ABSTRACT

Breast cancer is the most common cancer in women. Patients with breast cancer have a 4-fold increased risk of venous thromboembolism (VTE) compared to age- and sex-matched controls without cancer. VTE remains the second leading cause of death in cancer patients and an independent risk factor for mortality. In women with breast cancer, the main risk factors for developing VTE are increasing age, obesity, disease stage, central catheter placement and cancer treatments, including surgery, chemotherapy, hormonotherapy and cyclin-dependent kinase 4/6 inhibitors. In women receiving tamoxifen, the risk of VTE is particularly increased within the first 6 months after initiation of hormonotherapy, although some evidence suggests that this risk may persist through the first 2 years of treatment. The risk of VTE appears to be lower in patients receiving aromatase inhibitors. In breast cancer patients receiving cyclin-dependent kinase 4/6 inhibitors, the rate of VTE is approximately 6%. Current clinical practice guidelines for the treatment and prevention of VTE in patients with cancer suggest that thromboprophylaxis should not be used routinely in ambulatory cancer patients receiving chemotherapy or hormonotherapy. The risk-benefit ratio of thromboprophylaxis should be assessed on a case-by-case basis and be the subject of multidisciplinary discussion.

PMID:37474353 | DOI:10.1016/j.bulcan.2023.06.001

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PubMed articles on: Cancer & VTE/PE

Risk of thromboembolic events in patients with metastatic solid tumors treated with PARP inhibitors: A systematic review and meta-analysis of phase 3 randomized controlled trials

Cancer Treat Rev. 2023 Jul 17;119:102601. doi: 10.1016/j.ctrv.2023.102601. Online ahead of print.

ABSTRACT

BACKGROUND AND SCOPE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized cancer treatment in recent years. These drugs present a favorable safety profile, even though the potential risk of thromboembolic events (TEs) during their use has not been addressed yet. In addition, PARPi have been involved in an active scientific debate regarding non-oncologic indications, particularly during the Coronavirus Disease 2019 pandemic, including potential anti-thromboembolic effect.

METHODS: To clarify whether patients treated with PARPi for metastatic solid tumors are either at increased or decreased risk of TEs, we conducted a systematic review of the literature and meta-analysis, including all phase 3 randomized controlled trials (RCTs) which investigated PARPi in this setting. Search was conducted through Medline, EMBASE, Pubmed, SCOPUS and Google Scholar in February 2023, including the proceedings of the principal oncology meetings of the last 10 years, with no time restriction. For each included study, frequencies of TEs in experimental and control arm were collected.

RESULTS: Our search identified 2,369 reports, of which 20 were lastly selected. A total of 4,946 patients were included, across 12 different RCTs. The meta-analysis did not demonstrate either an increased or a reduced risk in TEs in patients treated with PARPi for metastatic disease (OR 1.50, range: 1.00-2.24; 95% CI; P = 0.050), with low heterogeneity and low publication bias.

CONCLUSION: Although our research did not confirm either increased or decreased risk of TEs for PARPi use, no safety alerts emerged. Thromboembolic risk assessment models should always be integrated in daily clinical routine, to identify high-risk patients.

PMID:37473517 | DOI:10.1016/j.ctrv.2023.102601

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PubMed articles on: Cancer & VTE/PE

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis

J Clin Oncol. 2023 Jul 20:JCO2300429. doi: 10.1200/JCO.23.00429. Online ahead of print.

ABSTRACT

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer.

METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT.

RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58).

CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

PMID:37471683 | DOI:10.1200/JCO.23.00429

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PubMed articles on: Cancer & VTE/PE

Comment on: Silent Pulmonary Thromboembolism in Patients Undergoing Craniotomy for Brain Tumor

Turk Neurosurg. 2023;33(4):711. doi: 10.5137/1019-5149.JTN.44181-23.0.

NO ABSTRACT

PMID:37470514 | DOI:10.5137/1019-5149.JTN.44181-23.0

02:47

PubMed articles on: Cancer & VTE/PE

Inferior Vena Cava Filters: Adherence to Clinical Practice Guidelines Recommendations, Retrieval Rates, and Filter Complications in a Tertiary Hospital

Angiology. 2023 Jul 20:33197231190184. doi: 10.1177/00033197231190184. Online ahead of print.

ABSTRACT

The present study evaluated the adherence to guideline recommendations regarding the indication for inferior vena cava filter (IVCF) placement, retrieval rates, complications, thrombotic recurrences, and mortality. Patients in whom an IVCF was placed between 2015 and 2020 in a tertiary hospital were retrospectively included. We considered absolute indication of IVCF placement if all the guidelines evaluated agreed on the indication, relative indication if only some guidelines recommended it and without indication if none of the evaluated guidelines recommended it. From the 185 patients included; 47% had an absolute indication, 15% a relative indication, and 38% had no indication. Filter-associated complications and non-removal rates were 12.4% and 41%, respectively. Venous thromboembolism recurrence rate was 17.8%, being filter-associated complications (24.2 vs 9.8%, P = .02) and thrombosis of the inferior cava or iliac veins (12.1 vs 2.6%, P = .03) more frequent in this group. The mortality rate was 40%, with higher mortality risk in patients with co-existing cancer. Previous major bleeding, filter-associated complications, and mortality were associated with a major risk of non-removal. In conclusion, the adherence to guidelines regarding the indication of IVCF placement is still low and IVCF complications are not negligible. This fact is of special concern in the elderly, comorbid, and cancer patients.

PMID:37470426 | DOI:10.1177/00033197231190184

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PubMed articles on: Cancer & VTE/PE

Glomerular hyperfiltration is an independent predictor of postoperative outcomes: A NSQIP multi-specialty surgical cohort analysis

Nephrology (Carlton). 2023 Jul 19. doi: 10.1111/nep.14221. Online ahead of print.

ABSTRACT

AIM: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30-day postoperative outcomes using a multi-specialty surgical cohort.

METHODS: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex-specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th95th percentile). The primary outcome was a composite of any 30-day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30-day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest.

RESULTS: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]).

CONCLUSION: Our findings support an association between high eGFR and adverse 30-day postoperative outcomes.

PMID:37468129 | DOI:10.1111/nep.14221

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PubMed articles on: Cancer & VTE/PE

A sensitive tissue factor activity assay determined by an optimized thrombin generation method

PLoS One. 2023 Jul 19;18(7):e0288918. doi: 10.1371/journal.pone.0288918. eCollection 2023.

ABSTRACT

BACKGROUND: Tissue factor (TF) is the principal activator of the coagulation system, but an increased concentration in the blood in cancer and inflammatory diseases has been suggested to play a role increasing the risk of venous thromboembolism. However, measurement of the TF concentration is difficult, and quantitation of activity is the most valid estimation. The objective of this study was to establish a sensitive method to measure TF activity based on thrombin generation.

METHODS: The assay is based on thrombin generation (TG) measured on the Calibrated Automated Thrombogram (CAT). Various low concentrations of TF were prepared from reagents containing 1 pM TF and 4 μM phospholipid (PPL), and no TF and 4 μM PPL, and a calibration curve was produced from Lagtime vs TF concentration. TF in blood samples was measured after isolation and resuspension of extracellular vesicles (EVs) in a standard plasma from which EVs had been removed. The same standard plasma was used for the calibrators.

RESULTS: Contact activation of the coagulation system was avoided using CTI plasma samples in Monovette tubes. EVs contain procoagulant phospholipids but addition of PPL only reduced lagtime slightly at very low concentrations of TF resulting in overestimation to a lesser extent at 10 fM but no interference at 30 fM or higher. Addition of EVs to the TG analysis induced a small unspecific TF-independent activity (i.e., an activity not inhibited by antibodies against TF) which also may result in a smaller error in estimation of TF activity at very low levels but the effect was negligible at higher concentrations. It was possible to measure TF activity in healthy controls which was found to be 1-6 fM (EVs were concentrated, i.e. solubilized in a lower volume than the original volume plasma). Coefficient of variation (CV) was below 20% at the low level, and below 10% at a level around 100 fM TF. However, the step with isolation of EVs have a higher inherent CV.

CONCLUSION: A sensitive and rather precise one-stage TG-based method to measure TF activity has been established.

PMID:37467256 | PMC:PMC10355404 | DOI:10.1371/journal.pone.0288918

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PubMed articles on: Cancer & VTE/PE

Does the Use of Negative Pressure Wound Therapy and Postoperative Drains Impact the Development of Surgical Site Infections?: A PARITY Trial Secondary Analysis

J Bone Joint Surg Am. 2023 Jul 19;105(Suppl 1):34-40. doi: 10.2106/JBJS.22.01185. Epub 2023 Jul 19.

ABSTRACT

BACKGROUND: Surgical site infections (SSIs) represent a major complication following oncologic reconstructions. Our objectives were (1) to assess whether the use of postoperative drains and/or negative pressure wound therapy (NPWT) were associated with SSIs following lower-extremity oncologic reconstruction and (2) to identify factors associated with the duration of postoperative drains and with the duration of NPWT.

