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3/23/26

ABSTRACT

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

PMID:37335828 | DOI:10.1161/CIRCULATIONAHA.123.064473

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PubMed articles on: Cancer & VTE/PE

Plasma microRNAs as potential biomarkers in diagnosis of acute venous thromboembolism

Clin Hemorheol Microcirc. 2023 Jun 10. doi: 10.3233/CH-231820. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the potential use of plasma microRNAs (miRNAs) in diagnosis of acute venous thromboembolism (VTE).

METHODS: Using BGISEQ-500 sequencing technology, we analyzed the miRNA profile of paired plasma samples from the acute and chronic phases of four patients with unprovoked VTE. Using real-time quantitative polymerase chain reaction (RT-qPCR), we verified nine upregulated named miRNAs in the acute phase in the plasma samples of 54 patients with acute VTE and 39 controls. We then compared the relative expression of the 9 candidate miRNAs between the acute VTE and control group, and plotted the receiver operating characteristic (ROC) curves of the differentially expressed miRNAs. We chose the miRNA with the greatest area under curve (AUC) to evaluate the effect of miRNA on coagulation and platelet function in the plasma samples of 5 healthy volunteers.

RESULTS: The plasma levels of miR-374b-3p, miR-660-5p, miR-378a-3p, miR-425-5p, miR-3613-5p, miR-130b-3p, miR-183-5p, and miR-103b were higher in patients with acute VTE than in the controls, with AUCs of 0.6776, 0.6614, 0.6648, 0.6885, 0.8048, 0.6871, 0.7298, and 0.7498, respectively, and P values of 0.0036, 0.0081, 0.0069, 0.0020,<0.0001,

CONCLUSION: miRNAs can be potential biomarkers for diagnosing acute VTE, and miR-3613-5p may be involved in the formation, coagulation, and platelet functions in acute VTE.

PMID:37334587 | DOI:10.3233/CH-231820

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PubMed articles on: Cancer & VTE/PE

Interventional radiological therapies in colorectal hepatic metastases

Front Oncol. 2023 May 30;13:963966. doi: 10.3389/fonc.2023.963966. eCollection 2023.

ABSTRACT

Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases.

PMID:37324012 | PMC:PMC10266282 | DOI:10.3389/fonc.2023.963966

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PubMed articles on: Cancer & VTE/PE

Contact system and intrinsic pathway activation in patients with advanced pancreatic cancer: a prospective cohort study

J Thromb Haemost. 2023 Jun 16:S1538-7836(23)00493-2. doi: 10.1016/j.jtha.2023.06.009. Online ahead of print.

ABSTRACT

BACKGROUND: Despite high risk of venous thromboembolism (VTE) in patients with pancreatic cancer, there is little data on contact system activation in these patients.

OBJECTIVES: To quantify contact system and intrinsic pathway activation and subsequent VTE risk in patients with pancreatic cancer.

METHODS: Patients with advanced pancreatic cancer were compared to controls. Blood was drawn at baseline and patients were followed for six months. Complexes of proteases with their natural inhibitors, C1-esterase inhibitor (C1-INH), anti-thrombin (AT) or alpha-1 antitrypsin (α1at), were measured for complexes containing kallikrein (PKa:C1-INH), factor XIIa (FXIIa:C1-INH) and factor XIa (FXIa:C1-INH, FXIa:AT, FXIa:α1at). The association of cancer with complex levels was assessed in a linear regression model, adjusted for age, sex and body mass index. In a competing risk regression model we assessed associations between complex levels and VTE.

RESULTS: 109 patients with pancreatic cancer and 22 controls were included. The mean age was 66 years (SD 8.4) in the cancer cohort and 52 years (SD 10.1) in controls. In the cancer cohort, 18 (16.7%) patients developed VTE during follow-up. In the multivariable regression model, pancreatic cancer was associated with increased complexes of PKa:C1-INH (p<0.001),<0.001)<0.001).

CONCLUSION: Complexes of proteases with their natural inhibitors were elevated in patients with cancer. These data suggest that the contact system and intrinsic pathway activation are increased in patients with pancreatic cancer.

