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10/12/25

 



ABSTRACT


A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRASG12D . The basal-like mRNA panel better captured the basal-like cell states than widely used protein markers. The panels corroborated the co-existence of the classical and basal-like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial-to-mesenchymal transition respectively. Mutant KRASG12D detection ascertained an epithelial origin of vimentin-positive cells in the tumour. Uneven spatial distribution of cancer-associated fibroblasts could recreate similar intra-organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


PMID:37842959 | DOI:10.1002/path.6212

15:06

PubMed articles on: Cardio-Oncology

Welcome to the Rising Stars in Cardio-Oncology Special Focus Issue


Future Cardiol. 2023 Sep;19(11):515-517. doi: 10.2217/fca-2022-0111. Epub 2023 Oct 18.


NO ABSTRACT


PMID:37850469 | DOI:10.2217/fca-2022-0111

15:06

PubMed articles on: Cardio-Oncology

Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs


J Natl Compr Canc Netw. 2023 Oct;21(10):1039-1049.e10. doi: 10.6004/jnccn.2023.7047.


ABSTRACT


BACKGROUND: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied.


METHODS: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation.


RESULTS: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant "on-treatment" hypertension was not associated with MACE.


CONCLUSIONS: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.


PMID:37856199 | DOI:10.6004/jnccn.2023.7047

15:06

PubMed articles on: Cardio-Oncology

Microparticles and cardiotoxicity secondary to doxorubicin-based chemotherapy in breast cancer patients


Int J Cardiol. 2023 Oct 16:131435. doi: 10.1016/j.ijcard.2023.131435. Online ahead of print.


ABSTRACT


Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients.


PMID:37852542 | DOI:10.1016/j.ijcard.2023.131435

15:06

PubMed articles on: Cancer & VTE/PE

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis


Medicina (Kaunas). 2023 Oct 20;59(10):1867. doi: 10.3390/medicina59101867.


ABSTRACT


Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.


PMID:37893585 | DOI:10.3390/medicina59101867

15:06

PubMed articles on: Cancer & VTE/PE

Risk and timing of venous thromboembolism after surgery for lung cancer: a nationwide cohort study


Ann Thorac Surg. 2023 Oct 25:S0003-4975(23)01073-1. doi: 10.1016/j.athoracsur.2023.10.015. Online ahead of print.


ABSTRACT


BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in lung cancer patients undergoing thoracic surgery. We examined the risk and timing of VTE following surgery for primary non-small cell lung cancer (NSCLC).


METHODS: in the Danish Lung Cancer Registry. VTE events in the year after surgery were assessed by stage, patient characteristics, and surgical procedure.


RESULTS: We identified 13,197 patients who underwent surgery for NSCLC in 2003-2021 (mean age 67.6 years, 50% female); 10,524 (79.7%) had stage I-II NSCLS and 2673 (20.3%) had stage III-IV. During one-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I versus 4.1% for stage IV), but varied little by pathological type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%, 95% CI 3.2-6.9), followed by pneumonectomy (3.6%, 95% CI 2.5-5.1). The hazard of VTE was highest during the first three months after surgery, whereafter it declined. For stage IV cancer hazards increased again after six months. At one-year, all-cause death was 12.6% (95% CI: 12.0-13.1 %).


CONCLUSIONS: Among patients undergoing surgery for NSCLC, 3.3% developed VTE, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.


PMID:37890818 | DOI:10.1016/j.athoracsur.2023.10.015

15:06

PubMed articles on: Cancer & VTE/PE

A Novel Model to Prevent Venous Thromboembolism in Patients with Lung Cancer


Altern Ther Health Med. 2023 Oct 27:AT9245. Online ahead of print.


ABSTRACT


OBJECTIVE: To observe the effect of nurse-patient co-management mode on preventing venous thromboembolism (VTE) in lung cancer patients with carboplatin and gemcitabine chemotherapy after peripheral venipuncture central venous catheterization (PICC).


METHODS: 100 patients with lung cancer admitted to the 2nd Affiliated Hospital of Hainan Medical University from April 2020 to April 2022 were selected. All patients received a combination chemotherapy of carboplatin and gemcitabine and PICC catheterization. The patients were divided into an observation group and a control group by 1:1 simple random method, with 50 cases in each group. Patients in the control group were given routine nursing for lung cancer, and patients in the observation group were treated with nurse-patient co-management mode, and nursing intervention lasted for 2 months. General Comfort Questionnaire, self-management ability, quality of life, Self-care ability Scale, self-rating Anxiety Scale (SAS), and self-rating depression Scale were compared before and after intervention between the two groups. The recovery of immune ability indices (CD3+, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) in 2 groups were detected. Complications after PICC catheterization were recorded in the two groups.


RESULTS: After nursing, self-rating depression Scale and self-rating Anxiety Scale scores in both groups were significantly decreased, which were lower in the observation group than the control group (P < .001). After nursing, scores of self-concept, self-responsibility, self-care skills, and health knowledge level were significantly increased in both groups, which were higher in the observation group than control group (P < .001). After nursing, scores on the General Comfort Questionnaire, self-management scale, and quality of life were increased in both groups, which were higher in the observation group than control group (P < .0501). After nursing care, the immune competence indices of both patients increased significantly, and the immune indexes of CD3+, CD3+CD4+, and CD3+ CD4+/CD3+CD8+ in the observation group were significantly higher than those in the control group (P < .05). The total incidence of complications in the observation group was significantly lower than that in the control group (8.00% vs. 26.00%, P < .001), and the incidence of venous thromboembolism was significantly lower than that in the control group (2.00% vs. 14.00%, P < .001).


CONCLUSION: The nurse-patient co-management model has shown to be effective in reducing the incidence of venous thromboembolism in patients who have undergone PICC catheterization while receiving carboplatin and gemcitabine chemotherapy. This model also helps patients improve their self-care and self-management abilities, alleviates adverse psychological effects, and contributes to the recovery of their immune system.


PMID:37883756

15:06

PubMed articles on: Cancer & VTE/PE

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients


Expert Rev Hematol. 2023 Oct 26:1-8. doi: 10.1080/17474086.2023.2276209. Online ahead of print.


ABSTRACT


OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC.


RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients.


RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs.


CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.


PMID:37883026 | DOI:10.1080/17474086.2023.2276209

15:06

PubMed articles on: Cancer & VTE/PE

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium


Pediatr Crit Care Med. 2023 Oct 26. doi: 10.1097/PCC.0000000000003383. Online ahead of print.


ABSTRACT


OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children.


DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry.


SETTING: PICUs within U.S. CHAT Consortium participating centers.


PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years.


INTERVENTIONS: None.


MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE.


CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.


PMID:37882641 | DOI:10.1097/PCC.0000000000003383

15:06

PubMed articles on: Cancer & VTE/PE

Guidelines in Practice: Prevention of Venous Thromboembolism


AORN J. 2023 Nov;118(5):321-328. doi: 10.1002/aorn.14019.


ABSTRACT


Venous thromboembolism (VTE), a condition involving deep vein thrombosis and embolism, can cause death when left untreated. Hospitalized patients and those who have recently undergone surgery or have a cancer diagnosis are at increased risk for VTE development. The updated AORN "Guideline for prevention of venous thromboembolism" provides perioperative nurses with a variety of evidence-based recommendations associated with the topic. This article provides an overview of the guideline and discusses recommendations for a VTE protocol, VTE and bleeding risk assessments, pharmacologic and mechanical VTE prophylaxis, postoperative ambulation, and patient and family education. It also includes a scenario that illustrates the importance of the VTE assessment and the use of mechanical prophylaxis for high-risk patients undergoing operative or other invasive procedures. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative and procedural settings.


PMID:37882602 | DOI:10.1002/aorn.14019

15:06

PubMed articles on: Cancer & VTE/PE

Heterogeneous distributions in clinical events preceding anticoagulant treatment nonpersistence in patients with venous thromboembolism stratified by active cancer: A nationwide cohort study


Cancer Med. 2023 Oct 26. doi: 10.1002/cam4.6626. Online ahead of print.


ABSTRACT


BACKGROUND: Nonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE).


METHODS: We investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database.


RESULTS: Clinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs).


CONCLUSION: These findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.


PMID:37882319 | DOI:10.1002/cam4.6626

15:06

PubMed articles on: Cancer & VTE/PE

How we manage a high D-dimer


Haematologica. 2023 Oct 26. doi: 10.3324/haematol.2023.283966. Online ahead of print.


ABSTRACT


D-dimer, a soluble fibrin degradation product that originates from plasmin-induced degradation of cross-linked fibrin, is an important biomarker of coagulation activation and secondary fibrinolysis that is routinely used to rule out venous thromboembolism (VTE), to evaluate the risk of VTE recurrence as well as the optimal duration of anticoagulant therapy. Besides VTE, D-dimer may be high due to physiologic conditions, including aging, pregnancy and strenuous physical activity. In addition, several disorders have been associated with increased D-dimer levels, spanning from disseminated intravascular coagulation to infectious diseases and cancers. Thus, it is far from unusual for hematologists to have to deal with ambulatory individuals presenting with increased Ddimer without signs or symptoms of thrombus formation. To the management of these cases by the hematologist is dedicated this narrative review.


PMID:37881856 | DOI:10.3324/haematol.2023.283966

15:06

PubMed articles on: Cancer & VTE/PE

Episodic Cocaine Use as a Cause of Venous Thromboembolism and Acute Liver Injury


Am J Case Rep. 2023 Oct 24;24:e941360. doi: 10.12659/AJCR.941360.


ABSTRACT


BACKGROUND Pulmonary embolism secondary to deep vein thrombosis (DVT) with cor pulmonale is commonly associated with risk factors including surgery, cancer, and prolonged immobility. Cocaine is known to cause vasoconstriction and has a prothrombotic effect. Prolonged and heavy use of cocaine can also cause inflammation and liver damage. However, data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. CASE REPORT A 34-year-old man with no significant medical history except for episodic cocaine use presented in respiratory distress. Workup revealed submassive pulmonary embolism with pulmonary infarctions complicated by pneumonia, hypoxemic respiratory failure, and anemia. He was treated with anticoagulation and intensive care. On day 5 of hospitalization, the patient had an acute hepatic injury. His alanine aminotransferase level peaked at over 2000 IU/L on day 7, until finally tapering. Liver failure was found to be secondary to cocaine use. Liver enzyme levels improved with supportive care. He was discharged with apixaban and continued liver enzyme monitoring. CONCLUSIONS When investigating the cause of venous thromboembolism and transaminitis, evaluating cocaine use via patient history or laboratory analysis of cocaine and its metabolites should be considered. Cocaine is known to cause vasoconstriction and has a prothrombotic effect, although data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Further investigation, such as cohort studies, could help strengthen our understanding of the relationship between cocaine use, acute hepatic injury, and pulmonary embolism.


PMID:37872733 | DOI:10.12659/AJCR.941360

15:06

PubMed articles on: Cancer & VTE/PE

Comparison of Direct Oral Anticoagulants versus Low Molecular Weight Heparin in Primary and Metastatic Brain Cancers: A Meta-Analysis and Systematic Review


J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00779-1. doi: 10.1016/j.jtha.2023.10.011. Online ahead of print.