METHODS: This is a secondary analysis of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial, a multi-institution randomized controlled trial of lower-extremity oncologic reconstructions. Data were recorded regarding the use of drains alone, NPWT alone, or both NPWT and drains, including the total duration of each postoperatively. We analyzed postoperative drain duration and associations with tourniquet use, intraoperative thromboprophylaxis or antifibrinolytic use, incision length, resection length, and total operative time, through use of a linear regression model. A Cox proportional hazards model was used to evaluate the independent predictors of SSI.

RESULTS: Overall, 604 patients were included and the incidence of SSI was 15.9%. Postoperative drains alone were used in 409 patients (67.7%), NPWT alone was used in 15 patients (2.5%), and both postoperative drains and NPWT were used in 68 patients (11.3%). The median (and interquartile range [IQR]) duration of drains and of NPWT was 3 days (IQR, 2 to 5 days) and 6 days (IQR, 4 to 8 days), respectively. The use of postoperative drains alone, NPWT alone, or both drains and NPWT was not associated with SSI (p = 0.14). Increased postoperative drain duration was associated with longer operative times and no intraoperative tourniquet use, as shown on linear regression analysis (p < 0.001 and p = 0.03, respectively). A postoperative drain duration of ≥14 days (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.3 to 9.6; p = 0.01) and an operative time of ≥8 hours (HR, 4.5; 95% CI, 1.7 to 11.9; p = 0.002) were independent predictors of SSI following lower-extremity oncologic reconstruction.

CONCLUSIONS: A postoperative drain duration of ≥14 days and an operative time of ≥8 hours were independent predictors of SSI following lower-extremity oncologic reconstruction. Neither the use of postoperative drains nor the use of NPWT was a predictor of SSI. Future research is required to delineate the association of the combined use of postoperative drains and NPWT with SSI.

LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

PMID:37466578 | DOI:10.2106/JBJS.22.01185

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PubMed articles on: Cancer & VTE/PE

Incidence of and Risk Factors for Thromboembolism After Endoprosthetic Reconstruction in Musculoskeletal Oncology Patients

J Bone Joint Surg Am. 2023 Jul 19;105(Suppl 1):29-33. doi: 10.2106/JBJS.22.01140. Epub 2023 Jul 19.

ABSTRACT

BACKGROUND: The aim of the present study was to assess the incidence of and risk factors for thromboembolic events-including assessment of the intraoperative use of tranexamic acid and postoperative use of chemical thromboprophylaxis-in patients undergoing operative treatment of primary bone or soft-tissue sarcoma or oligometastatic bone disease.

METHODS: This study was performed as a secondary analysis of prospective data collected from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) randomized controlled trial, which included 604 patients ≥12 years old who underwent surgical resection and endoprosthetic reconstruction for either primary bone or soft-tissue sarcoma or oligometastatic disease of the femur or tibia. We determined the incidence of thromboembolic events in these patients and evaluated potential risk factors, including patient age, sex, antibiotic treatment group, type of tumor (i.e., primary bone or soft-tissue sarcoma or metastatic bone disease), intraoperative tranexamic acid, tourniquet use, operative time, pathologic characteristics (i.e., American Joint Committee on Cancer grade, vascular invasion, and percent necrosis), postoperative chemical thromboprophylaxis regimen, and surgical site infection. Continuous variables were assessed with use of the Student t test. Categorical variables were assessed with use of the Pearson chi-square test, except when the expected cell counts were <5,

RESULTS: Postoperative thromboembolic events occurred in 11 (1.8%) of 604 patients. Patients who experienced a thromboembolic event had a significantly higher mean (± standard deviation) age (59.6 ± 17.5 years) than those who did not experience a thromboembolic event (40.9 ± 21.8; p = 0.002). Patients randomized to the long-term antibiotic group had a significantly higher incidence of thromboembolic events (9 of 293; 3.1%) than those randomized to the short-term antibiotic group (2 of 311; 0.64%; p = 0.03). Neither intraoperative tranexamic acid nor postoperative chemical thromboprophylaxis were significantly associated with the occurrence of a thromboembolic event.

CONCLUSIONS: Although relatively rare in the PARITY cohort, thromboembolic events were more likely to occur in older patients and those receiving long-term prophylactic antibiotics. Intraoperative tranexamic acid and postoperative chemical thromboprophylaxis were not associated with a greater incidence of thromboembolic events.

LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

PMID:37466577 | DOI:10.2106/JBJS.22.01140

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PubMed articles on: Cancer & VTE/PE

Advances in contraception: vaginal contraceptive rings

Ther Adv Reprod Health. 2023 Jul 14;17:26334941231186733. doi: 10.1177/26334941231186733. eCollection 2023 Jan-Dec.

ABSTRACT

The vaginal contraceptive ring is very effective and user dependent. In this article, we will discuss the different types of vaginal contraceptive rings, namely, the etonogestrel/ethinyl estradiol (ENG/EE) ring (NuvaRing, Merck, Rahway, NJ, USA) and the segesterone acetate (SA)/EE (Annovera, Mayne Pharma, Raleigh, NC, USA) ring. The details of dosing and administration, indications, advantages, disadvantages, and cost-effectiveness are presented. This literature review was conducted using PubMed and Google Scholar. The search terms included 'vaginal contraceptive ring', 'etonogestrel/ethinyl estradiol ring', and 'segesterone acetate/ethinyl estradiol ring'. The search was then sorted by year from 2000 until present, and the most recent articles were reviewed. The purpose of this article is to provide a comprehensive reference on the two vaginal contraceptive rings widely used in the United States for clinicians to guide management. Both vaginal contraceptive rings are combination of hormonal contraceptives that suppress ovulation and create physiologic conditions unfavorable for pregnancy. The ENG/EE ring is designed to be replaced monthly, while the SA/EE ring is a single device used over the course of 1 year. Common side effects of both devices include headaches, nausea, vomiting, and vaginitis. Serious adverse reactions can occur with the vaginal contraceptive rings including venous thromboembolism, psychiatric events, and hypersensitivity. Both devices are contraindicated in patients at high risk for arterial or venous thrombotic events, patients with a history of breast cancer or other estrogen/progesterone cancers, and patients with severe liver disease. Overall, the vaginal contraceptive ring is well tolerated and liked by patients. Patients should be well counseled on known severe adverse reactions. The vaginal contraceptive ring is more expensive than other forms of contraception and this should be an important point of discussion with patients.

PMID:37465002 | PMC:PMC10350750 | DOI:10.1177/26334941231186733

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PubMed articles on: Cancer & VTE/PE

A nomogram for predicting the risk of venous thromboembolism in patients with solid cancers

J Thromb Thrombolysis. 2023 Jul 18. doi: 10.1007/s11239-023-02856-0. Online ahead of print.

ABSTRACT

Cancer patients with venous thromboembolism (VTE) are prone to poor prognoses. Thus, we aimed to develop a nomogram to predict the risk of VTE in these patients. We retrospectively analyzed 791 patients diagnosed with solid tumors between January 2017 and May 2021 at Tongji Hospital. Univariate logistic analysis and multivariate logistic regression were adopted in this study. Our results indicated that age ≥ 60 years, tumor stages III-IV, platelet distribution width (PDW) ≤ 12.6%, albumin concentration ≤ 38.8 g/L, lactate dehydrogenase (LDH) concentration ≥ 198 U/L, D-dimer concentration ≥ 1.72 µg/mL, blood hemoglobin concentration ≤ 100 g/dL or the use of erythropoiesis-stimulating agents and cancer types were independent risk factors. The nomogram prediction model was developed based on the regression coefficients of these variables. We assessed the performance of the nomogram by calibration plot and the area under the receiver operating characteristic curve and compared it with the Khorana score. The concordance index (C- index) of the nomogram was 0.852 [95% confidence interval (CI) 0.823 to 0.880], while the Khorana score was 0.681 (95% CI 0.639 to 0.723). Given its performance, this nomogram could be used to select cancer patients at high risk for VTE and guide thromboprophylaxis treatment in clinical practice, provided it is validated in an external cohort.

PMID:37462901 | DOI:10.1007/s11239-023-02856-0

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PubMed articles on: Cancer & VTE/PE

Comorbidities and high in-hospital mortality of cancer-associated pulmonary embolism: findings from a real-world registry study

Chin Med J (Engl). 2023 Jul 17. doi: 10.1097/CM9.0000000000002670. Online ahead of print.

NO ABSTRACT

PMID:37461237 | DOI:10.1097/CM9.0000000000002670

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PubMed articles on: Cancer & VTE/PE

Burden of serious harms from diagnostic error in the USA

BMJ Qual Saf. 2023 Jul 17:bmjqs-2021-014130. doi: 10.1136/bmjqs-2021-014130. Online ahead of print.

ABSTRACT

BACKGROUND: Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts.

OBJECTIVE: We sought to estimate the annual US burden of serious misdiagnosis-related harms (permanent morbidity, mortality) by combining prior results with rigorous estimates of disease incidence.

