ABSTRACT

The aim of this study was to determine which type of prophylaxis was effective for postoperative symptomatic venous thromboembolism (VTE) in patients with gynecological malignancies. A total of 1756 consecutive patients undergoing laparotomy as first-line treatment were included. In Period 1 (2004-2009), low-molecular weight heparin (LMWH) was not available for postoperative VTE prophylaxis, but available in after Period 2 (2009-2013). In Period 3 (2013-2020), patients with pretreatment VTE could switch from LMWH to direct oral anticoagulant (DOAC) as of 2015. Preoperative VTE was screened by measuring D-dimer, followed by venous ultrasound imaging, and computed tomography and/or perfusion lung scintigraphy. Postoperative symptomatic VTE occurred with an incidence of 2.8% by the measures without prophylactic LMWH administration in Period 1. The incidence of postoperative symptomatic VTE was 0.6% in Period 2 and 0.3% in Period 3, being significantly reduced compared with Period 1 (P < .01 and < .0001). The incidences were not significantly different between Periods 2 and 3, but no patient switching to DOAC in Period 3 (n = 79) developed symptomatic VTE. Our preoperative VTE screening and postoperative selective LMWH administration were significantly preventive against postoperative symptomatic VTE.

PMID:37231620 | DOI:10.1177/10760296231178300

18:29

PubMed articles on: Cancer & VTE/PE

18:29

PubMed articles on: Cancer & VTE/PE

Cardiac Metastatic Tumors: Current Knowledge

Am J Clin Oncol. 2023 May 26. doi: 10.1097/COC.0000000000001013. Online ahead of print.

 

ABSTRACT

Introduction:Glioblastoma (GBM) patients have a 20-30 incidence of venous thromboembolic events. EGFR is a widely used prognostic marker for many cancers. Recent lung cancer studies have described relationships between EGFR amplification and an increased incidence of thromboembolic complications. We aim to explore this relationship in glioblastoma patients. Methods: Two hundred ninety-three consecutive patients with IDH wild-type GBM were included in the analysis. The amplification status of EGFR was measured using fluorescence in situ hybridization (FISH). Centromere 7 (CEP7) expression was recorded to calculate the EGFR-to-CEP7 ratio. All data were collected retrospectively through chart review. Molecular data were obtained through the surgical pathology report at the time of biopsy. Results:There were 112 subjects who were EGFR-amplified (38.2%) and 181 who were non-amplified (61.8%). EGFR amplification status was not significantly correlated with VTE risk overall (p = 0.2001). There was no statistically significant association between VTE and EGFR status after controlling for Bevacizumab therapy (p = 0.1626). EGFR non-amplified status was associated with an increased VTE risk in subjects greater than 60 years of age (p = 0.048). Conclusions:There was no significant difference in occurrence of VTE in patients with glioblastoma, regardless of EGFR amplification status. Patients older than 60 years of age with EGFR amplification experienced a lower rate of VTE, contrary to some reports on non-small-cell lung cancer linking EGFR amplification to VTE risk.

PMID:37232831 | PMC:PMC10217574 | DOI:10.3390/curroncol30050373

18:29

18:29

18:29

In reply to this message

PubMed articles on: Cancer & VTE/PE

Preoperative Venous Thromboembolism Screening and Postoperative Selective Anticoagulant Therapy Effectively Prevents Postoperative Symptomatic Venous Thromboembolism in Gynecological Malignancies: A 15-Year, Single-Center Study

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231178300. doi: 10.1177/10760296231178300.

 t.

ABSTRACT

BACKGROUND: GSK3368715, a first-in-class, reversible inhibitor of type I protein methyltransferases (PRMTs) demonstrated anticancer activity in preclinical studies. This Phase 1 study (NCT03666988) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK3368715 in adults with advanced-stage solid tumors.

METHODS: In part 1, escalating doses of oral once-daily GSK3368715 (50, 100, and 200 mg) were evaluated. Enrollment was paused at 200 mg following a higher-than-expected incidence of thromboembolic events (TEEs) among the first 19 participants, resuming under a protocol amendment starting at 100 mg. Part 2 (to evaluate preliminary efficacy) was not initiated.

