ABSTRACT

Oxidative stress has emerged as a significant contributor to skeletal muscle atrophy, influencing cellular processes that underlie muscle wasting. This review article delves into the intricate interplay between oxidative stress and muscle atrophy, shedding light on its mechanisms and implications. We begin by outlining the fundamental concepts of oxidative stress, delineating reactive oxygen species (ROS) and reactive nitrogen species (RNS), their sources, and the ensuing oxidative damage to cellular components. Subsequently, we delve into skeletal muscle atrophy, elucidating its diverse forms, molecular pathways, key signaling cascades, and the role of inflammation in exacerbating muscle wasting. Bridging these concepts, we explore the connections between oxidative stress and muscle atrophy, unveiling how oxidative stress impacts muscle protein synthesis and breakdown, perturbs cellular signaling pathways, and contributes to mitochondrial dysfunction. The review underscores the complexity of quantifying and interpreting oxidative stress markers, highlighting the challenges posed by the dynamic nature of oxidative stress and the presence of basal ROS levels. Addressing the specificity of oxidative stress markers, we emphasize the importance of selecting markers pertinent to muscle tissue and considering systemic influences. Standardization of experimental protocols emerges as a critical need to ensure consistency and reproducibility across studies. Looking ahead, we discuss the implications of oxidative stress in diverse scenarios, encompassing age-related muscle loss (sarcopenia), muscle wasting in chronic diseases like cancer cachexia, and disuse-induced muscle atrophy. Additionally, we delve into potential therapeutic strategies, including antioxidant supplementation, exercise, pharmacological interventions, nutritional approaches, and lifestyle modifications, as avenues to mitigate oxidative stress-driven muscle atrophy. The review concludes by outlining promising future directions in this field, calling for deeper exploration of specific oxidative stress markers, understanding the temporal dynamics of oxidative stress, validation through translational studies in humans, and the development of targeted therapeutic interventions. By advancing our understanding of the intricate relationship between oxidative stress and skeletal muscle atrophy, this review contributes to paving the way for innovative strategies to address muscle wasting and improve muscle health.

PMID:37779809 | PMC:PMC10540504 | DOI:10.7759/cureus.44367

07:08

PubMed articles on: Cancer & VTE/PE

Tissue factor pathway inhibitor is associated with risk of venous thromboembolism and all-cause mortality in patients with cancer

07:09

PubMed articles on: Cancer & VTE/PE

Major Intraoperative Complications During Minimally Invasive Esophagectomy

Ann Surg Oncol. 2023 Oct 2. doi: 10.1245/s10434-023-14340-3. Online ahead of print.

ABSTRACT

BACKGROUND: Studies have shown minimally invasive esophagectomy (MIE) to be a feasible surgical technique in treating esophageal carcinoma. Postoperative complications have been extensively reviewed, but literature focusing on intraoperative complications is limited. The main objective of this study was to report major intraoperative complications and 90-day mortality during MIE for cancer.

METHODS: Data were collected retrospectively from 10 European esophageal surgery centers. All intention-to-treat, minimally invasive laparoscopic/thoracoscopic esophagectomies with gastric conduit reconstruction for esophageal and GE junction cancers operated on between 2003 and 2019 were reviewed. Major intraoperative complications were defined as loss of conduit, erroneous transection of vascular structures, significant injury to other organs including bowel, heart, liver or lung, splenectomy, or other major complications including intubation injuries, arrhythmia, pulmonary embolism, and myocardial infarction.

RESULTS: Amongst 2862 MIE cases we identified 98 patients with 101 intraoperative complications. Vascular injuries were the most prevalent, 41 during laparoscopy and 19 during thoracoscopy, with injuries to 18 different vessels. There were 24 splenic vascular or capsular injuries, 11 requiring splenectomies. Four losses of conduit due to gastroepiploic artery injury and six bowel injuries were reported. Eight tracheobronchial lesions needed repair, and 11 patients had significant lung parenchyma injuries. There were 2 on-table deaths. Ninety-day mortality was 9.2%.

CONCLUSIONS: This study offers an overview of the range of different intraoperative complications during minimally invasive esophagectomy. Mortality, especially from intrathoracic vascular injuries, appears significant.

PMID:37782412 | DOI:10.1245/s10434-023-14340-3

07:09

PubMed articles on: Cancer & VTE/PE

Venous Thromboembolism Chemoprophylaxis Adherence Rates After Major Cancer Surgery

JAMA Netw Open. 2023 Sep 5;6(9):e2335311. doi: 10.1001/jamanetworkopen.2023.35311.

ABSTRACT

IMPORTANCE: Venous thromboembolism (VTE) represents a major source of preventable morbidity and mortality and is a leading cause of death in the US after cancer surgery. Previous research demonstrated variability in VTE chemoprophylaxis prescribing, although it is unknown how these rates compare with performance in the Veterans Health Administration (VHA).

OBJECTIVE: To determine VTE rates after cancer surgery, as well as rates of inpatient and outpatient (posthospital discharge) chemoprophylaxis adherence within the VHA.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study within 101 hospitals of the VHA health system included patients aged 41 years or older without preexisting bleeding disorders or anticoagulation usage who underwent surgical treatment for cancer with general surgery, thoracic surgery, or urology between January 1, 2015, and December 31, 2022. The VHA Corporate Data Warehouse, Pharmacy Benefits Management database, and the Veterans Affairs Surgical Quality Improvement Program database were used to identify eligible patients. Data analysis was conducted between January 2022 and July 2023.

EXPOSURES: Inpatient surgery for cancer with general surgery, thoracic surgery, or urology.

MAIN OUTCOMES AND MEASURES: Rates of postoperative VTE events within 30 days of surgery and VTE chemoprophylaxis adherence were determined. Multivariable Poisson regression was used to determine incidence-rate ratios of inpatient and postdischarge chemoprophylaxis adherence by surgical specialty.

RESULTS: Overall, 30 039 veterans (median [IQR] age, 67 [62-71] years; 29 386 men [97.8%]; 7771 African American or Black patients [25.9%]) who underwent surgery for cancer and were at highest risk for VTE were included. The overall postoperative VTE rate was 1.3% (385 patients) with 199 patients (0.7%) receiving a diagnosis during inpatient hospitalization and 186 patients (0.6%) receiving a diagnosis postdischarge. Inpatient chemoprophylaxis was ordered for 24 139 patients (80.4%). Inpatient chemoprophylaxis ordering rates were highest for patients who underwent procedures with general surgery (10 102 of 10 301 patients [98.1%]) and lowest for patients who underwent procedures with urology (11 471 of 17 089 patients [67.1%]). Overall, 3142 patients (10.5%) received postdischarge chemoprophylaxis, with notable variation by specialty.

CONCLUSIONS AND RELEVANCE: These findings indicate the overall VTE rate after cancer surgery within the VHA is low, VHA inpatient chemoprophylaxis rates are high, and postdischarge VTE chemoprophylaxis prescribing is similar to that of non-VHA health systems. Specialty and procedure variation exists for chemoprophylaxis and may be justified given the low risks of overall and postdischarge VTE.

PMID:37768664 | PMC:PMC10539988 | DOI:10.1001/jamanetworkopen.2023.35311

07:09

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prevention in cancer care: implementation strategies to address underuse

07:09

PubMed articles on: Cancer & VTE/PE

Risk of venous thromboembolism in patients undergoing gastric cancer surgery: a systematic review and meta-analysis

BMC Cancer. 2023 Oct 3;23(1):933. doi: 10.1186/s12885-023-11424-x.

 

ABSTRACT

PURPOSE: The risk of thromboembolic disease is high in patients with lung transplantation and is associated with significant morbidity and mortality with single healthy transplanted lung. We present a case involving successful endovascular management of life-threatening acute massive pulmonary embolism (PE) in a patient with single lung transplant and atrial septal defect (ASD).

CASE REPORT: A 65-year-old man with a history of interstitial lung disease status post single left orthotopic lung transplant in 2012 presented with acute massive PE and clot burden in the pulmonary arteries of the transplanted left lung. Severe right heart dysfunction, hemodynamic instability, and requirement for vasopressors persisted post systemic thrombolytic therapy. As a result, the patient underwent successful endovascular mechanical thrombectomy with immediate improvement in oxygen saturation and hemodynamic status. The procedure was performed without adverse outcomes or paradoxical embolization despite the presence of ASD. The right heart dysfunction resolved, the patient was extubated the next day, and was discharged to home 2 days post procedure.