METHODS: Cross-sectional analysis of US-based nationally representative observational data. We estimated annual incident vascular events and infections from 21.5 million (M) sampled US hospital discharges (2012-2014). Annual new cancers were taken from US-based registries (2014). Years were selected for coding consistency with prior literature. Disease-specific incidences for 15 major vascular events, infections and cancers ('Big Three' categories) were multiplied by literature-based rates to derive diagnostic errors and serious harms. We calculated uncertainty estimates using Monte Carlo simulations. Validity checks included sensitivity analyses and comparison with prior published estimates.

RESULTS: Annual US incidence was 6.0 M vascular events, 6.2 M infections and 1.5 M cancers. Per 'Big Three' dangerous disease case, weighted mean error and serious harm rates were 11.1% and 4.4%, respectively. Extrapolating to all diseases (including non-'Big Three' dangerous disease categories), we estimated total serious harms annually in the USA to be 795 000 (plausible range 598 000-1 023 000). Sensitivity analyses using more conservative assumptions estimated 549 000 serious harms. Results were compatible with setting-specific serious harm estimates from inpatient, emergency department and ambulatory care. The 15 dangerous diseases accounted for 50.7% of total serious harms and the top 5 (stroke, sepsis, pneumonia, venous thromboembolism and lung cancer) accounted for 38.7%.

CONCLUSION: An estimated 795 000 Americans become permanently disabled or die annually across care settings because dangerous diseases are misdiagnosed. Just 15 diseases account for about half of all serious harms, so the problem may be more tractable than previously imagined.

PMID:37460118 | DOI:10.1136/bmjqs-2021-014130

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PubMed articles on: Cancer & VTE/PE

Incidence of venous thromboembolism following head and neck surgery

Eur Arch Otorhinolaryngol. 2023 Jul 17. doi: 10.1007/s00405-023-08112-8. Online ahead of print.

 

ABSTRACT

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

PMID:37479891 | DOI:10.1007/s00277-023-05369-1

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PubMed articles on: Cancer & VTE/PE

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with VTE

J Thromb Haemost. 2023 Jul 19:S1538-7836(23)00565-2. doi: 10.1016/j.jtha.2023.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. Current guidelines recommend limited cancer screening in patients presenting with unprovoked VTE. Only half of the underlying cancer cases are detected by cancer screening, and the optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and elevated biomarkers of NET formation are associated with poor prognosis.

OBJECTIVES AND METHODS: This prospective cohort study investigated the association between blood biomarkers associated with NETs and neutrophil activation (circulating nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) and cancer during a one-year follow-up.

RESULTS AND CONCLUSIONS: Four-hundred-sixty VTE patients were included. Two hundred and twenty-one (48%) had isolated deep vein thrombosis, and 220 (48%) of all VTE cases were unprovoked. Cancer was diagnosed in 29 (7.0%) VTE patients during the follow-up period, and 43 patients had a known active cancer. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/ml increase of H3Cit-DNA was 1.79 [95% CI 1.03-3.10] suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE. Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA compared to cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, prior cancer and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/ml increase of H3Cit-DNA [95% CI 1.35-3.13]), indicating that elevated NET formation is a hallmark of cancer-associated VTE.

PMID:37479035 | DOI:10.1016/j.jtha.2023.07.007

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PubMed articles on: Cancer & VTE/PE

Risk of thromboembolic events in patients with metastatic solid tumors treated with PARP inhibitors: A systematic review and meta-analysis of phase 3 randomized controlled trials

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23 July 2023

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PubMed articles on: Cardio-Oncology

Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies

Cardiovasc Toxicol. 2023 Jul 21. doi: 10.1007/s12012-023-09800-x. Online ahead of print.

ABSTRACT

The advent of BCR-ABL tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. Mitochondria are the key organelles for the maintenance of myocardial tissue homeostasis. However, cardiotoxicity associated with BCR-ABL1 TKIs can directly or indirectly cause mitochondrial damage and dysfunction, playing a pivotal role in cardiomyocytes homeostatic system and putting the cancer survivors at higher risk. In this review, we summarize the cardiotoxicity caused by BCR-ABL1 TKIs and the underlying mechanisms, which contribute dominantly to the damage of mitochondrial structure and dysfunction: endoplasmic reticulum (ER) stress, mitochondrial stress, damage of myocardial cell mitochondrial respiratory chain, increased production of mitochondrial reactive oxygen species (ROS), and other kinases and other potential mechanisms of cardiotoxicity induced by BCR-ABL1 TKIs. Furthermore, detection and management of BCR-ABL1 TKIs will promote our rational use, and cardioprotection strategies based on mitochondria will improve our understanding of the cardiotoxicity from a mitochondrial perspective. Ultimately, we hope shed light on clinical decision-making. By integrate and learn from both research and practice, we will endeavor to minimize the mitochondria-mediated cardiotoxicity and reduce the adverse sequelae associated with BCR-ABL1 TKIs.

PMID:37479951 | DOI:10.1007/s12012-023-09800-x

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Severe cardiotoxicity induced by osimertinib in a patient with EGFR-mutated adenocarcinoma of the lung

BMJ Case Rep. 2023 Jul 21;16(7):e255245. doi: 10.1136/bcr-2023-255245.

ABSTRACT

A man in his 70s was detected an infiltrative shadow on the right lung. A bronchoscopy confirmed the diagnosis of adenocarcinoma of the lung, classified as cT2bN2M0 stage IIIA, with a deletion mutation in EGFRexon 19. Weekly carboplatin plus paclitaxel was administered in combination with thoracic radiotherapy, followed by maintenance therapy with durvalumab for 1 year. Four months later, he was diagnosed with a recurrence of adenocarcinoma in the lung. He started treatment with osimertinib. Six months after initiating osimertinib, a chest CT revealed bilateral pleural effusion and expansion of the inferior vena cava. Eleven months later, he entered our emergency department with progressive dyspnoea. A chest CT showed bilateral massive pleural effusion and cardiac enlargement. He was diagnosed with osimertinib-induced cardiac failure. Osimertinib was discontinued, and echocardiology demonstrated a gradual improvement in cardiac function. It is necessary to take care of osimertinib-related cardiotoxicity.

PMID:37479487 | DOI:10.1136/bcr-2023-255245

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PubMed articles on: Cardio-Oncology

Systolic myocardial function measured by echocardiographic speckle-tracking and peak oxygen consumption in pediatric childhood cancer survivors-a PACCS study

Front Cardiovasc Med. 2023 Jul 5;10:1221787. doi: 10.3389/fcvm.2023.1221787. eCollection 2023.

ABSTRACT

BACKGROUND: Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors.

METHODS: In this sub-study of the international study "Physical Activity and fitness in Childhood Cancer Survivors" (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9-18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function.

RESULTS: Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, -19.7% [95% confidence interval (CI) -20.1% to -19.3%] vs. -21.3% (95% CI: -22.2% to -20.3%) (p = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z-score. Mean RV-LS was similar in the childhood cancer survivors and the controls, -23.2% (95% CI: -23.7% to -22.6%) vs. -23.3% (95% CI: -24.6% to -22.0%) (p = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient (r) = -0.3 for LV-GLS]. Higher doses of anthracyclines (r = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment (r = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function.

CONCLUSIONS: Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk.

PMID:37476575 | PMC:PMC10354364 | DOI:10.3389/fcvm.2023.1221787

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PubMed articles on: Cardio-Oncology

Clinical features and outcomes of patients admitted to the ICU for Cyclophosphamide-associated cardiac toxicity: a retrospective cohort

Support Care Cancer. 2023 Jul 18;31(8):474. doi: 10.1007/s00520-023-07951-9.

ABSTRACT

PURPOSE: To describe the management and outcome of critically-ill patients with Cyclophosphamide (CY)-associated cardiac toxicity.

METHODS: All patients admitted to the intensive care units (ICUs) of the Nantes and Rennes University Hospitals for a CY-associated cardiac toxicity between January 2015 and December 2020 were included.

RESULTS: Of the thirty-four patients included in the study, twenty-four (70%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), four (12%) autologous HSCT, and six (18%) chemotherapy for hematological malignancies. Acute pulmonary edema (65%), cardiac arrest (9%), and cardiac arrhythmia (6%) were the most common reasons for ICU admission. Patients were admitted to the ICU 6.5 (4-12) days after the intravenous administration of a median dose of CY of 100 [60-101] mg/Kg. Echocardiographic findings showed moderate to severe left ventricular systolic dysfunction (69%) and pericardial effusion (52%). Eighteen (53%) patients ultimately developed cardiogenic shock and required vasopressors (47%) and/or inotropes (18%). Invasive mechanical ventilation and renal replacement therapy were required in twenty (59%) and five (14%) patients, respectively. Sixteen (47%) patients died of whom 12 (35.3%) died from refractory cardiogenic shock. The left ventricular ejection fraction improved over time in most survivors with a median time until full recovery of 33 (12-62) days. Two (11%) patients had a persistent left ventricular dysfunction at 6 months.

CONCLUSION: Refractory cardiogenic shock is the primary cause of death of patients with severe CY-related cardiotoxicity. Nonetheless, the cardiac function of most survivors recovered within a month.

