ABSTRACT

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart's energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

SIGNIFICANCE STATEMENT: This study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.

PMID:37292714 | PMC:PMC10245950 | DOI:10.1101/2023.05.24.542198

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PubMed articles on: Cardio-Oncology

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Lancet Gastroenterol Hepatol. 2023 Jun 5:S2468-1253(23)00141-3. doi: 10.1016/S2468-1253(23)00141-3. Online ahead of print.

ABSTRACT

BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.

METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10<20<1·32·67; NFS: <-1·4550·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.

FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001

INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.

FUNDING: Innovative Medicines Initiative 2.

PMID:37290471 | DOI:10.1016/S2468-1253(23)00141-3

10:04

PubMed articles on: Cardio-Oncology

The Efficacy of Multi-Leaf Collimator in the Reduction of Cardiac and Coronary Artery Dose in Left-Sided Breast Cancer Radiotherapy

Adv Biomed Res. 2023 Apr 25;12:89. doi: 10.4103/abr.abr_342_21. eCollection 2023.

ABSTRACT

BACKGROUND: Multi-leaf collimator (MLC) is one of the efficient and cost-effective methods for protecting sensitive tissues around the target. This study aimed to evaluate the protective effect of MLC on the protection of sensitive organs in patients with left breast cancer.

MATERIALS AND METHODS: This study was performed on computed tomography (CT) scans of 45 patients with left breast cancer. Two treatment plans were completed for each patient. Only the heart and left lung were considered organs at risk in the first treatment plan, and in the second treatment plan, the left anterior descending artery (LAD) was also considered the organ at risk. It was covered as much as possible by the MLC. Dosimetric results of tumor and organ at risk (OARs) were extracted from the dose-volume histogram and compared.

RESULTS: The results showed that more LAD coverage by MLC leads to a significant reduction in the mean dose of OARs (P-value <0.05).5 (volume received the dose of 5 Gy) and V20 for the lung, V10, V25, and V30 for LAD, and V5, V20, V25, and V30 for the heart also decreased significantly (P-value

CONCLUSIONS: In general, better protection of LAD, heart, and lungs can be achieved by maximal shielding organs at risk by MLC in radiation therapy for patients with left breast cancer.

PMID:37288034 | PMC:PMC10241641 | DOI:10.4103/abr.abr_342_21

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PubMed articles on: Cardio-Oncology

Natriuretic Peptides, Cardio-Oncology

10:04

PubMed articles on: Cardio-Oncology

Cancer Therapy-Related Pulmonary Hypertension: A Review of Mechanisms and Implications for Clinical Practice

10:04

PubMed articles on: Cardio-Oncology

Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer

10:04

PubMed articles on: Cardio-Oncology

An unusual case of checkpoint-inhibitor-induced pleuropericarditis

10:04

PubMed articles on: Cardio-Oncology

Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors

C

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PubMed articles on: Cancer & VTE/PE

Gemcitabine-associated digital necrosis in metastatic breast cancer

J Oncol Pharm Pract. 2023 Jun 12:10781552231182356. doi: 10.1177/10781552231182356. Online ahead of print.

ABSTRACT

INTRODUCTION: Gemcitabine is a nucleoside analog antimetabolite used in various malignancies, including metastatic breast cancer. Objective response rates in its use as a single agent in the treatment of metastatic breast cancer are not to be underestimated. Cutaneous, hematological, pulmonary, and vascular side effects are well-known side effects. Venous thromboembolism may occur with antineoplastics, such as platinum compounds. Arterial thromboembolism is rare in cancer, almost rare with chemotherapy. Here, we present a metastatic breast cancer patient who had digital necrosis due to arterial occlusion with gemcitabine monotherapy.

CASE REPORT: A 54-year-old metastatic breast cancer female patient had digital ischemia and necrosis in the left hand's fifth finger after the second course of single-agent gemcitabine as the fourth line setting. Gemcitabine was discontinued, and medical treatment was started. Thrombus was detected in the left subclavian artery digital angiography. Balloon angioplasty and stenting were applied. However, digital amputation had to be performed since tissue necrosis had not regressed despite radiological interventions and medical treatment.

