High-intermediate Risk Research Articles

Prognostic value of p14ARF expression in diffuse large B cell lymphoma

The p14ARF-Hdm2-p53 signaling pathway targets tumor growth suppression, inhibits clonal proliferation, and maintains genome stability. It is inactivated in most human malignancies. The p14ARF protein is one of the main participants in the cascade. The aim of the study was to determine the prognostic value of the number of p14ARF-expressing tumor cells in biopsies of patients with diffuse large B cell lymphoma (DLBCL). Material and methods. The formalin-fixed paraffin embedded samples of tumor tissue of 104 patients with newly diagnosed DLBCL were included to the study. The relative number of cells expressing p14ARF was determined by immunohistochemical and morphometric methods. Differences in the content of p14ARF-positive tumor cells between groups of patients divided according to clinical and laboratory parameters were determined using the Mann–Whitney U test. Prediction of an unfavorable response to therapy was carried out using binary logistic regression with calculation of the odds ratio and 95 % confidence interval; variables were selected using Wald backward elimination method. The risk of an event occurring was calculated using Cox regression analysis. Results. The content of p14ARF-positive cells is higher in tumor biopsies of patients with high and high-intermediate risk according to the international prognostic index than in patients with low and lowintermediate risk. A relationship between an increase in the number of p14ARF-positive tumor cells, the absence of a complete response to first-line R-CHOP therapy, and an increased risk of death in patients with DLBCL has been established. Conclusions. The studied marker p14ARF can be used as an additional morphological predictor of the unfavorable course of DLBCL.

Treatment of high- and intermediate-high-risk pulmonary embolism by the Pulmonary Embolism Response Team: Focus on catheter-directed therapies.

Multidisciplinary Pulmonary Embolism Response Teams (PERTs) were established to individualize the treatment of high-risk (HR) and intermediate-high-risk (IHR) pulmonary embolism (PE) patients, which pose a challenge in clinical practice. We retrospectively collected the data of all HR and IHR acute PE patients consulted by PERT CELZAT between September 2017 and October 2022. The patient population was divided into four different treatment methods: anticoagulation alone (AC), systemic thrombolysis (ST), surgical embolectomy (SE), and catheter-directed therapies (CDTx). Baseline clinical characteristics, risk stratification, PE severity parameters, and treatment outcomes were compared between the four groups. Of the 110 patients with HR and IHR PE, 67 (61%) patients were treated with AC only, 11 (10%) with ST, 15 (14%) underwent SE, and 17 (15%) were treated with CTDx. The most common treatment option in the HR group was reperfusion therapy, used in 20/24 (83%) cases, including ST in 7 (29%) patients, SE in 5 (21%) patients, and CTDx in 8 (33%) patients. In contrast, IHR patients were treated with AC alone in 63/86 (73%) cases. The in-hospital mortality rate was 9/24 (37.5%) in the HR group and 4/86 (4.7%) in the IHR group. The number of advanced procedures aimed at reperfusion was substantially higher in the HR group than in the IHR PE group. Despite the common use of advanced reperfusion techniques in the HR group, patient mortality remained high. There is a need further to optimize the treatment of patients with HR PE to improve outcomes.

Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

ObjectivesNodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition.Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. MethodsClinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. ResultsFifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case.Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT.Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. ConclusionsIn this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

Outcomes With Hybrid Catheter-Directed Therapy Compared With Aspiration Thrombectomy for Patients With Intermediate-High Risk Pulmonary Embolism.