ABSTRACT


BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known.


OBJECTIVE: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs. LMWH.


METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n=1,638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup.


RESULTS: The pooled RR for ICH in patients receiving DOACs vs. those receiving LMWH was 0.65 (95% confidence interval [CI], 0.36-1.17; P = 0.15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = 0.003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = 0.80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants.


DISCUSSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.


PMID:37866517 | DOI:10.1016/j.jtha.2023.10.011

15:07

PubMed articles on: Cancer & VTE/PE

Two Cases of Catheter-Related Venous Thrombosis Treated with Direct Oral Anticoagulants(DOAC)


Gan To Kagaku Ryoho. 2023 Sep;50(9):993-996.


ABSTRACT


The implantation of a totally implantable central venous(CV)access port is considered a risk factor for venous thromboembolism( VTE). In the treatment of catheter-related thrombosis(CRT), both European and American guidelines recommend anticoagulation therapy with catheters in place. We experienced 2 cases of upper extremity deep vein thrombosis (UEDVT)after the implantation of CV access ports through the left subclavian vein for adjuvant chemotherapy in patients with resected breast cancer. Both patients were successfully treated with direct oral anticoagulants(DOAC) while the port remained in place with a careful follow-up that included monitoring of serum D-dimer levels. The administration of DOAC to CRT that develops in patients undergoing postoperative adjuvant chemotherapy for breast cancer may be relatively safe, with a low potential for adverse events such as bleeding.


PMID:37800295

15:07

PubMed articles on: Cancer & VTE/PE

Computer image analysis with artificial intelligence: a practical introduction to convolutional neural networks for medical professionals


Postgrad Med J. 2023 Oct 4:qgad095. doi: 10.1093/postmj/qgad095. Online ahead of print.


ABSTRACT


Artificial intelligence tools, particularly convolutional neural networks (CNNs), are transforming healthcare by enhancing predictive, diagnostic, and decision-making capabilities. This review provides an accessible and practical explanation of CNNs for clinicians and highlights their relevance in medical image analysis. CNNs have shown themselves to be exceptionally useful in computer vision, a field that enables machines to 'see' and interpret visual data. Understanding how these models work can help clinicians leverage their full potential, especially as artificial intelligence continues to evolve and integrate into healthcare. CNNs have already demonstrated their efficacy in diverse medical fields, including radiology, histopathology, and medical photography. In radiology, CNNs have been used to automate the assessment of conditions such as pneumonia, pulmonary embolism, and rectal cancer. In histopathology, CNNs have been used to assess and classify colorectal polyps, gastric epithelial tumours, as well as assist in the assessment of multiple malignancies. In medical photography, CNNs have been used to assess retinal diseases and skin conditions, and to detect gastric and colorectal polyps during endoscopic procedures. In surgical laparoscopy, they may provide intraoperative assistance to surgeons, helping interpret surgical anatomy and demonstrate safe dissection zones. The integration of CNNs into medical image analysis promises to enhance diagnostic accuracy, streamline workflow efficiency, and expand access to expert-level image analysis, contributing to the ultimate goal of delivering further improvements in patient and healthcare outcomes.


PMID:37794609 | DOI:10.1093/postmj/qgad095

15:07

PubMed articles on: Cancer & VTE/PE

Artificial intelligence in the prediction of venous thromboembolism: A systematic review and pooled analysis


Eur J Haematol. 2023 Oct 4. doi: 10.1111/ejh.14110. Online ahead of print.


ABSTRACT


BACKGROUND: Accurate diagnostic and prognostic predictions of venous thromboembolism (VTE) are crucial for VTE management. Artificial intelligence (AI) enables autonomous identification of the most predictive patterns from large complex data. Although evidence regarding its performance in VTE prediction is emerging, a comprehensive analysis of performance is lacking.


AIMS: To systematically review the performance of AI in the diagnosis and prediction of VTE and compare it to clinical risk assessment models (RAMs) or logistic regression models.


METHODS: A systematic literature search was performed using PubMed, MEDLINE, EMBASE, and Web of Science from inception to April 20, 2021. Search terms included "artificial intelligence" and "venous thromboembolism." Eligible criteria were original studies evaluating AI in the prediction of VTE in adults and reporting one of the following outcomes: sensitivity, specificity, positive predictive value, negative predictive value, or area under receiver operating curve (AUC). Risks of bias were assessed using the PROBAST tool. Unpaired t-test was performed to compare the mean AUC from AI versus conventional methods (RAMs or logistic regression models).


RESULTS: A total of 20 studies were included. Number of participants ranged from 31 to 111 888. The AI-based models included artificial neural network (six studies), support vector machines (four studies), Bayesian methods (one study), super learner ensemble (one study), genetic programming (one study), unspecified machine learning models (two studies), and multiple machine learning models (five studies). Twelve studies (60%) had both training and testing cohorts. Among 14 studies (70%) where AUCs were reported, the mean AUC for AI versus conventional methods were 0.79 (95% CI: 0.74-0.85) versus 0.61 (95% CI: 0.54-0.68), respectively (p < .001). However, the good to excellent discriminative performance of AI methods is unlikely to be replicated when used in clinical practice, because most studies had high risk of bias due to missing data handling and outcome determination.


CONCLUSION: The use of AI appears to improve the accuracy of diagnostic and prognostic prediction of VTE over conventional risk models; however, there was a high risk of bias observed across studies. Future studies should focus on transparent reporting, external validation, and clinical application of these models.


PMID:37794526 | DOI:10.1111/ejh.14110

15:07

PubMed articles on: Cancer & VTE/PE

Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis


Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231206799. doi: 10.1177/10760296231206799.


ABSTRACT


This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P < .00001) with low heterogeneity (P = .17, I2 = 48%) and 1.21 (1.06-1.37, P = .004) in the ITB group with no heterogeneity (P = .95, I2 = 0%), respectively. Despite the heterogeneity identified, the evidence does suggest that VTE irAE occurrence could be served as a prognostic indicator, with higher frequencies of occurrence associated with poorer OS. However, the fundamental role of this association with clinical consequences should be further investigated in large cohorts and clinical trials.


PMID:37844585 | PMC:PMC10586005 | DOI:10.1177/10760296231206799

15:07

PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Unplugged: Catheter-Directed Therapies for Intermediate-Risk Pulmonary Embolism


JACC Cardiovasc Interv. 2023 Sep 27:S1936-8798(23)01212-8. doi: 10.1016/j.jcin.2023.08.029. Online ahead of print.


NO ABSTRACT


PMID:37855803 | DOI:10.1016/j.jcin.2023.08.029

15:07

PubMed articles on: Cancer & VTE/PE

Thrombin Generation Markers as Predictors of Cancer-Associated Venous Thromboembolism: A Systematic Review


Semin Thromb Hemost. 2023 Oct 9. doi: 10.1055/s-0043-1775856. Online ahead of print.


ABSTRACT


Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good (n = 13), fair (n = 8), to poor (n = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.


PMID:37813372 | DOI:10.1055/s-0043-1775856

15:07

PubMed articles on: Cancer & VTE/PE

Measurement of adherence and health-related quality of life during anticoagulation therapy in cancer-associated venous thromboembolism (VTE): a multicenter quantitative study


Support Care Cancer. 2023 Oct 6;31(10):615. doi: 10.1007/s00520-023-08073-y.


ABSTRACT


PURPOSE: Therapy for cancer-associated venous thromboembolism (VTE) includes long-term anticoagulation, which may have substantial impact on the health-related quality of life (HRQL) of patients. We assessed patient-reported outcomes to characterize the HRQL associated with VTE treatment and to begin to examine those HRQL elements impacting anticoagulation adherence (AA).


METHODS: Participants were adult cancer patients with confirmed symptomatic acute lower extremity deep venous thrombosis. Patients were excluded if there was an indication for anticoagulation other than VTE, ECOG performance status >3, or life expectancy < 3 months. Participants were assessed with a self-reported adherence tool. HRQL was measured with a 6-domain questionnaire using a seven-point Likert scale. Evaluations were performed at 30 days and 3 months after enrollment. For the primary objective, an overall adherence rate was calculated at each time point of evaluation. For the HRQL domains, non-parametric testing was used to compare results between subgroups.


RESULTS: Seventy-four patients were enrolled. AA and HRQL at 30 days and 3 months were assessed in 50 and 36 participants, respectively. At 30 days the AA rate was 90%, and at 3 months it was 83%. In regard to HRQL, patients suffered frequent and moderate-severe distress in the domains of emotional and physical symptoms, sleep disturbance, and limitations to physical activity. An association between emotional or physical distress and AA was observed.


CONCLUSION: Patients with VTE suffer a substantial impairment of their HRQL. Increased emotional distress correlated with better long-term AA. These results can be used to inform additional research aimed at developing novel strategies to improve AA.


PMID:37801086 | DOI:10.1007/s00520-023-08073-y

15:07

PubMed articles on: Cancer & VTE/PE

A - 119 A Case Study: the Cognitive Functioning of an Adult Patient with Recurrent Craniopharyngiomas


Arch Clin Neuropsychol. 2023 Oct 20;38(7):1291. doi: 10.1093/arclin/acad067.136.


 



ABSTRACT


A 'classical' and a 'basal-like' subtype of pancreatic cancer have been reported, with differential expression of GATA6 and different dosages of mutant KRAS. We established in situ detection of KRAS point mutations and mRNA panels for the consensus subtypes aiming to project these findings to paraffin-embedded clinical tumour samples for spatial quantitative analysis. We unveiled that, next to inter-patient and intra-patient inter-ductal heterogeneity, intraductal spatial phenotypes exist with anti-correlating expression levels of GATA6 and KRASG12D . The basal-like mRNA panel better captured the basal-like cell states than widely used protein markers. The panels corroborated the co-existence of the classical and basal-like cell states in a single tumour duct with functional diversification, i.e. proliferation and epithelial-to-mesenchymal transition respectively. Mutant KRASG12D detection ascertained an epithelial origin of vimentin-positive cells in the tumour. Uneven spatial distribution of cancer-associated fibroblasts could recreate similar intra-organoid diversification. This extensive heterogeneity with functional cooperation of plastic tumour cells poses extra challenges to therapeutic approaches. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


PMID:37842959 | DOI:10.1002/path.6212

15:06

PubMed articles on: Cardio-Oncology

Welcome to the Rising Stars in Cardio-Oncology Special Focus Issue


Future Cardiol. 2023 Sep;19(11):515-517. doi: 10.2217/fca-2022-0111. Epub 2023 Oct 18.


NO ABSTRACT


PMID:37850469 | DOI:10.2217/fca-2022-0111

15:06

PubMed articles on: Cardio-Oncology

Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs


J Natl Compr Canc Netw. 2023 Oct;21(10):1039-1049.e10. doi: 10.6004/jnccn.2023.7047.


ABSTRACT


BACKGROUND: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied.


METHODS: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation.


RESULTS: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant "on-treatment" hypertension was not associated with MACE.


CONCLUSIONS: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.


PMID:37856199 | DOI:10.6004/jnccn.2023.7047

15:06

PubMed articles on: Cardio-Oncology

Microparticles and cardiotoxicity secondary to doxorubicin-based chemotherapy in breast cancer patients


Int J Cardiol. 2023 Oct 16:131435. doi: 10.1016/j.ijcard.2023.131435. Online ahead of print.


