ABSTRACT

BACKGROUND: Pulmonary tumour embolism is a rare entity that can arise from a wide variety of neoplasms. It can initially manifest as a pulmonary embolism with right heart failure and be refractory to thrombolytic therapy. Cholangiocarcinoma is a rare malignancy that arises from the epithelium of the biliary tree, representing 3% of all the gastrointestinal malignancies, being the intrahepatic cholangiocarcinoma the second most common liver tumour after hepatocellular carcinoma.

CASE SUMMARY: This case regards a patient that presented to our centre with acute pulmonary embolism, deep vein thrombosis, and unrevealing previous medical history. Imaging studies revealed pulmonary embolism, an ovarian mass, and multiple hepatic hypodensities. Throughout the hospitalization, the patient's haemodynamic state and right heart failure worsened, eventually leading to multi-organ failure and death. Post-mortem evaluation revealed cholangiocarcinoma cells on the pulmonary arteries.

DISCUSSION: Pulmonary tumour embolism is a rare pathology that can present with acute right heart failure. The diagnosis of occult cancer can be challenging, and the appropriate treatment for this entity remains an unexplored subject.

PMID:37457051 | PMC:PMC10347672 | DOI:10.1093/ehjcr/ytad291

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PubMed articles on: Cancer & VTE/PE

PREDICTORS OF RETRIEVAL AND LONG-TERM MORTALITY IN PATIENTS TREATED WITH INFERIOR VENA CAVA FILTERS

J Vasc Surg Venous Lymphat Disord. 2023 Jul 13:S2213-333X(23)00251-2. doi: 10.1016/j.jvsv.2023.07.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Inferior vena cava filters are a therapeutic resource for the treatment of patients with thromboembolic disease who have a contraindication to full-dose anticoagulation.

OBJECTIVE: To report the retrieval rate and long-term mortality of patients receiving optional inferior vena cava filters. To identify predictors of retrieval and all-cause mortality during follow-up.

METHODS: We conducted a retrospective cohort study including 739 consecutive recipients of optional vena cava filters from January 2002 to December 2021 in two hospitals. Different clinical characteristics and procedure-related variables were included for this analysis. All-cause mortality rate, retrieval rate and its predictors were evaluated in a multivariate analysis.

RESULTS: Fifty three percent of the patients were female. The mean age was 69 ± 15 years. Sixty seven percent presented pulmonary thromboembolism and 43% deep vein thrombosis. A contraindication to anticoagulation was present in nearly 90% of the patients, mainly (47%) related to a surgical procedure. Forty four percent of the patients had active cancer. Follow-up was performed in 94% of the patients, for an average time of 6.08 ± 5.83 years. Long-term mortality was 53%. Cancer [OR 3.60 (95% CI 2.22-5.83)], age [OR 1.03 (95% CI 1.08-1.42)] and deep vein thrombosis [OR 2.01 (95% CI 1.08-1.42)] were identified as independent predictors of mortality. The retrieval rate at follow-up was 33%. As predictors of retrieval, we identified the indication of the filter related to a surgical procedure [OR 4.85 (95% CI 2.54-9.59)], the absence of cancer [OR 2.89 (95% CI 1.45-5.75)] and age [OR 0.98 (95% CI 0.97-0.99)].

CONCLUSIONS: A high long-term mortality was observed. Predictors of death were cancer, age and deep vein thrombosis. One third of the filters implanted were retrieved. Predictors of retrieval were contraindication to surgical-related anticoagulation, absence of cancer, and younger age.

PMID:37453550 | DOI:10.1016/j.jvsv.2023.07.005

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Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis

Eur Heart J. 2023 Jul 15:ehad417. doi: 10.1093/eurheartj/ehad417. Online ahead of print.

ABSTRACT

AIMS: Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations.

METHODS AND RESULTS: An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10.

CONCLUSION: The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study.

REGISTRATION: PROSPERO ID 89366.

PMID:37452732 | DOI:10.1093/eurheartj/ehad417

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Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial

Lancet Oncol. 2023 Jul 11:S1470-2045(23)00276-0. doi: 10.1016/S1470-2045(23)00276-0. Online ahead of print.

ABSTRACT

BACKGROUND: Immunotherapy-based combinations including pembrolizumab plus lenvatinib are the standard of care for patients with first-line clear-cell renal cell carcinoma, but these combinations are not well characterised in non-clear-cell renal cell carcinoma. We aimed to assess the activity and safety of pembrolizumab plus lenvatinib as a first-line treatment for patients with advanced non-clear-cell renal cell carcinoma.

METHODS: KEYNOTE-B61 is a single-arm, phase 2 trial being conducted at 48 sites (hospitals and cancer centres) in 14 countries (Australia, Canada, France, Hungary, Ireland, Italy, Poland, South Korea, Russia, Spain, Türkiye, Ukraine, the UK, and the USA). Adult patients (aged ≥18 years) with previously untreated stage IV non-clear-cell renal cell carcinoma and a Karnofsky performance status of 70% or higher were eligible for enrolment. All enrolled patients received pembrolizumab 400 mg intravenously every 6 weeks for up to 18 cycles (2 years) plus lenvatinib 20 mg orally once daily or until disease progression, unacceptable toxicity, or withdrawal; lenvatinib could be continued beyond 2 years. The primary endpoint was the proportion of patients with a confirmed objective response as per adjusted Response Evaluation Criteria in Solid Tumours (version 1.1) assessed by independent central review. Activity and safety were analysed in all patients who received at least one dose of study treatment (the as-treated population). This trial is registered with ClinicalTrials.gov (NCT04704219) and is no longer recruiting participants but is ongoing.

FINDINGS: Between Feb 23, 2021, and Jan 21, 2022, 215 patients were screened; 158 were enrolled and received treatment. Median age at baseline was 60 years (IQR 52-69), 112 (71%) of 158 patients were male, 46 (29%) were female, 128 (81%) were White, 12 (8%) were Asian, three (2%) were Black or African American, and 15 (9%) were missing data on race. As of data cutoff (Nov 7, 2022), median study follow-up was 14·9 months (IQR 11·1-17·4). 78 of 158 patients had a confirmed objective response (49%; 95% CI 41-57), including nine (6%) patients with a confirmed complete response and 69 (44%) with a confirmed partial response. Grade 3-4 treatment-related adverse events occurred in 81 (51%) of 158 patients, the most common of which were hypertension (37 [23%] of 158), proteinuria (seven [4%]), and stomatitis (six [4%]). Serious treatment-related adverse events occurred in 31 (20%) of 158 patients. Eight (5%) patients died due to adverse events, none of which was considered related to the treatment by the investigators (one each of cardiac failure, peritonitis, pneumonia, sepsis, cerebrovascular accident, suicide, pneumothorax, and pulmonary embolism).

INTERPRETATION: Pembrolizumab plus lenvatinib has durable antitumour activity in patients with previously untreated advanced non-clear-cell renal cell carcinoma, with a safety profile consistent with that of previous studies. Results from KEYNOTE-B61 support the use of pembrolizumab plus lenvatinib as a first-line treatment option for these patients.

FUNDING: Merck Sharp & Dohme (a subsidiary of Merck & Co, NJ, USA), and Eisai.

PMID:37451291 | DOI:10.1016/S1470-2045(23)00276-0

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Heparin reversal with protamine sulfate after Percutaneous Hepatic Perfusion (PHP): is less more?

Cancer Imaging. 2023 Jul 14;23(1):68. doi: 10.1186/s40644-023-00590-7.

ABSTRACT

PURPOSE: Percutaneous hepatic perfusion (PHP) is a palliative intraarterial therapy for unresectable hepatic malignancies. During PHP, high-dose melphalan is infused via the hepatic artery to saturate tumor in the liver with the chemotherapeutic substance. The venous hepatic blood is filtered by an extracorporeal melphalan specific filtration system. Blood clotting in the extracorporeal filter system is prevented by administering unfractionated heparin (UFH) in high doses, which might be reversed with protamine sulfate after the procedure. Aim of this retrospective two-center-study was to analyze the potential effect of UFH reversal with protamine sulfate on complication rates following PHP.

MATERIALS AND METHODS: All patients receiving PHP treatment between 10/2014 and 04/2021 were classified according to their intraprocedural coagulation management: 92 patients/192 PHP received full UFH reversal with protamine (groupPROTAMINE); 13 patients/21 PHP in groupREDUCED_PROTAMINE received a reduced amount of protamine, and 28 patients/43 PHP did not receive UFH reversal with protamine (groupNO_PROTAMINE). Periinterventional clinical reports, findings and laboratory values were retrospectively evaluated. Complications and adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAEv5.0).

RESULTS: Thromboembolic events were recorded after 10 PHP procedures (5%) in groupPROTAMINE, six of which (3%) were major events (CTCAE grade 3-5). No (0%) thromboembolic events were recorded in groupREDUCED_PROTAMINE and groupNO_PROTAMINE. Hemorrhagic events were registered after 24 PHP (13%) in groupPROTAMINE, two of which (1%) were major (CTCAE grade 3-4). In groupREDUCED_PROTAMINE, only minor bleeding events were recorded, and one major hemorrhagic event was documented in groupNO_PROTAMINE (2%). There was a significant difference between the percentage of post-interventional thrombopenia in groupPROTAMINE (39%) and groupREDUCED_PROTAMINE (14%) versus groupNO_PROTAMINE (23%) (p=.00024). In groupPROTAMINE one patient suffered from a severe anaphylactic shock after the administration of protamine.

CONCLUSION: Our retrospective study implies that there might be a link between the practice of protamine sulfate administration to reverse the full hemodilutive effect of UFH after PHP and the post-interventional risk of thromboembolic events as well as clinically significant thrombopenia. Our data suggest that the standard use of protamine sulfate after PHP in low-risk patients without clinical signs of active bleeding should be critically re-evaluated.

