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10/7/25

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a preventable, common vascular disease that has been estimated to affect up to 900,000 people per year. It has been associated with risk factors such as recent surgery, cancer, and hospitalization. VTE surveillance for patient management and safety can be improved via natural language processing (NLP). NLP tools have the ability to access electronic medical records, identify patients that meet the VTE case definition, and subsequently enter the relevant information into a database for hospital review.

OBJECTIVE: We aimed to evaluate the performance of a VTE identification model of IDEAL-X (Information and Data Extraction Using Adaptive Learning; Emory University)-an NLP tool-in automatically classifying cases of VTE by "reading" unstructured text from diagnostic imaging records collected from 2012 to 2014.

METHODS: After accessing imaging records from pilot surveillance systems for VTE from Duke University and the University of Oklahoma Health Sciences Center (OUHSC), we used a VTE identification model of IDEAL-X to classify cases of VTE that had previously been manually classified. Experts reviewed the technicians' comments in each record to determine if a VTE event occurred. The performance measures calculated (with 95% CIs) were accuracy, sensitivity, specificity, and positive and negative predictive values. Chi-square tests of homogeneity were conducted to evaluate differences in performance measures by site, using a significance level of .05.

RESULTS: The VTE model of IDEAL-X "read" 1591 records from Duke University and 1487 records from the OUHSC, for a total of 3078 records. The combined performance measures were 93.7% accuracy (95% CI 93.7%-93.8%), 96.3% sensitivity (95% CI 96.2%-96.4%), 92% specificity (95% CI 91.9%-92%), an 89.1% positive predictive value (95% CI 89%-89.2%), and a 97.3% negative predictive value (95% CI 97.3%-97.4%). The sensitivity was higher at Duke University (97.9%, 95% CI 97.8%-98%) than at the OUHSC (93.3%, 95% CI 93.1%-93.4%; P<.001),P

CONCLUSIONS: The VTE model of IDEAL-X accurately classified cases of VTE from the pilot surveillance systems of two separate health systems in Durham, North Carolina, and Oklahoma City, Oklahoma. NLP is a promising tool for the design and implementation of an automated, cost-effective national surveillance system for VTE. Conducting public health surveillance at a national scale is important for measuring disease burden and the impact of prevention measures. We recommend additional studies to identify how integrating IDEAL-X in a medical record system could further automate the surveillance process.

PMID:37206160 | PMC:PMC10193259 | DOI:10.2196/36877

09:16

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PubMed articles on: Cancer & VTE/PE

A Novel Risk Assessment Model Predicts Major Bleeding Risk at Admission in Medical Inpatients

medRxiv. 2023 May 2:2023.04.29.23289304. doi: 10.1101/2023.04.29.23289304. Preprint.

ABSTRACT

Oncologic emergencies are a wide spectrum of oncologic conditions caused directly by malignancies or their treatment. Oncologic emergencies may be classified according to the underlying physiopathology in metabolic, hematologic, and structural conditions. In the latter, radiologists have a pivotal role, through an accurate diagnosis useful to provide optimal patient care. Structural conditions may involve the central nervous system, thorax, or abdomen, and emergency radiologists have to know the characteristics imaging findings of each one of them. The number of oncologic emergencies is growing due to the increased incidence of malignancies in the general population and also to the improved survival of these patients thanks to the advances in cancer treatment. Artificial intelligence (AI) could be a solution to assist emergency radiologists with this rapidly increasing workload. To our knowledge, AI applications in the setting of the oncologic emergency are mostly underexplored, probably due to the relatively low number of oncologic emergencies and the difficulty in training algorithms. However, cancer emergencies are defined by the cause and not by a specific pattern of radiological symptoms and signs. Therefore, it can be expected that AI algorithms developed for the detection of these emergencies in the non-oncological field can be transferred to the clinical setting of oncologic emergency. In this review, a craniocaudal approach was followed and central nervous system, thoracic, and abdominal oncologic emergencies have been addressed regarding the AI applications reported in literature. Among the central nervous system emergencies, AI applications have been reported for brain herniation and spinal cord compression. In the thoracic district the addressed emergencies were pulmonary embolism, cardiac tamponade and pneumothorax. Pneumothorax was the most frequently described application for AI, to improve sensibility and to reduce the time-to-diagnosis. Finally, regarding abdominal emergencies, AI applications for abdominal hemorrhage, intestinal obstruction, intestinal perforation, and intestinal intussusception have been described.