PMID:37462731 | DOI:10.1007/s00520-023-07951-9

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

Unresectable stage III non-small cell lung cancer: could durvalumab be safe and effective in real-life clinical scenarios? Results of a single-center experience

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PubMed articles on: Cancer & VTE/PE

Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients

Ann Hematol. 2023 Jul 21. doi: 10.1007/s00277-023-05369-1. Online ahead of print.

ABSTRACT

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

PMID:37479891 | DOI:10.1007/s00277-023-05369-1

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PubMed articles on: Cancer & VTE/PE

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with VTE

J Thromb Haemost. 2023 Jul 19:S1538-7836(23)00565-2. doi: 10.1016/j.jtha.2023.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. Current guidelines recommend limited cancer screening in patients presenting with unprovoked VTE. Only half of the underlying cancer cases are detected by cancer screening, and the optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and elevated biomarkers of NET formation are associated with poor prognosis.

OBJECTIVES AND METHODS: This prospective cohort study investigated the association between blood biomarkers associated with NETs and neutrophil activation (circulating nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) and cancer during a one-year follow-up.

RESULTS AND CONCLUSIONS: Four-hundred-sixty VTE patients were included. Two hundred and twenty-one (48%) had isolated deep vein thrombosis, and 220 (48%) of all VTE cases were unprovoked. Cancer was diagnosed in 29 (7.0%) VTE patients during the follow-up period, and 43 patients had a known active cancer. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/ml increase of H3Cit-DNA was 1.79 [95% CI 1.03-3.10] suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE. Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA compared to cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, prior cancer and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/ml increase of H3Cit-DNA [95% CI 1.35-3.13]), indicating that elevated NET formation is a hallmark of cancer-associated VTE.

PMID:37479035 | DOI:10.1016/j.jtha.2023.07.007

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PubMed articles on: Cancer & VTE/PE

Primary prevention of cancer-associated venous thrombosis: Rationale and challenges in clinical practice

Curr Res Transl Med. 2023 Jul 13;71(3):103405. doi: 10.1016/j.retram.2023.103405. Online ahead of print.

ABSTRACT

Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences.

PMID:37478777 | DOI:10.1016/j.retram.2023.103405

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism and breast cancer

Bull Cancer. 2023 Jul 18:S0007-4551(23)00296-5. doi: 10.1016/j.bulcan.2023.06.001. Online ahead of print.

 

ABSTRACT

BACKGROUND: Surgical site infections (SSIs) represent a major complication following oncologic reconstructions. Our objectives were (1) to assess whether the use of postoperative drains and/or negative pressure wound therapy (NPWT) were associated with SSIs following lower-extremity oncologic reconstruction and (2) to identify factors associated with the duration of postoperative drains and with the duration of NPWT.

METHODS: This is a secondary analysis of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial, a multi-institution randomized controlled trial of lower-extremity oncologic reconstructions. Data were recorded regarding the use of drains alone, NPWT alone, or both NPWT and drains, including the total duration of each postoperatively. We analyzed postoperative drain duration and associations with tourniquet use, intraoperative thromboprophylaxis or antifibrinolytic use, incision length, resection length, and total operative time, through use of a linear regression model. A Cox proportional hazards model was used to evaluate the independent predictors of SSI.

RESULTS: Overall, 604 patients were included and the incidence of SSI was 15.9%. Postoperative drains alone were used in 409 patients (67.7%), NPWT alone was used in 15 patients (2.5%), and both postoperative drains and NPWT were used in 68 patients (11.3%). The median (and interquartile range [IQR]) duration of drains and of NPWT was 3 days (IQR, 2 to 5 days) and 6 days (IQR, 4 to 8 days), respectively. The use of postoperative drains alone, NPWT alone, or both drains and NPWT was not associated with SSI (p = 0.14). Increased postoperative drain duration was associated with longer operative times and no intraoperative tourniquet use, as shown on linear regression analysis (p < 0.001 and p = 0.03, respectively). A postoperative drain duration of ≥14 days (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.3 to 9.6; p = 0.01) and an operative time of ≥8 hours (HR, 4.5; 95% CI, 1.7 to 11.9; p = 0.002) were independent predictors of SSI following lower-extremity oncologic reconstruction.

CONCLUSIONS: A postoperative drain duration of ≥14 days and an operative time of ≥8 hours were independent predictors of SSI following lower-extremity oncologic reconstruction. Neither the use of postoperative drains nor the use of NPWT was a predictor of SSI. Future research is required to delineate the association of the combined use of postoperative drains and NPWT with SSI.

LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

PMID:37466578 | DOI:10.2106/JBJS.22.01185

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PubMed articles on: Cancer & VTE/PE

A nomogram for predicting the risk of venous thromboembolism in patients with solid cancers

J Thromb Thrombolysis. 2023 Jul 18. doi: 10.1007/s11239-023-02856-0. Online ahead of print.

ABSTRACT

Cancer patients with venous thromboembolism (VTE) are prone to poor prognoses. Thus, we aimed to develop a nomogram to predict the risk of VTE in these patients. We retrospectively analyzed 791 patients diagnosed with solid tumors between January 2017 and May 2021 at Tongji Hospital. Univariate logistic analysis and multivariate logistic regression were adopted in this study. Our results indicated that age ≥ 60 years, tumor stages III-IV, platelet distribution width (PDW) ≤ 12.6%, albumin concentration ≤ 38.8 g/L, lactate dehydrogenase (LDH) concentration ≥ 198 U/L, D-dimer concentration ≥ 1.72 µg/mL, blood hemoglobin concentration ≤ 100 g/dL or the use of erythropoiesis-stimulating agents and cancer types were independent risk factors. The nomogram prediction model was developed based on the regression coefficients of these variables. We assessed the performance of the nomogram by calibration plot and the area under the receiver operating characteristic curve and compared it with the Khorana score. The concordance index (C- index) of the nomogram was 0.852 [95% confidence interval (CI) 0.823 to 0.880], while the Khorana score was 0.681 (95% CI 0.639 to 0.723). Given its performance, this nomogram could be used to select cancer patients at high risk for VTE and guide thromboprophylaxis treatment in clinical practice, provided it is validated in an external cohort.

PMID:37462901 | DOI:10.1007/s11239-023-02856-0

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PubMed articles on: Cancer & VTE/PE

Comorbidities and high in-hospital mortality of cancer-associated pulmonary embolism: findings from a real-world registry study

Chin Med J (Engl). 2023 Jul 17. doi: 10.1097/CM9.0000000000002670. Online ahead of print.

NO ABSTRACT

PMID:37461237 | DOI:10.1097/CM9.0000000000002670

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PubMed articles on: Cancer & VTE/PE

Incidence of and Risk Factors for Thromboembolism After Endoprosthetic Reconstruction in Musculoskeletal Oncology Patients

J Bone Joint Surg Am. 2023 Jul 19;105(Suppl 1):29-33. doi: 10.2106/JBJS.22.01140. Epub 2023 Jul 19.

ABSTRACT

BACKGROUND: The aim of the present study was to assess the incidence of and risk factors for thromboembolic events-including assessment of the intraoperative use of tranexamic acid and postoperative use of chemical thromboprophylaxis-in patients undergoing operative treatment of primary bone or soft-tissue sarcoma or oligometastatic bone disease.

METHODS: This study was performed as a secondary analysis of prospective data collected from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) randomized controlled trial, which included 604 patients ≥12 years old who underwent surgical resection and endoprosthetic reconstruction for either primary bone or soft-tissue sarcoma or oligometastatic disease of the femur or tibia. We determined the incidence of thromboembolic events in these patients and evaluated potential risk factors, including patient age, sex, antibiotic treatment group, type of tumor (i.e., primary bone or soft-tissue sarcoma or metastatic bone disease), intraoperative tranexamic acid, tourniquet use, operative time, pathologic characteristics (i.e., American Joint Committee on Cancer grade, vascular invasion, and percent necrosis), postoperative chemical thromboprophylaxis regimen, and surgical site infection. Continuous variables were assessed with use of the Student t test. Categorical variables were assessed with use of the Pearson chi-square test, except when the expected cell counts were <5,

RESULTS: Postoperative thromboembolic events occurred in 11 (1.8%) of 604 patients. Patients who experienced a thromboembolic event had a significantly higher mean (± standard deviation) age (59.6 ± 17.5 years) than those who did not experience a thromboembolic event (40.9 ± 21.8; p = 0.002). Patients randomized to the long-term antibiotic group had a significantly higher incidence of thromboembolic events (9 of 293; 3.1%) than those randomized to the short-term antibiotic group (2 of 311; 0.64%; p = 0.03). Neither intraoperative tranexamic acid nor postoperative chemical thromboprophylaxis were significantly associated with the occurrence of a thromboembolic event.

CONCLUSIONS: Although relatively rare in the PARITY cohort, thromboembolic events were more likely to occur in older patients and those receiving long-term prophylactic antibiotics. Intraoperative tranexamic acid and postoperative chemical thromboprophylaxis were not associated with a greater incidence of thromboembolic events.

LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

PMID:37466577 | DOI:10.2106/JBJS.22.01140

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PubMed articles on: Cancer & VTE/PE

Advances in contraception: vaginal contraceptive rings

Ther Adv Reprod Health. 2023 Jul 14;17:26334941231186733. doi: 10.1177/26334941231186733. eCollection 2023 Jan-Dec.

ABSTRACT

The vaginal contraceptive ring is very effective and user dependent. In this article, we will discuss the different types of vaginal contraceptive rings, namely, the etonogestrel/ethinyl estradiol (ENG/EE) ring (NuvaRing, Merck, Rahway, NJ, USA) and the segesterone acetate (SA)/EE (Annovera, Mayne Pharma, Raleigh, NC, USA) ring. The details of dosing and administration, indications, advantages, disadvantages, and cost-effectiveness are presented. This literature review was conducted using PubMed and Google Scholar. The search terms included 'vaginal contraceptive ring', 'etonogestrel/ethinyl estradiol ring', and 'segesterone acetate/ethinyl estradiol ring'. The search was then sorted by year from 2000 until present, and the most recent articles were reviewed. The purpose of this article is to provide a comprehensive reference on the two vaginal contraceptive rings widely used in the United States for clinicians to guide management. Both vaginal contraceptive rings are combination of hormonal contraceptives that suppress ovulation and create physiologic conditions unfavorable for pregnancy. The ENG/EE ring is designed to be replaced monthly, while the SA/EE ring is a single device used over the course of 1 year. Common side effects of both devices include headaches, nausea, vomiting, and vaginitis. Serious adverse reactions can occur with the vaginal contraceptive rings including venous thromboembolism, psychiatric events, and hypersensitivity. Both devices are contraindicated in patients at high risk for arterial or venous thrombotic events, patients with a history of breast cancer or other estrogen/progesterone cancers, and patients with severe liver disease. Overall, the vaginal contraceptive ring is well tolerated and liked by patients. Patients should be well counseled on known severe adverse reactions. The vaginal contraceptive ring is more expensive than other forms of contraception and this should be an important point of discussion with patients.

PMID:37465002 | PMC:PMC10350750 | DOI:10.1177/26334941231186733

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PubMed articles on: Cancer & VTE/PE

Incidence of venous thromboembolism following head and neck surgery

Eur Arch Otorhinolaryngol. 2023 Jul 17. doi: 10.1007/s00405-023-08112-8. Online ahead of print.

ABSTRACT

PURPOSE: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in patients undergoing surgery, but conflicting data exist on VTE risk in patients undergoing head and neck surgery for malignant and non-malignant conditions. Our aim was to examine the risk of VTE among patients with and without cancer undergoing head and neck surgery.

METHODS: We conducted a nationwide cohort study to examine the risk of VTE among patients with an otolaryngological diagnosis using data from the Danish National Patient Register between 2010 and 2018. Analyses were stratified by cancer and anatomical areas of the surgical procedure.

RESULTS: In total, 116,953 patients were included of whom 10% (n = 12,083) had active cancer. After 3 months, 1.2% of the patients with cancer and 0.3% of the patients without cancer experienced VTE, respectively. For patients undergoing mouth/throat surgery, 0.8% with cancer and 0.2% without cancer had VTE, respectively. After nose/sinuses surgery 0.7% and 0.2%, respectively. No patients experienced VTE after ear surgery; and after endoscopies the numbers were 1.3% and 0.6% respectively.

CONCLUSIONS: While the minority of patients undergoing head and neck surgery develop VTE postoperatively, the risk increases among those with cancer. To support clinical decision making on anticoagulation, risk stratification tools could be further developed to recognize this hazard in patients with cancer undergoing head and neck surgery.

PMID:37458791 | DOI:10.1007/s00405-023-08112-8

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PubMed articles on: Cardio-Oncology

Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies

Cardiovasc Toxicol. 2023 Jul 21. doi: 10.1007/s12012-023-09800-x. Online ahead of print.

ABSTRACT

The advent of BCR-ABL tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. Mitochondria are the key organelles for the maintenance of myocardial tissue homeostasis. However, cardiotoxicity associated with BCR-ABL1 TKIs can directly or indirectly cause mitochondrial damage and dysfunction, playing a pivotal role in cardiomyocytes homeostatic system and putting the cancer survivors at higher risk. In this review, we summarize the cardiotoxicity caused by BCR-ABL1 TKIs and the underlying mechanisms, which contribute dominantly to the damage of mitochondrial structure and dysfunction: endoplasmic reticulum (ER) stress, mitochondrial stress, damage of myocardial cell mitochondrial respiratory chain, increased production of mitochondrial reactive oxygen species (ROS), and other kinases and other potential mechanisms of cardiotoxicity induced by BCR-ABL1 TKIs. Furthermore, detection and management of BCR-ABL1 TKIs will promote our rational use, and cardioprotection strategies based on mitochondria will improve our understanding of the cardiotoxicity from a mitochondrial perspective. Ultimately, we hope shed light on clinical decision-making. By integrate and learn from both research and practice, we will endeavor to minimize the mitochondria-mediated cardiotoxicity and reduce the adverse sequelae associated with BCR-ABL1 TKIs.

PMID:37479951 | DOI:10.1007/s12012-023-09800-x

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PubMed articles on: Cardio-Oncology

Severe cardiotoxicity induced by osimertinib in a patient with EGFR-mutated adenocarcinoma of the lung

BMJ Case Rep. 2023 Jul 21;16(7):e255245. doi: 10.1136/bcr-2023-255245.

ABSTRACT

A man in his 70s was detected an infiltrative shadow on the right lung. A bronchoscopy confirmed the diagnosis of adenocarcinoma of the lung, classified as cT2bN2M0 stage IIIA, with a deletion mutation in EGFRexon 19. Weekly carboplatin plus paclitaxel was administered in combination with thoracic radiotherapy, followed by maintenance therapy with durvalumab for 1 year. Four months later, he was diagnosed with a recurrence of adenocarcinoma in the lung. He started treatment with osimertinib. Six months after initiating osimertinib, a chest CT revealed bilateral pleural effusion and expansion of the inferior vena cava. Eleven months later, he entered our emergency department with progressive dyspnoea. A chest CT showed bilateral massive pleural effusion and cardiac enlargement. He was diagnosed with osimertinib-induced cardiac failure. Osimertinib was discontinued, and echocardiology demonstrated a gradual improvement in cardiac function. It is necessary to take care of osimertinib-related cardiotoxicity.

PMID:37479487 | DOI:10.1136/bcr-2023-255245

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PubMed articles on: Cardio-Oncology

Systolic myocardial function measured by echocardiographic speckle-tracking and peak oxygen consumption in pediatric childhood cancer survivors-a PACCS study

Front Cardiovasc Med. 2023 Jul 5;10:1221787. doi: 10.3389/fcvm.2023.1221787. eCollection 2023.

ABSTRACT

BACKGROUND: Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors.

METHODS: In this sub-study of the international study "Physical Activity and fitness in Childhood Cancer Survivors" (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9-18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function.

RESULTS: Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, -19.7% [95% confidence interval (CI) -20.1% to -19.3%] vs. -21.3% (95% CI: -22.2% to -20.3%) (p = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z-score. Mean RV-LS was similar in the childhood cancer survivors and the controls, -23.2% (95% CI: -23.7% to -22.6%) vs. -23.3% (95% CI: -24.6% to -22.0%) (p = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient (r) = -0.3 for LV-GLS]. Higher doses of anthracyclines (r = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment (r = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function.

CONCLUSIONS: Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk.

PMID:37476575 | PMC:PMC10354364 | DOI:10.3389/fcvm.2023.1221787

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PubMed articles on: Cardio-Oncology

Cardiovascular toxicity from therapies for light chain amyloidosis

Front Cardiovasc Med. 2023 Jul 5;10:1212983. doi: 10.3389/fcvm.2023.1212983. eCollection 2023.

ABSTRACT

Amyloid light-chain (AL) amyloidosis is a hematological disorder characterized by abnormal proliferation of a plasma cell clone producing monoclonal free light chains that misfold and aggregate into insoluble fibrils in various tissues. Cardiac involvement is a common feature leading to restrictive cardiomyopathy and poor prognosis. Current first-line treatments aim at achieving hematological response by targeting the plasma cell clones, and these have been adapted from multiple myeloma therapy. Patients with AL amyloidosis often exhibit multiorgan involvement, making them susceptible to cancer therapy-related cardiovascular toxicity. Managing AL amyloidosis is a complex issue that requires enhanced knowledge of the cardio-oncological implications of hematological treatments. Future research should focus on implementing and validating primary and secondary prevention strategies and understanding the biochemical basis of oncological therapy-related damage to mitigate cardiovascular toxicity.