PMID:37452405 | PMC:PMC10349410 | DOI:10.1186/s40644-023-00590-7

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Clinical presentations of acute pulmonary embolism: A retrospective cohort study

Medicine (Baltimore). 2023 Jul 14;102(28):e34224. doi: 10.1097/MD.0000000000034224.

ABSTRACT

We aimed to investigate whether the unusual clinical presentation of pulmonary embolism (PE) varies by the type of provocation. In this retrospective cohort study, we examined the electronic health records (EHR) records of all patients diagnosed with PE (upon presentation or during hospitalization) presented to our tertiary hospital during 2014 to 2019. Inclusion criteria were the diagnosis of acute PE and age above 18 years. Excluded were all patients to whom complete EHR were not available. The primary outcome was the main presenting symptom, categorized by a multidisciplinary consensus expert committee as either typical or atypical of PE. Comorbidities, vital signs, medications and laboratory results on presentations were recorded. 591 patients were included in the final analysis. Dyspnea was significantly less common and hemoptysis and chest pain more common in the unprovoked PE group (35%, 5%, and 25%, respectively) compared with nonmalignant (42.6%, 0%, and 16.3%) and malignancy-associated (47.7%, 0.9%, and 8.2%) PE (Pv = 0.02, 0.002 and 0.001, respectively). No recorded symptoms were the third most common presentation overall, accounting for a significantly (Pv < 0.001) higher proportion of PE patients with malignancy (19%) whereas atypical presentation was the hallmark of patients with nonmalignant provokation (19.7%) (Pv = 0.005). Accounting for multiple potential confounders, the risk of atypical or asymptomatic presentation was higher with lower heart rates (RR = 0.974 95%C.I. [0.957-0.990]) and higher pulse oximetry saturation (RR = 1.114 95%CI [1.034-1.201]). The clinical presentation of PE varies with different types of provoking factors, with atypical presentation most common in nonmalignant provocation and asymptomatic presentation most prevalent in patients with underlying malignancy. Further studies are needed to determine the effect of said variance on long term clinical outcomes.

PMID:37443506 | PMC:PMC10344497 | DOI:10.1097/MD.0000000000034224

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The impact of body mass index on oncoplastic breast surgery: A multicenter analysis

J Surg Oncol. 2023 Jul 13. doi: 10.1002/jso.27397. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity has nearly tripled in the last 50 years. During the last decades, oncoplastic breast surgery has become an important choice in the surgical treatment of breast cancer. An association exists between higher body mass index (BMI) and wound complications for major operations, but there is scarce literature on oncoplastic surgery. Hence, our aim was to compare the complication rates among patients who underwent oncoplastic surgery, stratified by BMI.

METHODS: Patient data were analyzed from the National Surgical Quality Improvement Program database (NSQIP) for oncoplastic breast procedures (2005-2020). Patients were stratified according to World Health Organization obesity classifications. Multivariate logistic regression was performed to assess risk factors for complications (overall, operative, and wound-related).

RESULTS: From a total of 6887 patients who underwent oncoplastic surgery, 4229 patients were nonobese, 1380 had Class 1 obesity (BMI: 30 to <352 ), 737 Class 2 obesity (BMI: 35 to <402 ), and 541 Class 3 obesity (BMI: ≥ 40 kg/m2 ). Greater operative time was found according to higher BMI (p < 0.001). Multivariate analysis adjusted for baseline characteristics showed that patients with obesity Class 2 (odds ratio [OR] = 1.51, 95% confidence interval [CI]: 1.03-2.23, p = 0.037) and 3 (OR = 1.87, 95% CI 1.24-2.83, p = 0.003) had increased risk of overall and wound complications compared with Nonobese patients. Comparing obese with nonobese patients, there were no differences in rates of deep SSI, organ/space SSI, pneumonia, reintubation, pulmonary embolism, deep vein thrombosis, urinary tract infection, stroke, bleeding, postoperative sepsis, length of stay, and readmission.

CONCLUSIONS: Oncoplastic surgery is a safe procedure for most patients. However, caution should be exercised when performing oncoplastic surgery for patients with Class 2 or 3 obesity (BMI ≥ 35 kg/m2 ), given there was a higher rate of overall and wound-specific complications, compared with patients who were not obese or had Class 1 obesity.

PMID:37448232 | DOI:10.1002/jso.27397

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High-intensity interval training and thromboembolic events during chemotherapy for testicular cancer: a retrospective analysis from the Body & Cancer cohort

Acta Oncol. 2023 Jun;62(6):666-672. doi: 10.1080/0284186X.2023.2225145. Epub 2023 Jul 14.

ABSTRACT

Background:Men with testicular cancer receiving platinum-based chemotherapy have an increased risk of thromboembolic events, with incidence rates between 8-24%. A recent trial evaluating the effect of high-intensity interval training (HIIT) prematurely closed as three out of nine participants (33%) in the intervention group developed a thromboembolic event. The purpose of this retrospective cohort study was: 1) (primary) to evaluate the incidence of thromboembolic events in men receiving chemotherapy for testicular cancer who had participated in HIIT during a 6-week exercise program (Body & Cancer) 2) to describe the feasibility of this program.Material and methods: Forty men who had participated in at least one HIIT session from February 2007 to February 2020 were included. Electronic medical records were searched for incident thromboembolic events (arterial and venous) during Body & Cancerand up to one-year post-chemotherapy. Attendance, cardiorespiratory fitness (VO2-peak), and upper and lower extremity muscular strength (1 repetition maximum (RM)) were obtained from the Body & Cancerdatabase.Results: One participant developed a thromboembolic event during Body & Cancer. No participants developed a thromboembolic event in the follow-up period. In all, data represent 160 HIIT sessions with a median attendance of eight sessions [range 1-19]. Statistically significant increases in upper and lower extremity strength were observed (8.6 (4.2 to 13.0) and 26.0 (14.9 to 37.0) kg, respectively). No significant increase in cardiorespiratory fitness was found (0.14 (-0.03 to 0.31) l/min).Conclusion: While conclusions on the safety of HIIT cannot be drawn, data from the present study do not support previous findings cautioning avoidance of HIIT due to a possible added risk of thromboembolic events in men receiving platinum-based chemotherapy for testicular cancer. Considering the potential for positive effects on cardiovascular outcomes associated with HIIT, future studies with robust design should be performed in this population to confirm these observations.

PMID:37450654 | DOI:10.1080/0284186X.2023.2225145

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PubMed articles on: Cancer & VTE/PE

Prevalence and outcomes of type 2 myocardial infarction in patients with cancer: A retrospective analysis from the National Inpatient Sample dataset

Int J Cardiol. 2023 Jul 11:131154. doi: 10.1016/j.ijcard.2023.131154. Online ahead of print.

 

ABSTRACT

BACKGROUND: Open fractures of the ankle are complex injuries requiring multidisciplinary input and are associated with significant morbidity and mortality. However, data on the clinical outcomes of open ankle fracture management in patients older than 70 is minimal.

AIM: To evaluate the clinical outcomes following open ankle fracture management in patients older than 70. Our secondary aim is to look at predictors of poor outcomes.

METHODS: Following local research and audit department registration, 22 years of prospectively collated data from an electronic database in a district general hospital were assessed. All patients older than 70 years of age with an open ankle fracture requiring surgical intervention were identified. Demographic information, the nature, and the number of surgical interventions were collated. Complications, including surgical site infection (SSI), venous thromboembolic events (VTEs) during hospital stay, and mortality rate, were reviewed.

RESULTS: A total of 37 patients were identified (median age: 84 years, range: 70-98); n= 30 females median age: 84 years, range: 70-97); n= 7 males median age: 74 years, range: 71-98)) who underwent surgical intervention after an open ankle fracture. Sixteen patients developed SSIs (43%). Superficial SSIs (n = 8) were managed without surgical intervention and treated with antibiotics and regular dressing changes. Deep SSIs (n = 8; 20%) required a median of 3 (range: 2-9) surgical interventions, with four patients requiring multiple washouts and one patient having metalwork removed. VTE incidence was 5% during the hospital stay. Eight patients died within 30 d, and mortality at one year was 19%. The 10-year mortality rate was 57%. The presence of a history of stroke, cancer, or prolonged inpatient stay was found to be predictive of lower survivorship in this population (log-rank test: cancer P= 0.008, stroke P= 0.001, length of stay > 33 d P= 0.015). The presence of a cardiac history was predictive of wound complications (logistic regression, P= 0.045). Age, number of operations, and diabetic history were found to be predictive of an increase in the length of stay (general linear model; age P< 0.001, number of operations P< 0.001, diabetes P= 0.041).

CONCLUSION: An open ankle fracture in a patient older than 70 years has at least a 20% chance of requiring repeated surgical intervention due to deep SSIs. The presence of a cardiac history appears to be the main predictor for wound complications.

PMID:37485433 | PMC:PMC10359747 | DOI:10.5312/wjo.v14.i7.554

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Using Machine Learning (ML) Models to Predict Risk of Venous Thromboembolism (VTE) Following Spine Surgery

Clin Spine Surg. 2023 Jul 24. doi: 10.1097/BSD.0000000000001498. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective cohort study.

OBJECTIVES: Venous thromboembolism (VTE) is a potentially high-risk complication for patients undergoing spine surgery. Although guidelines for assessing VTE risk in this population have been established, development of new techniques that target different aspects of the medical history may prove to be of further utility. The goal of this study was to develop a predictive machine learning (ML) model to identify nontraditional risk factors for predicting VTE in spine surgery patients.

