%) hospitalizations had a diagnosis of cancer. After propensity matching, hospitalizations with cancer diagnosis had higher in-hospital mortality (OR 3.0, 95% CI 1.5-6.2, p= 0.001), lower home discharge rates (OR 0.7, 95% CI 0.6-0.9, p< 0.001) as well as other complications such as major bleeding (OR 1.8, 95% CI 1.3-2.7, p= 0.001) and pulmonary embolism (OR 6.1, 95% CI 2.1-17.8, p< 0.001) but not associated with any major cardiac complications (OR 1.2, 95% CI 0.7-1.8, p= 0.53).

CONCLUSION: Patients with cancer who underwent CA for AF had significantly higher odds of in-hospital mortality, major bleeding, and pulmonary embolism. Further larger prospective observational studies are needed to validate these findings.

PMID:37224412 | DOI:10.1080/00325481.2023.2218188

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PubMed articles on: Cancer & VTE/PE

A new anticoagulant strategy: the factor XI inhibitors

G Ital Cardiol (Rome). 2023 Jun;24(6):0-454. doi: 10.1714/4041.40204.

ABSTRACT

In the last 10 years the introduction of the direct oral anticoagulants (DOACs) has revolutionized the anticoagulant treatment, one of the cornerstones of the therapy for cardiovascular diseases. Thanks to their efficacy at least not inferior compared to vitamin K antagonists and their better safety profile, particularly with regard to intracranial bleeding, DOACs are now the first choice for the prevention of cardioembolism in patients with non-valvular atrial fibrillation and for the treatment of venous thromboembolism (VTE). Other areas of clinical use for DOACs include the prevention of VTE in orthopedic and oncology surgery and in outpatient cancer patients treated with anticancer therapy, or the use of low-dose in association with aspirin in patients with coronary or peripheral artery disease.An increased risk of gastrointestinal bleeding has been reported for some DOACs. In addition, DOACs have also experienced some failures including stroke prevention in patients with mechanical prosthetic valves or rheumatic diseases and VTE therapy in patients with antiphospholipid antibody syndrome. Also, no data are available on DOACs in some particular areas, including severe renal impairment and thrombocytopenia.In recent years, the clinical use of factor XI and factor XII inhibitors has been proposed. Currently, factor XI inhibitors have more clinical data than factor XII inhibitors. This article will report the rationale for the clinical use and the main evidences currently available on factor XI inhibitors.

PMID:37227204 | DOI:10.1714/4041.40204

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PubMed articles on: Cancer & VTE/PE

Risk factors for pulmonary cement embolism after percutaneous vertebroplasty and radiofrequency ablation for spinal metastases

Front Oncol. 2023 May 5;13:1129658. doi: 10.3389/fonc.2023.1129658. eCollection 2023.

ABSTRACT

OBJECTIVE: Pulmonary cement embolism is a rare but underestimated complication of vertebroplasty due to the relative lack of study and examination. This study aims to investigate the incidence of pulmonary cement embolism in patients with spinal metastasis who undergo PVP with RFA and to analyze the relative risk factors.

METHODS: A total of 47 patients were retrospectively included and classified into pulmonary cement embolism (PCE) group and non-pulmonary cement embolism (NPCE) group by comparing pre- and postoperative pulmonary CT scan images. The demographic and clinical information of the patients was obtained. Demographic data in the two groups were compared using the chi-square test for qualitative data and the unpaired t test for quantitative data. Multiple logistic regression analysis was used to identify risk factors related to pulmonary cement embolism.

RESULTS: Pulmonary cement embolism was detected in 11 patients (23.4%), and all patients were asymptomatic and followed up regularly. Risk analysis showed that multiple segments (≥3, p=0.022), thoracic vertebrae (p=0.0008), and unipedicular puncture approach (p=0.0059) were risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra (p<0.0001).

CONCLUSION: The number of involved vertebrae, lesion location, and puncture approach are independent risk factors for pulmonary cement embolism. There was a high incidence of pulmonary cement embolism if bone cement leaked into the para vertebral venous plexus in the thoracic vertebra. Surgeons should consider these factors when formulating therapeutic strategies.

PMID:37213292 | PMC:PMC10196379 | DOI:10.3389/fonc.2023.1129658

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism secondary to hospitalization for COVID-19: patient management and long-term outcomes

C

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PubMed articles on: Cardio-Oncology

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue

bioRxiv. 2023 May 25:2023.05.24.542198. doi: 10.1101/2023.05.24.542198. Preprint.

ABSTRACT

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart's energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

SIGNIFICANCE STATEMENT: This study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.