ABSTRACT


Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients.


PMID:37852542 | DOI:10.1016/j.ijcard.2023.131435

15:06

PubMed articles on: Cancer & VTE/PE

Efficacy and Safety of Apixaban versus Dalteparin as a Treatment for Cancer-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis


Medicina (Kaunas). 2023 Oct 20;59(10):1867. doi: 10.3390/medicina59101867.


ABSTRACT


Background and Objectives: Venous thromboembolism (VTE) is common in cancer patients. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) and direct oral anticoagulants (DOACs), such as dalteparin and apixaban, have demonstrated efficacy and safety. However, more comparative research of these drugs is still needed. This study aimed to synthesize evidence on the efficacy of apixaban compared to dalteparin in reducing recurrent VTE, major bleeding, and clinically relevant non-major bleeding associated with cancer. Materials and Methods: We systematically searched the PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials databases up to 5 January 2023, for randomized controlled trials comparing apixaban versus dalteparin as treatment for cancer-associated VTE. Five studies were included. Effects according to meta-analyses were reported as relative risks (RRs) and their 95% confidence intervals (CIs). Results: It was found that 33 of 734 (4.5%) patients treated with apixaban and 56 of 767 (7.3%) with dalteparin had recurrent VTE as the efficacy outcome (RR 0.49, 95% CI 0.15-1.58, I2 38%). Major bleeding occurred in 25 of 734 patients treated with apixaban (3.4%) and 27 of 767 with dalteparin (3.5%) (RR 1.29, 95% CI 0.31-5.27, I2 59%). Likewise, clinically relevant non-major bleeding occurred in 64 of 734 patients treated with apixaban (8.7%) and 46 of 767 (5.9%) with dalteparin (RR 1.52, 95% CI 1.05-2.19, I2 0%). Conclusions: Apixaban showed a lower risk of recurrent VTE than dalteparin in patients with cancer-associated VTE, but without statistical significance. No statistical significance was observed in clinically relevant major or non-major bleeding.


PMID:37893585 | DOI:10.3390/medicina59101867

15:06

PubMed articles on: Cancer & VTE/PE

Risk and timing of venous thromboembolism after surgery for lung cancer: a nationwide cohort study


Ann Thorac Surg. 2023 Oct 25:S0003-4975(23)01073-1. doi: 10.1016/j.athoracsur.2023.10.015. Online ahead of print.


ABSTRACT


BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in lung cancer patients undergoing thoracic surgery. We examined the risk and timing of VTE following surgery for primary non-small cell lung cancer (NSCLC).


METHODS: in the Danish Lung Cancer Registry. VTE events in the year after surgery were assessed by stage, patient characteristics, and surgical procedure.


RESULTS: We identified 13,197 patients who underwent surgery for NSCLC in 2003-2021 (mean age 67.6 years, 50% female); 10,524 (79.7%) had stage I-II NSCLS and 2673 (20.3%) had stage III-IV. During one-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I versus 4.1% for stage IV), but varied little by pathological type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%, 95% CI 3.2-6.9), followed by pneumonectomy (3.6%, 95% CI 2.5-5.1). The hazard of VTE was highest during the first three months after surgery, whereafter it declined. For stage IV cancer hazards increased again after six months. At one-year, all-cause death was 12.6% (95% CI: 12.0-13.1 %).


CONCLUSIONS: Among patients undergoing surgery for NSCLC, 3.3% developed VTE, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.


PMID:37890818 | DOI:10.1016/j.athoracsur.2023.10.015

15:06

PubMed articles on: Cancer & VTE/PE

A Novel Model to Prevent Venous Thromboembolism in Patients with Lung Cancer


Altern Ther Health Med. 2023 Oct 27:AT9245. Online ahead of print.


ABSTRACT


OBJECTIVE: To observe the effect of nurse-patient co-management mode on preventing venous thromboembolism (VTE) in lung cancer patients with carboplatin and gemcitabine chemotherapy after peripheral venipuncture central venous catheterization (PICC).


METHODS: 100 patients with lung cancer admitted to the 2nd Affiliated Hospital of Hainan Medical University from April 2020 to April 2022 were selected. All patients received a combination chemotherapy of carboplatin and gemcitabine and PICC catheterization. The patients were divided into an observation group and a control group by 1:1 simple random method, with 50 cases in each group. Patients in the control group were given routine nursing for lung cancer, and patients in the observation group were treated with nurse-patient co-management mode, and nursing intervention lasted for 2 months. General Comfort Questionnaire, self-management ability, quality of life, Self-care ability Scale, self-rating Anxiety Scale (SAS), and self-rating depression Scale were compared before and after intervention between the two groups. The recovery of immune ability indices (CD3+, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) in 2 groups were detected. Complications after PICC catheterization were recorded in the two groups.


RESULTS: After nursing, self-rating depression Scale and self-rating Anxiety Scale scores in both groups were significantly decreased, which were lower in the observation group than the control group (P < .001). After nursing, scores of self-concept, self-responsibility, self-care skills, and health knowledge level were significantly increased in both groups, which were higher in the observation group than control group (P < .001). After nursing, scores on the General Comfort Questionnaire, self-management scale, and quality of life were increased in both groups, which were higher in the observation group than control group (P < .0501). After nursing care, the immune competence indices of both patients increased significantly, and the immune indexes of CD3+, CD3+CD4+, and CD3+ CD4+/CD3+CD8+ in the observation group were significantly higher than those in the control group (P < .05). The total incidence of complications in the observation group was significantly lower than that in the control group (8.00% vs. 26.00%, P < .001), and the incidence of venous thromboembolism was significantly lower than that in the control group (2.00% vs. 14.00%, P < .001).


CONCLUSION: The nurse-patient co-management model has shown to be effective in reducing the incidence of venous thromboembolism in patients who have undergone PICC catheterization while receiving carboplatin and gemcitabine chemotherapy. This model also helps patients improve their self-care and self-management abilities, alleviates adverse psychological effects, and contributes to the recovery of their immune system.


PMID:37883756

15:06

PubMed articles on: Cancer & VTE/PE

Evaluating the effect of immune checkpoint inhibitors on venous thromboembolism in non-small cell lung cancer patients


Expert Rev Hematol. 2023 Oct 26:1-8. doi: 10.1080/17474086.2023.2276209. Online ahead of print.


ABSTRACT


OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC.


RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients.


RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs.


CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.


PMID:37883026 | DOI:10.1080/17474086.2023.2276209

15:06

PubMed articles on: Cancer & VTE/PE

Hospital-Acquired Venous Thromboembolism and Invasive Mechanical Ventilation: A Report From the Children's Hospital Acquired Thrombosis Consortium


Pediatr Crit Care Med. 2023 Oct 26. doi: 10.1097/PCC.0000000000003383. Online ahead of print.


ABSTRACT


OBJECTIVES: To determine if the duration of invasive mechanical ventilation (IMV) was associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children.


DESIGN: A multicenter, matched case-control study as a secondary analysis of Children's Hospital Acquired Thrombosis (CHAT) Consortium registry.


SETTING: PICUs within U.S. CHAT Consortium participating centers.


PATIENTS: Children younger than 21 years old admitted to a PICU receiving IMV for greater than or equal to 1 day duration from January 2012 to March 2022 were included for study. Cases with HA-VTE were matched 1:2 to controls without HA-VTE by patient age groups: younger than 1, 1-12, and older than 12 years.


INTERVENTIONS: None.


MEASUREMENTS AND MAIN RESULTS: The primary outcome was IMV duration in days. Descriptive data included demographics, anthropometrics, HA-VTE characteristics (i.e., type, location, and timing), central venous catheterization data, thromboprophylaxis practices, and Braden Q mobility scores. Descriptive, comparative, and associative (multivariate conditional logistic regression for HA-VTE) statistics were employed. A total of 152 cases were matched to 304 controls. Cases with HA-VTE were diagnosed at a median of 7 days (interquartile range [IQR], 3-16 d) after IMV. The HA-VTE were limb deep venous thromboses in 130 of 152 (85.5%) and frequently central venous catheterization-related (111/152, 73%). Cases with HA-VTE experienced a longer length of stay (median, 34 d [IQR, 18-62 d] vs. 11.5 d [IQR, 6-21 d]; p < 0.001) and IMV duration (median, 7 d [IQR, 4-15 d] vs. 4 d [IQR, 1-7 d]; p < 0.001) as compared with controls. In a multivariate logistic model, greater IMV duration (adjusted odds ratio, 1.09; 95% CI, 1.01-1.17; p = 0.023) was independently associated with HA-VTE.


CONCLUSIONS: Among critically ill children undergoing IMV, HA-VTE was associated with greater IMV duration. If prospectively validated, IMV duration should be included as part of prothrombotic risk stratification and future pediatric thromboprophylaxis trials.


PMID:37882641 | DOI:10.1097/PCC.0000000000003383

15:06

PubMed articles on: Cancer & VTE/PE

Guidelines in Practice: Prevention of Venous Thromboembolism


AORN J. 2023 Nov;118(5):321-328. doi: 10.1002/aorn.14019.


ABSTRACT


Venous thromboembolism (VTE), a condition involving deep vein thrombosis and embolism, can cause death when left untreated. Hospitalized patients and those who have recently undergone surgery or have a cancer diagnosis are at increased risk for VTE development. The updated AORN "Guideline for prevention of venous thromboembolism" provides perioperative nurses with a variety of evidence-based recommendations associated with the topic. This article provides an overview of the guideline and discusses recommendations for a VTE protocol, VTE and bleeding risk assessments, pharmacologic and mechanical VTE prophylaxis, postoperative ambulation, and patient and family education. It also includes a scenario that illustrates the importance of the VTE assessment and the use of mechanical prophylaxis for high-risk patients undergoing operative or other invasive procedures. Perioperative nurses should review the guideline in its entirety and implement recommendations in operative and procedural settings.


PMID:37882602 | DOI:10.1002/aorn.14019

15:06

PubMed articles on: Cancer & VTE/PE

Heterogeneous distributions in clinical events preceding anticoagulant treatment nonpersistence in patients with venous thromboembolism stratified by active cancer: A nationwide cohort study


Cancer Med. 2023 Oct 26. doi: 10.1002/cam4.6626. Online ahead of print.


ABSTRACT


BACKGROUND: Nonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE).


METHODS: We investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database.


RESULTS: Clinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs).


CONCLUSION: These findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.


PMID:37882319 | DOI:10.1002/cam4.6626

15:06

PubMed articles on: Cancer & VTE/PE

How we manage a high D-dimer


Haematologica. 2023 Oct 26. doi: 10.3324/haematol.2023.283966. Online ahead of print.


ABSTRACT


D-dimer, a soluble fibrin degradation product that originates from plasmin-induced degradation of cross-linked fibrin, is an important biomarker of coagulation activation and secondary fibrinolysis that is routinely used to rule out venous thromboembolism (VTE), to evaluate the risk of VTE recurrence as well as the optimal duration of anticoagulant therapy. Besides VTE, D-dimer may be high due to physiologic conditions, including aging, pregnancy and strenuous physical activity. In addition, several disorders have been associated with increased D-dimer levels, spanning from disseminated intravascular coagulation to infectious diseases and cancers. Thus, it is far from unusual for hematologists to have to deal with ambulatory individuals presenting with increased Ddimer without signs or symptoms of thrombus formation. To the management of these cases by the hematologist is dedicated this narrative review.