SUMMARY OF BACKGROUND DATA: A cohort of 63 patients was identified who had undergone spine surgery at a single center from 2015 to 2021. Thirty-one patients had a confirmed VTE, while 32 had no VTE. A total of 113 attributes were defined and collected via chart review. Attribute categories included demographics, medications, labs, past medical history, operative history, and VTE diagnosis.

METHODS: The Waikato Environment for Knowledge Analysis (WEKA) software was used in creating and evaluating the ML models. Six classifier models were tested with 10-fold cross-validation and statistically evaluated using t tests.

RESULTS: Comparing the predictive ML models to the control model (ZeroR), all predictive models were significantly better than the control model at predicting VTE risk, based on the 113 attributes (P<0.001).

CONCLUSION: Further development of these tools may provide high diagnostic value and may guide chemoprophylaxis treatment in this setting of high-risk patients.

PMID:37482644 | DOI:10.1097/BSD.0000000000001498

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Automated detection and segmentation of pulmonary embolisms on computed tomography pulmonary angiography (CTPA) using deep learning but without manual outlining

Med Image Anal. 2023 Jul 14;89:102882. doi: 10.1016/j.media.2023.102882. Online ahead of print.

ABSTRACT

We present a novel computer algorithm to automatically detect and segment pulmonary embolisms (PEs) on computed tomography pulmonary angiography (CTPA). This algorithm is based on deep learning but does not require manual outlines of the PE regions. Given a CTPA scan, both intra- and extra-pulmonary arteries were firstly segmented. The arteries were then partitioned into several parts based on size (radius). Adaptive thresholding and constrained morphological operations were used to identify suspicious PE regions within each part. The confidence of a suspicious region to be PE was scored based on its contrast in the arteries. This approach was applied to the publicly available RSNA Pulmonary Embolism CT Dataset (RSNA-PE) to identify three-dimensional (3-D) PE negative and positive image patches, which were used to train a 3-D Recurrent Residual U-Net (R2-Unet) to automatically segment PE. The feasibility of this computer algorithm was validated on an independent test set consisting of 91 CTPA scans acquired from a different medical institute, where the PE regions were manually located and outlined by a thoracic radiologist (>18 years' experience). An R2-Unet model was also trained and validated on the manual outlines using a 5-fold cross-validation method. The CNN model trained on the high-confident PE regions showed a Dice coefficient of 0.676±0.168 and a false positive rate of 1.86 per CT scan, while the CNN model trained on the manual outlines demonstrated a Dice coefficient of 0.647±0.192 and a false positive rate of 4.20 per CT scan. The former model performed significantly better than the latter model (p<0.01).

PMID:37482032 | DOI:10.1016/j.media.2023.102882

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Polygenic risk scores for prediction of cancer-associated venous thromboembolism in the UK Biobank cohort study

J Thromb Haemost. 2023 Jul 20:S1538-7836(23)00571-8. doi: 10.1016/j.jtha.2023.07.009. Online ahead of print.

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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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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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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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: Cancer & VTE/PE

Optimal D-dimer cut-off values for diagnosing deep vein thrombosis in patients with comorbid malignancies

Ann Vasc Surg. 2023 Jul 14:S0890-5096(23)00513-7. doi: 10.1016/j.avsg.2023.06.033. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with malignancy are at high risk of VTE, and early diagnosis is important. The Khorana score is known as a risk assessment for cancer-related thrombosis during chemotherapy, but there are still few reports on its diagnostic potential, the optimal D-dimer cut-off values for indications other than chemotherapy and the use of the Khorana score in combination with D-dimers. In this study, we examined the clinical appropriateness of increasing the D-dimer cut-off value.

METHODS: We retrospectively studied 208 malignancies out of 556 patients who underwent lower extremity venous ultrasonography at our hospital over a two-year period from January 2018 to December 2019. The optimal D-dimer cut-off value for predicting DVT in patients with malignancy was calculated by the Youden index. The usefulness of the Khorana score alone and the model combining the Khorana score with D-dimer for predicting DVT diagnosis was compared using receiver operating characteristic analysis.

RESULTS: Of 208 eligible patients, 59 (28.4%) had confirmed DVT. The optimal D- dimer cut-off value for predicting DVT comorbidity in patients with malignancy was 3.96 μg/mL. When the new D-dimer cut-off value was set at 4.0 μg/mL, the odds ratio for DVT diagnosis was 4.23 (95% CI 2.10-8.55, p<0.001),

CONCLUSIONS: The optimal D-dimer cut-off value for the diagnosis of DVT in patients with malignancy was 4.0 μg/mL. It was also suggested that the combination of the Khorana score with the D-dimer level was more accurate in diagnosing DVT than the Khorana score alone.

PMID:37454901 | DOI:10.1016/j.avsg.2023.06.033

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PubMed articles on: Cancer & VTE/PE

Acute pulmonary tumour embolism and right systolic dysfunction in a hidden intrahepatic cholangiocarcinoma: case report

Eur Heart J Case Rep. 2023 Jun 28;7(7):ytad291. doi: 10.1093/ehjcr/ytad291. eCollection 2023 Jul.

 

ABSTRACT

AIMS: Cardiotoxicity is a seriously debilitating complication of trastuzumab (TRZ) therapy in patients with cancer as a consequence of overexpression of the human epidermal growth factor receptor 2. Although most TRZ-induced cardiotoxicity (TIC) cases are reversible, some patients experience chronic cardiac dysfunction, and these irreversible concepts may be associated with cardiomyocyte death. Acetylcholine receptor (AChR) activation has been shown to exert cardioprotection in several heart diseases, but the effects of AChR agonists against TIC have not been investigated.

MAIN METHOD: Forty adult male Wistar rats were randomized into 5 groups: (i) CON (0.9 % normal saline), (ii) TRZ (4 mg/kg/day), (iii) TRZ + α7nAChR agonist (PNU-282987: 3 mg/kg/day), (iv) TRZ + mAChR agonists (bethanechol: 12 mg/kg/day), and (v) TRZ + combined treatment (Combined PNU-282987 and bethanechol).

KEY FINDINGS: The progression of TIC was driven by mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including by pyroptosis, ferroptosis, and apoptosis, which were significantly alleviated by α7nAChR and mAChR agonists. Interestingly, necroptosis was not associated with development of TIC. More importantly, the in vitro study validated the cytoprotective effects of AChR activation in TRZ-treated H9c2 cells, while not interfering with the anticancer properties of TRZ. All of these findings indicated that TRZ induced mitochondrial dysfunction, autophagic deficiency, and excessive myocyte death including pyroptosis, ferroptosis, and apoptosis, leading to impaired cardiac function. These pathological alterations were attenuated by α7nAChR and mAChR agonists.

SIGNIFICANCE: α7nAChR and mAChR agonists might be used as a future therapeutic target in the mitigation of TIC.

PMID:37482212 | DOI:10.1016/j.lfs.2023.121971

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PubMed articles on: Cardio-Oncology

Identification and protection of early cardiotoxicity in acute myeloid leukemia patients undergoing transplantation

Hematology. 2023 Dec;28(1):2239569. doi: 10.1080/16078454.2023.2239569.

ABSTRACT

Cardiotoxicity of antitumor therapy results in declining survival rates. More specifically, cardiotoxicity is positively correlated with cumulative dose of anthracyclines and eventually develops from reversible to irreversible. In this context, early monitoring methods should be explored for the timely detection of cardiotoxicity and cardioprotective therapy should be performed in patients under consideration for potentially cardiotoxic therapy. This paper reports a 22-year-old male patient with acute myeloid leukemia who underwent whole-course cardiac monitoring after receiving antileukemia therapy. After the early detection of an asymptomatic decrease in left ventricular ejection fraction (LVEF), along with a significant decrease in global longitudinal strain (GLS), the patient was treated with sacubitril/valsartan (Sac/Val). Finally, the patient completed four courses of chemotherapy and subsequent hematopoietic stem cell transplantation as planned. The measurements of LVEF and GLS also recovered after 2 months treatment of Sac/Val. Therefore, the early identification and protection of patients with cardiotoxicity are of paramount importance and future prospective studies are expected to develop the management and treatment of cancer treatment-related cardiac dysfunction.

PMID:37489927 | DOI:10.1080/16078454.2023.2239569

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PubMed articles on: Cardio-Oncology

Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study

Front Oncol. 2023 Jun 27;13:1177681. doi: 10.3389/fonc.2023.1177681. eCollection 2023.

ABSTRACT

PURPOSE: Clinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients.

METHODS: We conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities.

RESULTS: From March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts.

CONCLUSION: Our findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes.

PMID:37441419 | PMC:PMC10335743 | DOI:10.3389/fonc.2023.1177681

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PubMed articles on: Cancer & VTE/PE

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study

J Am Heart Assoc. 2023 Jul 25:e029618. doi: 10.1161/JAHA.123.029618. Online ahead of print.

ABSTRACT

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

PMID:37489755 | DOI:10.1161/JAHA.123.029618

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PubMed articles on: Cancer & VTE/PE

Role of Intravascular Ultrasound in Pulmonary Embolism Patients Undergoing Mechanical Thrombectomy: A Systematic Review

Tomography. 2023 Jul 14;9(4):1393-1407. doi: 10.3390/tomography9040111.

ABSTRACT

BACKGROUND: Traditionally, mechanical thrombectomy performed for pulmonary embolism (PE) necessitates the utilization of iodinated contrast. Intravascular ultrasound (IVUS) has been used as a diagnostic and therapeutic modality in the management of acute high and intermediate-risk PE. Recently, with the shortage of contrast supplies and the considerable incidence of contrast-induced acute kidney injury (CI-AKI), other safer and more feasible IVUS methods have become desirable. The purpose of this systematic review was to evaluate the importance of IVUS in patients with PE undergoing thrombectomy.