RESULTS: Dose-limiting toxicities were reported in 3/12 (25%) patients at 200 mg. Nine of 31 (29%) patients across dose groups experienced 12 TEEs (8 grade 3 events and 1 grade 5 pulmonary embolism). Best response achieved was stable disease, occurring in 9/31 (29%) patients. Following single and repeat dosing, GSK3368715 maximum plasma concentration was reached within 1 h post dosing. Target engagement was observed in the blood, but was modest and variable in tumor biopsies at 100 mg.

CONCLUSION: Based on higher-than-expected incidence of TEEs, limited target engagement at lower doses, and lack of observed clinical efficacy, a risk/benefit analysis led to early study termination.

TRIAL REGISTRATION NUMBER: NCT03666988.

PMID:37237172 | DOI:10.1038/s41416-023-02276-0

18:29

In reply to this message

PubMed articles on: Cancer & VTE/PE

The Role of EGFR Amplification in Deep Venous Thrombosis Occurrence in IDH Wild-Type Glioblastoma

Curr Oncol. 2023 May 12;30(5):4946-4956. doi: 10.3390/curroncol30050373.

 

ABSTRACT

(1) Background: Cancer treatment, including chemotherapy, endocrine therapy, targeted therapy and radiotherapy, has been identified as an important independent risk factor for venous thromboembolism in cancer patients. The aim of the study was to evaluate the effect of adjuvant therapy on the coagulation and fibrinolysis components in invasive breast cancer. (2) Methods: Tissue factor pathway inhibitor (TFPI), tissue factor (TF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) antigen (concentration) and TFPI and TF activities were examined in the blood samples of 60 breast cancer patients treated by adjuvant chemotherapy, endocrine therapy, radiotherapy and immunotherapy. Blood samples were taken 24 h before primary surgery and 8 months after tumour removal surgery. (3) Results: Adjuvant therapy administrated to breast cancer patients significantly increased the concentration of plasma TF, the PAI-1 antigen and also the activity of TFPI and TF, but significantly decreased the level of the t-PA antigen. Combined chemotherapy and endocrine therapy, but not monotherapy, has an important effect on haemostatic biomarker levels. (4) Conclusions: Breast cancer patients receiving adjuvant therapy have an elevated risk of developing a hypercoagulability and hypofibrinolysis state leading to venous thromboembolism.

PMID:37240751 | PMC:PMC10222121 | DOI:10.3390/life13051106

18:29

In reply to this message

PubMed articles on: Cancer & VTE/PE

Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors

Br J Cancer. 2023 May 26. doi: 10.1038/s41416-023-02276-0. Online ahead of prin

 

ABSTRACT

BACKGROUND: The incidence of venous thromboembolism (VTE; pulmonary embolism [PE] and/or deep vein thrombosis [DVT]) in Japan is increasing, but relatively small numbers of patients from Japan have been included in studies investigating rivaroxaban (a direct factor Xa inhibitor) for the treatment of VTE and preventing its recurrence.Methods and Results: An open-label, prospective, observational study (XASSENT [NCT02558465]) investigated the safety profile and effectiveness of rivaroxaban for ≤2 years in the treatment of VTE and prevention of its recurrence in Japanese clinical practice. Primary outcomes were major bleeding and symptomatic recurrent VTE. Statistical analyses were exploratory and descriptive. Overall, 2,540 patients were enrolled (safety analysis population [SAP], n=2,387; effectiveness analysis population [EAP], n=2,386). In the SAP, >80% of patients received the approved rivaroxaban dose, the mean (standard deviation) age was 66.6 (15.0) years, ≈74% were >50 kg, and 43% had a creatinine clearance ≥80 mL/min. PE+DVT, PE only, and DVT only were reported in 42%, 8%, and 50% of patients, respectively, and active cancer in 17% of patients. Major bleeding was reported in 69 patients (2.89%; 3.60%/patient-year; SAP) and symptomatic PE/DVT recurrence in 26 patients (1.09%; 1.36%/patient-year; EAP) during the treatment period.

CONCLUSIONS: XASSENT provided information on the expected proportions of bleeding and VTE recurrence during rivaroxaban treatment in Japanese clinical practice; no new concerns of safety or effectiveness were found.