PMID:37292714 | PMC:PMC10245950 | DOI:10.1101/2023.05.24.542198

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PubMed articles on: Cardio-Oncology

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Lancet Gastroenterol Hepatol. 2023 Jun 5:S2468-1253(23)00141-3. doi: 10.1016/S2468-1253(23)00141-3. Online ahead of print.

ABSTRACT

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.

METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10<20<1·32·67; NFS: <-1·4550·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.

FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001

INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.

FUNDING: Innovative Medicines Initiative 2.

PMID:37290471 | DOI:10.1016/S2468-1253(23)00141-3

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PubMed articles on: Cardio-Oncology

The Efficacy of Multi-Leaf Collimator in the Reduction of Cardiac and Coronary Artery Dose in Left-Sided Breast Cancer Radiotherapy

Adv Biomed Res. 2023 Apr 25;12:89. doi: 10.4103/abr.abr_342_21. eCollection 2023.

 

ABSTRACT

Lung cancer can be revealed by thromboembolic complications. Its association with pregnancy is becoming more frequent due to the increasing number of smoking women. The care of a pregnant woman with cancer is quite delicate because it requires finding a balance between the treatment of the mother and the potential foetal risk.

CASE PRESENTATION: The authors report the case of a 38-year-old patient, with a twin pregnancy of 16 weeks, complicated by proximal and distal peripheral venous thrombosis of the left lower limb under low molecular weight heparin therapy at a curative dose. A week later, the patient presented to the emergency room with respiratory distress associated with chest pain and low-abundance metrorrhagia. The obstetrical ultrasound performed confirmed the vitality of only one of the two foetuses. The transthoracic ultrasound objectified a very abundant pericardial effusion producing a tamponade, which was drained percutaneously and whose cytological study revealed a liquid rich in tumour cells. After the unfortunate death of the second twin and an endouterine evacuation, a chest computed tomography angiogram demonstrated a bilateral proximal pulmonary embolism associated with bilateral moderate pulmonary effusion as well as multiple thrombosis and secondary aspect liver lesions with a suspicious parenchymal lymph node of the upper lung lobe. A liver biopsy concluded to a secondary hepatic localization of a moderately differentiated adenocarcinoma whose immunohistochemical complement revealed a pulmonary origin. A multidisciplinary consultation meeting leaned towards treatment with neoadjuvant chemotherapy. The patient died 7 months later.

DISCUSSION: Venous thromboembolic disease is more common in pregnant women. Delayed diagnosis is common in these cases, resulting in a high rate of locally advanced or metastatic disease. Since the treatment of pregnancy-associated cancer does not rely on a standardized approach, the decision on how to proceed must be made by a multidisciplinary team.

CONCLUSION: The cornerstone of management remains to find the balance between treating the mother as well as possible while preventing the foetus from the possible harm of cytotoxic drugs frequently used to treat lung cancer. Because of the delayed diagnosis, the maternal prognosis often remains poor.

PMID:37228933 | PMC:PMC10205297 | DOI:10.1097/MS9.0000000000000516

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PubMed articles on: Cancer & VTE/PE

Ten-Year Multicenter Retrospective Study Utilizing Machine Learning Algorithms to Identify Patients at High Risk of Venous Thromboembolism After Radical Gastrectomy

Int J Gen Med. 2023 May 18;16:1909-1925. doi: 10.2147/IJGM.S408770. eCollection 2023.

ABSTRACT

PURPOSE: This study aims to construct a machine learning model that can recognize preoperative, intraoperative, and postoperative high-risk indicators and predict the onset of venous thromboembolism (VTE) in patients.

PATIENTS AND METHODS: A total of 1239 patients diagnosed with gastric cancer were enrolled in this retrospective study, among whom 107 patients developed VTE after surgery. We collected 42 characteristic variables of gastric cancer patients from the database of Wuxi People's Hospital and Wuxi Second People's Hospital between 2010 and 2020, including patients' demographic characteristics, chronic medical history, laboratory test characteristics, surgical information, and patients' postoperative conditions. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor (KNN), were employed to develop predictive models. We also utilized Shapley additive explanation (SHAP) for model interpretation and evaluated the models using k-fold cross-validation, receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and external validation metrics.

RESULTS: The XGBoost algorithm demonstrated superior performance compared to the other three prediction models. The area under the curve (AUC) value for XGBoost was 0.989 in the training set and 0.912 in the validation set, indicating high prediction accuracy. Furthermore, the AUC value of the external validation set was 0.85, signifying good extrapolation of the XGBoost prediction model. The results of SHAP analysis revealed that several factors, including higher body mass index (BMI), history of adjuvant radiotherapy and chemotherapy, T-stage of the tumor, lymph node metastasis, central venous catheter use, high intraoperative bleeding, and long operative time, were significantly associated with postoperative VTE.