METHODS: Medline/PubMed, Embase, Scopus, and Google Scholar were searched for review studies, case reports, and case series. Clinical characteristics, outcomes and the usage of IVUS-guided mechanical thrombectomy during the treatment of acute high and intermediate-risk PE were examined in a descriptive analysis.

RESULTS: In this systematic review, we included one prospective study, two case series, and two case reports from July 2019 to May 2023. A total of 39 patients were evaluated; most were female (53.8%). The main presenting symptoms were dyspnea and chest pain (79.5%); three patients (7.9%) presented with syncope, one with shock and one with cardiac arrest. Biomarkers (troponin and BNP) were elevated in 94.6% of patients. Most patients (87.2%) had intermediate-risk PE, and 12.8% had high-risk PE. All patients presented with right-heart strain (RV/LV ratio ≥ 0.9, n= 39). Most patients (56.4%) had bilateral PE. Mechanical thrombectomy was performed using IVUS without contrast utilization in 39.4% of the patients. After the initial learning curve, contrast usage decreased gradually over time. There was a significant decrease in the composite mean arterial pressure immediately following IVUS-guided thrombectomy from 35.1 ± 7.2 to 25.2 ± 8.3 mmHg (p < 0.001). Post-procedure, there was no reported (0%) CI-AKI, no all-cause mortality, no major bleeding, or other adverse events. There was a significant improvement in symptoms and RV function at the mean follow-up.

CONCLUSIONS: New evidence suggests that IVUS-guided mechanical thrombectomy is safe, with visualization of the thrombus for optimal intervention, and reduces contrast exposure.

PMID:37489479 | PMC:PMC10366920 | DOI:10.3390/tomography9040111

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PubMed articles on: Cancer & VTE/PE

Recommendations for thromboembolic disease in oncological processes. A view from primary care

Semergen. 2023 Jul 22;49(7):102030. doi: 10.1016/j.semerg.2023.102030. Online ahead of print.

ABSTRACT

Venous thromboembolic disease (VTE) is a frequent complication in patients diagnosed with cancer and a cause of morbidity and mortality. Approximately 20% of thromboembolic episodes develop in association with active cancer. On the other hand, it is estimated that about 2-12% of cases, the thromboembolic episode is the first manifestation of an occult cancer, diagnosed at that time or subsequently, which offers an opportunity for early diagnosis and treatment. There are multiple factors that contribute to increase the risk of VTE in oncological patients in relation to specific characteristics of the patient, the tumor and the treatments. Knowledge of these risk factors will contribute to early diagnosis when signs of VTE appear, as well as the assessment of thromboprophylaxis if indicated. The diagnosis of VTE in patients with cancer does not differ of those who do not suffer from it. Regarding the treatment of VTE in these patients, low molecular weight heparin (LMWH), direct acting anticoagulants (DACs) and antivitamin K (VKA) are the most commonly used, although the dosing regimen and length are not clear yet. The management of these patients should be interdisciplinary and early, so the primary care physician plays a key role in this process as he/she is liaise with his/her patients. It is also necessary to update knowledge in order to improve the care of these patients. For these reasons, this document has been prepared by the Working Group on Vasculopathies of the Spanish Society of Primary Care Physicians (SEMERGEN) whose objective is to present the available information regarding the management of VTE that may appear in oncological patients, as well as the assessment of thromboprophylaxis and treatment, if appropriate, from an approach focused on a primary care field.

PMID:37487423 | DOI:10.1016/j.semerg.2023.102030

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PubMed articles on: Cancer & VTE/PE

Incidence and Risk Factors of Venous Thromboembolism in Patients with Lung Adenocarcinoma Receiving Anti-tumor Therapy

Zhongguo Fei Ai Za Zhi. 2023 Jun 20;26(6):439-448. doi: 10.3779/j.issn.1009-3419.2023.102.22.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) as the most common cancer-associated complication has become the second death-causing reason among cancer patients. The management of VTE in patients with lung adenocarcinoma should focus on early and timely detection of risk factors. The aim of the study is to investigate the current situation of VTE in patients with lung adenocarcinoma treated with anti-tumor therapy and then explore the risk factors associated with the occurrence of VTE during anti-tumor therapy for early detection and screening of VTE.

METHODS: The present study included patients diagnosed as lung adenocarcinoma undergoing anti-tumor therapy in First Affiliated Hospital of Nanjing Medical University between December 2019 and May 2021. The risk factors were identified via univariate and multivariate Cox analysis. The incidence of independent risk factors were investigated through Kaplan-Meier curves combined with Log-rank test.

RESULTS: The results of univariate and multivariate Cox regression showed that history of VTE, targeted therapy and radiotherapy were risk factors for VTE in patients with lung adenocarcinoma treated with anti-tumor therapy (P<0.05).

CONCLUSIONS: History of VTE, radiotherapy and targeted therapy are found as independent risk factors for the occurrence of VTE, which should be identified and monitored for reduction of VTE incidence. .

PMID:37488081 | DOI:10.3779/j.issn.1009-3419.2023.102.22

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PubMed articles on: Cancer & VTE/PE

Comparative Effectiveness of Anticoagulants in Patients With Cancer-Associated Thrombosis

JAMA Netw Open. 2023 Jul 3;6(7):e2325283. doi: 10.1001/jamanetworkopen.2023.25283.

ABSTRACT

IMPORTANCE: Patterns of clinical utilization and comparative effectiveness of anticoagulants for cancer-associated thrombosis (CAT) remain largely unexplored.

OBJECTIVES: To assess patterns of and factors associated with anticoagulant use and to evaluate the comparative effectiveness of contemporary anticoagulants in patients with active cancer in a clinical setting.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study obtained deidentified OptumLabs electronic health record claims data from January 1, 2012, to September 30, 2019. Adult patients (≥18 years of age) with a primary cancer diagnosis (except skin cancer) during at least 1 inpatient or 2 outpatient visits within 6 months before the venous thromboembolism (VTE) date were included. Data were analyzed from April 2020 to September 2021.

EXPOSURES: The patients were grouped according to the anticoagulant prescribed: (1) direct oral anticoagulants (DOACs), (2) low-molecular-weight heparin (LMWH), and (3) warfarin.

MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) were used to present the association between factors of interest and utilization of anticoagulants. Main efficacy outcomes included risk of VTE recurrence and all-cause mortality. Main safety outcomes included the risk of hospitalization due to major bleeding. Relative treatment effect estimates were expressed as hazard ratios (HRs) with 95% CIs.

RESULTS: This study included 5100 patients (mean [SD] age, 66.3 [12.3] years; 2670 [52.4%] women; 799 [15.7%] Black, 389 [7.6%] Hispanic, and 3559 [69.8%] White individuals). Overall, 2512 (49.3%), 1488 (29.2%), and 1460 (28.6%) filled prescriptions for DOACs, LMWH, and warfarin, respectively. The median (IQR) treatment duration was 3.2 (1.0-6.5) months for DOACs, 3.1 (1.0-6.8) months for warfarin, and 1.8 (0.9-3.8) months for LWMH. Patients with lung (OR, 2.07; 95% CI, 1.12-3.65), urological (OR, 1.94; 95% CI,1.08-3.49), gynecological (OR, 4.25; 95% CI, 2.31-7.82), and colorectal (OR, 2.26; 95% CI, 1.20-4.32) cancer were associated with increased prescriptions for LMWH compared with DOACs. LMWH (HR, 1.47; 95% CI, 1.14-1.90) and warfarin (HR, 1.46; 95% CI, 1.13-1.87) were associated with an increased risk of VTE recurrences compared with DOACs. LMWH was associated with an increased risk of major bleeding (HR, 2.27; 95% CI, 1.62-3.20) and higher all-cause mortality (HR, 1.61; 95% CI, 1.15-2.25) compared with DOACs.

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of claims-based data, patients with CAT received anticoagulation for a remarkably short duration in clinical settings. DOACs was associated with a lower risk of VTE recurrence, major bleeding, and mortality. Warfarin may still be considered for patients with contraindications to DOACs and those with poor persistence on LMWH.

PMID:37486628 | PMC:PMC10366701 | DOI:10.1001/jamanetworkopen.2023.25283

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PubMed articles on: Cancer & VTE/PE

Clinical outcome of open ankle fractures in patients above 70 years of age

World J Orthop. 2023 Jul 18;14(7):554-561. doi: 10.5312/wjo.v14.i7.554. eCollection 2023 Jul 18.

 

ABSTRACT

BACKGROUND: Postoperative venous thromboembolism (VTE) is a well-documented cause of morbidity and mortality in lung cancer patients. However, risk identification remains limited. In this study, we sought to analyze the risk factors for VTE and verify the predictive value of the modified Caprini risk assessment model (RAM).

METHODS: This prospective single-center study included patients with resectable lung cancer who underwent resection between October 2019 and March 2021. The incidence of VTE was estimated. Logistic regression was used to analyze the risk factors for VTE. Receiver operating characteristic (ROC) curve analysis was performed to test the ability of the modified Caprini RAM to predict VTE.

RESULTS: The VTE incidence was 10.5%. Several variables, including age, D-dimer, hemoglobin (Hb), bleeding, and patient confinement to bed were significantly associated with VTE after surgery. The difference between the VTE and non-VTE groups in the high-risk levels was statistically significant (P<0.001),

CONCLUSIONS: The risk-stratification approach of the modified Caprini RAM is not particularly valid after lung resection in our population. The use of the modified Caprini RAM combined with Hb and D-dimer levels shows a good diagnostic performance for VTE prediction in patients with lung cancer undergoing resection.