MANAGEMENT AND OUTCOME: Gemcitabine was discontinued. Low molecular weight heparin and acetylsalicylic acid were started. The distal phalanx was amputated due to necrosis during follow-up. Gemcitabine was permanently stopped.

DISCUSSION: Gemcitabine-related vascular events, including arterial thrombosis, may also occur in cancer patients, especially those with higher tumor burden. Therefore, predisposing factors for hypercoagulability and vascular occlusion should be questioned in more detail even before starting antineoplastics which are known to have a lower risk for thrombosis, such as gemcitabine monotherapy.

PMID:37309162 | DOI:10.1177/10781552231182356

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PubMed articles on: Cancer & VTE/PE

Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer

Sci Rep. 2023 Jun 12;13(1):9519. doi: 10.1038/s41598-023-36161-w.

ABSTRACT

Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Khorana score (KS) is the most studied tool to predict cancer-related VTE, however, it exerts poor sensitivity. Several single-nucleotide polymorphisms (SNPs) have been associated with VTE risk in the general population, but whether they are predictors of cancer-related VTE is a matter of discussion. Compared to other solid tumours, little is known about VTE in the setting of cervical cancer (CC) and whether thrombogenesis-related polymorphisms could be valuable biomarkers in patients with this neoplasia. This study aims to analyse the effect of VTE occurrence on the prognosis of CC patients, explore the predictive capability of KS and the impact of thrombogenesis-related polymorphisms on CC-related VTE incidence and patients' prognosis regardless of VTE. A profile of eight SNPs was evaluated. A retrospective hospital-based cohort study was conducted with 400 CC patients under chemoradiotherapy. SNP genotyping was carried on by using TaqMan® Allelic Discrimination methodology. Time to VTE occurrence and overall survival were the two measures of clinical outcome evaluated. The results indicated that VTE occurrence (8.5%) had a significant impact on the patient's survival (log-rank test, P < 0.001). KS showed poor performance (KS ≥ 3, χ2, P = 0.191). PROCR rs10747514 and RGS7 rs2502448 were significantly associated with the risk of CC-related VTE development (P = 0.021 and P = 0.006, respectively) and represented valuable prognostic biomarkers regardless of VTE (P = 0.004 and P = 0.010, respectively). Thus, thrombogenesis-related genetic polymorphisms may constitute valuable biomarkers among CC patients allowing a more personalized clinical intervention.

PMID:37308506 | DOI:10.1038/s41598-023-36161-w

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PubMed articles on: Cancer & VTE/PE

Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme

Ann Rheum Dis. 2023 Jun 12:ard-2023-223916. doi: 10.1136/ard-2023-223916. Online ahead of print.

ABSTRACT

OBJECTIVE: Increased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis (RA) aged ≥50 years enriched for cardiovascular (CV) risk (ORAL Surveillance). We assessed post hoc the potential risk of upadacitinib in a similar RA population.

METHODS: Pooled safety data from six phase III trials were evaluated post hoc for AEs in patients receiving upadacitinib 15 mg once a day (with or without conventional synthetic disease-modifying antirheumatic drugs), adalimumab 40 mg every other week with concomitant methotrexate (MTX), or MTX monotherapy in the overall trial population and in a subset of patients with higher CV risk (aged ≥50 years, ≥1 CV risk factor). Higher-risk patients from a head-to-head study of upadacitinib 15 mg versus adalimumab (SELECT-COMPARE) were assessed in parallel. Exposure-adjusted incidence rates for treatment-emergent AEs were summarised based on exposure to upadacitinib or comparators.

RESULTS: A total of 3209 patients received upadacitinib 15 mg, 579 received adalimumab and 314 received MTX monotherapy; ~54% of the patients were included in the overall and SELECT-COMPARE higher-risk populations. Major adverse cardiovascular events (MACE), malignancy (excluding non-melanoma skin cancer (NMSC)) and venous thromboembolism (VTE) were more frequent in the higher-risk cohorts versus the overall population but were generally similar across treatment groups. Rates of serious infections in higher-risk populations and herpes zoster (HZ) and NMSC in all populations were higher with upadacitinib 15 mg than comparators.