PMID:37245989 | DOI:10.1253/circj.CJ-23-0104

18:29

In reply to this message

PubMed articles on: Cancer & VTE/PE

Hypercoagulability State Combined with Post-Treatment Hypofibrinolysis in Invasive Breast Cancer: A Seven-Year Follow-Up Evaluating Disease-Free and Overall Survival

Life (Basel). 2023 Apr 28;13(5):1106. doi: 10.3390/life13051106.

 

ABSTRACT

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS.

METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record.

RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality.

CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.

PMID:37246305 | DOI:10.1097/LBR.0000000000000930

18:29

In reply to this message

PubMed articles on: Cancer & VTE/PE

Safety Profile and Effectiveness of Rivaroxaban for Patients With Venous Thromboembolism in Japan　- Results From Post-Marketing Surveillance (XASSENT)

Circ J. 2023 May 27. doi: 10.1253/circj.CJ-23-0104. Online ahead of print.

 

ABSTRACT

INTRODUCTION: Direct oral anticoagulants (DOACs) demonstrated similar efficacy and lower risk of intracranial hemorrhage than warfarin in patients with atrial fibrillation and venous thromboembolism. Given the lack of data identifying risk factors in patients who bled while on a DOAC, we sought to investigate these characteristics.

MATERIALS AND METHODS: This retrospective chart review was approved by the Mass General Brigham Institutional Review Board and assessed patients who experienced bleeding events while on DOAC therapy from 6/1/2015 to 7/1/2020. Patient characteristics were evaluated, including age, sex, body mass index (BMI), renal function, concomitant therapies, and baseline comorbidities.

RESULTS: Eighty-seven patients were included for analysis, with a median age of 75.8 years. Most patients were female (51.7%) and 24 (27.6%) had a BMI >30. At time-of-event, 21 patients (24.1%) had acute kidney injury. Thirty-three patients (37.9%) were on concomitant antiplatelet therapy (APT), with 31 (35.6%) on single APT and 2 on dual APT. Pertinent comorbidities included hypertension (74.7%), ischemic cerebrovascular accident (28.7%), thyroid abnormality (23.0%), active cancer (14.9%), and anemia (13.8%). Eleven patients (12.6%) had a prior bleeding event. Most patients were on apixaban (69.0%) for the indication of stroke prevention in nonvalvular atrial fibrillation/flutter (72.4%). FDA-approved dosing was used in most patients (92.0%), and all deviations reflected underdosing. Most bleeding events were defined as major (95.4%), occurred at a critical organ site (72.4%), and developed spontaneously (58.6%).

CONCLUSIONS: These data provide insight into characteristics of patients who experience bleeding events while on DOAC therapy. Understanding these potential risk factors may optimize the safe use of these agents.

PMID:37246422 | DOI:10.1177/10760296231172765

18:28

18:29

18:29

18:29

18:29

18:29

18:29

In reply to this message

PubMed articles on: Cancer & VTE/PE

Spray Cryotherapy for Benign Large Airway Stenosis: A Multicenter Retrospective Cohort Study of Safety and Practice Patterns

J Bronchology Interv Pulmonol. 2023 May 29. doi: 10.1097/LBR.0000000000000930. Online ahead of print.

 

ABSTRACT

INTRODUCTION: While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.

METHODS: We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.

RESULTS: Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.

CONCLUSIONS: The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.

PMID:37236862 | DOI:10.1016/j.clgc.2023.04.007

C

18:28

Cardiotoxicity News

18:28

18:28

In reply to this message

PubMed articles on: Cancer & VTE/PE

Thrombotic Risk Assessment in Patients with Lymphoid Neoplasm seen at the Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State

West Afr J Med. 2023 May 27;40(5):533-540. ABSTRACTBACKGROUND: Venous thromboembolism (VTE) is a cause of increased morbidity and mortality in cancer patients. VTE is the second leading cause of death in cancer patients. Risk assessment models have been developed to identify patients at risk of VTE for thromboprophylaxis. Risk scores of patients in our environment have not been adequately investigated.