Intermediate-high-risk pulmonary embolism (IHR PE) is a challenging form of embolism obstruction that causes right ventricular(RV) dysfunction. The optimal management of IHR PE has not been established. This single-center prospective, observational study aimed to evaluate the efficacy and safety of complex catheter-directedtherapy (CDT)-catheter-directed mechanical aspiration thrombectomy (CDMT) supplemented with catheter-directed thrombolysis (hybrid CDT)in comparison to CDMT alone for IHR PE. A propensity score based on the pulmonary embolism severity index class and Miller obstruction index (MOI) was calculated, and 21 hybrid CDT cases (mean age 54.8 (14.7) years, 9/21 women) were matched with 21 CDMT cases (mean age 58.8 (14.9) years, 13/21 women). The baseline demographics, clinical,and treatment characteristics were analyzed. No significant differences were detected regarding baseline demographics and PE severity parameters. Hybrid CDT demonstrated a higher reduction in mean pulmonary artery pressure (mPAP) (hybrid CDT: median mPAP reduction 8mmHg (IQR: 6-10mmHg) vs CDMT: median mPAP reduction 6mmHg (IQR: 4-7mmHg); P = 0.019), MOI score (hybrid CDT: median change - 5 points (IQR: 5-6 points) vs CDMT median change - 3 points (IQR: 3-5 points); P = 0.019), and median RV: left ventricular ratio (hybrid CDT: median change 0.4 (IQR: 0.3-0.45) vs CDMT median change 0.26 (IQR: 0.2-0.4); P = 0.007). No major bleeding was observed. Both the hybrid CDT and CDMT alone treatments are safe and effective in managing IHR PE. Hybrid CDT is a promising technique for the management of IHR PE with insufficient thrombus load reduction by CDMT. NCT0447356-registration date 16 July 2020.

Оптимизация терапии у пациентов с впервые диагностированной диффузной В-крупноклеточной лимфомой: эффективность и безопасность программы R-SD-EPOCH ± HDMTX в рамках одноцентрового нерандомизированного проспективного клинического исследования (предварительные результаты)

Оптимизация терапии у пациентов с впервые диагностированной диффузной В-крупноклеточной лимфомой: эффективность и безопасность программы R-SD-EPOCH ± HDMTX в рамках одноцентрового нерандомизированного проспективного клинического исследования (предварительные результаты)

SPO2/FIO2 and early echocardiographic findings on presentation to guide high risk and intermediate-high risk acute pulmonary embolism patients

SPO2/FIO2 and early echocardiographic findings on presentation to guide high risk and intermediate-high risk acute pulmonary embolism patients

Comparison of Treatment Approaches and Subsequent Outcomes within a Pulmonary Embolism Response Team Registry.

To characterize the association between pulmonary embolism (PE) severity and bleeding risk with treatment approaches, outcomes, and complications. Secondary analysis of an 11-hospital registry of adult ED patients treated by a PE response team (August 2016-November 2022). Predictors were PE severity and bleeding risk. The primary outcome was treatment approach: anticoagulation monotherapy vs. advanced intervention (categorized as "immediate" or "delayed" based on whether the intervention was received within 12 hours of PE diagnosis or not). Secondary outcomes were death, clinical deterioration, and major bleeding. Of the 1832 patients, 139 (7.6%), 977 (53.3%), and 9 (0.5%) were classified as high-risk, intermediate-high, intermediate-low, and low-risk severity, respectively. There were 94 deaths (5.1%) and 218 patients (11.9%) had one or more clinical deterioration events. Advanced interventions were administered to 86 (61.9%), 195 (27.6%), and 109 (11.2%) patients with high-risk, intermediate-high, and intermediate-low severity, respectively.Major bleeding occurred in 61/1440 (4.2%) on ACm versus 169/392 (7.6%) with advanced interventions (p <0.001): bleeding withcatheter-directed thrombolysiswas 19/145 (13.1%) versus 33/154(21.4%) with systemic thrombolysis,p= 0.07. High risk was twice as strong as intermediate-high risk for association with advanced intervention (OR: 5.3 (4.2 and 6.9) vs. 1.9 (1.6 and 2.2)). High risk (OR: 56.3 (32.0 and 99.2) and intermediate-high risk (OR: 2.6 (1.7 and 4.0)) were strong predictors of clinical deterioration. Major bleeding was significantly associated with advanced interventions (OR: 5.2 (3.5 and 7.8) for immediate, 3.3 (1.8 and 6.2)) for delayed, and high-risk PE severity (OR: 3.4 (1.9 and 5.8)). Advanced intervention use was associated with high-acuity patients experiencing death, clinical deterioration, and major bleeding with a trend towards less bleeding with catheter-directed interventions versus systemic thrombolysis.