PMID:37205309 | PMC:PMC10185441 | DOI:10.37349/etat.2023.00138

09:16

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PubMed articles on: Cancer & VTE/PE

Pre-Operative Embolization of a Symptomatic Dural-Based Lung Cancer Metastasis

J Vasc Interv Radiol. 2023 May 17:S1051-0443(23)00355-X. doi: 10.1016/j.jvir.2023.05.023. Online ahead of print.

NO ABSTRACT

PMID:37207811 | DOI:10.1016/j.jvir.2023.05.023

09:16

PubMed articles on: Cancer & VTE/PE

Exploring the Applicability of Using Natural Language Processing to Support Nationwide Venous Thromboembolism Surveillance: Model Evaluation Study

JMIR Bioinform Biotech. 2022 May 8;3(1):10.2196/36877. doi: 10.2196/36877.

ABSTRACT

Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The biological mechanisms are related to inflammation and increased coagulability, factors that play an important role in the pathogenesis of venous thromboembolism (VTE, i.e., deep vein thrombosis or pulmonary embolism). This study investigates if long-term exposure to air pollution is associated with increased VTE incidence. The study followed 29 408 participants from the Malmö Diet and Cancer (MDC) cohort, which consists of adults aged 44-74 recruited in Malmö, Sweden between 1991 and 1996. For each participant, annual mean residential exposures to particulate matter <2.52.5) and <1010), nitrogen oxides (NOx) and black carbon (BC) from 1990 up to 2016 were calculated. Associations with VTE were analysed using Cox proportional hazard models for air pollution in the year of the VTE event (lag0) and the mean of the prior 1-10 years (lag1-10). Annual air pollution exposures for the full follow-up period had the following means: 10.8 μg/m3 for PM2.5, 15.8 μg/m3 for PM10, 27.7 μg/m3 for NOx, and 0.96 μg/m3 for BC. The mean follow-up period was 19.5 years, with 1418 incident VTE events recorded during this period. Exposure to lag1-10 PM2.5 was associated with an increased risk of VTE (HR 1.17 (95%CI 1.01-1.37)) per interquartile range (IQR) of 1.2 μg/m3 increase in PM2.5 exposure. No significant associations were found between other pollutants or lag0 PM2.5 and incident VTE. When VTE was divided into specific diagnoses, associations with lag1-10 PM2.5 exposure were similarly positive for deep vein thrombosis but not for pulmonary embolism. Results persisted in sensitivity analyses and in multi-pollutant models. Long-term exposure to moderate concentrations of ambient PM2.5 was associated with increased risks of VTE in the general population in Sweden.

PMID:37209899 | DOI:10.1016/j.envpol.2023.121841

09:16

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PubMed articles on: Cancer & VTE/PE

Role of artificial intelligence in oncologic emergencies: a narrative review

Explor Target Antitumor Ther. 2023;4(2):344-354. doi: 10.37349/etat.2023.00138. Epub 2023 Apr 28.

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

09:15

PubMed articles on: Cancer & VTE/PE

Long-term ambient air pollution and venous thromboembolism in a population-based Swedish cohort

Environ Pollut. 2023 May 18:121841. doi: 10.1016/j.envpol.2023.121841. Online ahead of print.

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

09:15

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

BACKGROUND: Atrial fibrillation (AF) is the most common arrythmia 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)<0.001)

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

09:15

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

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

09:15

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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 24. doi: 10.1080/00325481.2023.2218188. 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

09:15

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

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

09:15

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

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

09:15

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

BACKGROUND: Venous thromboembolism (VTE) is a complication of COVID-19 in hospitalized patients. Little information is available on long-term outcomes of VTE in this population.