PMID:37881856 | DOI:10.3324/haematol.2023.283966

15:06

PubMed articles on: Cancer & VTE/PE

Episodic Cocaine Use as a Cause of Venous Thromboembolism and Acute Liver Injury


Am J Case Rep. 2023 Oct 24;24:e941360. doi: 10.12659/AJCR.941360.


ABSTRACT


BACKGROUND Pulmonary embolism secondary to deep vein thrombosis (DVT) with cor pulmonale is commonly associated with risk factors including surgery, cancer, and prolonged immobility. Cocaine is known to cause vasoconstriction and has a prothrombotic effect. Prolonged and heavy use of cocaine can also cause inflammation and liver damage. However, data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. CASE REPORT A 34-year-old man with no significant medical history except for episodic cocaine use presented in respiratory distress. Workup revealed submassive pulmonary embolism with pulmonary infarctions complicated by pneumonia, hypoxemic respiratory failure, and anemia. He was treated with anticoagulation and intensive care. On day 5 of hospitalization, the patient had an acute hepatic injury. His alanine aminotransferase level peaked at over 2000 IU/L on day 7, until finally tapering. Liver failure was found to be secondary to cocaine use. Liver enzyme levels improved with supportive care. He was discharged with apixaban and continued liver enzyme monitoring. CONCLUSIONS When investigating the cause of venous thromboembolism and transaminitis, evaluating cocaine use via patient history or laboratory analysis of cocaine and its metabolites should be considered. Cocaine is known to cause vasoconstriction and has a prothrombotic effect, although data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Further investigation, such as cohort studies, could help strengthen our understanding of the relationship between cocaine use, acute hepatic injury, and pulmonary embolism.


PMID:37872733 | DOI:10.12659/AJCR.941360

15:06

PubMed articles on: Cancer & VTE/PE

Comparison of Direct Oral Anticoagulants versus Low Molecular Weight Heparin in Primary and Metastatic Brain Cancers: A Meta-Analysis and Systematic Review


J Thromb Haemost. 2023 Oct 20:S1538-7836(23)00779-1. doi: 10.1016/j.jtha.2023.10.011. Online ahead of print.


ABSTRACT


BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known.


OBJECTIVE: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs. LMWH.


METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n=1,638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup.


RESULTS: The pooled RR for ICH in patients receiving DOACs vs. those receiving LMWH was 0.65 (95% confidence interval [CI], 0.36-1.17; P = 0.15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = 0.003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = 0.80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants.


DISCUSSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.


PMID:37866517 | DOI:10.1016/j.jtha.2023.10.011

15:07

PubMed articles on: Cancer & VTE/PE

Two Cases of Catheter-Related Venous Thrombosis Treated with Direct Oral Anticoagulants(DOAC)


Gan To Kagaku Ryoho. 2023 Sep;50(9):993-996.


ABSTRACT


The implantation of a totally implantable central venous(CV)access port is considered a risk factor for venous thromboembolism( VTE). In the treatment of catheter-related thrombosis(CRT), both European and American guidelines recommend anticoagulation therapy with catheters in place. We experienced 2 cases of upper extremity deep vein thrombosis (UEDVT)after the implantation of CV access ports through the left subclavian vein for adjuvant chemotherapy in patients with resected breast cancer. Both patients were successfully treated with direct oral anticoagulants(DOAC) while the port remained in place with a careful follow-up that included monitoring of serum D-dimer levels. The administration of DOAC to CRT that develops in patients undergoing postoperative adjuvant chemotherapy for breast cancer may be relatively safe, with a low potential for adverse events such as bleeding.


PMID:37800295

15:07

PubMed articles on: Cancer & VTE/PE

Computer image analysis with artificial intelligence: a practical introduction to convolutional neural networks for medical professionals


Postgrad Med J. 2023 Oct 4:qgad095. doi: 10.1093/postmj/qgad095. Online ahead of print.


ABSTRACT


Artificial intelligence tools, particularly convolutional neural networks (CNNs), are transforming healthcare by enhancing predictive, diagnostic, and decision-making capabilities. This review provides an accessible and practical explanation of CNNs for clinicians and highlights their relevance in medical image analysis. CNNs have shown themselves to be exceptionally useful in computer vision, a field that enables machines to 'see' and interpret visual data. Understanding how these models work can help clinicians leverage their full potential, especially as artificial intelligence continues to evolve and integrate into healthcare. CNNs have already demonstrated their efficacy in diverse medical fields, including radiology, histopathology, and medical photography. In radiology, CNNs have been used to automate the assessment of conditions such as pneumonia, pulmonary embolism, and rectal cancer. In histopathology, CNNs have been used to assess and classify colorectal polyps, gastric epithelial tumours, as well as assist in the assessment of multiple malignancies. In medical photography, CNNs have been used to assess retinal diseases and skin conditions, and to detect gastric and colorectal polyps during endoscopic procedures. In surgical laparoscopy, they may provide intraoperative assistance to surgeons, helping interpret surgical anatomy and demonstrate safe dissection zones. The integration of CNNs into medical image analysis promises to enhance diagnostic accuracy, streamline workflow efficiency, and expand access to expert-level image analysis, contributing to the ultimate goal of delivering further improvements in patient and healthcare outcomes.


PMID:37794609 | DOI:10.1093/postmj/qgad095

15:07

PubMed articles on: Cancer & VTE/PE

Artificial intelligence in the prediction of venous thromboembolism: A systematic review and pooled analysis


Eur J Haematol. 2023 Oct 4. doi: 10.1111/ejh.14110. Online ahead of print.


ABSTRACT


BACKGROUND: Accurate diagnostic and prognostic predictions of venous thromboembolism (VTE) are crucial for VTE management. Artificial intelligence (AI) enables autonomous identification of the most predictive patterns from large complex data. Although evidence regarding its performance in VTE prediction is emerging, a comprehensive analysis of performance is lacking.


AIMS: To systematically review the performance of AI in the diagnosis and prediction of VTE and compare it to clinical risk assessment models (RAMs) or logistic regression models.


METHODS: A systematic literature search was performed using PubMed, MEDLINE, EMBASE, and Web of Science from inception to April 20, 2021. Search terms included "artificial intelligence" and "venous thromboembolism." Eligible criteria were original studies evaluating AI in the prediction of VTE in adults and reporting one of the following outcomes: sensitivity, specificity, positive predictive value, negative predictive value, or area under receiver operating curve (AUC). Risks of bias were assessed using the PROBAST tool. Unpaired t-test was performed to compare the mean AUC from AI versus conventional methods (RAMs or logistic regression models).


RESULTS: A total of 20 studies were included. Number of participants ranged from 31 to 111 888. The AI-based models included artificial neural network (six studies), support vector machines (four studies), Bayesian methods (one study), super learner ensemble (one study), genetic programming (one study), unspecified machine learning models (two studies), and multiple machine learning models (five studies). Twelve studies (60%) had both training and testing cohorts. Among 14 studies (70%) where AUCs were reported, the mean AUC for AI versus conventional methods were 0.79 (95% CI: 0.74-0.85) versus 0.61 (95% CI: 0.54-0.68), respectively (p < .001). However, the good to excellent discriminative performance of AI methods is unlikely to be replicated when used in clinical practice, because most studies had high risk of bias due to missing data handling and outcome determination.


CONCLUSION: The use of AI appears to improve the accuracy of diagnostic and prognostic prediction of VTE over conventional risk models; however, there was a high risk of bias observed across studies. Future studies should focus on transparent reporting, external validation, and clinical application of these models.


PMID:37794526 | DOI:10.1111/ejh.14110

15:07

PubMed articles on: Cancer & VTE/PE

Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis


Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231206799. doi: 10.1177/10760296231206799.


ABSTRACT


This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P < .00001) with low heterogeneity (P = .17, I2 = 48%) and 1.21 (1.06-1.37, P = .004) in the ITB group with no heterogeneity (P = .95, I2 = 0%), respectively. Despite the heterogeneity identified, the evidence does suggest that VTE irAE occurrence could be served as a prognostic indicator, with higher frequencies of occurrence associated with poorer OS. However, the fundamental role of this association with clinical consequences should be further investigated in large cohorts and clinical trials.


PMID:37844585 | PMC:PMC10586005 | DOI:10.1177/10760296231206799

15:07

PubMed articles on: Cancer & VTE/PE

Pulmonary Embolism Unplugged: Catheter-Directed Therapies for Intermediate-Risk Pulmonary Embolism


JACC Cardiovasc Interv. 2023 Sep 27:S1936-8798(23)01212-8. doi: 10.1016/j.jcin.2023.08.029. Online ahead of print.


NO ABSTRACT


PMID:37855803 | DOI:10.1016/j.jcin.2023.08.029

15:07

PubMed articles on: Cancer & VTE/PE

Thrombin Generation Markers as Predictors of Cancer-Associated Venous Thromboembolism: A Systematic Review


Semin Thromb Hemost. 2023 Oct 9. doi: 10.1055/s-0043-1775856. Online ahead of print.


ABSTRACT


Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good (n = 13), fair (n = 8), to poor (n = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.


PMID:37813372 | DOI:10.1055/s-0043-1775856

15:07

PubMed articles on: Cancer & VTE/PE

Measurement of adherence and health-related quality of life during anticoagulation therapy in cancer-associated venous thromboembolism (VTE): a multicenter quantitative study


Support Care Cancer. 2023 Oct 6;31(10):615. doi: 10.1007/s00520-023-08073-y.


ABSTRACT


PURPOSE: Therapy for cancer-associated venous thromboembolism (VTE) includes long-term anticoagulation, which may have substantial impact on the health-related quality of life (HRQL) of patients. We assessed patient-reported outcomes to characterize the HRQL associated with VTE treatment and to begin to examine those HRQL elements impacting anticoagulation adherence (AA).


METHODS: Participants were adult cancer patients with confirmed symptomatic acute lower extremity deep venous thrombosis. Patients were excluded if there was an indication for anticoagulation other than VTE, ECOG performance status >3, or life expectancy < 3 months. Participants were assessed with a self-reported adherence tool. HRQL was measured with a 6-domain questionnaire using a seven-point Likert scale. Evaluations were performed at 30 days and 3 months after enrollment. For the primary objective, an overall adherence rate was calculated at each time point of evaluation. For the HRQL domains, non-parametric testing was used to compare results between subgroups.


RESULTS: Seventy-four patients were enrolled. AA and HRQL at 30 days and 3 months were assessed in 50 and 36 participants, respectively. At 30 days the AA rate was 90%, and at 3 months it was 83%. In regard to HRQL, patients suffered frequent and moderate-severe distress in the domains of emotional and physical symptoms, sleep disturbance, and limitations to physical activity. An association between emotional or physical distress and AA was observed.


CONCLUSION: Patients with VTE suffer a substantial impairment of their HRQL. Increased emotional distress correlated with better long-term AA. These results can be used to inform additional research aimed at developing novel strategies to improve AA.