PMID:37476571 | PMC:PMC10354454 | DOI:10.3389/fcvm.2023.1212983

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PubMed articles on: Cardio-Oncology

Mediators of Black-White inequities in cardiovascular mortality among survivors of 18 cancers in the USA

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PubMed articles on: Cardio-Oncology

Cisplatin-based combination therapy for cancer

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PubMed articles on: Cardio-Oncology

Unresectable stage III non-small cell lung cancer: could durvalumab be safe and effective in real-life clinical scenarios? Results of a single-center experience

20:59

PubMed articles on: Cardio-Oncology

Nuclear translocation of mitochondrial dehydrogenases as an adaptive cardioprotective mechanism

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PubMed articles on: Cancer & VTE/PE

Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients

Ann Hematol. 2023 Jul 21. doi: 10.1007/s00277-023-05369-1. Online ahead of print.

 

ABSTRACT

Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences.

PMID:37478777 | DOI:10.1016/j.retram.2023.103405

18:45

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism and breast cancer

Bull Cancer. 2023 Jul 18:S0007-4551(23)00296-5. doi: 10.1016/j.bulcan.2023.06.001. Online ahead of print.

ABSTRACT

Breast cancer is the most common cancer in women. Patients with breast cancer have a 4-fold increased risk of venous thromboembolism (VTE) compared to age- and sex-matched controls without cancer. VTE remains the second leading cause of death in cancer patients and an independent risk factor for mortality. In women with breast cancer, the main risk factors for developing VTE are increasing age, obesity, disease stage, central catheter placement and cancer treatments, including surgery, chemotherapy, hormonotherapy and cyclin-dependent kinase 4/6 inhibitors. In women receiving tamoxifen, the risk of VTE is particularly increased within the first 6 months after initiation of hormonotherapy, although some evidence suggests that this risk may persist through the first 2 years of treatment. The risk of VTE appears to be lower in patients receiving aromatase inhibitors. In breast cancer patients receiving cyclin-dependent kinase 4/6 inhibitors, the rate of VTE is approximately 6%. Current clinical practice guidelines for the treatment and prevention of VTE in patients with cancer suggest that thromboprophylaxis should not be used routinely in ambulatory cancer patients receiving chemotherapy or hormonotherapy. The risk-benefit ratio of thromboprophylaxis should be assessed on a case-by-case basis and be the subject of multidisciplinary discussion.

PMID:37474353 | DOI:10.1016/j.bulcan.2023.06.001

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PubMed articles on: Cancer & VTE/PE

Glomerular hyperfiltration is an independent predictor of postoperative outcomes: A NSQIP multi-specialty surgical cohort analysis

Nephrology (Carlton). 2023 Jul 19. doi: 10.1111/nep.14221. Online ahead of print.

ABSTRACT

AIM: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30-day postoperative outcomes using a multi-specialty surgical cohort.

METHODS: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex-specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th95th percentile). The primary outcome was a composite of any 30-day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30-day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest.

RESULTS: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]).

CONCLUSION: Our findings support an association between high eGFR and adverse 30-day postoperative outcomes.

PMID:37468129 | DOI:10.1111/nep.14221

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PubMed articles on: Cancer & VTE/PE

Risk of thromboembolic events in patients with metastatic solid tumors treated with PARP inhibitors: A systematic review and meta-analysis of phase 3 randomized controlled trials

Cancer Treat Rev. 2023 Jul 17;119:102601. doi: 10.1016/j.ctrv.2023.102601. Online ahead of print.

ABSTRACT

BACKGROUND AND SCOPE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized cancer treatment in recent years. These drugs present a favorable safety profile, even though the potential risk of thromboembolic events (TEs) during their use has not been addressed yet. In addition, PARPi have been involved in an active scientific debate regarding non-oncologic indications, particularly during the Coronavirus Disease 2019 pandemic, including potential anti-thromboembolic effect.

METHODS: To clarify whether patients treated with PARPi for metastatic solid tumors are either at increased or decreased risk of TEs, we conducted a systematic review of the literature and meta-analysis, including all phase 3 randomized controlled trials (RCTs) which investigated PARPi in this setting. Search was conducted through Medline, EMBASE, Pubmed, SCOPUS and Google Scholar in February 2023, including the proceedings of the principal oncology meetings of the last 10 years, with no time restriction. For each included study, frequencies of TEs in experimental and control arm were collected.

RESULTS: Our search identified 2,369 reports, of which 20 were lastly selected. A total of 4,946 patients were included, across 12 different RCTs. The meta-analysis did not demonstrate either an increased or a reduced risk in TEs in patients treated with PARPi for metastatic disease (OR 1.50, range: 1.00-2.24; 95% CI; P = 0.050), with low heterogeneity and low publication bias.

CONCLUSION: Although our research did not confirm either increased or decreased risk of TEs for PARPi use, no safety alerts emerged. Thromboembolic risk assessment models should always be integrated in daily clinical routine, to identify high-risk patients.

PMID:37473517 | DOI:10.1016/j.ctrv.2023.102601

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PubMed articles on: Cancer & VTE/PE

Clinical Presentation and Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis

J Clin Oncol. 2023 Jul 20:JCO2300429. doi: 10.1200/JCO.23.00429. Online ahead of print.

ABSTRACT

PURPOSE: Patients with isolated distal deep vein thrombosis (DVT) have lower rates of adverse outcomes (death, venous thromboembolism [VTE] recurrence or major bleeding) than those with proximal DVT. It is uncertain if such findings are also observed in patients with cancer.

METHODS: Using data from the international Registro Informatizado de la Enfermedad TromboEmbolica venosa registry, we compared the risks of adverse outcomes at 90 days (adjusted odds ratio [aOR]; 95% CI) and 1 year (adjusted hazard ratio [aHR; 95% CI]) in 886 patients with cancer-associated distal DVT versus 5,196 patients with cancer-associated proximal DVT and 5,974 patients with non-cancer-associated distal DVT.

RESULTS: More than 90% of patients in each group were treated with anticoagulants for at least 90 days. At 90 days, the adjusted risks of death, VTE recurrence, or major bleeding were lower in patients with non-cancer-associated distal DVT than in patients with cancer-associated distal DVT (reference): aOR = 0.16 (0.11-0.22), aOR = 0.34 (0.22-0.54), and aOR = 0.47 (0.27-0.80), respectively. The results were similar at 1-year follow-up: aHR = 0.12 (0.09-0.15), aHR = 0.39 (0.28-0.55), and aHR = 0.51 (0.32-0.82), respectively. Risks of death, VTE recurrence, and major bleeding were not statistically different between patients with cancer-associated proximal versus distal DVT, both at 90 days: aOR = 1.11 (0.91-1.36), aOR = 1.10 (0.76-1.62), and aOR = 1.18 (0.76-1.83), respectively, and 1 year: aHR = 1.01 (0.89-1.15), aHR = 1.02 (0.76-1.35), and aHR = 1.10 (0.76-1.61), respectively. However, more patients with cancer-associated proximal DVT, compared with cancer-associated distal DVT, developed fatal pulmonary embolism (PE) during follow-up: The risk difference was 0.40% (95% CI, 0.23 to 0.58).

CONCLUSION: Cancer-associated distal DVT has serious and relatively comparable outcomes compared with cancer-associated proximal DVT. The lower risk of fatal PE from cancer-associated distal DVT needs further investigation.

PMID:37471683 | DOI:10.1200/JCO.23.00429

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PubMed articles on: Cancer & VTE/PE

Comment on: Silent Pulmonary Thromboembolism in Patients Undergoing Craniotomy for Brain Tumor

Turk Neurosurg. 2023;33(4):711. doi: 10.5137/1019-5149.JTN.44181-23.0.

NO ABSTRACT

PMID:37470514 | DOI:10.5137/1019-5149.JTN.44181-23.0

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PubMed articles on: Cancer & VTE/PE

Inferior Vena Cava Filters: Adherence to Clinical Practice Guidelines Recommendations, Retrieval Rates, and Filter Complications in a Tertiary Hospital

Angiology. 2023 Jul 20:33197231190184. doi: 10.1177/00033197231190184. Online ahead of print.

ABSTRACT

The present study evaluated the adherence to guideline recommendations regarding the indication for inferior vena cava filter (IVCF) placement, retrieval rates, complications, thrombotic recurrences, and mortality. Patients in whom an IVCF was placed between 2015 and 2020 in a tertiary hospital were retrospectively included. We considered absolute indication of IVCF placement if all the guidelines evaluated agreed on the indication, relative indication if only some guidelines recommended it and without indication if none of the evaluated guidelines recommended it. From the 185 patients included; 47% had an absolute indication, 15% a relative indication, and 38% had no indication. Filter-associated complications and non-removal rates were 12.4% and 41%, respectively. Venous thromboembolism recurrence rate was 17.8%, being filter-associated complications (24.2 vs 9.8%, P = .02) and thrombosis of the inferior cava or iliac veins (12.1 vs 2.6%, P = .03) more frequent in this group. The mortality rate was 40%, with higher mortality risk in patients with co-existing cancer. Previous major bleeding, filter-associated complications, and mortality were associated with a major risk of non-removal. In conclusion, the adherence to guidelines regarding the indication of IVCF placement is still low and IVCF complications are not negligible. This fact is of special concern in the elderly, comorbid, and cancer patients.