OBJECTIVES: We aimed to compare the characteristics, management strategies, and long-term clinical outcomes between patients with COVID-19-associated VTE and patients with VTE provoked by hospitalization for other acute medical illnesses.

METHODS: This is an observational cohort study, with a prospective cohort of 278 patients with COVID-19-associated VTE enrolled between 2020 and 2021 and a comparison cohort of 300 patients without COVID-19 enrolled in the ongoing START2-Register between 2018 and 2020. Exclusion criteria included age <18<3

RESULTS: Patients with VTE secondary to COVID-19 had more frequent pulmonary embolism without deep vein thrombosis than controls (83.1% vs 46.2%, P<.001),P<.001),P<.001).P= 0.9) and the proportion of patients who discontinued anticoagulation (78.0% and 75.0%, P= 0.4) were similar between the 2 groups. Thrombotic event rates after discontinuation were 1.5 and 2.6 per 100 patient-years, respectively (P = 0.4).

CONCLUSION: The risk of recurrent thrombotic events in patients with COVID-19-associated VTE is low and similar to the risk observed in patients with VTE secondary to hospitalization for other medical diseases.

PMID:37229314 | PMC:PMC10131739 | DOI:10.1016/j.rpth.2023.100167

09:15

PubMed articles on: Cancer & VTE/PE

Pulmonary embolism complicated by tamponade revealing metastatic lung cancer in a woman pregnant with twin: about a case report

Ann Med Surg (Lond). 2023 Apr 7;85(5):1966-1970. doi: 10.1097/MS9.0000000000000516. eCollection 2023 May.

ABSTRACT

Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.

PMID:37225709 | DOI:10.1038/s41419-023-05859-0

07:31

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Cardiotoxicity News

PubMed articles on: Cancer & VTE/PE

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

Res Pract Thromb Haemost. 2023 May;7(4):100167. doi: 10.1016/j.rpth.2023.100167. Epub 2023 Apr 26.

ABSTRACT

Cancer alters the function of multiple organs beyond those targeted by metastasis1,2. Here we show that inflammation, fatty liver and dysregulated metabolism are hallmarks of systemically affected livers in mouse models and in patients with extrahepatic metastasis. We identified tumour-derived extracellular vesicles and particles (EVPs) as crucial mediators of cancer-induced hepatic reprogramming, which could be reversed by reducing tumour EVP secretion via depletion of Rab27a. All EVP subpopulations, exosomes and principally exomeres, could dysregulate hepatic function. The fatty acid cargo of tumour EVPs-particularly palmitic acid-induced secretion of tumour necrosis factor (TNF) by Kupffer cells, generating a pro-inflammatory microenvironment, suppressing fatty acid metabolism and oxidative phosphorylation, and promoting fatty liver formation. Notably, Kupffer cell ablation or TNF blockade markedly decreased tumour-induced fatty liver generation. Tumour implantation or pre-treatment with tumour EVPs diminished cytochrome P450 gene expression and attenuated drug metabolism in a TNF-dependent manner. We also observed fatty liver and decreased cytochrome P450 expression at diagnosis in tumour-free livers of patients with pancreatic cancer who later developed extrahepatic metastasis, highlighting the clinical relevance of our findings. Notably, tumour EVP education enhanced side effects of chemotherapy, including bone marrow suppression and cardiotoxicity, suggesting that metabolic reprogramming of the liver by tumour-derived EVPs may limit chemotherapy tolerance in patients with cancer. Our results reveal how tumour-derived EVPs dysregulate hepatic function and their targetable potential, alongside TNF inhibition, for preventing fatty liver formation and enhancing the efficacy of chemotherapy.