PMID:37426170 | PMC:PMC10323546 | DOI:10.21037/jtd-23-776

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PubMed articles on: Cancer & VTE/PE

A pilot study of anlotinib with third-generation epidermal growth factor receptor tyrosine kinase inhibitors in untreated EGFR-mutant patients with advanced non-small cell lung cancer

Transl Lung Cancer Res. 2023 Jun 30;12(6):1256-1263. doi: 10.21037/tlcr-23-175. Epub 2023 Jun 21.

ABSTRACT

BACKGROUND: In recent years, osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been recommended as a first-line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). A phase III study (AENEAS) to assess the efficacy and safety of aumolertinib, another third-generation EGFR-TKI, vs.gefitinib as a first-line treatment in patients with locally advanced or metastatic NSCLC harboring EGFRmutations has also achieved positive results. Despite the improvements in progression-free survival (PFS) and overall survival (OS) of third- vs.first-generation EGFR-TKIs, combined treatment strategies to postpone drug resistance and further prolong survival benefits remain to be explored.

METHODS: We conducted a nonrandomized phase II trial (ChiCTR2000035140) of an oral multitarget antiangiogenic TKI (anlotinib) with third-generation EGFR-TKIs (osimertinib or aumolertinib) in untreated patients with EGFRmutation and advanced NSCLC. Anlotinib and the third-generation EGFR-TKIs were orally administrated (anlotinib at a dose of 12 mg once every other day and osimertinib at 80 mg once daily or aumolertinib at 110 mg once daily). The primary end point of the study was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), OS, PFS, and safety of the combined treatment.

RESULTS: Enrollment was ceased due to treatment-related adverse events (trAEs) after 11 of 35 planned patients were treated. Among these 11 patients, two were lost to follow-up, and the treatment of five of the remaining nine patients was discontinued due to trAEs, including stomachache, rash, hyponatremia, pulmonary embolism, and interstitial pneumonia. AEs of grade 3 or worse were observed in five patients, but no treatment-related death occurred in these patients.

CONCLUSIONS: Combining anlotinib and third-generation EGFR-TKIs in untreated EGFR-mutant patients with advanced NSCLC demonstrated significantly increased toxicity, suggesting that the combined treatment strategy was an inappropriate therapeutic choice in this setting.

PMID:37425401 | PMC:PMC10326784 | DOI:10.21037/tlcr-23-175

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PubMed articles on: Cancer & VTE/PE

Psychiatric disorders and subsequent risk of cardiovascular disease: a longitudinal matched cohort study across three countries

EClinicalMedicine. 2023 Jun 22;61:102063. doi: 10.1016/j.eclinm.2023.102063. eCollection 2023 Jul. ABSTRACTBACKGROUND: Several psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown.

METHODS: In this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N = 875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N = 30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively.

FINDINGS: During up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79-1.98) and thereafter (1.37; 95% CI, 1.34-1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort.

INTERPRETATION: Independent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders.

FUNDING: This research was supported by EU Horizon 2020 Research and Innovation Action Grant, European Research Council Consolidator grant, Icelandic Research fund, Swedish Research Council, US NIMH, the Outstanding Clinical Discipline Project of Shanghai Pudong, the Fundamental Research Funds for the Central Universities, and the European Union through the European Regional Development Fund; the Research Council of Norway; the South-East Regional Health Authority, the Stiftelsen Kristian Gerhard Jebsen, and the EEA-RO-NO-2018-0535.

PMID:37425374 | PMC:PMC10329128 | DOI:10.1016/j.eclinm.2023.102063

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PubMed articles on: Cardio-Oncology

Penpulimab-induced complete atrioventricular block in a patient with metastatic renal cancer

HeartRhythm Case Rep. 2023 Apr 23;9(7):451-455. doi: 10.1016/j.hrcr.2023.04.007. eCollection 2023 Jul.

NO ABSTRACT

PMID:37492041 | PMC:PMC10363469 | DOI:10.1016/j.hrcr.2023.04.007

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PubMed articles on: Cardio-Oncology

Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer

Curr Cardiol Rep. 2023 Jul 25. doi: 10.1007/s11886-023-01909-3. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy.

RECENT FINDINGS: While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.

PMID:37490155 | DOI:10.1007/s11886-023-01909-3

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PubMed articles on: Cardio-Oncology

DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes

Noncoding RNA. 2023 Jul 13;9(4):39. doi: 10.3390/ncrna9040039.

ABSTRACT

Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called cardio-oncology. Doxorubicin is a chemotherapy drug widely used to treat cancer, such as bladder and breast cancer. However, this drug causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. Based on this evidence, we hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. To test this hypothesis, we analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. To confirm these findings, we treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB.

PMID:37489459 | PMC:PMC10366827 | DOI:10.3390/ncrna9040039

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PubMed articles on: Cardio-Oncology

Therapeutic potential of extracellular vesicles derived from cardiac progenitor cells in rodent models of chemotherapy-induced cardiomyopathy

Front Cardiovasc Med. 2023 Jul 7;10:1206279. doi: 10.3389/fcvm.2023.1206279. eCollection 2023.

ABSTRACT

BACKGROUND: Current treatments of chemotherapy-induced cardiomyopathy (CCM) are of limited efficacy. We assessed whether repeated intravenous injections of human extracellular vesicles from cardiac progenitor cells (EV-CPC) could represent a new therapeutic option and whether EV manufacturing according to a Good Manufacturing Practices (GMP)-compatible process did not impair their bioactivity.

METHODS: Immuno-competent mice received intra-peritoneal injections (IP) of doxorubicin (DOX) (4 mg/kg each; cumulative dose: 12 mg/kg) and were then intravenously (IV) injected three times with EV-CPC (total dose: 30 billion). Cardiac function was assessed 9-11 weeks later by cardiac magnetic resonance imaging (CMR) using strain as the primary end point. Then, immuno-competent rats received 5 IP injections of DOX (3 mg/kg each; cumulative dose 15 mg/kg) followed by 3 equal IV injections of GMP-EV (total dose: 100 billion). Cardiac function was assessed by two dimensional-echocardiography.

RESULTS: In the chronic mouse model of CCM, DOX + placebo-injected hearts incurred a significant decline in basal (global, epi- and endocardial) circumferential strain compared with sham DOX-untreated mice (p = 0.043, p= 0.042, p= 0.048 respectively) while EV-CPC preserved these indices. Global longitudinal strain followed a similar pattern. In the rat model, IV injections of GMP-EV also preserved left ventricular end-systolic and end-diastolic volumes compared with untreated controls.

CONCLUSIONS: Intravenously-injected extracellular vesicles derived from CPC have cardio-protective effects which may make them an attractive user-friendly option for the treatment of CCM.

PMID:37485274 | PMC:PMC10360184 | DOI:10.3389/fcvm.2023.1206279

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PubMed articles on: Cardio-Oncology

Clinical characteristics of patients referred to cardio-oncology clinic

Zhonghua Yi Xue Za Zhi. 2023 Jul 25;103(28):2183-2186. doi: 10.3760/cma.j.cn112137-20221108-02348.

ABSTRACT

To explore characteristics of outpatients in a single cardio-oncology clinic, patients visiting cardio-oncology clinic of Fuwai Hospital CAMS&PUMC (Beijing, China) from January 2020 to December 2021 were analyzed retrospectively. In total, 330 patients were included, the median age (Q1, Q3) was 58(46, 66) years, and there were 192 females (58.2%). The purposes for visit included an evaluation and treatment of cardiovascular adverse reactions (n=247, 74.8%), pre-antitumor therapy assessment (n=51, 15.5%), and management of primary or metastatic cardiac tumors (n=32, 9.7%). For patients with cardiovascular adverse reactions, the most common tumor type was breast cancer (n=88, 29.5%), followed by gastrointestinal cancer (n=70, 23.5%), and hematological cancers (n=62, 20.8%). Among them, 236 cases (95.5%) had received antitumor drugs in the past; 38 cases (15.4%) had a history of chest radiotherapy; some cases were complicated with hypertension (n=69, 23.2%) and/or hyperlipidemia (n=69, 23.2%); 42 cases (14.1%) had a history of coronary heart disease; and 16 cases (5.4%) were complicated with atrial fibrillation or flutter. Among 32 patients with cardiac tumors, 11 cases (34.4%) had primary malignant tumors; 6 cases (18.8%) had benign tumors; 2 cases (6.3%) had metastatic tumors; and 13 (40.6%) had unknown pathological types. This study explores the epidemiology of cardio-oncology in China and provides clinical insights for the future development of cardio-oncology. In the future, it is still necessary to study the benefits of cardio-oncology clinics and develop standardized indicators to evaluate their benefits.

PMID:37482731 | DOI:10.3760/cma.j.cn112137-20221108-02348

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PubMed articles on: Cardio-Oncology

Acetylcholine receptor agonists effectively attenuated multiple program cell death pathways and improved left ventricular function in trastuzumab-induced cardiotoxicity in rats

Life Sci. 2023 Jul 22;329:121971. doi: 10.1016/j.lfs.2023.121971. Online ahead of print.

 

ABSTRACT

BACKGROUND: This study aimed to investigate the prevalence, clinical characteristics and outcomes of type 2 myocardial infarction (T2AMI) in patients with versus without cancer.

METHODS: All hospitalizations with a primary discharge diagnosis of T2AMI were stratified according to cancer status (secondary diagnosis of any-cancer vs cancer-free) using data from the US National Inpatient Sample (2016-2019). The primary outcome was in-hospital all-cause mortality while secondary outcomes were in-hospital major adverse cardiovascular and cerebrovascular events (MACCE).