CONCLUSIONS: Endovascular mechanical thrombectomy was safely used to treat acute massive PE in a single transplanted lung in the presence of ASD.

CLINICAL IMPACT: Endovascular mechanical thrombectomy could be safely utilized to treat patients with lung transplant and acute massive or submassive pulmonary embolism. However, safely of mechanical thrombectomy should be determined in case-based scenarios and based on time interval from transplantation to when the thrombectomy is required.

PMID:37776207 | DOI:10.1177/15266028231201357

07:08

PubMed articles on: Cancer & VTE/PE

A New Risk Prediction Model for Venous Thromboembolism and Death in Ambulatory Lung Cancer Patients

Cancers (Basel). 2023 Sep 15;15(18):4588. doi: 10.3390/cancers15184588.

ABSTRACT

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively (p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed.

PMID:37760562 | PMC:PMC10527104 | DOI:10.3390/cancers15184588

07:08

PubMed articles on: Cancer & VTE/PE

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios

J Clin Med. 2023 Sep 13;12(18):5955. doi: 10.3390/jcm12185955.

ABSTRACT

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

PMID:37762897 | PMC:PMC10531873 | DOI:10.3390/jcm12185955

07:08

PubMed articles on: Cancer & VTE/PE

ReLiFiRa (Real Life Filgotinib in Rheumatoid Arthritis): Retrospective Study of Efficacy and Safety in Common Clinical Practice

J Pers Med. 2023 Aug 25;13(9):1303. doi: 10.3390/jpm13091303.

ABSTRACT

BACKGROUND: Filgotinib (FIL) is a selective JAK1 inhibitor with an affinity 30-fold higher than JAK2, approved to treat moderate to severe active rheumatoid arthritis (RA), in adults with inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).

METHODS: We conducted a retrospective, multicentric study in order to evaluate efficacy and safety of FIL 200 mg daily therapy, after 3 and 6 months, in 120 patients affected by RA, managed in Tuscany and Umbria rheumatological centers. The following clinical records were analyzed: demographical data, smoking status, previous presence of comorbidities (Herpes zoster -HZ- infection, venous thromboembolism -VTE-, major adverse cardiovascular events -MACE-, cancer, diabetes, and hypertension), disease duration, presence of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), number of biological failures, and prior csDMARDs utilized. At baseline, and after 3 (T3) and 6 (T6) months of FIL therapy, we evaluated mean steroid dosage, csDMARDs intake, clinimetric indexes (DAS28, CDAI, HAQ, patient and doctor PGA, VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and body mass index (BMI).

RESULTS: At baseline, the mean disease duration was 9.4 ± 7.5 years; the prevalence of previous HZ infection, VTE, MACE, and cancer was respectively 4.12%, 0%, 7.21%, and 0.83%, respectively. In total, 76.3% of patients failed one or more biologics (one biological failure, 20.6%; two biological failures, 27.8%; three biological failures, 16.5%; four biological failures, 10.3%; five biological failures, 1.1%). After 3 months of FIL therapy, all clinimetric index results significantly improved from baseline, as well as after 6 months. Also, ESR and CRP significatively decreased at T3 and T6. Two cases of HZ were recorded, while no new MACE, VTE, or cancer were recorded during the observation time.

CONCLUSION: Despite the limitations of the retrospective study and of the observational period of only 6 months, real-life data on the treatment of RA patients with FIL demonstrate that this Jak inhibitor therapy is safe in terms of CV, VTE events, and occurrence of cancer, and is also effective in a population identified as "difficult to treat" due to failure of previous b-DMARD therapy.

PMID:37763071 | PMC:PMC10532886 | DOI:10.3390/jpm13091303

07:08

PubMed articles on: Cancer & VTE/PE

Obstructive Sleep Apnea and Venous Thromboembolism: Unraveling the Emerging Association

Cureus. 2023 Aug 30;15(8):e44367. doi: 10.7759/cureus.44367. eCollection 2023 Aug.

 

ABSTRACT

Prior to the development of laparoscopic procedures, open appendectomy was the standard of care for the majority of appendicitis cases. Recently, studies have debated using antibiotics as a first-line treatment in uncomplicated appendicitis cases. The definition of uncomplicated appendicitis is not always clear-cut; however, with the large-scale accessibility of radiologic techniques, it is becoming increasingly easier to classify patient groups. As suggested by clinical and radiological patient data, this has raised the speculation of considering antibiotic therapy as the sole treatment modality in uncomplicated appendicitis cases. We aim to compare the options of surgery and antibiotics only in terms of efficacy, complications, and financial cost. A range of databases and search strategies were adopted, and various databases were used, including PubMed, ScienceDirect, Google Scholar, and JAMA. Collectively, 30 studies were reviewed, but only 18 were included. Efficacy rates were higher in the appendectomy group. Nevertheless, the antibiotics-only group maintained an efficacy rate greater than 70% at one-year follow-up. Risk factors that decreased the efficacy in medical management included the presence of appendicolith, neoplasm, appendiceal dilatation, peri-appendiceal fluid collection, higher mean temperature, CRP, and bilirubin. Complications were more frequent and significant in the surgery group. These included complications related to anaesthesia, surgical site infections, damage to nearby structures, and pulmonary embolism. Despite several years of follow-up and disease recurrences, higher financial costs were observed in surgically treated patients compared to the antibiotics-only group. Given the high success rates post-appendectomy for acute appendicitis over the decades, the efficacy of conservatively treated acute appendicitis raises a strong argument when choosing one of the two options. The efficacy remained consistently higher across the literature in the surgery group than in the antibiotics-only group. However, it is still arguable that antibiotics may be a preferable option given an efficacy rate of more than 70% at one year and overall higher complications associated with surgery. The argument of missing a neoplasm by avoiding surgery is valid. However, most are carcinoid neuroendocrine neoplasms with a low probability of metastasis (<5%)

PMID:37790034 | PMC:PMC10544542 | DOI:10.7759/cureus.44506

07:08

PubMed articles on: Cancer & VTE/PE

Ruptured Baker's cyst presenting with a palpable popliteal mass and crescent sign

BMJ Case Rep. 2023 Oct 4;16(10):e257869. doi: 10.1136/bcr-2023-257869.

NO ABSTRACT

PMID:37793850 | PMC:PMC10551967 | DOI:10.1136/bcr-2023-257869

07:08

PubMed articles on: Cancer & VTE/PE

Monocyte recruitment in venous pulmonary embolism at time of cancer diagnosis in upper gastrointestinal cancer patients

J Thromb Thrombolysis. 2023 Oct 4. doi: 10.1007/s11239-023-02897-5. Online ahead of print.

ABSTRACT

Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system.

PMID:37792208 | DOI:10.1007/s11239-023-02897-5

07:08

PubMed articles on: Cardio-Oncology

Proportion and number of incident cancer deaths in coronary artery disease

Cancer Med. 2023 Sep 27. doi: 10.1002/cam4.6595. Online ahead of print.

ABSTRACT

BACKGROUND: Globally, coronary artery disease (CAD) and cancer are the leading causes of death. Studies focusing on the proportion and spectrum of cancer mortality among CAD patients are lacking. We aim to characterize the proportion and spectrum of cancer-specific mortality among patients with CAD.

METHODS: We analyzed 93,797 hospitalized survivors with angiographically documented CAD between 2007 and 2020 (mean age: 62.8 ± 11.1 years, 24.7% female) from Cardiorenal ImprovemeNt II (CIN-II) cohort.

RESULTS: During the median follow-up of 4.8 years (IQR: 2.6-7.5), 13,162 (14.0%) patients died after discharge. A total of 1223/7703 (15.8% of cause-specific death) CAD patients died of cancer. The three most common types of cancer-specific death were lung (36.1%), liver (13.3%), and colorectum cancer (12.8%). Furthermore, male (adjusted HR 2.38, 95% CI: 1.99-2.85) and older (≥60 vs. <60

CONCLUSIONS: Our data suggest that nearly one-sixth of death is accounted for cancer among CAD patients within a median follow-up of 4.8 years. Lung, liver, and colorectum cancer are top three cancer-specific mortality. Further studies are needed to reduce cancer mortality for CAD patients, especially in older and male ones.

TRAIL REGISTRATION: (ClinicalTrials.gov NCT05050877).

PMID:37754571 | DOI:10.1002/cam4.6595

07:08

PubMed articles on: Cancer & VTE/PE

The Role of Mechanical Thrombectomy for Acute Massive Pulmonary Embolism in a Patient With Unilateral Lung Transplant and Atrial Septal Defect

J Endovasc Ther. 2023 Sep 30:15266028231201357. doi: 10.1177/15266028231201357. Online ahead of print.