PMID:37225988 | DOI:10.1038/s41586-023-06114-4

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PubMed articles on: Cardio-Oncology

Chemotherapy impairs ovarian function through excessive ROS-induced ferroptosis

Cell Death Dis. 2023 May 24;14(5):340. doi: 10.1038/s41419-023-05859-0.

ABSTRACT

INTRODUCTION: Breast cancer treated with adjuvant hypofractionation radiotherapy with two different techniques, i.e., volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) and their effects in terms of loco-regional control and adverse effects in terms of cutaneous, pulmonary, and cardiac outcomes are compared.

MATERIALS AND METHODS: This is a prospective non-randomized observational study. VMAT and IMRT plan for 30 breast cancer patients who were supposed to receive adjuvant radiotherapy were prepared using a hypofractionation schedule. The plans were dosimetrically evaluated.

OBJECTIVE: Dosimetric comparative analysis of IMRT and VMAT in hypofractionated radiotherapy in breast cancer is done and tested whether VMAT has a dosimetric advantage over IMRT. These patients were recruited for a clinical assessment of toxicities. They were followed up for at least three months.

RESULT: On dosimetric analysis, planning target volume (PTV) coverage (PTV_ V95) of both VMAT (96.41 ± 1.31) and IMRT (96.63 ± 1.56) were similar with significantly lower monitor units required with VMAT plans (1,084.36 ± 270.82 vs 1,181.55 ± 244.50, p = 0.043). Clinically, all patients tolerated hypofractionation through VMAT (n = 8) and IMRT (n = 8) satisfactorily in the short term. No cardiotoxicity or appreciable falls in pulmonary function test parameters were observed. Acute radiation dermatitis poses challenges similar to standard fractionation or any other delivery technique.

CONCLUSION: PVT dose, homogeneity, and conformity indices were similar in both VMAT and IMRT groups. In VMAT, there was high-dose sparing of some critical organs like the heart and lungs at the cost of the low-dose baths to these organs. Increased risk of secondary cancer will require a decade-long follow-up study to indict the VMAT technique. As we move toward precision in oncology, "one-size-fits-all" can never be an acceptable dictum. Each patient is unique and therefore we must offer, and the patient must "choose wisely."

PMID:37228558 | PMC:PMC10206676 | DOI:10.7759/cureus.38045

07:31

PubMed articles on: Cardio-Oncology

Tumour extracellular vesicles and particles induce liver metabolic dysfunction

Nature. 2023 May 24. doi: 10.1038/s41586-023-06114-4. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies focused on the impact of cardiovascular diseases (CVD) risk factors in breast cancer patients with chemotherapy (CT) or radiotherapy (RT). This study aimed to identify the impact of tumor characteristics on CVD death in these patients.

METHODS: Data of female breast cancer patients with CT or RT between 2004 and 2016 were included. The risk factors of CVD death were identified using Cox regression analyses. A nomogram was constructed to evaluate the predicted value of tumor characteristics, and then validated by the concordance indexes (C-index) and calibration curves.

RESULT: A total of 28,539 patients were included with an average follow-up of 6.1 years. Tumor size > 45 mm (adjusted HR = 1.431, 95% CI = 1.116-1.836, P= 0.005), regional (adjusted HR = 1.278, 95% CI = 1.048-1.560, P= 0.015) and distant stage (adjusted HR = 2.240, 95% CI = 1.444-3.474, P< 0.001) were risk factors of CVD death for breast cancer patients with CT or RT. The prediction nomogram of tumor characteristics (tumor size and stage) on CVD survival was established. The C-index of internal and external validation were 0.780 (95% Cl = 0.751-0.809), and 0.809 (95% Cl = 0.768-0.850), respectively. The calibration curves showed consistency between the actual observation and nomogram. The risk stratification was also significant distinction (P < 0.05).

CONCLUSION: Tumor size and stage were related to the risk of CVD death for breast cancer patients with CT or RT. The management of CVD death risk in breast cancer patients with CT or RT should focus not only on CVD risk factors but also on tumor size and stage.