Abstract 6223: Personalized MRI-informed forecasting of prostate cancer progression during active surveillance

Abstract Low and intermediate-risk prostate cancer (PCa) patients are eligible for active surveillance (AS), whereby treatment is delayed until progression to higher-risk disease is detected via longitudinal multiparametric magnetic resonance imaging (mpMRI) scans, biopsies, and prostate specific antigen (PSA) tests. However, AS relies on a population-based observational paradigm in which standard testing frequencies may not match the patient’s tumor dynamics, resulting in a delayed diagnosis of progressive disease. To address these issues, we propose to advance AS towards a patient-specific predictive paradigm by leveraging computational tumor forecasts obtained with a biomechanistic model informed by mpMRI and clinical data collected during standard AS. Here, we present a retrospective study with n = 16 PCa cases. All patients had three mpMRI scans obtained over 2.6 to 5.6 years during AS. Our biomechanistic model describes PCa growth in terms of the dynamics of tumor cell density as a combination of tumor cell mobility and net proliferation. The model is defined on the patient’s prostate geometry, which is segmented on T2-weighted MRI data. Tumor cell density estimates are derived from apparent diffusion coefficient (ADC) maps obtained from diffusion-weighted MRI data. To facilitate modeling, the longitudinal imaging datasets are non-rigidly co-registered for each patient. We initialize the model with the tumor cell density map obtained from the ADC map of the first scan. The model is parameterized by minimizing the model-data mismatch in tumor cell density at the second scan date, and then we perform a tumor forecast up to the third scan date. Finally, we build a logistic classifier from a panel of model-based biomarkers calculated from the personalized model forecasts (e.g., tumor volume, total proliferation activity) at the times of histopathological assessment (i.e., biopsy, surgery) to classify tumors as low risk (Gleason score 3+3, n = 16) or intermediate-high risk (Gleason score ≥ 3+4, n = 15). We obtained a concordance correlation coefficient (CCC) for tumor volume of 0.89 at both model calibration and forecasting horizon. The spatial fit of tumor cell density yielded a median Dice score and CCC of 0.80 and 0.59 at the second mpMRI date, and of 0.76 and 0.60 at the third mpMRI date, respectively. The logistic classifier of PCa risk yielded an area under the ROC curve of 0.90 and operates at optimal sensitivity, specificity, and accuracy of 86.7%, 93.8%, and 90.3%, respectively. The time trajectories of PCa risk obtained from the temporal predictions of the model-based biomarkers enabled identification of PCa progression by more than 1 year. Thus, while further development and validation over larger cohorts are required, these results suggest that our forecasting technology is a promising tool to predict PCa progression in AS and, hence, optimally guide monitoring and treatment decisions during AS. Citation Format: Guillermo Lorenzo Gomez, Chengyue Wu, Joshua P. Yung, John F. Ward, Hector Gomez, Alessandro Reali, Thomas E. Yankeelov, Aradhana M. Venkatesan, Thomas J. Hughes. Personalized MRI-informed forecasting of prostate cancer progression during active surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6223.

Abstract 6416: Early stage endometrioid endometrial cancer recurrence risk stratification using a machine learning RNA-seq gene expression signature

Abstract Endometrioid endometrial cancer (EEC) adjuvant therapy decisions rely on risk stratification using histology, grade, stage, and lymphovascular space invasion (LVSI). Recently, molecular classification systems originating from TCGA, evaluated in GOG-210 and PORTEC-3 defined four prognostic subtypes based on POLE, MSI-H/MMR-D, and p53 alterations. Although valuable, this molecular approach still has significant limitations such as applicability to the majority of EEC patients categorized as no-specific molecular profile (NSMP) and the potential need to resolve pathogenic and prognostic heterogeneity within MMR-D, and TP53 subtypes. These unmet needs were key motivators for Tempus to develop a molecular classifier predicting distant recurrence risk in early-stage EEC with a focus on high intermediate-risk (HIR) patients. The RNA-seq-based gene expression profiler (GEP) was trained using a machine-learning pipeline with TCGA data which resulted in a 24 gene signature that classifies EEC patients as molecular risk (MR) high or low (MR-high, MR-low). The GEP MR test was then evaluated on a de-identified cohort of EEC patients (N=1037) from Tempus to test associations with known pathologic or molecular prognostic features. The GEP-MR risk predictor showed significant enrichment of MR high-risk in G3 versus G1/2 histology (p-value &amp;lt; 5e-8). A high correlation was found between the MR score and copy number alteration score (t-test p-value &amp;lt; 1e-5). Next, a clinical evaluation was performed in an early-stage EEC case-control cohort of patients with documented recurrence or no recurrence event at four years (N=109), from Stanford. In the entire cohort, the MR-high group had a significantly higher rate of distant recurrence in comparison to the MR-low group (HR=4.8, N=109). Next, we performed a subgroup analysis in the clinically important HIR patients. In this subgroup, the MR-high group had a significantly higher rate of distant recurrence in comparison to the MR-low group (HR=8.0, N=56). Lastly, given the significance of genomic biomarkers in the evolution of EEC FIGO staging, we stratified outcomes by the established TCGA subtypes as a reference standard and performed a subgroup analysis in patients classified as having no specific molecular profile (NSMP). Among patients who were NSMP, the MR-high group showed a significantly higher rate of distant recurrence in comparison to the MR-low group (HR=7.92, N=67). These evaluation studies demonstrate the performance of the GEP MR test in early-stage EEC distant recurrence risk stratification, specifically HIR patients, necessitating further studies to validate the test for clinical use in informing adjuvant clinical management. Citation Format: Rafi Pelossof, Talal Ahmed, Seung Won Hyun, Chithra Sangali, Ben Terdich, Calvin Chao, Michael Toboni, Casey Cosgrove, Elizabeth Kidd, Brook Howitt, Timothy Taxter. Early stage endometrioid endometrial cancer recurrence risk stratification using a machine learning RNA-seq gene expression signature [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6416.