 

ABSTRACT

Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:37758192 | DOI:10.1146/annurev-pharmtox-032823-122811

07:08

PubMed articles on: Cancer & VTE/PE

The Role of Injectables in the Treatment and Prevention of Cancer-Associated Thrombosis

Cancers (Basel). 2023 Sep 20;15(18):4640. doi: 10.3390/cancers15184640.

ABSTRACT

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer.

PMID:37760609 | PMC:PMC10526875 | DOI:10.3390/cancers15184640

07:08

PubMed articles on: Cancer & VTE/PE

Long-term risk of venous thromboembolism among patients with gastrointestinal non-neoplastic and neoplastic diseases: A prospective cohort study of 484 211 individuals

Am J Hematol. 2023 Sep 27. doi: 10.1002/ajh.27106. Online ahead of print.

ABSTRACT

We conducted a prospective cohort study to examine the associations of 21 gastrointestinal diseases with the risk of incident venous thromboembolism (VTE). The study included 485 936 UK Biobank participants free of baseline VTE. The gastrointestinal diseases were defined by the International Classification of Disease (ICD)-9 and 10 codes with data from the nationwide inpatient data set, the primary care data set, and the cancer registries. Incident VTE cases were defined by ICD-9 and 10 codes with data from the nationwide inpatient data set. Cox proportional hazards regression was used to estimate the associations of baseline gastrointestinal diseases with incident VTE risk. During a median follow-up of 12.0 years, 13 646 incident VTE cases were diagnosed. Eleven gastrointestinal diseases (nine non-neoplastic and two neoplastic) were associated with an increased risk of incident VTE after Bonferroni corrections. The risk of VTE was >50% higher among patients with gallbladder and biliary tract cancer (hazard ratio [HR] 3.15, 95% confidence interval [CI] 95% CI 1.74-5.70), pancreatic cancer (HR 2.84, 95% CI 1.65-4.91), cirrhosis (HR 2.34, 95% CI 1.96-2.79), Crohn's disease (HR 1.61, 95% CI 1.33-1.95), or pancreatitis (HR 1.57, 95% CI 1.31-1.88) compared with individuals without each of these diseases. We observed multiplicative interactions of age, sex, and body mass index with some gastrointestinal diseases (p < .05). A more pronounced, increased risk of VTE was found among younger, female, or obese patients. The study suggests a 50% higher risk of developing VTE among patients with gallbladder and biliary tract cancer, pancreatic cancer, cirrhosis, Crohn's disease, or pancreatitis.

PMID:37753710 | DOI:10.1002/ajh.27106

07:08

PubMed articles on: Cancer & VTE/PE

Machine-Learning-Assisted Procoagulant Extracellular Vesicle Barcode Assay toward High-Performance Evaluation of Thrombosis-Induced Death Risk in Cancer Patients

ACS Nano. 2023 Oct 4. doi: 10.1021/acsnano.3c04615. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) is the most fatal complication in cancer patients. Unfortunately, the frequent misdiagnosis of VTE owing to the lack of accurate and efficient evaluation approaches may cause belated medical intervention and even sudden death. Herein, we present a rapid, easily operable, highly specific, and highly sensitive procoagulant extracellular vesicle barcode (PEVB) assay composed of TiO2 nanoflower (TiNFs) for visually evaluating VTE risk in cancer patients. TiNFs demonstrate rapid label-free EV capture capability by the synergetic effect of TiO2-phospholipids molecular interactions and topological interactions between TiNFs and EVs. From ordinary plasma samples, the PEVB assay can evaluate potential VTE risk by integrating TiNFs-based EV capture and in situ EV procoagulant ability test with machine-learning-assisted clinical data analysis. We demonstrate the feasibility of this PEVB assay in VTE risk evaluation by screening 167 cancer patients, as well as the high specificity (97.1%) and high sensitivity (96.8%), fully exceeding the nonspecific and posterior traditional VTE test. Together, we proposed a TiNFs platform allowing for highly accurate and timely diagnosis of VTE in cancer patients.

PMID:37791763 | DOI:10.1021/acsnano.3c04615

07:08

PubMed articles on: Cancer & VTE/PE

D-Dimers Variability in the Perioperative Period of Breast Cancer Surgery Helps to Predict Cancer Relapse: A Single-Centre Prospective Study

Cancer Control. 2023 Jan-Dec;30:10732748231204713. doi: 10.1177/10732748231204713.

ABSTRACT

BACKGROUND: The importance of D-dimers (DD) assessment in the diagnostic algorithm of venous thromboembolic (VTE) disease is well known. Increase of DD concentration may be also associated with neoplastic disease. Many studies documented that high concentration of DD before solid tumour surgery indicates more advanced disease and poor life expectancy. The prognostic value of the DD concentration variability in the perioperative period, in women undergoing breast cancer surgery, has not been analysed so far. Thus, the aim of the present prospective study was to assess whether the trend of DD concentration changes in the perioperative period may predict cancer recurrence in women undergoing breast cancer surgery.

MATERIALS AND METHODS: 189 consecutive women with histopathological diagnosis of breast cancer (BC) referred for surgical treatment were included. DD concentration was measured twice in each patient: at the time of admission to hospital and at the time of discharge home. Enoxaparin in standard dose of 40 mg daily s. c. was used as primary VTE prophylaxis in all of the patients.

RESULTS: The recurrence of BC, within 1 year observation time, occurred in 13 patients (6.8%), in 11 (5.8%) patients with DD increase after surgery and only in 2 (1.1%) without an increase in DD, P = .0179. Increase in DD concentration after BC surgery was an independent positive predictor of disease relapse (OR 8.600, LCI 1.451, UCI 96.80, P = .0371) together with the lack of postoperative radiotherapy (OR 6.009, LCI 1.305, UCI 31.95, P = .0245), whereas the lack of postoperative chemotherapy predicted no BC relapse (OR .07355, LCI .0056, UCI .58, P = .0245).

CONCLUSIONS: Increase of DD in the early postoperative period may be considered as additional independent predictor of recurrence of BC within 1 year.

PMID:37791647 | PMC:PMC10552458 | DOI:10.1177/10732748231204713

07:08

PubMed articles on: Cancer & VTE/PE

Are Antibiotics the New Appendectomy?

Cureus. 2023 Sep 1;15(9):e44506. doi: 10.7759/cureus.44506. eCollection 2023 Sep.

 

ABSTRACT

OBJECTIVE: This systematic review and meta-analysis compares the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCS) versus pharmacological thromboprophylaxis alone.

SUMMARY BACKGROUND DATA: Surgical inpatients have elevated VTE risk; recent studies cast doubt whether GCS confer additional protection against VTE, compared to pharmacological thromboprophylaxis alone.

METHODS: The review followed PRISMA guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched to November 2022. Randomised trials reporting VTE rate after surgical procedures, utilising pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism (PE), VTE-related mortality were pooled via fixed and random effects.

RESULTS: In head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms for GCS and pharmacological thromboprophylaxis was 0.54 (95% CI 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of PE for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-related mortality (27 trial arms, 3 events, 12,982 participants).

CONCLUSIONS: Evidence from head-to-head meta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTE-related mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients.

PMID:37753655 | DOI:10.1097/SLA.0000000000006096

07:08

PubMed articles on: Cancer & VTE/PE

Effect of factor XI inhibition on tumor cell-induced coagulation activation

J Thromb Haemost. 2023 Sep 24:S1538-7836(23)00717-1. doi: 10.1016/j.jtha.2023.09.015. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer-associated thrombosis (CAT) is a frequent complication in patients with malignancies. While FXI/FXIa inhibition is efficacious in preventing postoperative venous thromboembolism, its role in tumor cell-induced coagulation is less defined.

OBJECTIVES: We thus aimed to provide mechanistic insights into FXI/FXIa inhibition in tumor cell-induced coagulation activation.

METHODS: Procoagulant activity (PCA) of four different tissue factor (TF) expressing tumor cell lines was analyzed by single-stage clotting and thrombin generation assay in the presence of a FXIa inhibitor, BMS-262084 (BMS), an inhibitory FXI antibody (anti-FXI), or peak and trough concentrations of rivaroxaban or tinzaparin. Further, tumor cell-induced platelet aggregation was recorded. Recombinant human TF (rhTF) served as positive control.