PMID:37229229 | PMC:PMC10203988 | DOI:10.3389/fcvm.2023.1149633

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PubMed articles on: Cardio-Oncology

Editorial: Cardio-oncology and reverse cardio-oncology: the manifold interconnections between heart failure and cancer

Front Physiol. 2023 May 9;14:1205810. doi: 10.3389/fphys.2023.1205810. eCollection 2023.

NO ABSTRACT

PMID:37228811 | PMC:PMC10203590 | DOI:10.3389/fphys.2023.1205810

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PubMed articles on: Cardio-Oncology

Dosimetric Comparison of Hypofractionated Regimen in Breast Cancer Using Two Different Techniques: Intensity-Modulated Radiation Therapy (IMRT) and Volumetric-Modulated Arc Therapy (VMAT)

Cureus. 2023 Apr 24;15(4):e38045. doi: 10.7759/cureus.38045. eCollection 2023 Apr.

ABSTRACT

BACKGROUND: In addition to cardiotoxicity, ocular toxicity induced by chemotherapeutic agents is not uncommon.

OBJECTIVE: This study aimed to explore the association between ocular adverse events and major adverse cardiovascular events (composite endpoint) caused by chemotherapy, and whether specific ocular events could be potential predictors of some specific components of the composite endpoint.

METHODS: A total of 5378 newly diagnosed patients (age > 18 y/o) with any malignancy or metastatic solid tumors who received chemotherapy from January 1997 to December 2010 were enrolled from the Taiwan National Health Insurance Research Database. Patients who developed new incident ocular diseases were classified as the study group, and those who did not develop incident ocular diseases as the control group.

RESULTS: After propensity score matching, there was a significant increase in the incidence of stroke in the ocular diseases group compared to the no ocular diseases group (13.4% vs. 4.5%, p < 0.0001). Tear film insufficiency, keratopathy, glaucoma, and lens disorders were associated with a significantly higher risk of stroke. A longer duration of methotrexate and a longer duration with higher total amount of tamoxifen were associated with both incident ocular diseases and incident stroke. Cox proportional hazards regression showed that the only independent risk factor for stroke was incident ocular diseases [Adjusted relative risk (95% confidence interval): 2.96 (1.66-5.26), p = 0.0002]. In addition, incident ocular disease was the most significant risk factor compared with other traditional cardiovascular risk factors.

CONCLUSIONS: Incident ocular diseases related to chemotherapy were associated with a significantly higher risk of stroke.

PMID:37229341 | PMC:PMC10203719 | DOI:10.6515/ACS.202305_39(3).20221005A

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PubMed articles on: Cardio-Oncology

The impact of tumor characteristics on cardiovascular disease death in breast cancer patients with CT or RT: a population-based study

Front Cardiovasc Med. 2023 May 9;10:1149633. doi: 10.3389/fcvm.2023.1149633. eCollection 2023.

ABSTRACT

The overall survival of advanced melanoma has improved dramatically. Immunotherapies, specifically checkpoint inhibitors, have played a large role in this improvement. These agents have also shown benefit in the adjuvant setting, are approved for treatment of resected stage II, III, and IV melanoma, and play an evolving role in the neoadjuvant setting. Although generally well tolerated, immune-related adverse events occur and can be severe. Here we focus on some severe and potentially long term toxicities, including cardiovascular and neurologic toxicities. Our understanding of the acute and long-term toxicities of immune checkpoint inhibitors continues to evolve. Oncologists must continue to balance cancer risk and treatment-related toxicities.

PMID:37229626 | DOI:10.1200/EDBK_390594

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PubMed articles on: Cardio-Oncology

The Incident Ocular Diseases Related to Chemotherapy in Cancer Patients are Associated with Increasing Risk of Incident Stroke

Acta Cardiol Sin. 2023 May;39(3):435-448. doi: 10.6515/ACS.202305_39(3).20221005A.