Efficacy Assessment of Post-nephrectomy Adjuvant Therapies in Patients with Renal Cell Carcinoma.

The objective of our study was to integrate the efficacy results of post-nephrectomy adjuvant therapies in renal cell carcinoma (RCC) patients with risk of recurrence, and attempt to determine the optimal intervention choice. We performed standard meta-analysis procedures in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Embase, and Cochrane Library databases were searched from inception to 22 September 2022. Randomized controlled trials reporting overall survival (OS) or disease-free survival (DFS) of adjuvant therapies, including immune checkpoint inhibitors (ICIs) and targeted therapies, in adult post-nephrectomy RCC patients were eligible for inclusion. Seven studies involving 7548 participants were included in our analyses. In contrast with placebo, DFS benefit with ICIs was only observed in female RCC patients and RCC patients with high programmed death-ligand 1 (PD-L1) expression (≥ 1%), sarcomatoid features, and M0 intermediate-high risk. Network meta-analyses demonstrated that pembrolizumab exhibited both DFS and OS benefit compared with placebo, sunitinib, sorafenib, and girentuximab, and only DFS benefit compared with atezolizumab and nivolumab plus ipilimumab. Our results suggest that post-nephrectomy RCC patients with sarcomatoid differentiation and high PD-L1 expression were more responsive to ICIs. Furthermore, pembrolizumab monotherapy exhibited superior DFS and OS results over other adjuvant therapies.

High-dose methotrexate pharmacokinetics and its impact on prognosis of paediatric acute lymphoblastic leukaemia patients: A population pharmacokinetic study.

This study delivers a comprehensive evaluation of the efficacy and pharmacokinetics of high-dose methotrexate (HDMTX) in a large cohort of Chinese paediatric acute lymphoblastic leukaemia patients. A total of 533 patients were included in the prognostic analysis. An association was observed between lower steady-state MTX concentrations (<56 μmol/L) and poorer outcomes in intermediate-/high-risk (IR/HR) patients. Subgroup analysis further revealed that this relationship between concentrations and prognosis was even more pronounced in patients with MLL rearrangements. In contrast, such an association did not emerge within the low-risk patient group. Additionally, utilizing population pharmacokinetic modelling (6051 concentrations from 815 patients), we identified the significant impact of physiological maturation, estimated glomerular filtration rate, sex and concurrent dasatinib administration on MTX pharmacokinetics. Simulation-based recommendations include a reduced dosage regimen for those with renal insufficiency and a specific 200 mg/kg dosage for infants under 1 year. The findings underscore the critical role of HDMTX in treating IR/HR populations and call for a reassessment of its application in lower-risk groups. An individualized pharmacokinetic dosage regimen could achieve the most optimal results, ensuring the largest proportion of steady-state concentrations within the optimal range.

SADDLE PULMONARY EMBOLISM: A RARE CASE OF PROXIMAL PULMONARY EMBOLISM

Saddle pulmonary embolism is defined as the presence of a visible thrombus located at the bifurcation of the pulmonary artery trunkshowing an aspect of saddle on a chest contrasted tomography scan. This is a rare case occurring in only 5.2% of patients with pulmonary embolism. (1)We report the case of a 93-year-old female patient who had no thrombo-embolic past medical history, she had got the gall bladder operation 25 years ago. The patient was admitted for a dyspnea associated with a chest pain and desaturation related to a pulmonary embolism confirmed on a chest contrasted tomography scan that has shown a typical aspect of saddle pulmonary embolism. Our patient was stable on hemodynamic state and had a high intermediate prognostic risk score. She was managed at the cardiac intensive care unit with anticoagulation that improved her clinically.