PMID:37801086 | DOI:10.1007/s00520-023-08073-y

15:07

PubMed articles on: Cancer & VTE/PE

A - 119 A Case Study: the Cognitive Functioning of an Adult Patient with Recurrent Craniopharyngiomas


Arch Clin Neuropsychol. 2023 Oct 20;38(7):1291. doi: 10.1093/arclin/acad067.136.


 



ABSTRACT


The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized. Different mechanical and pharmacological interventions to protect the ischemic/reperfused myocardium in elective percutaneous coronary interventions and coronary artery bypass grafting, in acute myocardial infarction and in cardiotoxicity from cancer therapy are detailed. The second part keeps the focus on ROS providing a comprehensive overview of molecular and cellular mechanisms involved in ischemia/reperfusion injury. Starting from mitochondria as the main sources and targets of ROS in ischemic/reperfused myocardium, a complex network of cellular and extracellular processes is discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk with NAPDH oxidases, exosomes, cytokines and growth factors. While mechanistic insights are needed to improve our current therapeutic approaches, advancements in knowledge of ROS-mediated processes indicate that detrimental facets of oxidative stress are opposed by ROS requirement for physiological and protective reactions. This inevitable contrast is likely to underlie unsuccessful clinical trials and limits the development of novel cardioprotective interventions simply based upon ROS removal.


PMID:37839355 | PMC:PMC10590874 | DOI:10.1016/j.redox.2023.102894

15:05

PubMed articles on: Cardio-Oncology

Influencing factors of anthracycline-induced subclinical cardiotoxicity in acute leukemia patients


BMC Cancer. 2023 Oct 13;23(1):976. doi: 10.1186/s12885-023-11060-5.


ABSTRACT


BACKGROUND: Current treatment of acute leukemia is based on anthracycline chemotherapy. Anthracyclines, despite improving patient survival, have serious cardiotoxicity and therefore cardiac monitoring should be a priority. The purpose of this study is to explore the possible early predictors of anthracycline-induced subclinical cardiotoxicity(AISC)in acute leukemia patients.


METHODS: We conducted a prospective observational study involving 51 patients with acute leukemia treated with anthracycline. Demographic data, clinical variables, echocardiography variables and biochemical variables were collected at baseline and after 3 cycles of chemotherapy. Patients were divided into the AISC and No-AISC groups according to changes of global longitudinal peak systolic strain. Regression models and receiver operating characteristic curve analysis were used to explore the relationship between the variables and AISC.


RESULT: 17 of the patients suffered subclinical cardiotoxicity after 3 cycles of anthracycline treatment. Multiple logistic regression analysis showed a significant association of DBil (OR 0.612, 95% CI 0.409-0.916, p = 0.017), TBil (OR 0.841, 95% CI 0.717-0.986, p = 0.033), PLT (OR 1.012, 95% CI 1.002-1.021, p = 0.016) and Glu (OR 1.873, 95% CI 1.009-3.475, p = 0.047) with the development of AISC. After 3 cycles of chemotherapy, there was a significant difference in PLT between the AISC and NO-AISC groups. Moreover, the dynamic changes in PLT from baseline to after 3 cycles of chemotherapy were each statistically significant in the AISC and NO-AISC groups. The combination of PLT and N-terminal pro-B-type natriuretic peptide (NT-proBNP) had the highest area under curves (AUC) for the diagnosis of AISC than PLT and NT-proBNP alone (AUC = 0.713, 95%CI: 0.56-0.87, P = 0.017).


CONCLUSION: Total bilirubin (TBil), direct bilirubin (DBil), platelets (PLT) and blood glucose (Glu) are independent influencing factors for AISC in acute leukemia patients receiving anthracycline therapy. Bilirubin may be a protective factor and PLT may be a contributing factor for AISC. The combination of baseline PLT and baseline NT-proBNP shows satisfactory predictive ability for AISC in acute leukemia cases treated with 3 cycles of chemotherapy.


PMID:37833648 | PMC:PMC10571315 | DOI:10.1186/s12885-023-11060-5

15:05

PubMed articles on: Cardio-Oncology

Clinical outcomes of takotsubo syndrome in patients with cancer: a systematic review and meta-analysis


Front Cardiovasc Med. 2023 Sep 29;10:1244808. doi: 10.3389/fcvm.2023.1244808. eCollection 2023.


ABSTRACT


BACKGROUND: Recent studies suggested a relationship between Takotsubo syndrome (TTS) and malignancy. However, clinical outcomes of TTS associated with cancer have not been assessed completely. This study was aimed to investigate the outcomes of patients with TTS and cancer.


METHODS: We performed a systematic review and meta-analysis to evaluate the clinical outcomes of TTS in patients with and without malignancy. We systematically reviewed and analyzed 14 studies (189,210 patients) published in PubMed and Cochrane Library databases until December 2022. The primary outcome was all-cause mortality at the longest follow-up.


RESULTS: The prevalence of current or previous malignancy in patients with TTS was 8.7% (16,461 patients). Patients with TTS and malignancy demonstrated a higher risk of mortality at the longest follow-up than those with TTS alone (odds ratio [OR], 2.41; 95% confidence interval [CI]; 1.95-2.98; P < 0.001). Moreover, cancer was significantly associated with an increased risk of in-hospital or 30-day mortality (OR 2.36; 95% CI, 1.67-3.33; P < 0.001), shock (OR 1.42; 95% CI, 1.30-1.55; P < 0.001), mechanical respiratory support (OR 1.68; 95% CI, 1.59-1.77; P < 0.001), arrhythmia (OR 1.27; 95% CI, 1.21-1.34; P < 0.001), and major adverse cardiac events (OR 1.69; 95% CI, 1.18-2.442; P < 0.001).


CONCLUSIONS: This study revealed significant associations between previous or active cancer and an increased risk of all-cause mortality and in-hospital adverse events in patients with TTS.


PMID:37840966 | PMC:PMC10570743 | DOI:10.3389/fcvm.2023.1244808

15:05

PubMed articles on: Cardio-Oncology

The Role of Nrf2 and Inflammation on the Dissimilar Cardiotoxicity of Doxorubicin in Two-Time Points: a Cardio-Oncology In Vivo Study Through Time


Inflammation. 2023 Oct 14. doi: 10.1007/s10753-023-01908-0. Online ahead of print.


ABSTRACT


Doxorubicin (DOX) is a topoisomerase II inhibitor used in cancer therapy. Despite its efficacy, DOX causes serious adverse effects, such as short- and long-term cardiotoxicity. This work aimed to assess the short- and long-term cardiotoxicity of DOX and the role of inflammation and antioxidant defenses on that cardiotoxicity in a mice model. Adult CD-1 male mice received a cumulative dose of 9.0 mg/kg of DOX (2 biweekly intraperitoneal injections (ip), for 3 weeks). One week (1W) or 5 months (5M) after the last DOX administration, the heart was collected. One week after DOX, a significant increase in p62, tumor necrosis factor receptor (TNFR) 2, glutathione peroxidase 1, catalase, inducible nitric oxide synthase (iNOS) cardiac expression, and a trend towards an increase in interleukin (IL)-6, TNFR1, and B-cell lymphoma 2 associated X (Bax) expression was observed. Moreover, DOX induced a decrease on nuclear factor erythroid-2 related factor 2 (Nrf2) cardiac expression. In both 1W and 5M, DOX led to a high density of infiltrating M1 macrophages, but only the 1W-DOX group had a significantly higher number of nuclear factor κB (NF-κB) p65 immunopositive cells. As late effects (5M), an increase in Nrf2, myeloperoxidase, IL-33, tumor necrosis factor-α (TNF-α), superoxide dismutase 2 (SOD2) expression, and a trend towards increased catalase expression were observed. Moreover, B-cell lymphoma 2 (Bcl-2), cyclooxygenase-2 (COX-2), and carbonylated proteins expression decreased, and a trend towards decreased p38 mitogen-activated protein kinase (MAPK) expression were seen. Our study demonstrated that DOX induces adverse outcome pathways related to inflammation and oxidative stress, although activating different time-dependent response mechanisms.


PMID:37833616 | DOI:10.1007/s10753-023-01908-0

15:05

PubMed articles on: Cardio-Oncology

In-Hospital and readmission outcomes of patients with myeloproliferative neoplasms and atrial fibrillation: insights from the National Readmissions Database


J Thromb Thrombolysis. 2023 Oct 15. doi: 10.1007/s11239-023-02900-z. Online ahead of print.


ABSTRACT


INTRODUCTION: Patients with myeloproliferative neoplasms (MPNs) and atrial fibrillation (AF) are at increased risk of thrombosis and bleeding. However, the risk of thrombosis and bleeding in patients with AF and MPN compared with the general population with AF is unclear. Additionally, traditional risk scores (CHA2DS2-VASC and HAS-BLED) for risk/benefit estimation of thromboprophylaxis in AF do not account for MPN status. Therefore, we aimed to investigate bleeding and thrombosis risk in patients with MPN hospitalized for AF.


METHODS: We utilized the National Readmission Database (NRD) to identify patients with AF with and without MPN. Primary bleeding and thrombosis outcomes were in-hospital or 30-day readmission for bleeding or thrombosis, respectively. We propensity score (PS) matched patients with and without MPN. Risk of primary outcomes in MPN was assessed in PS matched cohort using logistic regression. Receiver operating characteristic (ROC) curve used to evaluate predictive ability of CHA2DS2-VASC and HAS-BLED of primary thrombosis and bleeding outcomes, respectively.


RESULTS: 24,185 patients without MPN were matched with 1,617 patients with MPN and variables were balanced between groups. Patients with MPN were at increased risk of meeting the thrombosis (OR 1.98, 95% CI 1.23-3.21) but not bleeding (OR 0.87, 95% CI 0.63-1.19) primary outcomes. In MPN, CHA2DS2-VASC predicted thrombosis (C-statistic 0.66, 95% CI 0.54-0.78) but HAS-BLED was a poor predictor of bleeding (C-statistic 0.55, 95% CI 0.46-0.64).


CONCLUSION: In patients with AF, MPN was associated with increased risk of bleeding and thrombosis. HAS-BLED scores did not accurately predict bleeding in MPN. Further investigation is needed to refine risk scores in MPN.


PMID:37839025 | DOI:10.1007/s11239-023-02900-z

15:05

PubMed articles on: Cardio-Oncology

Empagliflozin treatment of cardiotoxicity: A comprehensive review of clinical, immunobiological, neuroimmune, and therapeutic implications


Biomed Pharmacother. 2023 Oct 13;168:115686. doi: 10.1016/j.biopha.2023.115686. Online ahead of print.


ABSTRACT


Cancer and cardiovascular disorders are known as the two main leading causes of mortality worldwide. Cardiotoxicity is a critical and common adverse effect of cancer-related chemotherapy. Chemotherapy-induced cardiotoxicity has been associated with various cancer treatments, such as anthracyclines, immune checkpoint inhibitors, and kinase inhibitors. Different methods have been reported for the management of chemotherapy-induced cardiotoxicity. In this regard, sodium-glucose cotransporter-2 inhibitors (SGLT2i), a class of antidiabetic agents, have recently been applied to manage heart failure patients. Further, SGLT2i drugs such as EMPA exert protective cardiac and systemic effects. Moreover, it can reduce inflammation through the mediation of major inflammatory components, such as Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, Adenosine 5'-monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal kinase (JNK) pathways, Signal transducer and activator of transcription (STAT), and overall decreasing transcription of proinflammatory cytokines. The clinical outcome of EMPA administration is related to improving cardiovascular risk factors, including body weight, lipid profile, blood pressure, and arterial stiffness. Intriguingly, SGLT2 suppressors can regulate microglia-driven hyperinflammation affecting neurological and cardiovascular disorders. In this review, we discuss the protective effects of EMPA in chemotherapy-induced cardiotoxicity from molecular, immunological, and neuroimmunological aspects to preclinical and clinical outcomes.