CONCLUSION: The machine learning algorithm XGBoost derived from this study enables the development of a predictive model for postoperative VTE in patients after radical gastrectomy, thereby assisting clinicians in making informed clinical decisions.

PMID:37228741 | PMC:PMC10202705 | DOI:10.2147/IJGM.S408770

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PubMed articles on: Cancer & VTE/PE

Ambulatory cancer patients: who should definitely receive antithrombotic prophylaxis and who should never receive

Intern Emerg Med. 2023 May 25. doi: 10.1007/s11739-023-03306-8. Online ahead of print.

ABSTRACT

Up to 15-20% of cancer patients experience one or more episodes of venous thromboembolism during cancer disease. Approximately 80% of all cancer-associated venous thromboembolic events occur in non-hospitalized patients. Routine thromboprophylaxis for outpatients with cancer who start new anticancer treatment is currently not recommended by the international guidelines due to the high heterogeneity of these patients in terms of VTE or bleeding risks, the difficulties in selecting patients at high risk, and the uncertainty of duration of prophylaxis. Although the international guidelines endorsed the Khorana score for estimating the thrombotic risk in ambulatory cancer patients, the discriminatory performance of this score is not completely convincing and varies according to the cancer type. Consequently, a minority of ambulatory patients with cancer receive an accurate screening for primary prophylaxis of VTE. The aim of this review is to provide support to physicians in identifying those ambulatory patients with cancer for whom thromboprophylaxis should be prescribed and those that should not be candidate to thromboprophylaxis. In absence of high bleeding risk, primary thromboprophylaxis should be recommended in patients with pancreatic cancer and, probably, in patients with lung cancer harboring ALK/ROS1 translocations. Patients with upper gastrointestinal cancers are at high risk of VTE, but a careful assessment of bleeding risk should be made before deciding on antithrombotic prophylaxis. Primary prevention of VTE is not recommended in cancer patients at increased risk of bleeding as patients with brain cancer, with moderate-to-severe thrombocytopenia or severe renal impairment.

PMID:37227679 | DOI:10.1007/s11739-023-03306-8

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PubMed articles on: Cancer & VTE/PE

Application of Machine Learning to the Prediction of Cancer-Associated Venous Thromboembolism

Res Sq. 2023 May 8:rs.3.rs-2870367. doi: 10.21203/rs.3.rs-2870367/v1. Preprint.

ABSTRACT

Venous thromboembolism (VTE) is a common and impactful complication of cancer. Several clinical prediction rules have been devised to estimate the risk of a thrombotic event in this patient population, however they are associated with limitations. We aimed to develop a predictive model of cancer-associated VTE using machine learning as a means to better integrate all available data, improve prediction accuracy and allow applicability regardless of timing for systemic therapy administration. A retrospective cohort was used to fit and validate the models, consisting of adult patients who had next generation sequencing performed on their solid tumor for the years 2014 to 2019. A deep learning survival model limited to demographic, cancer-specific, laboratory and pharmacological predictors was selected based on results from training data for 23,800 individuals and was evaluated on an internal validation set including 5,951 individuals, yielding a time-dependent concordance index of 0.72 (95% CI = 0.70-0.74) for the first 6 months of observation. Adapted models also performed well overall compared to the Khorana Score (KS) in two external cohorts of individuals starting systemic therapy; in an external validation set of 1,250 patients, the C-index was 0.71 (95% CI = 0.65-0.77) for the deep learning model vs 0.66 (95% CI = 0.59-0.72) for the KS and in a smaller external cohort of 358 patients the C-index was 0.59 (95% CI = 0.50-0.69) for the deep learning model vs 0.56 (95% CI = 0.48-0.64) for the KS. The proportions of patients accurately reclassified by the deep learning model were 25% and 26% respectively. In this large cohort of patients with a broad range of solid malignancies and at different phases of systemic therapy, the use of deep learning resulted in improved accuracy for VTE incidence predictions. Additional studies are needed to further assess the validity of this model.

PMID:37214902 | PMC:PMC10197737 | DOI:10.21203/rs.3.rs-2870367/v1

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PubMed articles on: Cancer & VTE/PE

Effective long-term sirolimus treatment in hypoxemia mainly due to intrapulmonary right-to-left shunt in a patient with multiple vascular anomalies

Orphanet J Rare Dis. 2023 May 24;18(1):124. doi: 10.1186/s13023-023-02732-3.