CONCLUSIONS: An increased risk of MACE, malignancy (excluding NMSC) and VTE was observed in higher-risk populations with RA, yet risk was comparable between upadacitinib-treated and adalimumab-treated patients. Higher rates of NMSC and HZ were observed with upadacitinib versus comparators across all populations, and increased rates of serious infections were detected in upadacitinib-treated patients at higher CV risk.

TRIAL REGISTRATION NUMBERS: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847 and NCT03086343.

PMID:37308218 | DOI:10.1136/ard-2023-223916

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PubMed articles on: Cancer & VTE/PE

A surgical case of pulmonary adenocarcinoma in the right upper lobe associated with a systemic artery-to-pulmonary artery fistula

Thorac Cancer. 2023 Jun 12. doi: 10.1111/1759-7714.14985. Online ahead of print.

ABSTRACT

A 52-year-old female never-smoker with an abnormal shadow in the right lung detected on radiography was referred to our institution. Contrast-enhanced computed tomography revealed an irregular nodule in the upper lobe of the right lung, suggestive of a pulmonary vascular abnormality. Angiography revealed a direct communication between the right internal mammary artery (IMA) and the right upper lobe pulmonary artery branches, with dilated and tortuous vascular proliferation. As multiple branch arteries were seen flowing into the upper lobe from the IMA, transcatheter selective embolization of these vessels and right upper lobectomy by video-assisted thoracoscopic surgery were performed. Contrary to the clinical diagnosis, the pathological finding was a pulmonary adenocarcinoma of the right upper lobe. Additional lymph node dissection was performed later. We report an extremely rare and unprecedented case of pulmonary adenocarcinoma fed by the right IMA, with a literature review.

PMID:37308179 | DOI:10.1111/1759-7714.14985

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PubMed articles on: Cancer & VTE/PE

Venous thromboembolism risk score during hospitalization in pregnancy: results of 10694 prospective evaluations in a clinical trial

Clinics (Sao Paulo). 2023 Jun 10;78:100230. doi: 10.1016/j.clinsp.2023.100230. Online ahead of print.

ABSTRACT

OBJECTIVES: Hospitalization during pregnancy and childbirth increases the risk of Venous Thromboembolism Risk (VTE). This study applied a VTE risk score to all hospitalized pregnant women to ascertain its effectiveness in preventing maternal death from VTE until 3 months after discharge.

METHODS: In this interventional study, patients were classified as low- or high-risk according to the VTE risk score (Clinics Hospital risk score). High-risk patients (score ≥ 3) were scheduled for pharmacological Thromboprophylaxis (TPX). Interaction analysis of the main risk factors was performed using Odds Ratio (OR) and Poisson regression with robust variance.

RESULTS: The data of 10694 cases (7212 patients) were analyzed; 1626 (15.2%, 1000 patients) and 9068 (84.8%, 6212 patients) cases were classified as high-risk (score ≥ 3) and low-risk (score < 3), respectively. The main risk factors (Odds Ratio, 95% Confidence Interval) for VTE were age ≥ 35 and < 40 years (1.6, 1.4-1.8), parity ≥ 3 (3.5, 3.0-4.0), age ≥ 40 years (4.8, 4.1-5.6), multiple pregnancies (2.1, 1.7-2.5), BMI ≥ 40 kg/m2 (5.1, 4.3-6.0), severe infection (4.1, 3.3-5.1), and cancer (12.3, 8.8-17.2). There were 10 cases of VTE: 7/1636 (0.4%) and 3/9068 (0.03%) in the high- and low-risk groups, respectively. No patient died of VTE. The intervention reduced the VTE risk by 87%; the number needed to treat was 3.

CONCLUSIONS: This VTE risk score was effective in preventing maternal deaths from VTE, with a low indication for TPX. Maternal age, multiparity, obesity, severe infections, multiple pregnancies, and cancer were the main risk factors for VTE.