PMID:37839109 | DOI:10.1016/j.biopha.2023.115686

15:05

PubMed articles on: Cardio-Oncology

Cancer and Atrial Fibrillation Comorbidities Among 25 Million Citizens in Shanghai, China: Medical Insurance Database Study


JMIR Public Health Surveill. 2023 Oct 17;9:e40149. doi: 10.2196/40149.


ABSTRACT


BACKGROUND: With population aging, the prevalence of both cancer and atrial fibrillation (AF) have increased. However, there is scarce epidemiological data concerning the comorbid state of cancer and AF in low- and middle-income countries, including China.


OBJECTIVE: We aimed to evaluate the site-, sex-, and age-specific profiles of cancer and AF comorbidities in Chinese populations.


METHODS: Data from the Shanghai Municipal Health Commission database between 2015 and 2020 were screened, covering all medical records of Shanghai residents with medical insurance. Site-specific cancer profiles were evaluated for the population with AF relative to the age- and sex-adjusted population of residents without AF. The sex distribution and peak age of cancer diagnosis were also assessed.


RESULTS: A total of 25,964,447 adult patients were screened. Among them, 22,185 patients presented cancers comorbid with AF (median 77, IQR 67-82 years of age; men: n=13,631, 61.44%), while 839,864 presented cancers without AF (median 67, IQR 57-72 years of age; men: n=419,020, 49.89%), thus yielding a higher cancer prevalence among residents with AF (8.27%) than among those without AF (6.05%; P<.001).


CONCLUSIONS: Patients with AF are associated with increased prevalence, heightened male predominance, and younger peak age of cancer. Further studies are needed to determine whether early screening of specific cancers is cost-effective and beneficial for patients with AF.


PMID:37847541 | DOI:10.2196/40149

15:05

PubMed articles on: Cardio-Oncology

Brugada phenocopy with altered ST-segment elevation in pericardial diffuse large B-cell lymphoma and effusive-constrictive pericarditis: a case report


Eur Heart J Case Rep. 2023 Oct 17;7(10):ytad463. doi: 10.1093/ehjcr/ytad463. eCollection 2023 Oct.


ABSTRACT


BACKGROUND: Cardiac lymphoma is a rare disease. Effusive-constrictive pericarditis can be a characteristic of pericardial involvement in patients with this disease. Conversely, a phenotype with electrocardiogram changes similar to those of Brugada syndrome is called Brugada phenocopy, and these changes improve after treatment.


CASE SUMMARY: A 71-year-old man was transported to our hospital with chest pain, hypotension, and ST-segment elevation in V1 and V2 leads during maintenance dialysis for renal failure. After arrival at the hospital, his ST-segment elevation disappeared, and emergency coronary angiography scan revealed no significant coronary artery stenoses or obstructions. His computed tomography and echocardiography scans revealed pericardial effusion and an intrapericardial mass. Further, his blood pressure dropped and ST-segment elevation recurred during dialysis after 7 days. Thus, pericardiocentesis was performed, but haemodynamic improvement was insufficient, and right catheterization findings suggested effusive-constrictive pericarditis. Meanwhile, flow cytometry of the pericardial fluid suggested the diagnosis of B-cell lymphoma; however, radical chemoradiotherapy was impossible because of cardiogenic shock. The patient died on Day 17. Further, autopsy revealed diffuse large B-cell lymphoma with pericardial and myocardial infiltration.


DISCUSSION: Cardiac lymphoma is rare but can be associated with effusive-constrictive pericarditis, which may be difficult to manage even with pericardial drainage. In such cases, radical treatment, including chemotherapy, should be promptly considered, if possible. Our patient presented with Brugada-type electrocardiogram but no syncope or family history, suggesting Brugada phenocopy and not true Brugada syndrome due to cardiac lymphoma. Notably, temporary improvement in ST-segment elevation was observed despite the absence of treatment.


PMID:37854103 | PMC:PMC10580269 | DOI:10.1093/ehjcr/ytad463

15:05

PubMed articles on: Cardio-Oncology

Social disparities in cardiovascular mortality of patients with cancer in the USA between 1999 and 2019


Int J Cardiol Cardiovasc Risk Prev. 2023 Oct 3;19:200218. doi: 10.1016/j.ijcrp.2023.200218. eCollection 2023 Dec.


ABSTRACT


BACKGROUND: Temporal trends of the impact of social determinants on cardiovascular outcomes of cancer patients has not been previously studied.


OBJECTIVES: This study examined social disparities in cardiovascular mortality of people with and without cancer in the US population between 1999 and 2019.


METHODS: Primary cardiovascular deaths were identified from the Multiple Cause of Death database and grouped by cancer status. The cancer cohort was subcategorized into breast, lung, prostate, colorectal, and haematological. The number of cardiovascular deaths, crude cardiovascular mortality rate, cardiovascular age-adjusted mortality rate (AAMR), and percentage change in cardiovascular AAMR were calculated by cancer status and cancer type, and stratified by sex, race, ethnicity, and urban-rural setting.


RESULTS: 17.9 million cardiovascular deaths were analysed. Of these, 572,222 occurred in patients with a record of cancer. The cancer cohort were older and included more men and White racial groups. Regardless of cancer status, cardiovascular AAMR was higher in men, rural settings, and Black or African American races. Cardiovascular AAMR declined over time, with greater reduction in those with cancer (-51.6% vs -38.3%); the greatest reductions were in colorectal (-68.4%), prostate (-60.0%), and breast (-58.8%) cancers. Sex, race, and ethnic disparities reduced over time, with greater narrowing in the cancer cohort. There was increase in urban-rural disparities, which appeared greater in those with cancer.


CONCLUSIONS: While most social disparities narrowed over time, urban-rural disparities widened, with greater increase in those with cancer. Healthcare plans should incorporate strategies for reduction of health inequality equitable access to cardio-oncology services.


PMID:37841449 | PMC:PMC10568337 | DOI:10.1016/j.ijcrp.2023.200218

15:05

PubMed articles on: Cardio-Oncology

Multimodal Imaging of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer-A State-of-the-Art Review


J Clin Med. 2023 Sep 29;12(19):6295. doi: 10.3390/jcm12196295.


ABSTRACT


BACKGROUND: This review focuses on multimodality imaging of cardiotoxicity in cancer patients, with the aim of evaluating the effectiveness of different techniques in detecting and monitoring cardiac changes associated with cancer therapy.


METHODS: Eight studies were included in the review, covering various imaging modalities such as cardiac magnetic resonance imaging, echocardiography, and multigated acquisition scanning.


RESULTS: Cardiac magnetic resonance imaging emerged as the most definitive modality, offering real-time detection, comprehensive assessment of cardiac function, the ability to detect early myocardial changes, and superior detection of cardiotoxicity when compared to the other imaging modalities. The studies also emphasize the importance of parameters such as left ventricular ejection fraction and global longitudinal strain in assessing cardiac function and predicting cardiotoxicity.


CONCLUSION: Due to the common use of HER2 agents and anthracyclines within the breast cancer population, the LVEF as a critical prognostic measurement for assessing heart health and estimating the severity of left-sided cardiac malfunction is a commonly used endpoint. CTRCD rates differed between imaging modalities, with cardiac MRI the most sensitive. The use of multimodal cardiac imaging remains a nuanced area, influenced by local availability, the clinical question at hand, body habits, and medical comorbidities. All of the imaging modalities listed have a role to play in current care; however, focus should be given to increasing the provision of cardiac MRI for breast cancer patients in the future to optimize the detection of CTRCD and patient outcomes thereafter.


PMID:37834939 | PMC:PMC10573256 | DOI:10.3390/jcm12196295

15:05

PubMed articles on: Cardio-Oncology

Adjuvant Therapy-Free Strategy for Stage IB to IIIA Non-Small-Cell Lung Cancer Patients After Radical Resection Based on Longitudinal Undetectable Molecular Residual Disease: Prospective, Multicenter, Single-Arm Study (CTONG 2201)


Clin Lung Cancer. 2023 Oct 6:S1525-7304(23)00189-4. doi: 10.1016/j.cllc.2023.09.008. Online ahead of print.


ABSTRACT


BACKGROUND: The utility of circulating tumor DNA to monitor molecular residual disease (MRD) has been clinically confirmed to predict disease recurrence in non-small cell lung cancer (NSCLC) patients after radical resection. Patients with longitudinal undetectable MRD show a favorable prognosis and might not benefit from adjuvant therapy.


PATIENTS AND METHODS: The CTONG 2201 trial is a prospective, multicenter, single-arm study (ClinicalTrials.gov identifier, NCT05457049), designed to evaluate the hypothesis that no adjuvant therapy is needed for patients with longitudinal undetectable MRD. Pathologically confirmed stage IB-IIIA NSCLC patients who have undergone radical resection will be screened. Only patients with 2 consecutive rounds of undetectable MRD will be enrolled (first at days 3-10, second at days 30 ± 7 after surgery), and admitted for imaging and MRD monitoring every 3 months without adjuvant therapy. The primary endpoint is the 2-year disease-free survival rate for those with longitudinal undetectable MRD. The recruitment phase began in August 2022 and 180 patients will be enrolled.


CONCLUSIONS: This prospective trial will contribute data to confirm the negative predictive value of MRD on adjuvant therapy for NSCLC patients.


CLINICAL TRIAL REGISTRATION: NCT05457049 (CTONG 2201).


PMID:37880076 | DOI:10.1016/j.cllc.2023.09.008

15:05

PubMed articles on: Cardio-Oncology

Incident Cardiovascular Disease Risk Among Older Asian, Native Hawaiian and Pacific Islander Breast Cancer Survivors


Cancer Epidemiol Biomarkers Prev. 2023 Oct 16. doi: 10.1158/1055-9965.EPI-23-0679. Online ahead of print.


ABSTRACT


BACKGROUND: Cardiotoxicity among breast cancer survivors is associated with chemotherapy and radiation therapy. The risk of cardiovascular disease (CVD) among Asian, Native Hawaiian and Pacific Islander (ANHPI) breast cancer survivors in the US is unknown.


METHODS: We used the SEER-Medicare linked database to estimate the risk of CVD among older breast cancer survivors. ICD diagnosis codes were used to identify incident CVD outcomes. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) comparing ANHPI to Non-Hispanic White (NHW) breast cancer patients for CVD, and among ANHPI race and ethnicity groups.