RESULTS: Although BMS and anti-FXI potently inhibited FXIa amidolytic activity, both inhibitors efficiently mitigated rhTF- and tumor cell-induced fibrin clot formation and platelet aggregation only in the presence of low TF PCA. The anticoagulant effects showed an inverse correlation with the magnitude of cellular TF PCA expression. Similarly, BMS markedly interfered with tumor cell-induced thrombin generation, with the most prominent effects on peak and total thrombin. In addition, anticoagulant effects of FXIa inhibition by 10 μM BMS were in a similar range to those obtained by 600 nM rivaroxaban and 1.6 μM tinzaparin at low TF PCA levels. However, rivaroxaban and tinzaparin also exerted marked anticoagulant activity at high TF PCA levels.

CONCLUSIONS: Our findings indicate that FXI/FXIa inhibition interferes with tumor cell-induced coagulation activation only at low TF PCA expression levels, a finding with potential implications for future in-vivo studies.

PMID:37751848 | DOI:10.1016/j.jtha.2023.09.015

07:08

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism prophylaxis practices for patients with sickle cell disease prior to and during the COVID-19 pandemic

Blood Coagul Fibrinolysis. 2023 Sep 21. doi: 10.1097/MBC.0000000000001250. Online ahead of print.

ABSTRACT

Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state due to alterations in the coagulation system. Despite concern for the development of venous thromboembolism (VTE) in this population, there are no standardized guidelines for routine thromboprophylaxis. The objective of this study was to assess thromboprophylaxis practices of adult and pediatric treaters of SCD before and during the coronavirus disease of 2019 (COVID-19) pandemic. A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through seven SCD-specific interest groups between May 29, 2020, and July 13, 2020. Of 93 total responses, 14% (N = 13) reported they only treat patients more than 21 years old; 38.7% (N = 36) only treat patients 0-21 years old and 47.3% (N = 44) reported they treat both. Our study showed that before the COVID-19 pandemic, 96% of adult practitioners would recommend pharmacologic thromboprophylaxis, mechanical thromboprophylaxis or both for hospitalized adults with thromboprophylaxis, but only 76% of pediatric treaters would recommend any thromboprophylaxis in hospitalized children (P < 0.0001), with 24% of pediatric treaters choosing no thromboprophylaxis at all. During the COVID-19 pandemic, pharmacologic thromboprophylaxis specifically was recommended for adults by 94% of treaters and for pediatric patients by 76% of treaters. These findings suggest that despite the lack of evidence-based thromboprophylaxis guidelines in adults and children with thromboprophylaxis, subspecialty treaters routinely provide pharmacologic thromboprophylaxis in their adult patients and will modify their practice in pediatric patients who are considered at a high risk for VTE.

PMID:37756203 | DOI:10.1097/MBC.0000000000001250

07:08

PubMed articles on: Cancer & VTE/PE

Oral Anticoagulants Beyond Warfarin

Annu Rev Pharmacol Toxicol. 2023 Sep 27. doi: 10.1146/annurev-pharmtox-032823-122811. Online ahead of print.

 

ABSTRACT

Pulmonary tumor thrombotic microangiopathy is a malignancy-related complication with rapid progression and high mortality. To improve the understanding of the disease, early diagnosis and treatment are key to successful treatment. A 39-year-old patient with pulmonary hypertension transferred from another hospital was admitted to the First Affiliated Hospital of Guangzhou Medical University on September 26, 2021. The patient developed shortness of breath and progressive exacerbation over the past month. No pulmonary artery embolism was seen on computed tomography pulmonary angiography (CTPA) at the outside hospital where the breast cancer was diagnosed. Pulmonary tumor thrombotic microangiopathy was immediately considered on admission and oncological endocrine therapy was started. After treatment, the patient's dyspnoea improved, PET-CT showed significant tumor regression, and cardiac ultrasound showed a significant decrease in pulmonary artery pressure. The successful treatment experience of this case was summarized for reference.

PMID:37752045 | DOI:10.3760/cma.j.cn112147-20230521-00253

07:07

PubMed articles on: Cancer & VTE/PE

An Updated Systematic Review and Meta-Analysis of the Impact of Graduated Compression Stockings in Addition to Pharmacological Thromboprophylaxis for Prevention of Venous Thromboembolism in Surgical Inpatients

Ann Surg. 2023 Sep 27. doi: 10.1097/SLA.0000000000006096. Online ahead of print.

 

ABSTRACT

INTRODUCTION: Limited data exist on the risk of venous and arterial thromboembolisms (VTE and ATE) in patients receiving cetuximab plus chemotherapy. We aimed to determine the thromboembolic risk of patients with recurrent/metastatic colorectal cancer (CRC) treated with cetuximab plus chemotherapy compared to chemotherapy alone.

METHODS: This population-based study used nationwide claims data from the Health Insurance Review and Assessment Service of South Korea from 2013 to 2020. Patients with recurrent/metastatic CRC treated with first-line oxaliplatin- or irinotecan-based doublets with or without cetuximab and no secondary prevention for VTE and ATE were included. Primary outcomes were the occurrence of any thromboembolic events, VTE, and ATE, which were determined using the cumulative incidence method incorporating death as a competing event.

RESULTS: We identified 19,723 patients (cetuximab plus chemotherapy, N = 7630; chemotherapy alone, N = 12,093). The cumulative incidence of any thromboembolic events in patients with cetuximab plus chemotherapy was significantly higher than in those receiving chemotherapy alone (6-month, 5.62 % vs. 3.58 %, P < 0.0001). The rates of VTE (6-month, 5.11 % vs. 3.28 %, P < 0.0001) and ATE (6-month, 0.53 % vs. 0.32 %, P = 0.0218) were also higher in patients receiving cetuximab plus chemotherapy. In multivariable analysis, cetuximab plus chemotherapy was independently associated with developing any thromboembolic events (hazard ratio [HR], 1.63; 95 % confidence interval [CI], 1.42-1.87), VTE (HR, 1.62; 95 % CI, 1.40-1.87), and ATE (HR, 1.77; 95 % CI, 1.16-2.71).

CONCLUSIONS: Cetuximab with irinotecan- or oxaliplatin-based doublet chemotherapy was associated with an increased risk of any thromboembolic events, VTE, and ATE; further studies are warranted to examine the underlying mechanisms.

PMID:37804738 | DOI:10.1016/j.thromres.2023.10.005

07:07

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

07:07

PubMed articles on: Cancer & VTE/PE

A multifaceted quality improvement intervention on venous thromboembolism prophylaxis compliance in hospitalized medical patients at a comprehensive cancer center

J Oncol Pharm Pract. 2023 Oct 6:10781552231205779. doi: 10.1177/10781552231205779. Online ahead of print.

ABSTRACT

INTRODUCTION: Previous studies suggest that quality improvement initiatives focused on hospital-acquired venous thromboembolism have a positive impact on prescribing rates of venous thromboembolism prophylaxis, especially those that incorporate computerized changes.

METHODS: We conducted a quality improvement project to determine whether education and computerized prescriber order entry system changes affect venous thromboembolism prophylaxis compliance rates in hospitalized medical patients at a Comprehensive Cancer Center. Between 1 January 2021 and 31 January 2023, 37,739 non-surgical, adult patient encounters with a length of stay > 48 h were analyzed in our study. From 18 December 2021 to 8 March 2022, provider education was delivered to the three largest admitting services, and computerized prescriber order entry changes were implemented incorporating a mandatory requirement to either order venous thromboembolism prophylaxis or document a contraindication for all patients at moderate venous thromboembolism risk.

RESULTS: Monthly venous thromboembolism prophylaxis compliance rates, as defined by the Centers for Medicare and Medicaid Services VTE-1 metric, increased from a mean of 74% to 93% after the interventions. This change was driven primarily by an increased utilization of mechanical venous thromboembolism prophylaxis from 37% to 53%.

CONCLUSION: Our study demonstrated that a multi-faceted intervention incorporating provider education and computerized prescriber order entry system changes can significantly increase venous thromboembolism prophylaxis compliance rates in cancer patients.

PMID:37801550 | DOI:10.1177/10781552231205779

07:07

PubMed articles on: Cancer & VTE/PE

A case of metastatic breast cancer complicated by pulmonary tumor thrombotic microangiopathy

Zhonghua Jie He He Hu Xi Za Zhi. 2023 Oct 12;46(10):1014-1018. doi: 10.3760/cma.j.cn112147-20230521-00253.