PMID:37307627 | DOI:10.1016/j.clinsp.2023.100230

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Venous thromboembolism incidence in postoperative breast cancer patients

Clinics (Sao Paulo). 2023 Jun 10;78:100229. doi: 10.1016/j.clinsp.2023.100229. Online ahead of print.

ABSTRACT

BACKGROUND: Venous Thromboembolism (VTE) is an important cause of morbidity in cancer patients. Breast cancer patients undergoing surgical treatment are at an increased risk of VTE. The aim of this study was to determine the frequency of VTE in patients who underwent surgery for the treatment of breast cancer and to identify the related risk factors.

METHODS: A historical cohort of patients at the São Paulo State Cancer Institute (ICESP) underwent surgery for breast cancer. The inclusion criteria covered patients with invasive breast cancer or ductal carcinoma in situ who had breast surgery anytime from January 2016 to December 2018.

RESULTS: Of the 1672 patients included in the study, 15 had a confirmed diagnosis of VTE (0.9%), and 3 of these had deep vein thrombosis (0.2%), and 12, had pulmonary thromboembolism (0.7%). Clinical and tumoral characteristics did not differ between the groups. The incidence of VTE was higher in patients who had undergone skin-sparing mastectomy or nipple-sparing mastectomy (p = 0.032). Immediate reconstruction, particularly with abdominal-based flaps (4.7%), increased VTE events (p = 0.033). Median surgical time was higher in patients with VTE episodes (p = 0.027), and total hospital length of stay increased in days (6 days vs. 2 days, p = 0.001). Neoadjuvant chemotherapy and postoperative prophylaxis with Low Molecular Weight Heparin (LMWH) were associated with lower VTE rates (0.2% vs. 1.2%, p = 0.048 and 0.7% vs. 2.7%, p = 0.039; respectively) in these patients.

CONCLUSIONS: The incidence of VTE events in breast cancer patients who underwent surgery was 0.9%. Immediate reconstruction (especially with abdominal-based flaps), skin-sparing/nipple-sparing mastectomies, and longer surgeries were associated with increased risk. The LMWH postoperative prophylaxis reduced this risk.

PMID:37307626 | DOI:10.1016/j.clinsp.2023.100229

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PubMed articles on: Cancer & VTE/PE

Pressurized intraperitoneal aerosol chemotherapy, reasons for interrupting treatment: a systematic review of the literature

Pleura Peritoneum. 2023 Apr 19;8(2):45-53. doi: 10.1515/pp-2023-0004. eCollection 2023 Jun.

ABSTRACT

OBJECTIVES: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) gives encouraging results in the treatment of peritoneal metastasis (PM). The current recommendations require at least 3 sessions of PIPAC. However, some patients do not complete the full treatment course and stop after only 1 or 2 procedures, hence the limited benefit. A literature review was performed, with search terms including "PIPAC" and "pressurised intraperitoneal aerosol chemotherapy."

CONTENT: Only articles describing the causes for premature termination of the PIPAC treatment were analysed. The systematic search identified 26 published clinical articles related to PIPAC and reporting causes for stopping PIPAC.

SUMMARY: The series range from 11 to 144 patients, with a total of 1352 patients treated with PIPAC for various tumours. A total of 3088 PIPAC treatments were performed. The median number of PIPAC treatments per patient was 2.1, the median PCI score at the time of the first PIPAC was 19 and the number of patients who did not complete the recommended 3 sessions of PIPAC was 714 (52.8%). Disease progression was the main reason for early termination of the PIPAC treatment (49.1%). The other causes were death, patients' wishes, adverse events, conversion to curative cytoreductive surgery and other medical reasons (embolism, pulmonary infection, etc…).

OUTLOOK: Further investigations are necessary to better understand the causes for interrupting PIPAC treatment and also improving the selection of patients who are most likely to benefit from PIPAC.