RESULTS: Among 61,305 included hospitalizations with primary diagnosis of T2AMI, 3745 (6.1%) were associated with a diagnosis of cancer. Patients with T2AMI and cancer presented more frequently with acute respiratory failure (23.2% vs 18.1%), acute pulmonary embolism (3.7% v 1.3%), major bleeding (6.8% vs 4.1%) and renal failure (51.0% vs 46.8%), compared to patients without. On adjusted analysis, diagnosis of cancer was associated with lower odds of invasive coronary angiography (aOR 0.75, 95% CI 0.60 to 0.93, p = 0.009) but greater odds of mortality (aOR 1.95, 95% C.I. 1.26-2.99 p = 0.002). Among the different types of cancer, adjusted risk of all-cause mortality was higher in patients with colorectal (aOR 4.17 95% CI 1.68-10.32, p = 0.002), lung (aOR 3.63, 95% CI 1.83-7.18, p < 0.001) and haematologic (aOR 2.48, 95% CI 1.22-5.05, p = 0.001) cancer.

CONCLUSIONS: Patients with cancer presenting with T2AMI have lower odds of management with invasive diagnostic coronary angiography and have higher rates of in-hospital all-cause death. Further studies are warranted to improve overall care and outcomes of cancer patients and cardiovascular diseases.

PMID:37442352 | DOI:10.1016/j.ijcard.2023.131154

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PubMed articles on: Cancer & VTE/PE

Incidence of venous thromboembolism in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy: Is it time for thromboprophylaxis?

Gynecol Oncol. 2023 Jul 11;176:36-42. doi: 10.1016/j.ygyno.2023.06.577. Online ahead of print.

ABSTRACT

OBJECTIVES: Our objectives were to determine the incidence, timing, and risk factors for venous thromboembolisms (VTEs) in patients with advanced stage epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT). We explored the utilization of direct-acting oral anticoagulants (DOACs) for VTE treatment.

METHODS: This retrospective cohort study included patients with advanced stage EOC receiving NACT followed by interval cytoreductive surgery (ICS) at a single institution. Risk factors were compared between patients with versus without VTE between EOC diagnosis and 180 days after ICS. Bleeding complications were compared between patient who received a DOAC versus non-DOAC.

RESULTS: VTE cases occurred amongst 33 of the 154 (21.4%) patients with 4 (2.6%) concurrent with EOC diagnosis, 9 (5.8%) between EOC diagnosis and NACT start, 13 (8.4%) between NACT start and ICS, and 7 (4.5%) within 180 days after ICS. There were no statistically significant differences in risk factors assessed (age, body mass index, functional status, histology, Khorana score, and smoking history) between patients with versus without VTE. Eleven patients (33.3%) received a DOAC for VTE treatment. There were no significant differences in number of intraoperative blood transfusions (p = 0.38), blood loss (p = 0.95), or bleeding complications (p = 0.53) between patients treated with a DOAC versus a non-DOAC.

CONCLUSION: There is a high incidence of VTE events (21.4%) in patients with advanced stage EOC undergoing NACT. Two-thirds of the VTEs may have been prevented with thromboprophylaxis as they occurred between EOC diagnosis and ICS. These data support consideration of thromboprophylaxis in all patients with advanced stage EOC undergoing NACT.

PMID:37442024 | DOI:10.1016/j.ygyno.2023.06.577

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PubMed articles on: Cancer & VTE/PE

A MALDI Mass Spectrometry Imaging Sample Preparation Method for Venous Thrombosis with Initial Lipid Characterization of Lab-Made and Murine Clots

J Am Soc Mass Spectrom. 2023 Jul 13. doi: 10.1021/jasms.3c00079. Online ahead of print.

ABSTRACT

Venous thromboembolism (VTE) and its complications affect over 900,000 people in the U.S. annually, with a third of cases resulting in fatality. Despite such a high incidence rate, venous thrombosis research has not led to significant changes in clinical treatments, with standard anti-coagulant therapy (heparin followed by a vitamin K antagonist) being used since the 1950s. Mechanical thrombectomy is an alternative strategy for treating venous thrombosis; however, clinical guidelines for patient selection have not been well-established or accepted. The effectiveness of both treatments is impacted by the heterogeneity of the thrombus, including the mechanical properties of its cellular components and its molecular makeup. A full understanding of the complex interplay between disease initiation and progression, biochemical molecular changes, tissue function, and mechanical properties calls for a multiplex and multiscale approach. In this work, we establish a protocol for using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to characterize spatial heterogeneity of biomolecules in lab-made blood clots and ex vivomurine thrombi. In this work, we compared (1) tissue preservation and cryosectioning methods, (2) various matrixes, 9-aminoacridine hydrochloride monohydrate (9AA), 2,5-dihydroxybenzoic acid (DHB), and alpha-cyano-4-hydroxycinnamic acid matrix (CHCA), (3) plasma-rich versus red-blood-cell rich lab-made blood clots, and (4) lab-made blood clots versus ex vivomurine thrombi. This project is the first step in our work to combine mass spectrometry imaging with biomechanical testing of blood clots to improve our understanding of VTE.

PMID:37439461 | DOI:10.1021/jasms.3c00079

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PubMed articles on: Cancer & VTE/PE

Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding

TH Open. 2023 Jul 10;7(3):e206-e216. doi: 10.1055/s-0043-1770783. eCollection 2023 Jul.

ABSTRACT

This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60-1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71-1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key PointsRivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.

PMID:37435565 | PMC:PMC10332896 | DOI:10.1055/s-0043-1770783

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PubMed articles on: Cancer & VTE/PE

Direct oral anticoagulants (DOACs) use for prolonged venous thromboembolism prophylaxis following surgery for gynaecological malignancies in Australia and New Zealand - A clinician survey

Aust N Z J Obstet Gynaecol. 2023 Jul 11. doi: 10.1111/ajo.13737. Online ahead of print.

ABSTRACT

BACKGROUND: Current international guidelines recommend 28 days of enoxaparin as venous thromboembolism (VTE) prophylaxis after surgery for gynaecologic cancer. Direct oral anticoagulants (DOACs) have been investigated as an alternative to enoxaparin for post-operative VTE prophylaxis. High-quality evidence to demonstrate safety and efficacy is lacking.

AIMS: We aim to investigate the current practice regarding VTE prophylaxis among gynaecological oncologists in Australia and New Zealand following laparotomy for gynaecological malignancy, in particular the use of DOACs for VTE prophylaxis.

MATERIALS AND METHODS: Sixty-seven practising gynaecologic oncologists (GO) were identified through Royal Australia and New Zealand College of Obstetricians and Gynaecologists database and emailed online surveys that asked about VTE prophylaxis practice and views of DOACs in this setting. Data were then collected through Survey Monkey and evaluated.

RESULTS: The majority (77.1%) routinely prescribed 28 days of enoxaparin following laparotomy for gynaecological malignancies. In clinical circumstance such as laparoscopy for gynaecological malignancies and surgery for vulva malignancies, there was variation in thromboprophylaxis practices. No GO reported routine use of DOACs in any clinical circumstance. There were 56% of GOs who used a DOAC in their practice at some point. Barriers to routine use of DOACs in current practice included insufficient evidence (68%), issue with cost (40.4%) and concerns about safety (29.7%).

CONCLUSIONS: Enoxaparin prescribed for 28 days remains the current clinical practice in preventing VTE following laparotomy for gynaecological malignancy. The main barrier to routine DOAC use as post-operative thromboprophylaxis is a lack of evidence which reflects the need for a larger prospective study.

PMID:37434425 | DOI:10.1111/ajo.13737

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PubMed articles on: Cancer & VTE/PE

Lung cancer presenting with acute myocardial infarction and pulmonary embolism within 1 month

SAGE Open Med Case Rep. 2023 Jul 6;11:2050313X231181979. doi: 10.1177/2050313X231181979. eCollection 2023.

ABSTRACT

Acute myocardial infarction and pulmonary embolism can have life-threatening consequences such as congestive heart and respiratory failure, respectively. Cancer patients are at great risk of both acute myocardial infarction and pulmonary embolism complications because the malignancy sparks the patient's blood hypercoagulable state. Nevertheless, the literature currently offers only a few reports on acute myocardial infarction associated with pulmonary embolism, and two of them occurred in the same cancer patient. Here, we present a case of a 60-year-old woman who had been diagnosed with lung cancer. She was admitted to the emergency department twice. She was diagnosed with acute myocardial infarction at her first admission, when she experienced sudden-onset chest pain. Electrocardiography showed ST-segment elevation in leads V1-V3 with inverted T wave and pathological Q wave, suggesting an acute myocardial infarction. Coronary angiography revealed a thrombus in the left anterior descending coronary artery, and thrombus aspiration was performed. After 1 month, she had an attack of pulmonary embolism with syncope upon the second admission. A computed tomographic pulmonary angiography showed branches of right and left pulmonary embolism. Anticoagulation and antiplatelet measures were taken. In this article, we discuss the relationship between cancer and thrombosis with a special focus on the conservative management strategy regarding anticoagulant and antiplatelet therapy in our case.

PMID:37434900 | PMC:PMC10331209 | DOI:10.1177/2050313X231181979

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PubMed articles on: Cancer & VTE/PE

COMPASS-CAT versus Khorana risk assessment model for predicting venous thromboembolic events in patients with non-small cell lung cancer on active treatment with chemotherapy and/or immunotherapy, the CK-RAM study

J Thromb Thrombolysis. 2023 Jul 11. doi: 10.1007/s11239-023-02860-4. Online ahead of print.