OBJECTIVE: The study evaluates the association of thrombotic risk assessment scores (using the modified Khorana risk assessment tool) and soluble P-selectin levels with thrombotic events in patients with lymphoid cancer.

METHODS: This is a comparative cross-sectional study conducted at Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, Anambra State). Forty-five patients with lymphoid malignancy and 45 apparently healthy subjects participated in the study. The modified Khorana risk assessment score was used to assess cancer-associated thrombotic risk. Blood sample was collected for soluble P-selectin estimation. Data were analyzed with SPSS version 23.

RESULTS: The age of subjects with lymphoid neoplasm and controls were 49.1±15.8 years, and 49.6±11.1 years respectively (p = 0.548). Subjects with lymphoid neoplasm consist of 26 (57.8%) males and 19 (42.2%) females while the controls consist of 25 (55.6%) males and 20 (44.4%) females. Non-Hodgkin's lymphoma was the most frequent of lymphoid neoplasm (18, 40.0%), followed by multiple myeloma (10, 22%), CLL (9, 20%), ALL (6, 13.0%) and Hodgkin's lymphoma (2, 4.0%). Thirty-five (77.8%) subjects with lymphoid neoplasm had intermediate risk scores and 10 (22.2%) had high-risk scores. Nineteen (42.2%) of the controls had intermediate risk and 26 (57.8%) low risk. The differences in proportion were statistically significant (p < 0.001). The median (IQR) levels of soluble P-selectin were significantly higher in patients with lymphoid neoplasm (12.2 vs. 7.0ng/mL, p <0.001).

CONCLUSION: Lymphoid malignancy is associated with relatively higher thrombotic risk scores, sP-selectin levels, and venous thromboembolic events.

CONTEXTE: La thromboembolie veineuse (TEV) est une cause de morbidité et de mortalité accrues chez les patients atteints de cancer. La TEV est la deuxième cause de décès chez les patients atteints de cancer. Des modèles d’évaluation des risques ont été mis au point pour identifier les patients présentant un risque de TEV en vue d’une thromboprophylaxie. Les scores de risque des patients dans notre environnement n’ont pas été étudiés de manière adéquate.

OBJECTIF: L’étude évalue l’association des scores d’évaluation du risque thrombotique (en utilisant l’outil modifié d’évaluation du risque de Khorana) et des niveaux de P-sélectine soluble avec les événements thrombotiques chez les patients atteints d’un cancer lymphoïde.

MÉTHODES: Il s’agit d’une étude transversale comparative menée au Nnamdi Azikiwe University Teaching Hospital (NAUTH, Nnewi, État d’Anambra). Quarante-cinq patients atteints d’un cancer lymphoïde et 45 sujets apparemment sains ont participé à l’étude. Le score modifié d’évaluation du risque de Khorana a été utilisé pour évaluer le risque thrombotique associé au cancer. Un échantillon de sang a été prélevé pour l’estimation de la P-sélectine soluble. Les données ont été analysées avec SPSS version 23.

RÉSULTATS: L’âge des sujets atteints de néoplasme lymphoïde et des témoins était respectivement de 49,1±15,8 ans et 49,6±11,1 ans (p = 0,548). Les sujets atteints de néoplasme lymphoïde sont 26 (57,8 %) hommes et 19 (42,2 %) femmes, tandis que l[...]

18:28

In reply to this message

PubMed articles on: Cancer & VTE/PE

Evaluation of Patient Characteristics Linked to Major Bleeding Events in Patients Prescribed Direct Oral Anticoagulants

Clin Appl Thromb Hemost. 2023 Jan-Dec;29:10760296231172765. doi: 10.1177/10760296231172765.

 

ABSTRACT

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

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

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

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

PMID:37237439 | DOI:10.1080/09638288.2023.2212915

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

Association between RCT methodology and disease indication with mineralocorticoid-related toxicity for patients receiving abiraterone acetate for advanced prostate cancer: A meta-analysis of RCTs

Clin Genitourin Cancer. 2023 Apr 23:S1558-7673(23)00093-9. doi: 10.1016/j.clgc.2023.04.007. Online ahead of print.