PMID:37304159 | PMC:PMC10249753 | DOI:10.1515/pp-2023-0004

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Risk of admission to hospital with arterial or venous thromboembolism among patients diagnosed in the ambulatory setting with covid-19 compared with influenza: retrospective cohort study

BMJ Med. 2023 Jun 6;2(1):e000421. doi: 10.1136/bmjmed-2022-000421. eCollection 2023.

ABSTRACT

OBJECTIVE: To measure the 90 day risk of arterial thromboembolism and venous thromboembolism among patients diagnosed with covid-19 in the ambulatory (ie, outpatient, emergency department, or institutional) setting during periods before and during covid-19 vaccine availability and compare results to patients with ambulatory diagnosed influenza.

DESIGN: Retrospective cohort study.

SETTING: Four integrated health systems and two national health insurers in the US Food and Drug Administration's Sentinel System.

PARTICIPANTS: Patients with ambulatory diagnosed covid-19 when vaccines were unavailable in the US (period 1, 1 April-30 November 2020; n=272 065) and when vaccines were available in the US (period 2, 1 December 2020-31 May 2021; n=342 103), and patients with ambulatory diagnosed influenza (1 October 2018-30 April 2019; n=118 618).

MAIN OUTCOME MEASURES: Arterial thromboembolism (hospital diagnosis of acute myocardial infarction or ischemic stroke) and venous thromboembolism (hospital diagnosis of acute deep venous thrombosis or pulmonary embolism) within 90 days after ambulatory covid-19 or influenza diagnosis. We developed propensity scores to account for differences between the cohorts and used weighted Cox regression to estimate adjusted hazard ratios of outcomes with 95% confidence intervals for covid-19 during periods 1 and 2 versus influenza.

RESULTS: 90 day absolute risk of arterial thromboembolism with covid-19 was 1.01% (95% confidence interval 0.97% to 1.05%) during period 1, 1.06% (1.03% to 1.10%) during period 2, and with influenza was 0.45% (0.41% to 0.49%). The risk of arterial thromboembolism was higher for patients with covid-19 during period 1 (adjusted hazard ratio 1.53 (95% confidence interval 1.38 to 1.69)) and period 2 (1.69 (1.53 to 1.86)) than for patients with influenza. 90 day absolute risk of venous thromboembolism with covid-19 was 0.73% (0.70% to 0.77%) during period 1, 0.88% (0.84 to 0.91%) during period 2, and with influenza was 0.18% (0.16% to 0.21%). Risk of venous thromboembolism was higher with covid-19 during period 1 (adjusted hazard ratio 2.86 (2.46 to 3.32)) and period 2 (3.56 (3.08 to 4.12)) than with influenza.

CONCLUSIONS: Patients diagnosed with covid-19 in the ambulatory setting had a higher 90 day risk of admission to hospital with arterial thromboembolism and venous thromboembolism both before and after covid-19 vaccine availability compared with patients with influenza.

PMID:37303490 | PMC:PMC10254785 | DOI:10.1136/bmjmed-2022-000421

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PubMed articles on: Cancer & VTE/PE

Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial

JAMA. 2023 Jun 2. doi: 10.1001/jama.2023.7843. Online ahead of print.

ABSTRACT

IMPORTANCE: In patients with cancer who have venous thromboembolism (VTE) events, long-term anticoagulation with low-molecular-weight heparin (LMWH) is recommended to prevent recurrent VTE. The effectiveness of a direct oral anticoagulant (DOAC) compared with LMWH for preventing recurrent VTE in patients with cancer is uncertain.

OBJECTIVE: To evaluate DOACs, compared with LMWH, for preventing recurrent VTE and for rates of bleeding in patients with cancer following an initial VTE event.

DESIGN, SETTING, AND PARTICIPANTS: Unblinded, comparative effectiveness, noninferiority randomized clinical trial conducted at 67 oncology practices in the US that enrolled 671 patients with cancer (any invasive solid tumor, lymphoma, multiple myeloma, or chronic lymphocytic leukemia) who had a new clinical or radiological diagnosis of VTE. Enrollment occurred from December 2016 to April 2020. Final follow-up was in November 2020.