 

ABSTRACT

Cardiovascular diseases (CVD) and cancer are the top deadly diseases in the world. Both CVD and cancer have common risk factors; therefore, with the advances in treatment and life span, both diseases may occur simultaneously in patients. It is becoming evident that CVD and cancer are highly connected, establishing a novel discipline known as cardio-oncology. This includes the cardiomyocyte death following any anti-tumor therapy known as cardiotoxicity as well the intricate interplay between heart failure and cancer. Recent studies, using various mouse models, showed that heart failure promotes tumor growth and metastasis spread. Indeed, patients with heart failure were found to be at higher risk of developing malignant diseases. While the effect of heart failure on cancer is well established, little is known regarding the effect of tumors on heart failure. A recent study from our lab has demonstrated that tumor growth and metastasis ameliorate cardiac remodeling in a pressure-overload mouse model. Nevertheless, this study was inconclusive regarding whether tumor growth solely suppresses cardiac remodeling or is able to reverse existing heart failure outcomes as well. Here, we used a regulable transgenic mouse model for cardiac hypertrophy and fibrosis. Cancer cell implantation suppressed cardiac dysfunction and fibrosis as shown using echocardiography, qRT-PCR and fibrosis staining. In addition, tumor growth resulted in an M1 to M2 macrophage switch, which is correlated with cardiac repair. Macrophage depletion using clodronate liposomes completely abrogated the tumors' beneficial effect. This study highly suggests that harnessing tumor paradigms may lead to the development of novel therapeutic strategies for CVDs and fibrosis.

PMID:37759510 | PMC:PMC10528851 | DOI:10.3390/cells12182289

07:07

PubMed articles on: Cardio-Oncology

Social Determinants of Health Data Improve the Prediction of Cardiac Outcomes in Females with Breast Cancer

Cancers (Basel). 2023 Sep 19;15(18):4630. doi: 10.3390/cancers15184630.

ABSTRACT

Cardiovascular disease is the leading cause of mortality among breast cancer (BC) patients aged 50 and above. Machine Learning (ML) models are increasingly utilized as prediction tools, and recent evidence suggests that incorporating social determinants of health (SDOH) data can enhance its performance. This study included females ≥ 18 years diagnosed with BC at any stage. The outcomes were the diagnosis and time-to-event of major adverse cardiovascular events (MACEs) within two years following a cancer diagnosis. Covariates encompassed demographics, risk factors, individual and neighborhood-level SDOH, tumor characteristics, and BC treatment. Race-specific and race-agnostic Extreme Gradient Boosting ML models with and without SDOH data were developed and compared based on their C-index. Among 4309 patients, 11.4% experienced a 2-year MACE. The race-agnostic models exhibited a C-index of 0.78 (95% CI 0.76-0.79) and 0.81 (95% CI 0.80-0.82) without and with SDOH data, respectively. In non-Hispanic Black women (NHB; n = 765), models without and with SDOH data achieved a C-index of 0.74 (95% CI 0.72-0.76) and 0.75 (95% CI 0.73-0.78), respectively. Among non-Hispanic White women (n = 3321), models without and with SDOH data yielded a C-index of 0.79 (95% CI 0.77-0.80) and 0.79 (95% CI 0.77-0.80), respectively. In summary, including SDOH data improves the predictive performance of ML models in forecasting 2-year MACE among BC females, particularly within NHB.

PMID:37760599 | PMC:PMC10526347 | DOI:10.3390/cancers15184630

07:07

PubMed articles on: Cardio-Oncology

Development and Phenotype of Heart Failure in Long-Term Survivors of Childhood Cancer: The CVSS Study

J Am Heart Assoc. 2023 Oct 3;12(19):e030020. doi: 10.1161/JAHA.123.030020. Epub 2023 Sep 26.

ABSTRACT

Background The CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study aimed to investigate the prevalence of different stages of heart failure (HF) in childhood cancer survivors (CCSs) compared with the general population. Methods and Results A total of 1002 CCSs (age range, 23-48 years) diagnosed with neoplasia before an age of 15 years underwent a comprehensive cardiovascular screening. An age- and sex-matched sample from the population-based GHS (Gutenberg Health Study) served as a comparison group. Although prevalence of HF was significantly higher in CCSs, prevalence of different HF stages varied strongly by specific tumor history. Compared with the population, the prevalence ratio was 2.6 (95% CI, 2.4-2.8) for HF stage A and 4.6 (95% CI, 4.1-5.1) for the composite of HF stage B to D in an age- and sex-adjusted Poisson regression model. Multivariable linear regression, adjusting for tumor entities, age, sex, and cardiovascular risk factors, revealed a lower left ventricular ejection fraction in patients with history of bone tumors (β, -4.30 [95% CI, -5.70 to -2.80]), soft tissue sarcoma (β, -1.60 [95% CI, -2.90 to -0.30]), and renal tumors (β, -1.60 [95% CI, -2.80 to -0.29]) compared with the population. The same model for the diastolic marker, ratio of the peak early diastolic filling velocity/lateral mitral annular early diastolic velocity, showed an association only with cardiovascular risk factors but not with tumor entities. Conclusions The prevalence of HF stage A to D was significantly higher among long-term CCSs compared with the population and varied strongly by tumor entity. Systolic dysfunction was primarily associated with tumor entities, whereas diastolic dysfunction was associated with a higher burden of cardiovascular risk factors in CCSs.

PMID:37750584 | DOI:10.1161/JAHA.123.030020

07:07

PubMed articles on: Cardio-Oncology

Towards a more widespread clinical use of cardio-ankle vascular index (CAVI) and CAVI0:Defining reference values in healthy Russians

Am J Hypertens. 2023 Sep 27:hpad092. doi: 10.1093/ajh/hpad092. Online ahead of print.

NO ABSTRACT

PMID:37758230 | DOI:10.1093/ajh/hpad092

07:07

PubMed articles on: Cardio-Oncology

α-Bisabolol, a Dietary Sesquiterpene, Attenuates Doxorubicin-Induced Acute Cardiotoxicity in Rats by Inhibiting Cellular Signaling Pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 Inflammasomes Regulating Oxidative Stress and Inflammatory Cascades

Int J Mol Sci. 2023 Sep 13;24(18):14013. doi: 10.3390/ijms241814013.

ABSTRACT

Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the underlying pharmacological and molecular mechanisms. DOX (12.5 mg/kg, single dose) was injected intraperitoneally into the rats for induction of acute cardiotoxicity. BSB was given orally to rats (25 mg/kg, p.o. twice daily) for a duration of five days. DOX administration induced cardiac dysfunction as evidenced by altered body weight, hemodynamics, and release of cardio-specific diagnostic markers. The occurrence of oxidative stress was evidenced by a significant decline in antioxidant defense along with a rise in lipid peroxidation and hyperlipidemia. Additionally, DOX also increased the levels and expression of proinflammatory cytokines and inflammatory mediators, as well as activated NF-κB/MAPK signaling in the heart, following alterations in the Nrf2/Keap-1/HO-1 and Akt/mTOR/GSK-3β signaling. DOX also perturbed NLRP3 inflammasome activation-mediated pyroptosis in the myocardium of rats. Furthermore, histopathological studies revealed cellular alterations in the myocardium. On the contrary, treatment with BSB has been observed to preserve the myocardium and restore all the cellular, molecular, and structural perturbations in the heart tissues of DOX-induced cardiotoxicity in rats. Results of the present study clearly demonstrate the protective role of BSB against DOX-induced cardiotoxicity, which is attributed to its potent antioxidant, anti-inflammatory, and antihyperlipidemic effects resulting from favorable modulation of numerous cellular signaling regulatory pathways, viz., Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 inflammasomes, in countering the cascades of oxidative stress and inflammation. The observations suggest that BSB can be a promising agent or an adjuvant to limit the cardiac injury caused by DOX. Further studies including the role in tumor-bearing animals as well as regulatory toxicology are suggested.

PMID:37762315 | PMC:PMC10530367 | DOI:10.3390/ijms241814013

07:07

PubMed articles on: Cancer & VTE/PE

Increased risk of venous and arterial thromboembolism in patients with colorectal cancer receiving cetuximab-based combination chemotherapy: A population-based study in Korea

Thromb Res. 2023 Oct 4;231:50-57. doi: 10.1016/j.thromres.2023.10.005. Online ahead of print.

 

ABSTRACT

[This retracts the article DOI: 10.1155/2022/2471039.].