PMID:37470426 | DOI:10.1177/00033197231190184

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PubMed articles on: Cancer & VTE/PE

Burden of serious harms from diagnostic error in the USA

BMJ Qual Saf. 2023 Jul 17:bmjqs-2021-014130. doi: 10.1136/bmjqs-2021-014130. Online ahead of print.

ABSTRACT

BACKGROUND: Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts.

OBJECTIVE: We sought to estimate the annual US burden of serious misdiagnosis-related harms (permanent morbidity, mortality) by combining prior results with rigorous estimates of disease incidence.

METHODS: Cross-sectional analysis of US-based nationally representative observational data. We estimated annual incident vascular events and infections from 21.5 million (M) sampled US hospital discharges (2012-2014). Annual new cancers were taken from US-based registries (2014). Years were selected for coding consistency with prior literature. Disease-specific incidences for 15 major vascular events, infections and cancers ('Big Three' categories) were multiplied by literature-based rates to derive diagnostic errors and serious harms. We calculated uncertainty estimates using Monte Carlo simulations. Validity checks included sensitivity analyses and comparison with prior published estimates.

RESULTS: Annual US incidence was 6.0 M vascular events, 6.2 M infections and 1.5 M cancers. Per 'Big Three' dangerous disease case, weighted mean error and serious harm rates were 11.1% and 4.4%, respectively. Extrapolating to all diseases (including non-'Big Three' dangerous disease categories), we estimated total serious harms annually in the USA to be 795 000 (plausible range 598 000-1 023 000). Sensitivity analyses using more conservative assumptions estimated 549 000 serious harms. Results were compatible with setting-specific serious harm estimates from inpatient, emergency department and ambulatory care. The 15 dangerous diseases accounted for 50.7% of total serious harms and the top 5 (stroke, sepsis, pneumonia, venous thromboembolism and lung cancer) accounted for 38.7%.

CONCLUSION: An estimated 795 000 Americans become permanently disabled or die annually across care settings because dangerous diseases are misdiagnosed. Just 15 diseases account for about half of all serious harms, so the problem may be more tractable than previously imagined.

PMID:37460118 | DOI:10.1136/bmjqs-2021-014130

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PubMed articles on: Cancer & VTE/PE

A sensitive tissue factor activity assay determined by an optimized thrombin generation method

PLoS One. 2023 Jul 19;18(7):e0288918. doi: 10.1371/journal.pone.0288918. eCollection 2023.

ABSTRACT

BACKGROUND: Tissue factor (TF) is the principal activator of the coagulation system, but an increased concentration in the blood in cancer and inflammatory diseases has been suggested to play a role increasing the risk of venous thromboembolism. However, measurement of the TF concentration is difficult, and quantitation of activity is the most valid estimation. The objective of this study was to establish a sensitive method to measure TF activity based on thrombin generation.

METHODS: The assay is based on thrombin generation (TG) measured on the Calibrated Automated Thrombogram (CAT). Various low concentrations of TF were prepared from reagents containing 1 pM TF and 4 μM phospholipid (PPL), and no TF and 4 μM PPL, and a calibration curve was produced from Lagtime vs TF concentration. TF in blood samples was measured after isolation and resuspension of extracellular vesicles (EVs) in a standard plasma from which EVs had been removed. The same standard plasma was used for the calibrators.

RESULTS: Contact activation of the coagulation system was avoided using CTI plasma samples in Monovette tubes. EVs contain procoagulant phospholipids but addition of PPL only reduced lagtime slightly at very low concentrations of TF resulting in overestimation to a lesser extent at 10 fM but no interference at 30 fM or higher. Addition of EVs to the TG analysis induced a small unspecific TF-independent activity (i.e., an activity not inhibited by antibodies against TF) which also may result in a smaller error in estimation of TF activity at very low levels but the effect was negligible at higher concentrations. It was possible to measure TF activity in healthy controls which was found to be 1-6 fM (EVs were concentrated, i.e. solubilized in a lower volume than the original volume plasma). Coefficient of variation (CV) was below 20% at the low level, and below 10% at a level around 100 fM TF. However, the step with isolation of EVs have a higher inherent CV.

CONCLUSION: A sensitive and rather precise one-stage TG-based method to measure TF activity has been established.

PMID:37467256 | PMC:PMC10355404 | DOI:10.1371/journal.pone.0288918

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PubMed articles on: Cancer & VTE/PE

Does the Use of Negative Pressure Wound Therapy and Postoperative Drains Impact the Development of Surgical Site Infections?: A PARITY Trial Secondary Analysis

J Bone Joint Surg Am. 2023 Jul 19;105(Suppl 1):34-40. doi: 10.2106/JBJS.22.01185. Epub 2023 Jul 19.

 

ABSTRACT

[This retracts the article DOI: 10.1155/2022/7963146.].

PMID:37475923 | PMC:PMC10356376 | DOI:10.1155/2023/9783196

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PubMed articles on: Cardio-Oncology

Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer

Zhongguo Zhong Yao Za Zhi. 2023 Jul;48(13):3472-3484. doi: 10.19540/j.cnki.cjcmm.20230410.301.

ABSTRACT

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01).<0.05).<0.05),

PMID:37474984 | DOI:10.19540/j.cnki.cjcmm.20230410.301

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PubMed articles on: Cardio-Oncology

Nuclear translocation of mitochondrial dehydrogenases as an adaptive cardioprotective mechanism

Nat Commun. 2023 Jul 19;14(1):4360. doi: 10.1038/s41467-023-40084-5.

ABSTRACT

Chemotherapy-induced cardiac damage remains a leading cause of death amongst cancer survivors. Anthracycline-induced cardiotoxicity is mediated by severe mitochondrial injury, but little is known about the mechanisms by which cardiomyocytes adaptively respond to the injury. We observed the translocation of selected mitochondrial tricarboxylic acid (TCA) cycle dehydrogenases to the nucleus as an adaptive stress response to anthracycline-cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes and in vivo. The expression of nuclear-targeted mitochondrial dehydrogenases shifts the nuclear metabolic milieu to maintain their function both in vitro and in vivo. This protective effect is mediated by two parallel pathways: metabolite-induced chromatin accessibility and AMP-kinase (AMPK) signaling. The extent of chemotherapy-induced cardiac damage thus reflects a balance between mitochondrial injury and the protective response initiated by the nuclear pool of mitochondrial dehydrogenases. Our study identifies nuclear translocation of mitochondrial dehydrogenases as an endogenous adaptive mechanism that can be leveraged to attenuate cardiomyocyte injury.

PMID:37468519 | PMC:PMC10356764 | DOI:10.1038/s41467-023-40084-5

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PubMed articles on: Cardio-Oncology

Tales from the future - Nuclear cardio-oncology, from prediction to diagnosis and monitoring

Eur Heart J Cardiovasc Imaging. 2023 Jul 19:jead168. doi: 10.1093/ehjci/jead168. Online ahead of print.

ABSTRACT

Cancer and cardiovascular disease often share common risk factors, and patients with cardiovascular disease who develop cancer are at high risk of experiencing major adverse cardiac events. Additionally, cancer treatment can induce short- and long-term adverse cardiovascular events. Given the improvement in oncological patients' prognosis, the burden in this vulnerable population is slowly shifting towards increased cardiovascular mortality. Consequently, the field of cardio-oncology is steadily expanding, prompting the need for new markers to stratify and monitor the cardiovascular risk in oncological patients before, during, and after the completion of treatment. Advanced noninvasive cardiac imaging has raised great interest in the early detection of cardiovascular diseases and cardiotoxicity in oncological patients. Nuclear medicine has long been a pivotal exam to robustly assess and monitor the cardiac function of patients undergoing potentially cardiotoxic chemotherapies. In addition, recent radiotracers have shown great interest in the early detection of cancer treatment-related cardiotoxicity. In this review, we summarize the current and emerging nuclear cardiology tools that can help identify cardiotoxicity and assess the cardiovascular risk in patients undergoing cancer treatments, and discuss the specific role of nuclear cardiology alongside other noninvasive imaging techniques.

PMID:37467476 | DOI:10.1093/ehjci/jead168

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PubMed articles on: Cardio-Oncology

Protocol: Can coronary artery calcium score identified on thoracic planning CT scans be used and actioned to identify cancer survivors at high risk of cardiac events: A feasibility study in cancer survivors undergoing radiotherapy in Australia

BMJ Open. 2023 Jul 18;13(7):e072376. doi: 10.1136/bmjopen-2023-072376.

ABSTRACT

INTRODUCTION: A coronary artery calcium (CAC) CT scan can identify calcified plaque and predict risk of future cardiac events. Cancer survivors undergoing thoracic radiotherapy routinely undergo a planning CT scan, which presents a unique opportunity to use already obtained medical imaging to identify those at the highest risk of cardiac events. While radiation therapy is an important modality for many cancer treatments, radiation dose to the heart in thoracic radiotherapy leads to cardiotoxicity and may accelerate pre-existing atherosclerosis. The primary aims of this study are to investigate the feasibility of using CAC scores calculated on thoracic radiotherapy planning CT scans to identify a subset of cancer survivors at an increased risk of future cardiac events, and to establish and evaluate a referral pathway for assessment and management in a cardio-oncology clinic. An optional substudy aims to investigate using abdominal aortic calcification (AAC) as a practical, low-radiation alternative to CAC to evaluate and monitor vascular health.