The pathogenesis of cancer-associated thrombosis.

Patients with cancer have a higher risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), compared to the general population. Cancer-associated thrombosis (CAT) is a thrombotic event that occurs as a complication of cancer or cancer therapy. Major factors determining VTE risk in cancer patients include not only treatment history and patient characteristics, but also cancer type and site. Cancer types can be broadly divided into three groups based on VTE risk: high risk (pancreatic, ovarian, brain, stomach, gynecologic, and hematologic), intermediate risk (colon and lung), and low risk (breast and prostate). This implies that the mechanism of VTE differs between cancer types and that specific VTE pathways may exist for different cancer types. This review summarizes the specific pathways that contribute to VTE in cancer patients, with a particular focus on leukocytosis, neutrophil extracellular traps (NETs), tissue factor (TF), thrombocytosis, podoplanin (PDPN), plasminogen activator inhibitor-1 (PAI-1), the intrinsic coagulation pathway, and von Willebrand factor (VWF).

Surgical aortic valve replacement in octogenarians: Single-center perioperative outcomes and five-year survival

Introduction and objectivesAortic stenosis is the most common valvular heart disease. The number of octogenarians proposed for intervention is growing due to increased lifespan. In this manuscript we aim to evaluate perioperative outcome and long-term survival after surgical aortic valve replacement (SAVR) in octogenarians, comparing patients with low surgical risk (EuroscoreII <4%) with intermediate-high risk (EuroscoreII ≥4%). MethodsA retrospective observational single-center cohort study with 195 patients aged ≥80 years old, who underwent SAVR between 2017 and 2021, was conducted. Patients were divided into two groups according to EuroscoreII: (1) Low risk (EuroscoreII <4%) with intermediate-high risk (EuroscoreII ≥4%). Continuous variables are presented in median (IQR), analyzed using Wilcoxon rank sum test; categorical variables in percentages, analyzed using chi-squared test; and survival was analyzed by Kaplan–Meier, open cohort, and the log-rank test was performed. ResultsThe overall median age was 82 (IQR 81–83), with 4.6% of the patients ≥85 years old. 23.6% of the patients presented EuroscoreII ≥4%. No complications were observed in 26.2%, with a significantly higher rate in intermediate-high risk patients. Postoperative need for hemodynamic support was the most frequent complication, followed by postoperative acute kidney injury and the use of blood products. Overall median ICU stay was three days (2–4) and hospital length of stay (LOS) six days (5–8). Patients with intermediate-high risk and those with complications had longer ICU LOS. At 12 months, overall survival was 96.4%, at three years 94.1% and 5 years 75.4%. Patients with low surgical risk had higher survival proportions up to 5 years. ConclusionSAVR in patients ≥80 years is associated with low in-hospital mortality, although a significant proportion of patients develop complications. Long-term follow-up up to five years after surgery is acceptable in octogenarians with low surgical risk.

Detection performance and prognostic value of initial bone marrow involvement in diffuse large B-cell lymphoma: a single centre 18F-FDG PET/CT and bone marrow biopsy evaluation study.

Detection of bone marrow involvement (BMI) in diffuse large B-cell lymphoma (DLBCL) typically relies on invasive bone marrow biopsy (BMB) that faces procedure limitations, while 18F-FDG PET/CT imaging offers a noninvasive alternative. The present study assesses the performance of 18F-FDG PET/CT in DLBCL BMI detection, its agreement with BMB, and the impact of BMI on survival outcomes. This retrospective study analyzes baseline 18F-FDG PET/CT and BMB findings in145 stage II-IV DLBCL patients, evaluating both performance of the two diagnostic procedures and the impact of BMI on survival. DLBCL BMI was detected in 38 patients (26.2%) using PET/CT and in 18 patients (12.4%) using BMB. Concordant results were seen in 79.3% of patients, with 20.7% showing discordant results. Combining PET/CT and BMB data, we identified 29.7% of patients with BMI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for detecting DLBCL BMI were 88.4%, 100%, 100%, 95.3%, and 96.5%, respectively, while BMB showed lower sensitivity (41.9%) and NPV (46.8%). The median overall survival (OS) was not reached in any gender subgroup, with 5-year OS rates of 82% (total), 84% (female), and 80% (male) (p = 0.461), while different International Prognostic Index (IPI) groups exhibited varied 5-year OS rates: 94% for low risk (LR), 91% for low-intermediate risk (LIR), 84% for high-intermediate risk (HIR), and 65% for high risk (HR) (p = 0.0027). Bone marrow involvement did not impact OS significantly (p = 0.979). 18F-FDG PET/CT demonstrated superior diagnostic accuracy compared to BMB. While other studies reported poorer overall and BMI 5-year OS in DLBCL, our findings demonstrated favourable survival data.