 

ABSTRACT

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

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

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

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

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

 

ABSTRACT

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

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

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

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

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

 

ABSTRACT

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

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

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

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

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

 

ABSTRACT

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

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

16:44

16:44

16:44

16:44

16:44

16:44

PubMed articles on: Cardio-Oncology

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

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

 

ABSTRACT

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

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

16:44

16:44

PubMed articles on: Cardio-Oncology

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

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

 

ABSTRACT

BACKGROUND: Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage.

METHODS: Using transmission electron microscopy, we evaluated cells' morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1/3), inflammation (TNFα, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase).

RESULTS: Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival.

CONCLUSION: Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.

PMID:37242170 | PMC:PMC10222879 | DOI:10.3390/nu15102287

16:44

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

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

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

 

ABSTRACT

Doxorubicin (Dox) is a highly potent chemotherapy drug. Despite its efficacy, Dox's clinical application is limited due to its association with significant complications, namely cardiotoxicity and the risk of heart failure. Recent intriguing findings by Ozcan et al. indicate that alternate-day fasting (ADF) significantly exacerbates the cardiotoxicity of Dox.

PMID:37246117 | DOI:10.1016/j.tem.2023.05.003

16:44

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice

Nutrients. 2023 May 12;15(10):2287. doi: 10.3390/nu15102287.

 

ABSTRACT

Clinical application of doxorubicin (Dox) in cancer chemotherapy is limited by its cardiotoxicity. Present study aimed to demonstrate the effect and mechanism of hyperoside in Dox-induced cardiotoxicity. C57BL/6 mice were injected with 12 mg/kg of Dox, and 1 μM Dox was exposed to primary cardiomyocytes. Cardiac function was evaluated by echocardiographic and myocardial enzyme levels. Cardiomyocyts apoptosis was analyzed by TUNEL staining and flow cytometry. Network pharmacology and molecular docking were utilized to explore potential targets of hyperoside. Protein expressions were detected by western blot and enzyme activities were determined by colorimetry. Cardiac dysfunction and cardiomyocyte apoptosis induced by Dox were attenuated by hyperoside. Mechanism of hyperoside was mainly related to "oxidative stress" pathway. Hyperoside exhibited strong binding activities with nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs, the main source of ROS in cardiomyocytes) and cyclooxygenases (COXs). Experiments proved that hyperoside suppressed the ROS generation and the elevated activities of NOXs and COXs induced by Dox. Dox also triggered the activation of NLRP3 inflammasome, which was reversed by hyperoside. Hyperoside bound to NOXs and COXs, which prevents Dox-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway. Hyperoside holds promise as a therapeutic strategy for Dox-induced cardiotoxicity.

PMID:37246409 | DOI:10.1002/ptr.7900

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

Alternate-day fasting exacerbates doxorubicin cardiotoxicity in cancer chemotherapy

Trends Endocrinol Metab. 2023 May 26:S1043-2760(23)00093-0. doi: 10.1016/j.tem.2023.05.003. Online ahead of print.

 

ABSTRACT

Cardiovascular diseases, such as myocardial infarction, ischemic stroke, and pulmonary embolism, are the most common causes of disability and death worldwide. Blood clot hydrolysis by thrombolytic enzymes and thrombectomy are key clinical interventions. The most widely used thrombolytic enzyme is alteplase, which has been used in clinical practice since 1986. Another clinically used thrombolytic protein is tenecteplase, which has modified epitopes and engineered glycosylation sites, suggesting that carbohydrate modification in thrombolytic enzymes is a viable strategy for their improvement. This comprehensive review summarizes current knowledge on computational and experimental identification of glycosylation sites and glycan identity, together with methods used for their reengineering. Practical examples from previous studies focus on modification of glycosylations in thrombolytics, e.g., alteplase, tenecteplase, reteplase, urokinase, saruplase, and desmoteplase. Collected clinical data on these glycoproteins demonstrate the great potential of this engineering strategy. Outstanding combinatorics originating from multiple glycosylation sites and the vast variety of covalently attached glycan species can be addressed by directed evolution or rational design. Directed evolution pipelines would benefit from more efficient cell-free expression and high-throughput screening assays, while rational design must employ structure prediction by machine learning and in silico characterization by supercomputing. Perspectives on challenges and opportunities for improvement of thrombolytic enzymes by engineering and evolution of protein glycosylation are provided.

