ABSTRACT

BACKGROUND: Guidelines recommend thromboprophylaxis for cancer patients at high risk of venous thromboembolism (VTE). Polygenic risk scores may improve VTE prediction, but have not yet been evaluated in cancer patients.

METHODS: We assessed the performance of the 5-SNP, 37-SNP, 297-SNP, extended 297-SNP (additionally including factor V Leiden and prothrombin G20210A), and 100-SNP scores in predicting cancer-associated VTE in the UK Biobank, a population-based, prospective cohort study. The primary outcome was VTE during 12 months after cancer diagnosis. Cancer and VTE diagnosis were based on ICD-10 codes. Discrimination was evaluated by c-indices and subdistribution hazard ratios (SHR) in the upper vs three lower quartiles of the scores in a competing risk model. As a comparison, the c-index was calculated for the Khorana cancer type risk classification.

FINDINGS: Of 36,150 cancer patients (median age, 66 years; 48.7% females), 1,018 (2.8%) developed VTE. C-indices at 12 months ranged from 0.56 (95%CI, 0.54-0.58) for the 5-SNP to 0.60 (95%CI, 0.58-0.62) for the extended 297-SNP scores. SHRs ranged from 1.36 (95%CI, 1.19-1.56) for the 5-SNP to 1.90 (95%CI, 1.68-2.16) for the extended 297-SNP scores, and were consistent after adjusting for cancer type. For the Khorana cancer type classification the c-index was 0.60 (95%CI, 0.58-0.61), which increased to 0.65 (95%CI, 0.63-0.67; +0.05, 95%CI, 0.04-0.07) when combined with the extended 297-SNP score.

INTERPRETATION: These findings demonstrate that polygenic VTE risk scores can identify cancer patients with a 1.9-fold higher VTE risk independent of cancer type. Combined clinical-genetic scores to improve cancer-associated VTE prediction should be evaluated further.

PMID:37481074 | DOI:10.1016/j.jtha.2023.07.009

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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

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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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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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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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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Advances in contraception: vaginal contraceptive rings

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