RESULTS: A total of 7,122 ANHPI breast cancer survivors and 21,365 NHW breast cancer survivors were identified. The risks of incident heart failure and ischemic heart disease were lower among ANHPI compared to NHW breast cancer survivors (HRheart failure=0.72, 95%CI=0.61, 0.84; HRheart disease=0.74, 95%CI=0.63, 0.88). Compared to Japanese breast cancer patients, Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer survivors had higher risks of heart failure. ischemic heart disease and death. Among ANHPI breast cancer survivors, risk factors for heart failure included older age, higher comorbidity score, distant cancer stage and chemotherapy.


CONCLUSIONS: Our results support heterogeneity in CVD outcomes among breast cancer survivors among ANHPI race and ethnicity groups. Further research is needed to elucidate the disparities experienced among ANHPI cancer survivors.


IMPACT: Filipino, Asian Indian and Pakistani, and Native Hawaiian breast cancer patients had higher risks of heart failure, ischemic heart disease and death among ANHPI breast cancer patients.


PMID:37843411 | DOI:10.1158/1055-9965.EPI-23-0679

15:05

PubMed articles on: Cardio-Oncology

ATP protects anti-PD-1/radiation-induced cardiac dysfunction by inhibiting anti-PD-1 exacerbated cardiomyocyte apoptosis, and improving autophagic flux


Heliyon. 2023 Oct 5;9(10):e20660. doi: 10.1016/j.heliyon.2023.e20660. eCollection 2023 Oct.


ABSTRACT


The synergy between radiotherapy and immunotherapy in treating thoracic cancers presents a potent therapeutic advantage, yet it also carries potential risks. The extent and nature of cumulative cardiac toxicity remain uncertain, prompting the need to discern its mechanisms and devise effective mitigation strategies. Radiation alone or in combination with an anti- Programmed cell death protein1 (PD-1) antibody significantly reduced cardiac function in C57BL/6J mice, and this pathologic effect was aggravated by anti-PD-1 (anti-PD-1 + radiation). To examine the cellular mechanism that causes the detrimental effect of anti-PD-1 upon cardiac function after radiation, AC16 human cardiomyocytes were used to study cardiac apoptosis and cardiac autophagy. Radiation-induced cardiomyocyte apoptosis was significantly promoted by anti-PD-1 treatment, while anti-PD-1 combined radiation administration blocked the cardiac autophagic flux. Adenosine 5'-triphosphate (ATP) (a molecule that promotes lysosomal acidification) not only improved autophagic flux in AC16 human cardiomyocytes, but also attenuated apoptosis induced by radiation and anti-PD-1 treatment. Finally, ATP administration in vivo significantly reduced radiation-induced and anti-PD-1-exacerbated cardiac dysfunction. We demonstrated for the first time that anti-PD-1 can aggravate radiation-induced cardiac dysfunction via promoting cardiomyocyte apoptosis without affecting radiation-arrested autophagic flux. ATP enhanced cardiomyocyte autophagic flux and inhibited apoptosis, improving cardiac function in anti-PD-1/radiation combination-treated animals.


PMID:37842574 | PMC:PMC10570000 | DOI:10.1016/j.heliyon.2023.e20660

15:05

PubMed articles on: Cardio-Oncology

An online home-based exercise program improves autonomic dysfunction in breast cancer survivors


Front Physiol. 2023 Sep 29;14:1256644. doi: 10.3389/fphys.2023.1256644. eCollection 2023.


ABSTRACT


Introduction: Exercise interventions for breast cancer survivors have proved their potential to improve clinical, physical, and psychosocial outcomes. However, limited studies have explored exercise effects on autonomic dysfunction and the measurement of exercise tolerance and progression through daily heart rate variability (HRV). Purpose: To analyze the effects of a 16-wk exercise intervention on the autonomic modulation of breast cancer survivors, as well as to examine the evolution of daily measured HRV and its interaction with exercise sessions in this population. Methods: A total of 29 patients who had undergone chemotherapy and radiotherapy were randomly assigned to the exercise group or to the control group. The exercise intervention was delivered remotely through online meetings and consisted of supervised training resistance and cardiovascular exercise 3 times per week. During the intervention all patients measured their HRV daily obtaining the napierian logarithm of the root mean square of successive differences between normal heartbeats (lnrMSSD) and the napierian logarithm of the standard deviation of the interbeat interval of normal sinus beats (lnSDNN) values at four moments: day 0 (the morning of the training sessions), 24, 48, and 72 h after exercise. Results: The results revealed a significant interaction between group and months during the intervention period for lnrMSSD and lnSDNN (p < 0.001). Additionally, there were significant differences in lnSDNN recovery time between months (p < 0.05), while differences in lnrMSSD become apparent only 24 h after exercise (p = 0.019). The control group experienced a significant decrease in both variables monthly (p < 0.05) while exercise group experienced a significant increment (p < 0.05). Conclusion: HRV is daily affected by exercise training sessions in cancer patients. Although results strongly support the role of exercise as a post-chemotherapy and radiotherapy rehabilitation strategy for breast cancer survivors to improve autonomic imbalance, further research is necessary to validate these initial findings.


PMID:37841312 | PMC:PMC10570414 | DOI:10.3389/fphys.2023.1256644

15:05

PubMed articles on: Cardio-Oncology

Nuclear medicine imaging methods of early radiation-induced cardiotoxicity: a ten-year systematic review


Front Oncol. 2023 Oct 9;13:1240889. doi: 10.3389/fonc.2023.1240889. eCollection 2023.


ABSTRACT


INTRODUCTION: Radiotherapy has significantly improved cancer survival rates, but it also comes with certain unavoidable complications. Breast and thoracic irradiation, for instance, can unintentionally expose the heart to radiation, leading to damage at the cellular level within the myocardial structures. Detecting and monitoring radiation-induced heart disease early on is crucial, and several radionuclide imaging techniques have shown promise in this regard.


METHOD: In this 10-year review, we aimed to identify nuclear medicine imaging modalities that can effectively detect early cardiotoxicity following radiation therapy. Through a systematic search on PubMed, we selected nineteen relevant studies based on predefined criteria.


RESULTS: The data suggest that incidental irradiation of the heart during breast or thoracic radiotherapy can cause early metabolic and perfusion changes. Nuclear imaging plays a prominent role in detecting these subclinical effects, which could potentially serve as predictors of late cardiac complications.


DISCUSSION: However, further studies with larger populations, longer follow-up periods, and specific heart dosimetric data are needed to better understand the relationship between early detection of cardiac abnormalities and radiation-induced heart disease.


PMID:37876964 | PMC:PMC10591197 | DOI:10.3389/fonc.2023.1240889

15:05

PubMed articles on: Cardio-Oncology

Complications in patients with transfusion dependent thalassemia: A descriptive cross-sectional study


Health Sci Rep. 2023 Oct 11;6(10):e1624. doi: 10.1002/hsr2.1624. eCollection 2023 Oct.


ABSTRACT


BACKGROUND AND AIMS: One of the most common hemoglobinopathies globally related to blood transfusion and iron overload in the body is thalassemia syndrome. Increasing ferritin levels can cause severe damage to the patient's body organs. This study aims to evaluate the complications of iron overload on vital body organs in patients with transfusion-dependent beta-thalassemia.


METHODS: This descriptive cross-sectional study was performed in Iran University of Medical Sciences Hospitals on patients with a beta-thalassemia major with frequent blood transfusions. To evaluate the effect of iron overload on vital body organs, hematologic and blood analysis, echocardiography with measurement of pulmonary artery pressure (PAP) and ejection fraction (EF) tests, bone densitometry, and audiometric tests were performed for all patients.


RESULTS: Of the 1010 patients participating in this study, 497 (49%) were males, 513 were (51%) females aged 5-74 years, and the majority of participants (85%) were over 20 years old. This study demonstrated that increasing ferritin levels had no notable correlation with sex, cholesterol, low-density lipoprotein, parathyroid hormone, T4, and aspartate aminotransferase. However, elevating ferritin levels had significant correlations with increasing triglyceride, phosphorus, thyroid stimulating hormone, alkaline phosphatase, alanine transaminase, and PAP levels, age, hearing disorders, splenectomy, osteoporosis, and decreasing high-density lipoprotein, body mass index, calcium, and EF levels.


CONCLUSION: Improvement in beta-thalassemia patients' survival and quality of life can be due to multidisciplinary care in a comprehensive unit through regular follow-up and early complication detection.


PMID:37841947 | PMC:PMC10568004 | DOI:10.1002/hsr2.1624

15:05

PubMed articles on: Cardio-Oncology

Role of Statin Therapy in Prevention of Anthracycline-Induced Cardiotoxicity: A three dimentional echocardiography study


Curr Probl Cardiol. 2023 Oct 17:102130. doi: 10.1016/j.cpcardiol.2023.102130. Online ahead of print.


ABSTRACT


BACKGROUND: Recent advances in the treatment of breast cancer have resulted in improved overall cancer survival; however, cancer therapy related cardiac dysfunction is considered a major adverse effect of several chemotherapeutic agents, particularly anthracyclines. Hence, there is a need to develop proper cardioprotective strategies to limit myocardial injury following chemotherapy.


OBJECTIVE: To evaluate the effect of statin therapy on prevention of anthracycline- induced cardiotoxicity in female patients with breast cancer.


PATIENTS AND METHODS: The current study is a prospective, randomized, single-blind, placebo-controlled trial in which we enrolled a total of 110 female patients with newly diagnosed breast cancer who received anthracycline based chemotherapy. Patients were randomly assigned in 1:1 ratio into two groups, study group in which patients received 40 mg of oral atorvastatin and control group in which patients received placebo. A comprehensive echocardiographic examination was performed to all patients prior to receiving the chemotherapy and after 6 months, assessment of LV ejection fraction was done by 3D-echocardiography. All echocardiographers were blinded to all the patients' characteristics and assignment to either group.


RESULTS: The mean age of patients assigned to the control group was 49.8±10.51 years old, while patients assigned to the intervention group had mean age of 47.84± 9.16 years old, both the control group and the intervention group were similar in demographic data and baseline clinical characteristics. There was a highly significant difference between the two groups regarding both the absolute LVEF assessed by 3D- echocardiography at 6 months and the percentage of change compared to baseline values, patients assigned to the control group had mean LVEF of 52.92% at 6 months with percentage of change reaching -7.06%, while those assigned to the intervention group had mean LVEF reaching 56.22% at 6 months with a percentage of change reaching -3.64% (P-value: 0.008 and 0.004 for the absolute value and percentage of change respectively). There was a significant difference between the two groups regarding incidence of development of cancer therapy related cardiac dysfunction (CTRCD); defined as drop in LVEF more than 10% and to a value below 53% assessed by 3D echocardiography, among the control group 15 patients (30%) developed CTRCD after 6 months from starting Anthracyclines based chemotherapy, while, among the intervention group only 6 patients (12%) developed CTRCD. (P-value= 0.027) CONCLUSION: : Prophylactic use of atorvastatin may prevent the development of cancer therapy related cardiac dysfunction in breast cancer patients receiving anthracycline based chemotherapy.


PMID:37858847 | DOI:10.1016/j.cpcardiol.2023.102130

15:05

PubMed articles on: Cardio-Oncology

CXCL10 deficiency limits macrophage infiltration, preserves lung matrix, and enables lung growth in bronchopulmonary dysplasia


Inflamm Regen. 2023 Oct 24;43(1):52. doi: 10.1186/s41232-023-00301-6.


