ABSTRACT

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are widely used in the treatment of hematologic malignancies. Limited studies have shown an association between treatment-limiting arrhythmias and TKI, particularly ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. We sought to comprehensively assess the arrhythmia burden in patients receiving ibrutinib vs non-BTK TKI vs non-TKI therapies.

METHODS: We performed a retrospective analysis of consecutive patients who received long-term cardiac event monitors while on ibrutinib, non-BTK TKIs, or non-TKI therapy for a hematologic malignancy between 2014 and 2022.

RESULTS: One hundred ninety-three patients with hematologic malignancies were included (ibrutinib = 72, non-BTK TKI = 46, non-TKI therapy = 75). The average duration of TKI therapy was 32 months in the ibrutinib group vs 64 months in the non-BTK TKI group (p = 0.003). The ibrutinib group had a higher prevalence of atrial fibrillation (n = 32 [44%]) compared to the non-BTK TKI (n = 7 [15%], p = 0.001) and non-TKI (n = 15 [20%], p = 0.002) groups. Similarly, the prevalence of non-sustained ventricular tachycardia was higher in the ibrutinib group (n = 31, 43%) than the non-BTK TKI (n = 8 [17%], p = 0.004) and non-TKI groups (n = 20 [27%], p = 0.04). TKI therapy was held in 25% (n = 18) of patients on ibrutinib vs 4% (n = 2) on non-BTK TKIs (p = 0.005) secondary to arrhythmias.

CONCLUSIONS: In this large retrospective analysis of patients with hematologic malignancies, patients receiving ibrutinib had a higher prevalence of atrial and ventricular arrhythmias compared to those receiving other TKI, with a higher rate of treatment interruption due to arrhythmias.

PMID:37256462 | DOI:10.1007/s10840-023-01575-z

14:05

In reply to this message

PubMed articles on: Cardio-Oncology

An unusual case of checkpoint-inhibitor-induced pleuropericarditis

J Oncol Pharm Pract. 2023 May 30:10781552231179369. doi: 10.1177/10781552231179369. Online ahead of print.

ABSTRACT

INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor that promotes effector T-cell functions on malignant cells by binding to programmed cell death protein 1 (PD-1). Pembrolizumab is well tolerated in most cases with an adverse event profile consisting mainly of pruritus, fatigue, and anorexia. Cardiotoxicity comprises 1% of the total adverse events.

CASE REPORT: We present a case of a 64-year-old female with non-small cell lung cancer (NSCLC) who developed pleuropericarditis following pembrolizumab therapy.

MANAGEMENT & OUTCOME: The patient was successfully managed with colchicine, furosemide, and timely initiation of methylprednisolone with the improvement of her symptoms. The decision to discontinue pembrolizumab was made, and six months after this intervention, the patient has remained asymptomatic.

DISCUSSION: Clinicians should recognize these potential immune-mediated adverse effects to provide effective and timely management and optimize patient care.

PMID:37254508 | DOI:10.1177/10781552231179369

C

15:43

Cardiotoxicity News

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

15:43

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

15:43

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

15:43

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

15:43

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

15:43

PubMed articles on: Cancer & VTE/PE

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

15:43

PubMed articles on: Cancer & VTE/PE

Epidemiology of Cancer-Associated Venous Thromboembolism in Patients With Solid and Hematologic Neoplasms in the Veterans Affairs Health Care System

JAMA Netw Open. 2023 Jun 1;6(6):e2317945. doi: 10.1001/jamanetworkopen.2023.17945. ABSTRACTIMPORTANCE: Identifying changes in epidemiologic patterns of the incidence and risk of cancer-associated thrombosis (CAT), particularly with evolving cancer-directed therapy, is essential for risk stratification.

OBJECTIVE: To assess the incidence of CAT over time and to determine pertinent patient-specific, cancer-specific, and treatment-specific factors associated with its risk.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, retrospective cohort study was conducted from 2006 to 2021. Duration of follow-up was from the date of diagnosis until first venous thromboembolism (VTE) event, death, loss of follow-up (defined as a 90-day gap without clinical encounters), or administrative censoring on April 1, 2022. The study took place within the US Department of Veterans Affairs national health care system. Patients with newly diagnosed invasive solid tumors and hematologic neoplasms were included in the study. Data were analyzed from December 2022 to February 2023.