PMID:37182613 | DOI:10.1016/j.biotechadv.2023.108174

C

16:44

Cardiotoxicity News

16:44

16:44

In reply to this message

PubMed articles on: Cardio-Oncology

Hyperoside prevents doxorubicin-induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway

Phytother Res. 2023 May 28. doi: 10.1002/ptr.7900. Online ahead of print.

 

ABSTRACT

INTRODUCTION: Hypercoagulable state contributing to thrombotic complications worsens COVID-19 severity and outcomes, while anticoagulation improves outcomes by alleviating hypercoagulability.

OBJECTIVES: Examine whether hemophilia, an inherent hypocoagulable condition, offers protection against COVID-19 severity and reduces VTE risk in persons with hemophilia (PwH).

PATIENTS/METHODS: A 1: 3 propensity score (PS) matched retrospective cohort study used national COVID-19 registry data (January 2020 through January 2022) to compare outcomes between 300 male PwH and 900 matched controls without hemophilia.

RESULTS: Analyses of PwH demonstrated known risk-factors (older age, heart failure, hypertension, cancer/malignancy, dementia, renal and liver disease) contributed to severe COVID-19 and/or 30-day-all-cause mortality. Non-CNS bleeding was an additional risk-factor for poor outcomes in PwH. Odds of developing VTE with COVID-19 in PwH were associated with pre-COVID VTE diagnosis (OR 51.9, 95% CI 12.8-266, p<0.001),<0.001)<0.001).<0.001)

CONCLUSION: After adjusting for patient characteristics/comorbidities, hemophilia increased bleeding risk with COVID-19 but did not protect against severe disease and VTE.

PMID:37182697 | PMC:PMC10181864 | DOI:10.1016/j.jtha.2023.04.040

14:29

PubMed articles on: Cancer & VTE/PE

Identification, characterization, and engineering of glycosylation in thrombolytics

Biotechnol Adv. 2023 May 12;66:108174. doi: 10.1016/j.biotechadv.2023.108174. Online ahead of print.

 

ABSTRACT

BACKGROUND: P-selectin levels are elevated following acute deep vein thrombosis (DVT) and reported to predict recurrent venous thromboembolism (VTE) and cancer-associated VTE. Yet, it is unknown whether plasma P-selectin levels are associated with incident VTE.

OBJECTIVES: Investigate the association between plasma P-selectin levels and risk of future incident VTE.

METHODS: We performed a nested case-control study in 415 VTE patients and 843 age- and sex-matched controls derived from the general population (Tromsø IV Study). Plasma P-selectin levels were measured by ELISA. Logistic regression models were used to estimate odds ratios (OR) for VTE across quartiles of plasma P-selectin level. Sex-stratified analysis was also performed.

RESULTS: Plasma P-selectin levels were higher in men (41.4 ng/mL) than women (38.7 ng/mL, p = 0.0046). We found no association between plasma P-selectin levels and risk of VTE in the overall analyses. However, sex-stratified analyses revealed that women with P-selectin levels in the highest quartile (>44.3 ng/mL) had higher risk of VTE (OR 1.63, 95% CI: 1.01-2.64) compared with women with P-selectin levels in the lowest quartile (≤29.9 ng/mL). In contrast, higher levels of P-selectin were apparently associated with lower risk of VTE in men (OR for highest vs. lowest quartile of P-selectin: 0.69, 95% CI: 0.42-1.15). The observed associations were stronger when the time between blood sampling and VTE was shorter.

CONCLUSIONS: Elevated levels of plasma P-selectin were associated with increased risk of VTE in women, but not in men, suggesting a differential impact of sex for the association between P-selectin and VTE risk.

PMID:37182696 | DOI:10.1016/j.jtha.2023.04.038

14:29

PubMed articles on: Cancer & VTE/PE

COVID-19 outcomes in persons with hemophilia: results from a US-based national COVID-19 surveillance registry

J Thromb Haemost. 2023 May 12:S1538-7836(23)00401-4. doi: 10.1016/j.jtha.2023.04.040. Online ahead of print.