Catheter-directed therapies for high and intermediate-high risk patients with acute pulmonary embolism: Results from a multiparametric follow-up protocol

Introduction: Intermediate-high- and high-risk pulmonary embolism (PE) patients treated with anticoagulation alone are associated with a considerable risk of circulatory collapse, death, or long-term pulmonary hypertension. Pulmonary Embolism Response Teams (PERT) have been created to deliver PE patients a better care. Catheter-Directed Therapies (CDT), with mechanical thrombolysis and/or local fibrinolysis allow faster reperfusion and hemodynamic improvement without the systemic bleeding risk of systemic fibrinolysis. However, clinical evidence of its safety and benefits are lacking. Objectives: This analysis aims to describe the hemodynamics, morphological and perfusion improvement over time in intermediate-high- and high-risk acute PE patients submitted to CDT. Methods: Prospective registry of consecutive intermediate-high- and high-risk PE patients submitted to CDT (mechanical thrombolysis with Penumbra aspiration system and/or intrapulmonary local fibrinolysis with alteplase) in a single tertiary center. A multiparametric follow-up protocol was designed to evaluate echocardiographic, CT-scan, pulmonary angiogram, and right heart catheterization data at admission and at 3 months after CDT.

Emergency Ultrasound Unveils Intermediate-High Risk Saddle Pulmonary Embolism with Extensive Bilateral Clot Burden, Masquerading as Micturition Syncope: A Case Report

BackgroundIsolated syncope as the manifestation of pulmonary embolism (PE) is a rare and diagnostically challenging presentation that often leads to delayed or missed diagnosis, increasing morbidity and mortality. In spite of emphasizing cardiovascular etiologies of syncope, current guidelines offer essentially no guidance in establishing a diagnostic workup for PE in these patients. By performing bedside echocardiography, emergency physicians can accurately identify concerning features suggestive of PE in patients with syncope. Case ReportA 78-year-old man, receiving ertapenem via a peripherally inserted central catheter for treatment of extended spectrum β-lactamase urinary tract infection, presented to the emergency department for isolated syncope with collapse while urinating. Arriving asymptomatic with normal vital signs and a benign physical examination, a presumptive diagnosis of micturition syncope was made. However, subtle vital sign changes on reassessment prompted performance of a point-of-care echocardiogram, which revealed signs of right heart strain. A computed tomography angiogram confirmed a saddle PE with extensive bilateral clot burden. Catheter-directed thrombectomy was performed via interventional radiology, with successful removal of pulmonary emboli. Why Should an Emergency Physician Be Aware of This?Pulmonary embolism presenting as isolated syncope represents a daunting diagnostic dilemma, as emergency physicians may not consider it, or anchor on more benign etiologies of syncope. Although lacking sufficient sensitivity to rule out PE, point-of-care echocardiography to evaluate for signs of right heart strain can quickly and effectively point toward the diagnosis, while also assessing for other emergent cardiovascular causes of syncope. Given the lack of evidence-based guidance concerning PE presenting as syncope, bedside echocardiography should be highly considered as a part of the emergency physician's diagnostic workup, especially in patients with abnormal vital signs.