ABSTRACT

Cancer patients are at higher risk for venous thromboembolism (VTE). Several risk assessment models (RAM), including the Khorana and COMPASS-CAT, were developed to help predict the occurrence of VTE in cancer patients on active anti-cancer therapy. We aim to study the prevalence and predictors of VTE among patients with non-small cell lung cancer (NSCLC) and compare both RAMs in predicting VTE in patients with NSCLC were retrospectively reviewed. Variables known to increase the risk of VTE were collected and risk of VTE was assessed using both Khorana and COMPASS-CAT RAM. A total of 508 patients (mean age ± SD, 58.4 ± 12.2 years) were enrolled. Most (n = 357, 70.3%) patients had adenocarcinoma, and 333 (65.6%) patients had metastatic disease. VTE were confirmed in 76 (15.0%) patients. Rates were higher among patients with metastatic disease (19.8%, p < 0.001), adenocarcinoma (17.4%, p = 0.01) and those treated with immunotherapy (23.5%, p = 0.014). VTE rates were 21.2%, 14.1% and 13.9% among those with high (n = 66), intermediate (n = 341) and low (n = 101) Khorana risk scores, respectively (p = 0.126). On the other hand, 190 (37.4%) were classified as high risk by the COMPASS-CAT RAM; 52 (27.4%) of them had VTE compared to 24 (7.5%) of the remaining 318 (62.6%) classified as Low/Intermediate risk level, p < 0.001. In conclusion, patients with NSCLC are at high risk for VTE, especially those with adenocarcinoma, metastatic disease and when treated with immunotherapy. Compared to Khorana RAM, COMPASS-CAT RAM was better in identifying more patients in high-risk group, with higher VTE rate.

PMID:37430158 | DOI:10.1007/s11239-023-02860-4

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PubMed articles on: Cancer & VTE/PE

Intravenous tranexamic acid is associated with an increased risk of pulmonary embolism following sarcoma resection

J Surg Oncol. 2023 Jul 10. doi: 10.1002/jso.27391. Online ahead of print.

ABSTRACT

INTRODUCTION: Tranexamic acid (TXA) is an antifibrinolytic drug that has been shown to reduce blood loss following surgery. The use of TXA during orthopedic procedures has gained widespread acceptance, with multiple clinical studies demonstrating no increase in thrombotic complications. While TXA has been shown to be safe and effective for several orthopedic procedures, its use in orthopedic sarcoma surgery is not well established. Cancer-associated thrombosis remains a significant cause of morbidity and mortality in patients with sarcoma. It is unknown if intraoperative TXA use will increase the risk of developing a postoperative thrombotic complication in this population. This study aimed to compare the risk of postoperative thrombotic complications in patients who received TXA during sarcoma resection to patients who did not receive TXA.

METHODS: A retrospective review was performed of 1099 patients who underwent resection of a soft tissue or bone sarcoma at our institution between 2010 and 2021. Baseline demographics and postoperative outcomes were compared between patients who did and did not receive intraoperative TXA. We evaluated 90-day complication rates, including: deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), cerebrovascular accident (CVA), and mortality.

RESULTS: TXA was used more commonly for bone tumors (p < 0.001), tumors located in the pelvis (p = 0.004), and larger tumors (p < 0.001). Patients who received intraoperative TXA were associated with a significant increase in developing a postoperative DVT (odds ratio [OR]: 2.22, p = 0.036) and PE (OR: 4.62, p < 0.001), but had no increase in CVA, MI, or mortality (all p > 0.05) within 90 days of surgery, following univariate analysis. Multivariable analysis confirmed that TXA was independently associated with developing a postoperative PE (OR: 10.64, 95% confidence interval: 2.23-50.86, p = 0.003). We found no association with DVT, MI, CVA, or mortality within 90 days postoperatively, following intraoperative TXA use.

CONCLUSION: Our results demonstrate a higher associated risk of PE following TXA use in sarcoma surgery and caution is warranted with TXA use in this patient population.

PMID:37428014 | DOI:10.1002/jso.27391

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PubMed articles on: Cancer & VTE/PE

Stratification of Risk Factors of Lung Cancer-Associated Venous Thromboembolism and Determining the Critical Point for Preemptive Intervention: A Systematic Review With Meta-analysis

Clin Med Insights Oncol. 2023 Jun 28;17:11795549231175221. doi: 10.1177/11795549231175221. eCollection 2023.

ABSTRACT

BACKGROUND: Several biomarkers or risk factors have been identified and several prediction models exist. The major limitations inherent in these models include cost-ineffectiveness and lack of systematic stratification of risk factors resulting in the inclusion of clinically insignificant biomarkers in the models. This review aimed to systematically stratify the risk factors of lung cancer-associated venous thromboembolism (VTE) and determine the critical point for preemptive intervention.

METHODS: This systematic review was structured as per the Preferred Reporting Item for Systematic Reviews and Meta-analyses. We searched MEDLINE, PubMed, Cochrane Library, CINAHL, Academic Search Complete, and PsycINFO from the onset to June 2022. We included studies that reported the risk factors of lung cancer-associated VTE and corresponding risk estimates, irrespective of treatment status but studies were excluded if patients were on anti-VTE medications. We employed random effects models of meta-analysis and computed risk stability index and risk weight (Rw) to achieve the review objectives. The review protocol is registered with PROSPERO (CRD42022336476).

RESULTS: The clinically significant risk factors of VTE in lung cancer patients were D-dimer (odds ratio [OR] = 5.510, 95% CI = 2.6-11.7; Rw = 5.0), albumin (OR = 2.2, 95% CI = 1.0-4.8; Rw = 1.79), leukocyte (OR = 2.48, 95% CI = 1.9-3.2; Rw = 1.77), histological type (OR = 1.69 , 95% CI = 1.2-2.4; Rw = 1.3), age (OR = 1.56; Rw = 0.99), and hemoglobin (OR = 1.85, 95% CI = 1.3-2.6; Rw = 0.92). Based on the distribution of Rw across risk factors, the critical point (upper third of the upper quartile class) was 4.5 and may mark the point at which preemptive intervention should be commenced.

CONCLUSIONS: Targeted screening for VTE in lung cancer patients could be patient-specific and should be based on a combination of the most significant risk factors required to meet the critical point, provided that such a combination is affordable as illustrated in the ALBAH model.

REGISTRATION: The review protocol is registered with PROSPERO (ID: CRD42022336476).

PMID:37426681 | PMC:PMC10328178 | DOI:10.1177/11795549231175221

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PubMed articles on: Cancer & VTE/PE

Risk assessment for postoperative venous thromboembolism using the modified Caprini risk assessment model in lung cancer

J Thorac Dis. 2023 Jun 30;15(6):3386-3396. doi: 10.21037/jtd-23-776. Epub 2023 Jun 26.

 

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: Cancer & VTE/PE

Acute pulmonary tumour embolism and right systolic dysfunction in a hidden intrahepatic cholangiocarcinoma: case report

Eur Heart J Case Rep. 2023 Jun 28;7(7):ytad291. doi: 10.1093/ehjcr/ytad291. eCollection 2023 Jul.

ABSTRACT

BACKGROUND: Pulmonary tumour embolism is a rare entity that can arise from a wide variety of neoplasms. It can initially manifest as a pulmonary embolism with right heart failure and be refractory to thrombolytic therapy. Cholangiocarcinoma is a rare malignancy that arises from the epithelium of the biliary tree, representing 3% of all the gastrointestinal malignancies, being the intrahepatic cholangiocarcinoma the second most common liver tumour after hepatocellular carcinoma.

CASE SUMMARY: This case regards a patient that presented to our centre with acute pulmonary embolism, deep vein thrombosis, and unrevealing previous medical history. Imaging studies revealed pulmonary embolism, an ovarian mass, and multiple hepatic hypodensities. Throughout the hospitalization, the patient's haemodynamic state and right heart failure worsened, eventually leading to multi-organ failure and death. Post-mortem evaluation revealed cholangiocarcinoma cells on the pulmonary arteries.

DISCUSSION: Pulmonary tumour embolism is a rare pathology that can present with acute right heart failure. The diagnosis of occult cancer can be challenging, and the appropriate treatment for this entity remains an unexplored subject.

PMID:37457051 | PMC:PMC10347672 | DOI:10.1093/ehjcr/ytad291

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PubMed articles on: Cancer & VTE/PE

Optimal D-dimer cut-off values for diagnosing deep vein thrombosis in patients with comorbid malignancies

Ann Vasc Surg. 2023 Jul 14:S0890-5096(23)00513-7. doi: 10.1016/j.avsg.2023.06.033. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with malignancy are at high risk of VTE, and early diagnosis is important. The Khorana score is known as a risk assessment for cancer-related thrombosis during chemotherapy, but there are still few reports on its diagnostic potential, the optimal D-dimer cut-off values for indications other than chemotherapy and the use of the Khorana score in combination with D-dimers. In this study, we examined the clinical appropriateness of increasing the D-dimer cut-off value.

METHODS: We retrospectively studied 208 malignancies out of 556 patients who underwent lower extremity venous ultrasonography at our hospital over a two-year period from January 2018 to December 2019. The optimal D-dimer cut-off value for predicting DVT in patients with malignancy was calculated by the Youden index. The usefulness of the Khorana score alone and the model combining the Khorana score with D-dimer for predicting DVT diagnosis was compared using receiver operating characteristic analysis.

RESULTS: Of 208 eligible patients, 59 (28.4%) had confirmed DVT. The optimal D- dimer cut-off value for predicting DVT comorbidity in patients with malignancy was 3.96 μg/mL. When the new D-dimer cut-off value was set at 4.0 μg/mL, the odds ratio for DVT diagnosis was 4.23 (95% CI 2.10-8.55, p<0.001),

CONCLUSIONS: The optimal D-dimer cut-off value for the diagnosis of DVT in patients with malignancy was 4.0 μg/mL. It was also suggested that the combination of the Khorana score with the D-dimer level was more accurate in diagnosing DVT than the Khorana score alone.