PMID:37331518 | DOI:10.1016/j.jtha.2023.06.009

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PubMed articles on: Cancer & VTE/PE

First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group

Lancet Oncol. 2023 Jun 14:S1470-2045(23)00219-X. doi: 10.1016/S1470-2045(23)00219-X. Online ahead of print. ABSTRACTBACKGROUND: Patients with initially unresectable colorectal cancer liver metastases might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. We aimed to compare the currently most active induction regimens.

METHODS: In this open-label, multicentre, randomised, phase 3 study (CAIRO5), patients aged 18 years or older with histologically confirmed colorectal cancer, known RAS/BRAFV600E mutation status, WHO performance status of 0-1, and initially unresectable colorectal cancer liver metastases were enrolled at 46 Dutch and one Belgian secondary and tertiary centres. Resectability or unresectability of colorectal cancer liver metastases was assessed centrally by an expert panel of liver surgeons and radiologists, at baseline and every 2 months thereafter by predefined criteria. Randomisation was done centrally with the minimisation technique via a masked web-based allocation procedure. Patients with right-sided primary tumour site or RAS or BRAFV600E mutated tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group A) or FOLFOXIRI plus bevacizumab (group B). Patients with left-sided and RAS and BRAFV600E wild-type tumours were randomly assigned (1:1) to receive FOLFOX or FOLFIRI plus bevacizumab (group C) or FOLFOX or FOLFIRI plus panitumumab (group D), every 14 days for up to 12 cycles. Patients were stratified by resectability of colorectal cancer liver metastases, serum lactate dehydrogenase concentration, choice of irinotecan versus oxaliplatin, and BRAFV600E mutation status (for groups A and B). Bevacizumab was administered intravenously at 5 mg/kg. Panitumumab was administered intravenously at 6 mg/kg. FOLFIRI consisted of intravenous infusion of irinotecan at 180 mg/m2 with folinic acid at 400 mg/m2, followed by bolus fluorouracil at 400 mg/m2 intravenously, followed by continuous infusion of fluorouracil at 2400 mg/m2. FOLFOX consisted of oxaliplatin at 85 mg/m2 intravenously together with the same schedule of folinic acid and fluorouracil as in FOLFIRI. FOLFOXIRI consisted of irinotecan at 165 mg/m2 intravenously, followed by intravenous infusion of oxaliplatin at 85 mg/m2 with folinic acid at 400 mg/m2, followed by continuous infusion of fluorouracil at 3200 mg/m2. Patients and investigators were not masked to treatment allocation. The primary outcome was progression-free survival, analysed on a modified intention-to-treat basis, excluding patients who withdrew consent before starting study treatment or violated major entry criteria (no metastatic colorectal cancer, or previous liver surgery for colorectal cancer liver metastases). The study is registered with ClinicalTrials.gov, NCT02162563, and accrual is complete.

FINDINGS: Between Nov 13, 2014, and Jan 31, 2022, 530 patients (327 [62%] male and 203 [38%] female; median age 62 years [IQR 54-69]) were randomly assigned: 148 (28%) patients to group A, 146 (28%) patients to group B, 118 (22%) patients to group C, and 118 (22%) patients to group D. Groups C and D were prematurely closed for futility. 521 patients were included in the modified intention-to-treat population (147 in group A, 144 in group B, 114 in group C, and 116 in group D). The median follow-up at the time of this analysis was 51·1 months (95% CI 47·7-53·1) in groups A and B and 49·9 months (44·5-52·5) in in groups C and D. [...]

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PubMed articles on: Cancer & VTE/PE

Anticoagulant therapy in COVID-19: A narrative review

Clin Transl Sci. 2023 Jun 16. doi: 10.1111/cts.13569. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS-CoV-2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized venous thromboembolism (VTE) patients, particularly those admitted to intensive care units (ICUs). Moreover, various forms of arterial and venous thrombosis, or micro- or macro-vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in COVID-19 patients accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life-threatening condition. In the current article, we present a thorough review of the pathophysiology of COVID-19-induced hypercoagulable state and the use of anticoagulants to treat SARS-CoV-2 infections in different patient groups, as well as their pros and cons.

PMID:37326220 | DOI:10.1111/cts.13569