ABSTRACT


Preterm infants with oxygen supplementation are at high risk for bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. Inflammation with macrophage activation is central to the pathogenesis of BPD. CXCL10, a chemotactic and pro-inflammatory chemokine, is elevated in the lungs of infants evolving BPD and in hyperoxia-based BPD in mice. Here, we tested if CXCL10 deficiency preserves lung growth after neonatal hyperoxia by preventing macrophage activation. To this end, we exposed Cxcl10 knockout (Cxcl10-/-) and wild-type mice to an experimental model of hyperoxia (85% O2)-induced neonatal lung injury and subsequent regeneration. In addition, cultured primary human macrophages and murine macrophages (J744A.1) were treated with CXCL10 and/or CXCR3 antagonist. Our transcriptomic analysis identified CXCL10 as a central hub in the inflammatory network of neonatal mouse lungs after hyperoxia. Quantitative histomorphometric analysis revealed that Cxcl10-/- mice are in part protected from reduced alveolar. These findings were related to the preserved spatial distribution of elastic fibers, reduced collagen deposition, and protection from macrophage recruitment/infiltration to the lungs in Cxcl10-/- mice during acute injury and regeneration. Complimentary, studies with cultured human and murine macrophages showed that hyperoxia induces Cxcl10 expression that in turn triggers M1-like activation and migration of macrophages through CXCR3. Finally, we demonstrated a temporal increase of macrophage-related CXCL10 in the lungs of infants with BPD. In conclusion, our data demonstrate macrophage-derived CXCL10 in experimental and clinical BPD that drives macrophage chemotaxis through CXCR3, causing pro-fibrotic lung remodeling and arrest of alveolarization. Thus, targeting the CXCL10-CXCR3 axis could offer a new therapeutic avenue for BPD.


PMID:37876024 | PMC:PMC10594718 | DOI:10.1186/s41232-023-00301-6

15:06

PubMed articles on: Cardio-Oncology

Angiotensin IV ameliorates doxorubicin-induced cardiotoxicity by increasing glutathione peroxidase 4 and alleviating ferroptosis


Toxicol Appl Pharmacol. 2023 Oct 12;479:116713. doi: 10.1016/j.taap.2023.116713. Online ahead of print.


ABSTRACT


BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in cancer patients treated with DOX. Angiotensin IV (Ang IV) has multiple protective effects against cardiovascular diseases, including diabetic cardiomyopathy and myocardial infarction, but its role in DOX-induced cardiotoxicity is currently unclear. In this study, we investigated the effects of Ang IV on DOX-induced cardiotoxicity.


METHODS: The viability of primary cardiomyocytes was measured by Cell Counting Kit-8 assays and Hoechst 33342/propidium iodide staining in vitro. ELISAs (serum cTnT and CK-MB) and echocardiography were performed to assess myocardial injury and cardiac function in vivo. Phalloidin staining, haematoxylin and eosin staining and wheat germ agglutinin staining were conducted to detect cardiomyocyte atrophy. We also performed C11 BODIPY staining, measured the levels of Ptgs2 and malondialdehyde and detected the concentrations of ferrous ions, glutathione and oxidized glutathione to indicate ferroptosis.


RESULTS: Ang IV not only attenuated DOX-induced atrophy and cardiomyocyte injury in vitro but also alleviated myocardial injury and improved cardiac function in DOX-treated mice in vivo. Moreover, Ang IV reversed DOX-induced downregulation of glutathione peroxidase 4 (GPX4) and inhibited ferroptosis both in vitro and in vivo. Knockdown of GPX4 by siRNA abolished the cardioprotective effects of Ang IV. Furthermore, Ang IV increased GPX4 levels and ameliorated ferroptosis in RAS-selective lethal 3-treated primary cardiomyocytes.


CONCLUSIONS: Ang IV ameliorates DOX-induced cardiotoxicity by upregulating GPX4 and inhibiting ferroptosis. Ang IV may be a promising candidate to protect against DOX-induced cardiotoxicity in the future.


PMID:37838222 | DOI:10.1016/j.taap.2023.116713

15:06

PubMed articles on: Cardio-Oncology

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial


BMC Cancer. 2023 Oct 14;23(1):980. doi: 10.1186/s12885-023-11489-8.


ABSTRACT


BACKGROUND: Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed.


METHODS: Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR).


RESULTS: A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49-0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors.


CONCLUSIONS: Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients.


TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.


PMID:37838670 | PMC:PMC10576321 | DOI:10.1186/s12885-023-11489-8

15:06

PubMed articles on: Cardio-Oncology

Evolving cardiac biomarkers for immune checkpoint inhibitor related myocarditis in cancer patients


Int J Cardiol Heart Vasc. 2023 Oct 8;49:101278. doi: 10.1016/j.ijcha.2023.101278. eCollection 2023 Dec.


NO ABSTRACT


PMID:37842144 | PMC:PMC10570005 | DOI:10.1016/j.ijcha.2023.101278

15:06

PubMed articles on: Cardio-Oncology

CDK4/6 inhibitors: basics, pros, and major cons in breast cancer treatment with specific regard to cardiotoxicity - a narrative review


Ther Adv Med Oncol. 2023 Oct 11;15:17588359231205848. doi: 10.1177/17588359231205848. eCollection 2023.


ABSTRACT


Breast cancer is characterized by the uncontrolled proliferation of breast cells, with a high incidence reported in 2020 to have affected over 2 million women. In recent years, the conventional methods of treating breast cancer have involved radiotherapy and chemotherapy. However, the emergence of CDK4/6 inhibitors has shown potential as a promising cancer therapy. Cyclin-dependent kinases (CDK) inhibitors are a class of molecules that impede the formation of an active kinase complex, thereby hindering its activity and consequently halting the progression of the cell cycle. It was discovered that they have a significant impact on impeding the progression of the cancer. This is evident with the Food and Drug Administration's approval of drugs such as palbociclib, ribociclib, and abemaciclib for hormone receptor-positive metastatic breast cancer in combination with specific endocrine therapies. In spite of enormous success in breast cancer treatment, certain obstacles have emerged, such as therapy resistance, side effects, and most of all, cardiotoxicity. Some of these drawbacks have been successfully overcome by dosage reduction, different combinations of the drugs, and the assessment of each patient's condition and suitability prior to treatment. Yet other drawbacks still require tenacious research, especially certain cases of cardiotoxicities. This article delves into the biological mechanisms of CDK4/6 in the cell cycle and cancer, as well as the clinical advantages and most common adverse events (AEs) associated with CDK4/6 inhibitors. The primary objective of this review is to provide a comprehensive analysis of cardiotoxic AEs and elucidate the underlying pathophysiological mechanisms responsible for the cardiotoxicity of CDK4/6 inhibitors.


PMID:37841752 | PMC:PMC10571689 | DOI:10.1177/17588359231205848

15:06

PubMed articles on: Cardio-Oncology

Smoking, Diabetes Mellitus, and Previous Cardiovascular Disease as Predictors of Anticancer Treatment-Induced Cardiotoxicity in Non-Small-Cell Lung Cancer: A Real-World Study


Clin Lung Cancer. 2023 Oct 4:S1525-7304(23)00187-0. doi: 10.1016/j.cllc.2023.09.007. Online ahead of print.


ABSTRACT


PURPOSE: Cardiotoxicity is a common and under-reported side effect of tyrosine-kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI). Baseline risk factors may help in risk-stratifying patients at increased risk of cardiotoxicity. This real-world study investigated the effects of baseline risk factors in cardiotoxicity on patients with non-small-cell lung cancer (NSCLC) treated with TKIs and ICIs.


METHODS: This is a retrospective study carried out at The Royal Marsden Hospital, UK. Newly diagnosed patients with localized or metastatic NSCLC who received anticancer therapy with TKIs and/or ICIs were eligible. Patients who received only chemotherapy were excluded. Patients were followed up from the time of diagnosis until death or discharge. The relationship between cardiotoxicity and risk factors were tested by logistic regression.


RESULTS: Of 88/451 (19.5%) patients developed cardiotoxicity. Risk factors hypothesized to have a causal relationship with anticancer treatment-induced cardiotoxicity were analyzed. Cardiotoxicity risk was increased with prior diabetes mellitus (OR = 1.93, 95% CI, 1.04-3.61, P = .038), history of smoking (OR = 1.91, 95% CI, 1.13-3.22, P = .016) and presence of baseline cardiovascular disease (OR = 2.03, 95% CI, 1.13-3.64, P = .018). The risk of developing cardiotoxicity increased in patients for smokers with diabetes mellitus (OR = 3.03, 95% CI, 1.40-6.55, P < .01) and for smokers with previous cardiovascular disease (OR = 1.99, 95% CI, 1.03-3.84, P = .041).


CONCLUSION: Diabetes mellitus, smoking and baseline cardiovascular disease may synergistically contribute to cardiotoxicity when a patient is exposed to potentially cardiotoxic anticancer agents. Risk stratification at baseline may improve cardio-oncology care.


PMID:37880075 | DOI:10.1016/j.cllc.2023.09.007

15:06

PubMed articles on: Cardio-Oncology

Outcomes of chronic total occlusion percutaneous coronary intervention from the RAIAN (RAjaie - Iran) registry


Indian Heart J. 2023 Oct 20:S0019-4832(23)00166-9. doi: 10.1016/j.ihj.2023.10.002. Online ahead of print.


ABSTRACT


OBJECTIVE: While most of the evidence in CTO interventions emerge from Western and Japanese studies, few data have been published up today from the Middle East. Objective of this study was to evaluate technical success rates and clinical outcomes of an Iranian population undergoing CTO PCI in a tertiary referral hospital. Moreover, we sought to evaluate the efficacy of our CTO teaching program.


METHODS: This is a retrospective single-center cohort study including 790 patients who underwent CTO PCI performed by operators with different volumes of CTOs PCI performed per year. According to PCI result, all patients have been divided into successful (n = 555, 70.3 %) and unsuccessful (n = 235, 29.7 %) groups. Study endpoints were Major Adverse Cardiovascular Events and Health Status Improvement evaluated using the Seattle Angina Questionnaire at one year.


RESULTS: A global success rate of 70 % for antegrade and 80 % for retrograde approach was shown despite the lack of some CTO-dedicated devices. During the enrollment period, the success rate increased significantly among operators with a lower number of CTO procedures per year. One-year MACE rate was similar in both successful and unsuccessful groups (13.5 % in successful and 10.6 % in unsuccessful group, p = 0.173). One year patients' health status improved significantly only in successful group.


CONCLUSIONS: No significant differences of in-hospital and one-year MACE were found between the successful and unsuccessful groups. Angina symptoms and quality of life significantly improved after successful CTO PCI. The RAIAN registry confirmed the importance of operator expertise for CTO PCI success.


PMID:37866775 | DOI:10.1016/j.ihj.2023.10.002

15:06

PubMed articles on: Cardio-Oncology

High-resolution and quantitative spatial analysis reveal intra-ductal phenotypic and functional diversification in pancreatic cancer


J Pathol. 2023 Oct 16. doi: 10.1002/path.6212. Online ahead of print.


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  ABSTRACT Doxorubicin (Dox) is a highly potent chemotherapy drug. Despite its efficacy, Dox's clinical application is limited due to it...