INTERVENTION: Participants were randomized in a 1:1 ratio to either a DOAC (n = 335) or LMWH (n = 336) and were followed up for 6 months or until death. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) and physicians selected drug doses.

MAIN OUTCOMES AND MEASURES: The primary outcome was the recurrent VTE rate at 6 months. Noninferiority of anticoagulation with a DOAC vs LMWH was defined by the upper limit of the 1-sided 95% CI for the difference of a DOAC relative to LMWH of less than 3% in the randomized cohort that received at least 1 dose of assigned treatment. The 6 prespecified secondary outcomes included major bleeding, which was assessed using a 2.5% noninferiority margin.

RESULTS: Between December 2016 and April 2020, 671 participants were randomized and 638 (95%) completed the trial (median age, 64 years; 353 women [55%]). Among those randomized to a DOAC, 330 received at least 1 dose. Among those randomized to LMWH, 308 received at least 1 dose. Rates of recurrent VTE were 6.1% in the DOAC group and 8.8% in the LMWH group (difference, -2.7%; 1-sided 95% CI, -100% to 0.7%) consistent with the prespecified noninferiority criterion. Of 6 prespecified secondary outcomes, none were statistically significant. Major bleeding occurred in 5.2% of participants in the DOAC group and 5.6% in the LMWH group (difference, -0.4%; 1-sided 95% CI, -100% to 2.5%) and did not meet the noninferiority criterion. Severe adverse events occurred in 33.8% of participants in the DOAC group and 35.1% in the LMWH group. The most common serious adverse events were anemia and death.

CONCLUSIONS AND RELEVANCE: Among adults with cancer and VTE, DOACs were noninferior to LMWH for preventing recurrent VTE over 6-month follow-up. These findings support use of a DOAC to prevent recurrent VTE in patients with cancer.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02744092.

PMID:37266947 | DOI:10.1001/jama.2023.7843

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PubMed articles on: Cancer & VTE/PE

Cerebral infarction related to nonbacterial thrombotic endocarditis in a middle-aged woman with uterine adenomyosis: A case report

Medicine (Baltimore). 2023 Jun 2;102(22):e33871. doi: 10.1097/MD.0000000000033871.

ABSTRACT

RATIONALE: Few isolated case reports and case series have reported arterial and venous thromboembolism related to adenomyosis; however, the underlying mechanism remains unclear.

PATIENT CONCERNS: A 47-year-old woman presented with dizziness, nausea, vomiting, and loss of consciousness after red blood cell transfusion. She was being treated for menorrhagia and severe anemia.

DIAGNOSES: Magnetic resonance imaging showed multiple infarctions in right cerebellum and bilateral frontal, parietal, and occipital lobes. Echocardiography performed during the evaluation for the source of emboli revealed multiple echogenic masses on the tricuspid aortic valve. There was no evidence of infection, and the masses on the aortic valve were diagnosed as nonbacterial thrombotic endocarditis. The levels of autoimmune antibodies and tumor markers except for carbohydrate antigen 19-9 and cancer antigen 125 were within the normal range. Uterine ultrasound showed a large adenomyosis. The patient was diagnosed with multiple cerebral and cerebellar infarctions due to nonbacterial thrombotic endocarditis, and hormone therapy and anticoagulation with warfarin were initiated.

INTERVENTIONS: The patient did not develop recurrent infarction during anticoagulant therapy; however, menorrhagia worsened requiring total hysterectomy.

OUTCOMES: The patient did not experience recurrent infarction despite the absence of anticoagulant therapy during the 3-year follow-up period.

LESSONS: The present case adds to the limited number of previously reported cases and supports that, albeit rare, adenomyosis can be associated with embolic infarction and suggests that nonbacterial thrombotic endocarditis might be the link between adenomyosis and embolic infarction.

PMID:37266639 | PMC:PMC10238019 | DOI:10.1097/MD.0000000000033871

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PubMed articles on: Cancer & VTE/PE

Prevention of venous thromboembolism in patients with cancer

BMJ. 2023 Jun 1;381:e072715. doi: 10.1136/bmj-2022-072715.