EXPOSURE: Newly diagnosed invasive solid tumors and hematologic neoplasms.

MAIN OUTCOMES: Incidence of VTE was assessed using a combination of International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification and natural language processing confirmed outcomes. Cumulative incidence competing risk functions were used to estimate incidence of CAT. Multivariable Cox regression models were built to assess the association of baseline variables with CAT. Pertinent patient variables included demographics, region, rurality, area deprivation index, National Cancer Institute comorbidity index, cancer type, staging, first-line systemic treatment within 3 months (time-varying covariate), and other factors that could be associated with the risk of VTE.

RESULTS: A total of 434 203 patients (420 244 men [96.8%]; median [IQR] age, 67 [62-74] years; 7414 Asian or Pacific Islander patients [1.7%]; 20 193 Hispanic patients [4.7%]; 89 371 non-Hispanic Black patients [20.6%]; 313 157 non-Hispanic White patients [72.1%]) met the inclusion criteria. Overall incidence of CAT at 12 months was 4.5%, with yearly trends ranging stably from 4.2% to 4.7%. The risk of VTE was associated with cancer type and stage. In addition to confirming well-known risk distribution among patients with solid tumors, a higher risk of VTE was observed among patients with aggressive lymphoid neoplasms compared with patients with indolent lymphoid or myeloid hematologic neoplasms. Compared with no treatment, patients receiving first-line chemotherapy (hazard ratio [HR], 1.44; 95% CI, 1.40-1.49) and immune checkpoint inhibitors (HR, 1.49; 95% CI, 1.22-1.82) had a higher adjusted relative risk than patients receiving targeted therapy (HR, 1.21; 95% CI, 1.13-1.30) or endocrine therapy (HR, 1.20; 95% CI, 1.12-1.28). Finally, adjusted VTE risk was significantly higher among Non-Hispanic Black patients (HR, 1.23; 95% CI, 1.19-1.27) and significantly lower in Asian or Pacific Islander patients (HR, 0.84; 95% CI, 0.76-0.93) compared with Non-Hispanic White patients.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with cancer, a high incidence of VTE was observed, with yearly trends that remained stable over the 16-year study period. Both novel and known factors associated with the risk of CAT were identified, providing valuable and applicable insights in this current treatment landscape.

PMID:37306999 | DOI:10.1001/jamanetworkopen.2023.17945

15:43

PubMed articles on: Cancer & VTE/PE

Quantitative assessment of the relationship between body mass index and risk of pulmonary embolism: a retrospective case-control study

Acute Med. 2023;22(2):67-71. doi: 10.52964/AMJA.0937.

ABSTRACT

In the context of a significant increase in obesity rates, quantifying the relationship between body mass index (BMI) and risk of pulmonary embolism (PE) is an essential component of accurate clinical risk assessment. This observational study is the first to explore this association by clinician-defined cause of the PE. We demonstrate that the association between BMI and PE is driven by patients with otherwise 'unprovoked' PE where there is a strong positive correlation with odds ratios equivalent to well-recognised major risk factors such as cancer, pregnancy and surgery. We make a case for the inclusion of BMI in risk-prediction tools.

PMID:37306131 | DOI:10.52964/AMJA.0937

15:43

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

15:43

PubMed articles on: Cancer & VTE/PE

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

15:43

PubMed articles on: Cancer & VTE/PE

Plasma thiol levels and methylenetetrahydrofolate reductase gene c.665C > T and c.1286A > C variants affect fibrin clot properties in Polish venous thromboembolic patients

Mol Genet Metab. 2023 Jun 2;139(3):107623. doi: 10.1016/j.ymgme.2023.107623. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Aminothiols, including cysteine (Cys) and glutathione (GSH) in relation to fibrin clot phenotype were not investigated in patients with venous thromboembolism (VTE) and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene variants. We aimed to explore the associations between MTHFR variants and plasma oxidative stress indicators including aminothiols as well as fibrin clot properties with plasma oxidative status and fibrin clot properties in this group of patients.

METHODS: In 387 VTE patients the MTHFR c.665C > T and c.1286A > C variants were genotyped, together with chromatographic separation of plasma thiols. We also determined nitrotyrosine levels and fibrin clot properties, including clot permeability (Ks), lysis time (CLT), and fibrin fibers thickness.