PMID:37454901 | DOI:10.1016/j.avsg.2023.06.033

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PubMed articles on: Cancer & VTE/PE

High-intensity interval training and thromboembolic events during chemotherapy for testicular cancer: a retrospective analysis from the Body & Cancer cohort

Acta Oncol. 2023 Jun;62(6):666-672. doi: 10.1080/0284186X.2023.2225145. Epub 2023 Jul 14.

ABSTRACT

Background:Men with testicular cancer receiving platinum-based chemotherapy have an increased risk of thromboembolic events, with incidence rates between 8-24%. A recent trial evaluating the effect of high-intensity interval training (HIIT) prematurely closed as three out of nine participants (33%) in the intervention group developed a thromboembolic event. The purpose of this retrospective cohort study was: 1) (primary) to evaluate the incidence of thromboembolic events in men receiving chemotherapy for testicular cancer who had participated in HIIT during a 6-week exercise program (Body & Cancer) 2) to describe the feasibility of this program.Material and methods: Forty men who had participated in at least one HIIT session from February 2007 to February 2020 were included. Electronic medical records were searched for incident thromboembolic events (arterial and venous) during Body & Cancerand up to one-year post-chemotherapy. Attendance, cardiorespiratory fitness (VO2-peak), and upper and lower extremity muscular strength (1 repetition maximum (RM)) were obtained from the Body & Cancerdatabase.Results: One participant developed a thromboembolic event during Body & Cancer. No participants developed a thromboembolic event in the follow-up period. In all, data represent 160 HIIT sessions with a median attendance of eight sessions [range 1-19]. Statistically significant increases in upper and lower extremity strength were observed (8.6 (4.2 to 13.0) and 26.0 (14.9 to 37.0) kg, respectively). No significant increase in cardiorespiratory fitness was found (0.14 (-0.03 to 0.31) l/min).Conclusion: While conclusions on the safety of HIIT cannot be drawn, data from the present study do not support previous findings cautioning avoidance of HIIT due to a possible added risk of thromboembolic events in men receiving platinum-based chemotherapy for testicular cancer. Considering the potential for positive effects on cardiovascular outcomes associated with HIIT, future studies with robust design should be performed in this population to confirm these observations.

PMID:37450654 | DOI:10.1080/0284186X.2023.2225145

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PubMed articles on: Cancer & VTE/PE

The impact of body mass index on oncoplastic breast surgery: A multicenter analysis

J Surg Oncol. 2023 Jul 13. doi: 10.1002/jso.27397. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity has nearly tripled in the last 50 years. During the last decades, oncoplastic breast surgery has become an important choice in the surgical treatment of breast cancer. An association exists between higher body mass index (BMI) and wound complications for major operations, but there is scarce literature on oncoplastic surgery. Hence, our aim was to compare the complication rates among patients who underwent oncoplastic surgery, stratified by BMI.

METHODS: Patient data were analyzed from the National Surgical Quality Improvement Program database (NSQIP) for oncoplastic breast procedures (2005-2020). Patients were stratified according to World Health Organization obesity classifications. Multivariate logistic regression was performed to assess risk factors for complications (overall, operative, and wound-related).

RESULTS: From a total of 6887 patients who underwent oncoplastic surgery, 4229 patients were nonobese, 1380 had Class 1 obesity (BMI: 30 to <352 ), 737 Class 2 obesity (BMI: 35 to <402 ), and 541 Class 3 obesity (BMI: ≥ 40 kg/m2 ). Greater operative time was found according to higher BMI (p < 0.001). Multivariate analysis adjusted for baseline characteristics showed that patients with obesity Class 2 (odds ratio [OR] = 1.51, 95% confidence interval [CI]: 1.03-2.23, p = 0.037) and 3 (OR = 1.87, 95% CI 1.24-2.83, p = 0.003) had increased risk of overall and wound complications compared with Nonobese patients. Comparing obese with nonobese patients, there were no differences in rates of deep SSI, organ/space SSI, pneumonia, reintubation, pulmonary embolism, deep vein thrombosis, urinary tract infection, stroke, bleeding, postoperative sepsis, length of stay, and readmission.

CONCLUSIONS: Oncoplastic surgery is a safe procedure for most patients. However, caution should be exercised when performing oncoplastic surgery for patients with Class 2 or 3 obesity (BMI ≥ 35 kg/m2 ), given there was a higher rate of overall and wound-specific complications, compared with patients who were not obese or had Class 1 obesity.

PMID:37448232 | DOI:10.1002/jso.27397

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PubMed articles on: Cancer & VTE/PE

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial

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PubMed articles on: Cancer & VTE/PE

Clinical presentations of acute pulmonary embolism: A retrospective cohort study

Medicine (Baltimore). 2023 Jul 14;102(28):e34224. doi: 10.1097/MD.0000000000034224.

ABSTRACT

We aimed to investigate whether the unusual clinical presentation of pulmonary embolism (PE) varies by the type of provocation. In this retrospective cohort study, we examined the electronic health records (EHR) records of all patients diagnosed with PE (upon presentation or during hospitalization) presented to our tertiary hospital during 2014 to 2019. Inclusion criteria were the diagnosis of acute PE and age above 18 years. Excluded were all patients to whom complete EHR were not available. The primary outcome was the main presenting symptom, categorized by a multidisciplinary consensus expert committee as either typical or atypical of PE. Comorbidities, vital signs, medications and laboratory results on presentations were recorded. 591 patients were included in the final analysis. Dyspnea was significantly less common and hemoptysis and chest pain more common in the unprovoked PE group (35%, 5%, and 25%, respectively) compared with nonmalignant (42.6%, 0%, and 16.3%) and malignancy-associated (47.7%, 0.9%, and 8.2%) PE (Pv = 0.02, 0.002 and 0.001, respectively). No recorded symptoms were the third most common presentation overall, accounting for a significantly (Pv < 0.001) higher proportion of PE patients with malignancy (19%) whereas atypical presentation was the hallmark of patients with nonmalignant provokation (19.7%) (Pv = 0.005). Accounting for multiple potential confounders, the risk of atypical or asymptomatic presentation was higher with lower heart rates (RR = 0.974 95%C.I. [0.957-0.990]) and higher pulse oximetry saturation (RR = 1.114 95%CI [1.034-1.201]). The clinical presentation of PE varies with different types of provoking factors, with atypical presentation most common in nonmalignant provocation and asymptomatic presentation most prevalent in patients with underlying malignancy. Further studies are needed to determine the effect of said variance on long term clinical outcomes.

PMID:37443506 | PMC:PMC10344497 | DOI:10.1097/MD.0000000000034224

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PubMed articles on: Cancer & VTE/PE

Markers of right ventricular dysfunction predict 30-day adverse prognosis of pulmonary embolism on pulmonary computed tomographic angiography

Medicine (Baltimore). 2023 Jul 14;102(28):e34304. doi: 10.1097/MD.0000000000034304.

ABSTRACT

To investigate the value of parameters of the pulmonary artery and right ventricular function in predicting the 30-day poor prognosis of patients with acute pulmonary embolism (APE). The heart rate, respiratory rate, systolic blood pressure, Wells score for APE, history of recent operation or immobilization, history of cancer, respiratory failure, smoking were significantly (P < .05) different among the control, good prognosis, and poor prognosis groups. The maximal short diameter of the right and left ventricle (RVD/LVD) ratio (P < .001) and left pulmonary artery (LPA) (P = .01) were significantly different between the good and poor prognosis groups. Systolic blood pressure (odds ratio [OR]: 0.98, P = .045) and the RVD/LVD ratio (OR: 12.57, P = .02) were significant independent risk factors for poor prognosis. The risk for poor prognosis significantly increased when the RVD/LVD ratio was >1.11 (cutoff value) with the area under the curve (AUC) of 0.71 (95% confidence interval [CI]: 0.61-0.80, P < .001). LPA (OR: 9.12, P = .01) and RVD/LVD (OR: 4.62, P = .012) were the significant independent risk factors for poor prognosis in the central pulmonary embolism. The LPA of 2.1 cm had the highest predictive value for poor prognosis in the central APE (AUC: 0.68; sensitivity 84.6%; specificity 53.1%). The RVD/LVD ratio and systolic blood pressure are significant risk factors for short-term prognosis in patients with APE. When the LPA is >2.1 cm in the central APE or the RVD/LVD is >1.11, the risk of poor prognosis increases, which can be used as important indicators for predicting the prognosis of patients with APE. Two hundred forty-three APE patients and 61 patients without APE who underwent computed tomographic pulmonary angiography (CTPA) were retrospectively enrolled as the experimental and the control group, respectively. APE patients who were followed up at the 30-day time point were divided into the good prognosis (n = 195) and poor prognosis group (n = 32). The main pulmonary artery (MPA) to the aorta (AO) ratio, maximal diameter of the LPA and right pulmonary artery (RPA), ratio of the RVD/LVD and the height and volume of the pulmonary artery (PAh and PAV, respectively) were analyzed after indexing to the body surface area.

PMID:37443496 | PMC:PMC10344539 | DOI:10.1097/MD.0000000000034304

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PubMed articles on: Cancer & VTE/PE

Prevalence and outcomes of type 2 myocardial infarction in patients with cancer: A retrospective analysis from the National Inpatient Sample dataset

Int J Cardiol. 2023 Jul 11:131154. doi: 10.1016/j.ijcard.2023.131154. Online ahead of print.