METHODS AND ANALYSIS: This is an observational, prospective study in a minimum of 100 cancer survivors commencing radiotherapy. Participants will have CAC scored from thoracic radiotherapy planning CT scans. Those identified as high risk (CAC score>0) will be referred to a cardio-oncology clinic. Feasibility, determined by adherence to the recommended pathway, and impact on quality of life and anxiety measured via questionnaire, will be assessed. Participants in Western Australia will be invited to participate in a 12-month observational pilot substudy, investigating lifestyle behaviours and the use of a dual-energy X-ray absorptiometry machine to measure musculoskeletal health and AAC.

ETHICS AND DISSEMINATION: Ethics approval has been obtained from St Vincent's Hospital, Sydney (Project number 2021/ETH11847), GenesisCare and Edith Cowan University (2022-03326-DALLAVIA). Study results will be reported in peer-reviewed academic journals, at scientific conferences, and at clinical forums, irrespective of the results observed.

TRIAL REGISTRATION NUMBER: ACTRN12621001343897.

PMID:37463809 | PMC:PMC10357636 | DOI:10.1136/bmjopen-2023-072376

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PubMed articles on: Cardio-Oncology

Mediators of Black-White inequities in cardiovascular mortality among survivors of 18 cancers in the USA

Int J Epidemiol. 2023 Jul 20:dyad097. doi: 10.1093/ije/dyad097. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to quantify Black-White inequities in cardiovascular disease (CVD) mortality among US survivors of 18 adult-onset cancers and the extent to which these inequities are explained by differences in socio-economic and clinical factors.

METHODS: Survivors of cancers diagnosed at ages 20-64 years during 2007-16 were identified from 17 Surveillance, Epidemiology and End Results registries. Associations between race and CVD mortality were examined using proportional hazards models. Mediation analyses were performed to quantify the contributions of potential mediators, including socio-economic [health insurance, neighbourhood socio-economic status (nSES), rurality] and clinical (stage, surgery, chemotherapy, radiotherapy) factors.

RESULTS: Among 904 995 survivors, 10 701 CVD deaths occurred (median follow-up, 43 months). Black survivors were more likely than White survivors to die from CVD for all 18 cancers with hazard ratios ranging from 1.30 (95% CI = 1.15-1.47) for lung cancer to 4.04 for brain cancer (95% CI = 2.79-5.83). The total percentage mediations (indirect effects) ranged from 24.8% for brain (95% CI=-5.2-59.6%) to 99.8% for lung (95% CI = 61.0-167%) cancers. Neighbourhood SES was identified as the strongest mediator for 14 cancers with percentage mediations varying from 25.0% for kidney cancer (95% CI = 14.1-36.3%) to 63.5% for lung cancer (95% CI = 36.5-108.7%). Insurance ranked second for 12 cancers with percentage mediations ranging from 12.3% for leukaemia (95% CI = 0.7-46.7%) to 31.3% for thyroid cancer (95% CI = 10.4-82.7%).

CONCLUSIONS: Insurance and nSES explained substantial proportions of the excess CVD mortality among Black survivors. Mitigating the effects of unequal access to care and differing opportunities for healthy living among neighbourhoods could substantially reduce racial inequities in CVD mortality among cancer survivors.

PMID:37471575 | DOI:10.1093/ije/dyad097

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PubMed articles on: Cardio-Oncology

Cisplatin-based combination therapy for cancer

J Cancer Res Ther. 2023 Jul-Sep;19(3):530-536. doi: 10.4103/jcrt.jcrt_792_22.

ABSTRACT

Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferred as prior treatment against several solid tumors and malignancies like ovaries, head and neck, testicular, and lung cancers because of its anticancer activity. Cisplatin binds at the N7 position of purine and forms adducts, leading to altered activity of DNA that triggers apoptosis. DNA damage is followed by several signaling pathways like induced oxidative stress, upregulated p53, mitogen-activated protein kinase (MAPK), and Jun N-terminal kinases (JNK) or Akt pathways along with induced apoptosis. Additionally, cisplatin treatment comes with few disadvantages such as toxic effects, that is, hepatotoxicity, cardiotoxicity, neurotoxicity, etc., and drug resistance. Furthermore, to overcome cisplatin resistance and toxicological effects, combination drug therapy has been considered. The aim of the review is to focus on the molecular mechanism of action of cisplatin and combination drug therapy to reduce the side effects in cancer therapy.

PMID:37470570 | DOI:10.4103/jcrt.jcrt_792_22

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18:45

Cardiotoxicity News

PubMed articles on: Cancer & VTE/PE

Antithrombotic secondary prophylaxis with low dose of apixaban or rivaroxaban in the onco-hematologic patients: comparison with non-neoplastic patients

Ann Hematol. 2023 Jul 21. doi: 10.1007/s00277-023-05369-1. Online ahead of print.

ABSTRACT

Management of cancer-associated thrombosis (CAT) is usually performed employing low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs). Low-intensity DOACs are the mainstay for extended duration therapy for VTE in non-oncologic patients. The aim of our study was to evaluate the efficacy and the safety of low doses of apixaban or rivaroxaban as secondary prophylaxis in patients affected by hematological malignancies with follow-up > 12 months. We report an observational, retrospective, single-center study that evaluated consecutive patients referred to our center between January 2016 and January 2023. The DOACs were administered at full dose during the acute phase of VTE and then at low dose for the extended phase. We included 154 patients: 53 patients affected by hematological malignancies compared to 101 non-neoplastic patients. During full-dose treatment, no thrombotic recurrences were observed in the two groups. During low-dose therapy, 2 (1.9%) thrombotic events (tAE) were observed in the control group. During full-dose treatment, the rate of bleeding events (bAE) was 9/154 (5.8%): 6/53 (11%) in hematological patients and 3/101 (2.9%) in non-hematological patients (p = 0.0003). During low-dose therapy, 4/154 (2.6%) bAE were observed: 3/53 (5.5%) in the hematologic group and 1 (1%) in the control group (p = 0.07). We found encouraging data on the safety and efficacy of low doses of DOACs as secondary prophylaxis in the onco-hematologic setting; no thrombotic complications were observed, and the incidence of hemorrhagic events was low.

PMID:37479891 | DOI:10.1007/s00277-023-05369-1

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PubMed articles on: Cancer & VTE/PE

Neutrophil extracellular trap formation is an independent risk factor for occult cancer in patients presenting with VTE

J Thromb Haemost. 2023 Jul 19:S1538-7836(23)00565-2. doi: 10.1016/j.jtha.2023.07.007. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE), particularly unprovoked VTE, is associated with occult cancer. Current guidelines recommend limited cancer screening in patients presenting with unprovoked VTE. Only half of the underlying cancer cases are detected by cancer screening, and the optimal screening regimen remains controversial. Neutrophil extracellular traps (NETs) are implicated in cancer-associated thrombosis and elevated biomarkers of NET formation are associated with poor prognosis.

OBJECTIVES AND METHODS: This prospective cohort study investigated the association between blood biomarkers associated with NETs and neutrophil activation (circulating nucleosomal citrullinated histone H3 [H3Cit-DNA], cell-free DNA, and neutrophil elastase) and cancer during a one-year follow-up.

RESULTS AND CONCLUSIONS: Four-hundred-sixty VTE patients were included. Two hundred and twenty-one (48%) had isolated deep vein thrombosis, and 220 (48%) of all VTE cases were unprovoked. Cancer was diagnosed in 29 (7.0%) VTE patients during the follow-up period, and 43 patients had a known active cancer. After adjustment for age and unprovoked VTE, the hazard ratio of cancer during follow-up per 500 ng/ml increase of H3Cit-DNA was 1.79 [95% CI 1.03-3.10] suggesting that H3Cit-DNA is potentially a useful diagnostic marker for cancer in patients with VTE. Furthermore, patients with cancer-associated VTE (known active cancer or cancer diagnosed during follow-up) had higher levels of H3Cit-DNA compared to cancer-free patients with VTE after adjustment for age, hemoglobin, gender, chronic obstructive pulmonary disease, prior cancer and start of anticoagulant treatment (odds ratio 2.06 per 500 ng/ml increase of H3Cit-DNA [95% CI 1.35-3.13]), indicating that elevated NET formation is a hallmark of cancer-associated VTE.

PMID:37479035 | DOI:10.1016/j.jtha.2023.07.007

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PubMed articles on: Cancer & VTE/PE

Primary prevention of cancer-associated venous thrombosis: Rationale and challenges in clinical practice

Curr Res Transl Med. 2023 Jul 13;71(3):103405. doi: 10.1016/j.retram.2023.103405. Online ahead of print.