RESULTS: There were 193 patients with MTHFR c.665C > T (49.9%) and 214 (55.3%) with c.1286A > C variants. Both allele carriers with total homocysteine (tHcy) levels >15 μM (n = 71, 18.3%), compared to patients with tHcy ≤15 μM had 11.5% and 12.5% higher Cys levels, 20.6% and 34.3% higher GSH levels as well as 28.1% and 57.4% increased nitrotyrosine levels, respectively (all P < 0.05). The MTHFR c.665C > T carriers with tHcy levels >15 μM compared to tHcy ≤15 μM had 39.4% reduced Ks and 9% reduced fibrin fibers thickness (both P < 0.05) with no differences in CLT. In the MTHFR c.1286A > C carriers with tHcy levels >15 μM, Ks was decreased by 44.5%, CLT prolonged by 46.1%, and fibrin fibers thickness was reduced by 14.5% compared to patients with tHcy ≤15 μM (all P < 0.05). Nitrotyrosine levels in MTHFR variants carriers correlated with Ks (r = -0.38, P < 0.05) and fibrin fibers diameter (r = -0.50, P < 0.05).

CONCLUSIONS: Our study indicates that patients with MTHFR variants and tHcy >15 μM are characterized by elevated Cys and nitrotyrosine levels associated with prothrombotic fibrin clot properties.

PMID:37302269 | DOI:10.1016/j.ymgme.2023.107623

15:43

PubMed articles on: Cancer & VTE/PE

Adult breast, lung, pancreatic, upper and lower gastrointestinal cancer patients with hospitalized venous thromboembolism in the national French hospital discharge database

BMC Cancer. 2023 Jun 10;23(1):531. doi: 10.1186/s12885-023-10877-4.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) and cancer are strongly associated. In France, evidence on patients with pancreatic, upper GI [gastrointestinal], lower GI, lung, or breast cancer-associated VTE and their hospital management is limited. The aims of this study were to provide data on the number of hospitalized VTE events among cancer patients, the patients' characteristics, and their hospital management to estimate the burden of disease and the hospital burden of cancer-related VTE and to provide guidance on research.

METHODS: This longitudinal, observational, and retrospective study was based on the comprehensive hospital discharge database (PMSI). Adult patients (≥ 18 years old) hospitalized with a cancer of interest in 2016 and hospitalized (within 2 years with VTE (captured a as a principal, related, or significant associated diagnosis) were included in the study.

RESULTS: We identified 340,946 cancer patients, of which 7.2% (24,433 patients) were hospitalized with VTE. The proportions of hospitalized VTE were 14.6% (3,237) for patients with pancreatic cancer, 11.2% (8,339) for lung cancer, 9.9% (2,232) for upper GI cancer, 6.7% (7,011) for lower GI cancer, and 3.1% (3,614) for breast cancer. Around two thirds of cancer patients with a hospitalized VTE had active cancer (with metastases and/or receiving chemotherapy during the six months prior to the index date): from 62% of patients with pancreatic cancer to 72% with breast cancer. Around a third of patients were admitted to the hospital through the emergency room, up to 3% of patients stayed in an intensive care unit. The average length of stay ranged from 10 (breast cancer) to 15 days (upper GI cancer). Nine (lower GI cancer) to 18% (pancreatic cancer) of patients died during the VTE hospital stay.

CONCLUSIONS: The burden of cancer-associated VTE is substantial, both in terms of the number of patients affected and in the hospital use. These findings offer guidance on future research on VTE prophylaxis in a very high-risk population, particularly in patients with active cancer.

PMID:37301828 | PMC:PMC10257306 | DOI:10.1186/s12885-023-10877-4

15:43

PubMed articles on: Cancer & VTE/PE

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group

Clin Transl Oncol. 2023 Jun 10:1-7. doi: 10.1007/s12094-023-03233-2. Online ahead of print.

ABSTRACT

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation.

METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification.

RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375).

CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

PMID:37301805 | PMC:PMC10257483 | DOI:10.1007/s12094-023-03233-2

15:43

PubMed articles on: Cancer & VTE/PE

Total Hip Arthroplasty Outcomes in Patients with a History of Prior Radiation

J Arthroplasty. 2023 Jun 8:S0883-5403(23)00609-5. doi: 10.1016/j.arth.2023.05.066. Online ahead of print.