PMID:37810512 | PMC:PMC10551532 | DOI:10.1155/2023/9839816

07:07

PubMed articles on: Cancer & VTE/PE

Acute venous thromboembolism in patients with brain cancer: clinical course

Res Pract Thromb Haemost. 2023 Aug 20;7(6):102172. doi: 10.1016/j.rpth.2023.102172. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: Patients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH).

OBJECTIVES: The aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer.

METHODS: This was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome.

RESULTS: Overall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors.

CONCLUSION: In patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

PMID:37810416 | PMC:PMC10551887 | DOI:10.1016/j.rpth.2023.102172

07:07

PubMed articles on: Cardio-Oncology

Cardio-oncology and cancer rehabilitation: is an integrated approach possible?

Can J Cardiol. 2023 Sep 25:S0828-282X(23)01739-7. doi: 10.1016/j.cjca.2023.09.024. Online ahead of print.

ABSTRACT

With significant improvements in the understanding of cancer biology, improved detection and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study aiming to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish 'cardio-oncology' rehabilitation from 'cancer' rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this paper is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

PMID:37758015 | DOI:10.1016/j.cjca.2023.09.024

07:07

PubMed articles on: Cardio-Oncology

Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced Cardiac Dysfunction

Int J Mol Sci. 2023 Sep 7;24(18):13826. doi: 10.3390/ijms241813826.

ABSTRACT

The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs via droplet digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of left ventricular pressure-overload; (ii) to compare RNAseq findings with those of ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF. Male Wistar rats subjected to transverse aortic constriction (TAC, n = 5) showed significant systolic dysfunction vs. sham operated animals (SHAM, n = 5) via echocardiography. In TAC vs. SHAM hearts, RNAseq identified 69, and ddPCR identified 27 significantly differentially expressed GPCR mRNAs, 8 of which were identified using both methods, thus showing a correlation between the two methods. Of these, Prostaglandin-F2α-receptor (Ptgfr) was further investigated and localized on cardiomyocytes and fibroblasts in murine hearts via RNA-Scope. Antagonizing Ptgfr via AL-8810 reverted angiotensin-II-induced cardiomyocyte hypertrophy in vitro. In conclusion, using ddPCR as a novel screening method, we were able to identify GPCR targets in HF. We also show that the antagonism of Ptgfr could be a novel target in HF by alleviating cardiomyocyte hypertrophy.

PMID:37762130 | PMC:PMC10531061 | DOI:10.3390/ijms241813826

07:07

PubMed articles on: Cardio-Oncology

Tumor Progression Reverses Cardiac Hypertrophy and Fibrosis in a Tetracycline-Regulated ATF3 Transgenic Mouse Model

Cells. 2023 Sep 15;12(18):2289. doi: 10.3390/cells12182289.

 

ABSTRACT

INTRODUCTION AND IMPORTANCE: The thromboembolic complication of kidney's tumor is rare, and they can be the reason for the discovery of those tumor. Also the collision kidney tumor, such as a simultaneous occurrence of different histological types of adjacent neoplasms in the same organ is rare.

CASE PRESENTATION: We report a patient diagnosed with a kidney tumor discovered in the context of an etiological assessment of thrombosis, presenting with pulmonary embolism and deep vein thrombosis of the lower limb. This tumor treated by a cytoreductive nephrectomy. The histologic diagnosis of PRCC (Papillary Renal Cell Carcinoma) associated with a chromophobe cell carcinoma and sarcomatoid component was rendered.

CLINICAL DISCUSSION: The development of the tumor process and its progression to the metastatic stage is largely favored by the hypercoagulable state, and the cancer itself promotes the appearance of thrombo-enmbolic phenomena due to this phenomenon. Two major studies recommend that immediate cytoreductive nephrectomy should be offered to metastatic patients with a good general condition.

CONCLUSION: A renal tumor collision is rare, whereas the risk factors for a renal tumor collision are the same as a renal tumor without collision, just as the management of a metastatic renal tumor is the same. Understanding the thromboembolic physiopathology in the case of kidney cancer has made it possible to optimize management.

PMID:37812961 | DOI:10.1016/j.ijscr.2023.108922

07:07

PubMed articles on: Cancer & VTE/PE

Impact of venous thromboembolism on the mortality in patients with cancer: a population-based cohort study

Lancet Reg Health Eur. 2023 Sep 28;34:100739. doi: 10.1016/j.lanepe.2023.100739. eCollection 2023 Nov.

ABSTRACT

BACKGROUND: Despite recent improvements in the treatment of cancer, little is known about the long-term survival in patients with cancer and venous thromboembolism. We aimed to examine the five-year mortality of venous thromboembolism in cancer patients in a large population-based cohort study.

METHODS: Using Danish healthcare registries from 1995 to 2020, we obtained data on cancer patients with venous thromboembolism and comparison cohorts of cancer patients without venous thromboembolism, matched in terms of cancer type, age, sex, and year of cancer diagnosis, and adjusted for level of comorbidity and frailty using the Charlson Comorbidity Index Score and Hospital Frailty Risk Score, marital status, use of selected medications, and recent surgery (<90

FINDINGS: During the study period, 886,536 patients were diagnosed with cancer. Of 1882 cancer patients diagnosed at the time of their venous thromboembolism, 44.4% (835/1882) had distant metastases. In this cohort, the one- and five-year mortality cumulative incidences were 68% (1284/1882) and 84% (1578/1882), respectively, in contrast to 38% (2135/5549) and 67% (3653/5549) in the comparison cohort. The mortality rate ratio was 4.34 (95% confidence interval [CI], 3.95-4.78) for the first year of follow-up and 3.44 (95% CI 3.17-3.73) for the five-year follow-up period. Of the 23,366 patients diagnosed with venous thromboembolism after cancer diagnosis, 18% (4183/23,366) had distant metastases at the time of cancer diagnosis. The cumulative incidence of death at one year was 45% (10,465/23,366; mortality rate ratio 3.48, 95% CI 3.37-3.60) and at five years 69% (15,669/23,366; mortality rate ratio 2.57, 95% CI 2.50-2.63).

INTERPRETATION: Despite improved cancer treatment, venous thromboembolism in cancer patients is strongly associated with a poor prognosis.

FUNDING: The study was supported by grants from the Independent Research Fund Denmark (record no. 3101-00102B) and the Karen Elise Jensen Foundation.

PMID:37809052 | PMC:PMC10558815 | DOI:10.1016/j.lanepe.2023.100739

07:07

PubMed articles on: Cancer & VTE/PE

Retracted: Effect Evaluation of Bronchial Artery Embolization for Hemoptysis of Lung Cancer and Changes in Serum Tumor Markers and miR-34 Levels

Contrast Media Mol Imaging. 2023 Sep 27;2023:9839816. doi: 10.1155/2023/9839816. eCollection 2023.

 

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

07:07

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

07:07

PubMed articles on: Cancer & VTE/PE

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma

Thromb J. 2023 Oct 4;21(1):105. doi: 10.1186/s12959-023-00534-y.

ABSTRACT

BACKGROUND: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients.

METHODS: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis.

RESULTS: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively.

CONCLUSIONS: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

PMID:37794471 | PMC:PMC10552366 | DOI:10.1186/s12959-023-00534-y

07:07

PubMed articles on: Cancer & VTE/PE

An etiological assessment of a deep vein thrombosis led to the discovery of a renal tumor collision: Case report

Int J Surg Case Rep. 2023 Oct 5;111:108922. doi: 10.1016/j.ijscr.2023.108922. Online ahead of print.

 

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

07:07

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

Arterial (ATE) and venous (VTE) thromboembolic complications are common causes of morbidity and mortality in BCR-ABL-negative myeloproliferative neoplasms (MPNs). However, there are few studies that include all MPN subtypes and focus on both MPN-associated ATE and VTE. In our single-center retrospective study of 832 MPN patients, a total of 180 first thromboembolic events occurred during a median follow-up of 6.6 years (range: 0-37.6 years), of which 105 were VTE and 75 were ATE. The probability of a vascular event at the end of the follow-up period was 36.2%, and the incidence rate for all first ATE/VTE was 2.43% patient/year. The most frequent VTE localizations were deep vein thrombosis with or without pulmonary embolism (incidence rate: 0.59% patient/year), while strokes were the most frequent ATE with an incidence rate of 0.32% patient/year. When comparing the group of patients with ATE/VTE (n = 180) and the group without such an event (n = 652) using multivariate Cox regression analyses, patients with polycythemia vera (hazard ratio [HR]: 1.660; [95% confidence interval [CI] 1.206, 2.286]) had a significantly higher risk of a thromboembolic event than the other MPN subtypes. In contrast, patients with a CALR mutation had a significantly lower risk of thromboembolism compared with JAK2-mutated MPN patients (HR: 0.346; [95% CI: 0.172, 0.699]). In summary, a high incidence of MPN-associated VTE and ATE was observed in our retrospective study. While PV patients or generally JAK2-mutated MPN patients had a significantly increased risk of such vascular events, this risk was reduced in CALR-mutated MPN patients.