ABSTRACT

BACKGROUND: Postoperative mortality and morbidity rates are high in patients with obstructing colon cancer (OCC). Different treatment options have been evaluated over the years, mainly for left sided OCC. Optimising the preoperative health condition in elective colorectal cancer (CRC) treatment shows promising results. The aim of this study is to determine whether preoptimisation is feasible in patients with OCC, with a special interest/focus on right-sided OCC, and if, ultimately, optimisation reduces mortality and morbidity (stoma rates, major and minor complications) rates in OCC.

METHODS: This is a prospective registration study including all patients presenting with OCC in our hospital. Patients with OCC, treated with curative intent, will be screened for eligibility to receive preoptimisation before surgery. The preoptimisation protocol includes; decompression of the small bowel with a NG-tube for right sided obstruction and SEMS or decompressing ileostomy or colostomy, proximal to the site of obstruction, for left sided colonic obstructions. For the additional work-up, additional nutrition by means of parenteral feeding (for patients who are dependent on a NG tube) or oral/enteral nutrition (in case the obstruction is relieved) is provided. Physiotherapy with attention to both cardio and muscle training prior surgical resection is provided. The primary endpoint is complication-free survival (CFS) at the 90 day period after hospitalisation. Secondary outcomes include pre- and postoperative complications, patient- and tumour characteristics, surgical procedures, total in hospital stay, creation of decompressing and/or permanent ileo- or colostomy and long-term (oncological) outcomes.

DISCUSSION: Preoptimisation is expected to improve the preoperative health condition of patients and thereby reduce postoperative complications.

TRIAL REGISTRATION: Trial Registry: NL8266 date of registration: 06-jan-2020.

STUDY STATUS: Open for inclusion.

PMID:37231376 | DOI:10.1186/s12876-023-02799-z

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PubMed articles on: Cardio-Oncology

A Brain, A Heart, and the Courage: Balancing Benefit and Toxicity of Immunotherapy in Melanoma

Am Soc Clin Oncol Educ Book. 2023 May;43:EDBK39059. doi: 10.1200/EDBK_390594.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is the leading cause of preventable hospital death in the US. Guidelines from the American College of Chest Physicians and American Society for Hematology recommend providing pharmacological VTE prophylaxis to acutely or critically ill medical patients at acceptable bleeding risk, but there is currently only one validated risk assessment model (RAM) for estimating bleeding risk. We developed a RAM using risk factors at admission and compared it with the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) model.

METHODS: A total of 46,314 medical patients admitted to a Cleveland Clinic Health System hospital from 2017-2020 were included. Data were split into training (70%) and validation (30%) sets with equivalent bleeding event rates in each set. Potential risk factors for major bleeding were identified from the IMPROVE model and literature review. Penalized logistic regression using LASSO was performed on the training set to select and regularize important risk factors for the final model. The validation set was used to assess model calibration and discrimination and compare performance with IMPROVE. Bleeding events and risk factors were confirmed through chart review.

RESULTS: The incidence of major in-hospital bleeding was 0.58%. Active peptic ulcer (OR = 5.90), prior bleeding (OR = 4.24), and history of sepsis (OR = 3.29) were the strongest independent risk factors. Other risk factors included age, male sex, decreased platelet count, increased INR, increased PTT, decreased GFR, ICU admission, CVC or PICC placement, active cancer, coagulopathy, and in-hospital antiplatelet drug, steroid, or SSRI use. In the validation set, the Cleveland Clinic Bleeding Model (CCBM) had better discrimination than IMPROVE (0.86 vs. 0.72, p < .001) and, at equivalent sensitivity (54%), categorized fewer patients as high-risk (6.8% vs. 12.1%, p < .001).

CONCLUSIONS: From a large population of medical inpatients, we developed and validated a RAM to accurately predict bleeding risk at admission. The CCBM may be used in conjunction with VTE risk calculators to decide between mechanical and pharmacological prophylaxis for at-risk patients.

PMID:37205327 | PMC:PMC10187332 | DOI:10.1101/2023.04.29.23289304