PMID:37813367 | DOI:10.1055/a-2159-8767

07:07

PubMed articles on: Cancer & VTE/PE

Persistent underuse of extended venous thromboembolism prophylaxis in patients undergoing major abdominal cancer operations

J Surg Oncol. 2023 Oct 6. doi: 10.1002/jso.27473. Online ahead of print.

ABSTRACT

BACKGROUND: Guidelines recommend extended venous thromboembolism (VTE) prophylaxis for high-risk populations undergoing major abdominal cancer operations. Few studies have evaluated extended VTE prophylaxis in the Medicare population who are at higher risk due to age.

METHODS: We performed a retrospective study using a 20% random sample of Medicare claims, 2012-2017. Patients ≥65 years with an abdominal cancer undergoing resection were included. Primary outcome was the proportion of patients receiving new extended VTE prophylaxis prescriptions at discharge. Secondary outcomes included postdischarge VTE and hemorrhagic events.

RESULTS: The study included 72 983 patients with a mean age of 75. Overall, 8.9% of patients received extended VTE prophylaxis. This proportion increased (7.2% in 2012, 10.6% in 2017; p < 0.001). Incidence of postdischarge hemorrhagic events was 1.0% in patients receiving extended VTE prophylaxis and 0.8% in those who did not. The incidence of postdischarge VTE events was 5.2% in patients receiving extended VTE prophylaxis and 2.4% in those who did not.

CONCLUSION: Adherence to guideline-recommended extended VTE prophylaxis in high-risk patients undergoing major abdominal cancer operations is low. The higher rate of VTE in the prophylaxis group may suggest we captured some therapeutic anticoagulation, which would mean the actual rate of thromboprophylaxis is lower than reported herein.

PMID:37800390 | DOI:10.1002/jso.27473

07:07

PubMed articles on: Cancer & VTE/PE

Risk factors for bleeding in cancer patients treated with conventional dose followed by low dose apixaban for venous thromboembolism

Thromb Haemost. 2023 Oct 10. doi: 10.1055/a-2188-8773. Online ahead of print.

ABSTRACT

BACKGROUND: Incidence of and risk factors for bleeding in cancer patients with venous thromboembolism (VTE) treated with apixaban are poorly described.

METHODS: We analyzed data from the prospective CAP study where 298 cancer patients with any type of VTE received 5 mg apixaban twice daily for 6 months, and then 2.5 mg apixaban twice daily for 30 months. For most analyses major bleedings and clinically relevant non-major bleedings were merged to "clinically relevant bleedings". Risk factors were estimated by odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: The incidence of clinically relevant bleedings was 38% per person year during the first 6 months of treatment, 21% per person year from 7 to 12 months, and between 4% and 8% per person year from 13 to 36 months. Clinically relevant bleedings were associated with age above 74 years (OR 2.0, 95% CI 1.0-4.1), BMI below 21.7 (OR 2.3, 95% CI 1.1-4.8), and hemoglobin at baseline below 10.5 for females (OR 2.8, 95% CI 1.1-7.3) and 11.1 for males (OR 3.3, 95% CI 1.3-8.4) during the first 6 months. Gastrointestinal (GI) or urogenital cancer were not associated with clinically relevant bleedings compared with other cancers. Among patients with luminal GI-cancer, non-resected cancer had increased risk of bleeding (OR 3.4, 95% CI 1.0-11.6) compared with resected GI-cancer.

CONCLUSION: It was very few bleedings while patients were on low-dose apixaban. Factors associated with bleeding in patients treated with full-dose apixaban were high age, low BMI, and low hemoglobin, and probably non-resected luminal GI-cancer.

PMID:37816388 | DOI:10.1055/a-2188-8773

07:07

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

Having established the significance of cardiovascular side-effects of anti-neoplastic drugs, present day cardio-oncology has forayed into newer territories buoyed by research into the multiple connections that exist between cardiovascular disease and cancer. An emerging concept of reverse cardio-oncology focuses on the heightened risk of cancer in patients with cardiovascular disease. Common mechanistics of cancer and heart failure (HF) like chronic inflammation and clonal haematopoesis as well as common predisposing factors like obesity and diabetes underline the relation between both cardiovascular disease and various cancers.This review discusses the potential magnitude of the problem, the underlying pathophysiological mechanisms and classification of this novel subject.

PMID:37774949 | DOI:10.1016/j.ihj.2023.09.004

07:06

PubMed articles on: Cardio-Oncology

The broad spectrum of cardiotoxicities from immunotherapies

Front Cardiovasc Med. 2023 Sep 15;10:1259620. doi: 10.3389/fcvm.2023.1259620. eCollection 2023.

NO ABSTRACT

PMID:37781307 | PMC:PMC10540439 | DOI:10.3389/fcvm.2023.1259620

07:06

PubMed articles on: Cardio-Oncology

Echocardiographic Parameters Associated With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors

J Phys Act Health. 2023 Oct 4:1-10. doi: 10.1123/jpah.2023-0100. Online ahead of print.

ABSTRACT

BACKGROUND: Children's exposure to chemotherapeutic agents causes several long-term adverse effects but physical activity has been evidenced to be an effective strategy to improve cardiac function. This cross-sectional study aimed to explore the association between physical activity levels, cardiorespiratory fitness, and cardiac parameters measured by echocardiography.

METHODS: Participants were 216n childhood acute lymphoblastic leukemia survivors who underwent a maximal cardiopulmonary exercise test and self-reported their daily minutes of moderate to vigorous physical activity. They underwent a complete transthoracic echocardiographic assessment. Systolic and diastolic function analysis and strain images analysis were performed. The associations were studied through the preventive fraction (examined with univariate crude and adjusted logistic regression models) of regular physical activity (≥150 min·wk-1) and adequate cardiorespiratory fitness levels (above the median ≥ 32.0 mL·kg-1·min-1) on cardiac parameters.

RESULTS: Crude analysis shows that regular physical activity was associated with a significant preventive fraction in mitral E/A ratio (56%; P = .013), while adjusted analyses highlighted a nonsignificant reduction of 74% to 37% in the prevalence of cardiac parameters associated with physical activity. Similar associations of adequate cardiorespiratory fitness on cardiac parameters were observed. Adjusted analyses revealed a nonsignificant reduction of 7% to 86% in the prevalence of cardiac parameters associated with cardiorespiratory fitness.

CONCLUSION: This study reports that regular physical activity and adequate cardiorespiratory fitness were associated with a higher preventive fraction. Thus, engaging in physical activity prevents childhood acute lymphoblastic leukemia survivors' cardiac dysfunctions. These findings are novel and clinically relevant in pediatric cardiooncology and provide additional evidence to strengthen the benefits of exercise as long-term care in childhood cancer survivors.

PMID:37793652 | DOI:10.1123/jpah.2023-0100

07:06

PubMed articles on: Cancer & VTE/PE

Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry

J Am Geriatr Soc. 2023 Oct 10. doi: 10.1111/jgs.18626. Online ahead of print.

ABSTRACT

BACKGROUND: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90

METHODS: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE.

RESULTS: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90

CONCLUSIONS: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

PMID:37814983 | DOI:10.1111/jgs.18626

07:06

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

07:06

PubMed articles on: Cancer & VTE/PE

Arterial and Venous Thromboembolic Complications in 832 Patients with BCR-ABL-Negative Myeloproliferative Neoplasms

Hamostaseologie. 2023 Oct 9. doi: 10.1055/a-2159-8767. Online ahead of print.

 

ABSTRACT

Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.

PMID:37765020 | PMC:PMC10534320 | DOI:10.3390/ph16091212

07:06

PubMed articles on: Cardio-Oncology

Sheng-Mai-Yin inhibits doxorubicin-induced ferroptosis and cardiotoxicity through regulation of Hmox1

Aging (Albany NY). 2023 Sep 28;15. doi: 10.18632/aging.205062. Online ahead of print.

ABSTRACT

Doxorubicin (DOX) is a potent chemotherapeutic drug used for treating various cancers. However, its clinical use is limited due to its severe cardiotoxicity, which often results in high mortality rates. Sheng-Mai-Yin (SMY), a Traditional Chinese medicine (TCM) prescription, has been reported to exert a cardioprotective effect in various cardiovascular diseases, including DOX-induced cardiotoxicity (DIC). This study aimed to provide novel insights into the underlying cardioprotective mechanism of SMY. SMY, composed of Codonopsis pilosula (Franch.), Ophiopogon japonicus (Thunb.), and Schisandra chinensis (Turcz.) at a ratio of 3:2:1, was intragastrically administered to male C57BL/6 mice for five days prior to the intraperitoneal injection of mitoTEMPO. One day later, DOX was intraperitoneally injected. Hematoxylin-eosin staining and Sirius red staining were carried out to estimate the pharmacological effect of SMY on cardiotoxicity. Mitochondrial function and ferroptosis biomarkers were also examined. AAV was utilized to overexpress Hmox1 to confirm whether Hmox1-mediated ferroptosis is associated with the cardioprotective effect of SMY on DOX-induced cardiotoxicity. The findings revealed that SMY therapy reduced the number of damaged cardiomyocytes. SMY therapy also reversed the inductions of cardiac MDA, serum MDA, LDH, and CK-MB contents, which dramatically decreased nonheme iron levels. In the meantime, SMY corrected the changes to ferroptosis indices brought on by DOX stimulation. Additionally, Hmox1 overexpression prevented SMY's ability to reverse cardiotoxicity. Our results showed that SMY effectively restrained lipid oxidation, reduced iron overload, and inhibited DOX-induced ferroptosis and cardiotoxicity, possibly via the mediation of Hmox1.

PMID:37770231 | DOI:10.18632/aging.205062

07:06

PubMed articles on: Cardio-Oncology

Early Echocardiography and ECG Changes Following Radiotherapy in Patients with Stage II-III HER2-Positive Breast Cancer Treated with Anthracycline-Based Chemotherapy with or without Trastuzumab-Based Therapy

Med Sci Monit. 2023 Sep 20;29:e941754. doi: 10.12659/MSM.941754.

ABSTRACT

BACKGROUND Cardiotoxicity from radiotherapy and anti-cancer therapies have been reported in patients with breast cancer. This study aimed to investigate the early echocardiography and ECG changes following radiotherapy in 68 patients ages 30-78 years with stages II-III HER2-positive breast cancer treated with anthracycline-based chemotherapy with or without trastuzumab-based therapy from 2015 to 2021. MATERIAL AND METHODS We analyzed data of 68 breast cancer patients aged 30-78 years, predominantly in AJCC stages II-III (61) and HER2-positive (58), treated and monitored from 2015 to 2021. Cardiac function was assessed using echo- and electrocardiography. We employed univariate logistic models to gauge associations between pre-existing cardiac conditions, treatment modalities, and changes in cardiac function. RESULTS A decrease in the left ventricle ejection fraction (EF) by >5% was associated with heart doses >49.3 Gy and with maximum and average doses to the left anterior descending artery (LAD) exceeding 46.9 Gy and 32.7 Gy, respectively. An EF drop of ≥10% was correlated with anti-HER2 therapy, pre-existing ECG changes, and the onset of conditions in the left ventricle, major vessels, and valves. Conditions were exacerbated in patients with prior echocardiographic abnormalities, while some emerged concurrent with the EF decline. CONCLUSIONS This research emphasizes the importance of personalized heart monitoring and care for breast cancer patients undergoing multimodal therapies. Significant and potentially irreversible EF declines can result from radiation and anti-HER2 treatments.

PMID:37772333 | PMC:PMC10521333 | DOI:10.12659/MSM.941754

07:06

PubMed articles on: Cardio-Oncology

Reverse cardio-oncology: A budding concept

Indian Heart J. 2023 Sep 27:S0019-4832(23)00163-3. doi: 10.1016/j.ihj.2023.09.004. Online ahead of print.

 

ABSTRACT

Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Surgical valve replacement, transcatheter valve implantation, balloon valvuloplasty, and medical therapy are possible treatments for aortic valve stenosis, but when malignancy is present, the choice between these options must take into account the stage of cancer and associated treatment, expected outcome, and comorbidities. Physical examination and Doppler echocardiography are critical in the diagnosis and evaluation of aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer and the therapeutic options.

PMID:37762745 | PMC:PMC10532214 | DOI:10.3390/jcm12185804

07:06

PubMed articles on: Cardio-Oncology

Pyrotinib-based therapeutic approaches for HER2-positive breast cancer: the time is now

Breast Cancer Res. 2023 Oct 3;25(1):113. doi: 10.1186/s13058-023-01694-5.

ABSTRACT

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is a highly aggressive subtype associated with poor prognosis. The advent of HER2-targeted drugs, including monoclonal antibodies, tyrosine-kinase inhibitors (TKIs) and antibody-drug conjugates, has yielded improved prognosis for patients. Compared with widely used monoclonal antibodies, small-molecule TKIs have unique advantages including oral administration and favorable penetration of blood-brain barrier for brain metastatic BC, and reduced cardiotoxicity. Pyrotinib is an irreversible TKI of the pan-ErbB receptor, and has recently been shown to be clinically effective for the treatment of HER2-positive BC in metastatic and neoadjuvant settings. This review highlights the development on the application of pyrotinib-based therapeutic approaches in the clinical settings of HER2-positive BC.

PMID:37789330 | PMC:PMC10546716 | DOI:10.1186/s13058-023-01694-5

07:06

PubMed articles on: Cardio-Oncology

Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals

Front Cardiovasc Med. 2023 Sep 15;10:1223660. doi: 10.3389/fcvm.2023.1223660. eCollection 2023.

ABSTRACT

In cancer, a patient is considered a survivor from the time of initial diagnosis until the end of life. With improvements in early diagnosis and treatment, the number of cancer survivors (CS) has grown considerably and includes: (1) Patients cured and free from cancer who may be at risk of late-onset cancer therapy-related cardiovascular toxicity (CTR-CVT); (2) Patients with long-term control of not-curable cancers in whom CTR-CVT may need to be addressed. This paper highlights the importance of the cancer care continuum, of a patient-centered approach and of a prevention-oriented policy. The ultimate goal is a personalized care of CS, achievable only through a multidisciplinary-guided survivorship care plan, one that replaces the fragmented management of current healthcare systems. Collaboration between oncologists and cardiologists is the pillar of a framework in which primary care providers and other specialists must be engaged and in which familial, social and environmental factors are also taken into account.

PMID:37786510 | PMC:PMC10541962 | DOI:10.3389/fcvm.2023.1223660

07:06

PubMed articles on: Cardio-Oncology

Approaches for reducing chemo/radiation-induced cardiotoxicity by nanoparticles

Environ Res. 2023 Sep 28:117264. doi: 10.1016/j.envres.2023.117264. Online ahead of print.

ABSTRACT

Nanoparticles are fascinating and encouraging carriers for cancer treatment due to their extraordinary properties and potential applications in targeted drug delivery, treatment, and diagnosis. Experimental studies including in vitro and in vivo examinations show that nanoparticles can cause a revolution in different aspects of cancer therapy. Normal tissue toxicity and early and late consequences are the major limitations of cancer therapy by radiotherapy and chemotherapy. However, the delivery of drugs into tumors or reducing the accumulation of drugs in normal tissues can permit a more satisfactory response of malignancies to therapy with more inferior side effects. Cardiac toxicity is one of the major problems for chemotherapy and radiotherapy. Therefore, several experimental studies have been performed to minimize the degenerative impacts of cancer treatment on the heart and also enhance the influences of radiotherapy and chemotherapy agents in cancers. This review article emphasizes the benefits of nanoparticle-based drug delivery techniques, including minimizing the exposure of the heart to anticancer drugs, enhancing the accumulation of drugs in cancers, and expanding the effectiveness of radiotherapy. The article also discusses the challenges and problems accompanied with nanoparticle-based drug delivery techniques such as toxicity, which need to be addressed through further research. Moreover, the article emphasizes the importance of developing safe and effective nanoparticle-based therapies that can be translated into clinical practice.

PMID:37776941 | DOI:10.1016/j.envres.2023.117264

07:06

PubMed articles on: Cardio-Oncology

Hyperhomocysteinaemia Promotes Doxorubicin-Induced Cardiotoxicity in Mice

Pharmaceuticals (Basel). 2023 Aug 28;16(9):1212. doi: 10.3390/ph16091212.