Prognostic Role of Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Artery Pressure Ratio for the Identification of Early Clinical Deterioration in Intermediate-High–Risk Pulmonary Embolism Patients

The ratio of tricuspid annular plane systolic excursion (TAPSE) to echocardiographically measured systolic pulmonary artery pressure (PASP) has been proposed as a surrogate of RV-arterial coupling. In this analysis, we assess the prognostic role of TAPSE/PASP for early clinical deterioration and short-term mortality in an often clinically challenging population of intermediate high-risk PE patients. A post-hoc analysis of intermediate-high risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (ClinicalTrials.gov: NCT01604538) was performed. All patients underwent a transthoracic echocardiography (TTE) at admission. The primary and secondary outcomes were clinical deterioration within 48 hours from admission and 30-day all-cause mortality, respectively. Among 422 intermediate high-risk PE patients (mean age 71.2±5.3 years, 238 males), 37 (8.7%) experienced clinical deterioration within 48 hours of admission. The 30-day mortality rate was 6.6% (n=28). Receiver operating characteristic analysis established 0.33 as the optimal cut-off value for the TAPSE/PASP in predicting 48-h clinical deterioration (AUC of 0.79 ± 0.1). Sensitivity, specificity, PPV and NPV were 81%, 88.5%, 40.5% and 97.9%, respectively. Multivariate Cox regression analysis showed that a TAPSE/PASP≤0.33 was an independent predictor of 48-h clinical deterioration (HR: 2.06, 95% CI 1.98-2.11, p<0.0001) and 30-day mortality (HR: 2.28, 95% CI: 2.25-2.33, p<0.001). TAPSE/PASP shows promise as a non-invasive prognostic predictor to identify intermediate-high risk PE patients at higher risk of early clinical deterioration and short-term mortality.

Symptomatic Lymphocele After Robot-Assisted Pelvic Lymphadenectomy as Part of the Primary Surgical Treatment for Cervical and Endometrial Cancer: A Retrospective Cohort Study

Pelvic lymph node dissection (PLND) is part of the primary treatment for early-stage cervical cancer and high-intermediate risk or high-risk endometrial cancer. Pelvic lymphocele is a postoperative complication of PLND and when symptomatic, lymphoceles necessitate treatment. The aim of this study was to investigate the incidence and risk factors of symptomatic lymphocele after robot-assisted laparoscopic PLND in cervical and endometrial cancer. Retrospective cohort study. Single-center academic hospital. Two hundred and fifty-eight patients with cervical cancer and one hundred and twenty-nine patients with endometrial cancer. Pelvic lymphadenectomy by robot-assisted laparoscopic surgery. We retrospectively included all patients with early-stage cervical cancer and high- intermediate risk or high-risk endometrial cancer who underwent pelvic lymphadenectomy by robot-assisted laparoscopic surgery between 2008 and 2022. Medical records were reviewed for the occurrence of a symptomatic lymphocele. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for developing a symptomatic lymphocele. In total 387 patients, 258 with cervical cancer and 129 with endometrial cancer, were included in the study. The overall incidence of symptomatic lymphoceles was 9.6% with a median follow-up of 47 months [IQR 23-61]. For the entire cohort, smoking was the only significant risk factor for symptomatic lymphoceles identified in univariate (OR 2.47, 95% CI 1.19-5.11) and multivariate analysis (OR 2.42, 95% CI 1.16-5.07). For cervical cancer, BMI (OR 1.09, 95% CI 1.00-1.17) and prior abdominal surgery (OR 2.75, 95% CI 1.22-6.17) were also identified as significant independent risk factors. For endometrial cancer, age was identified as significant independent risk factor (OR 0.90, 95% CI 0.83-0.97). This single-center cohort study demonstrated an incidence of almost 10% of symptomatic lymphoceles after robot-assisted laparoscopic PLND for cervical cancer and endometrial cancer, with a higher risk observed among patients who smoke at the time of diagnosis. Furthermore, risk factors differ between the two populations, necessitating further studies to establish risk models.

Clot ratio, new clot burden score with deep learning, correlates with the risk stratification of patients with acute pulmonary embolism.

Risk stratification for patients with acute pulmonary embolism (APE) is significantly important for treatment and prognosis evaluation. We aimed to develop a novel clot burden score on computed tomography pulmonary angiography (CTPA) based on deep learning (DL) algorithm for risk stratification of APE. The study retrospectively enrolled patients newly diagnosed with APE in China-Japan Friendship Hospital consecutively. We collected baseline data and CTPA parameters, and calculated four different clot burden scores, including Qanadli score, Mastora score, clot volume and clot ratio. The former two were calculated by two radiologists separately, while clot volume and clot ratio were based on the DL algorithm. The area under the curve (AUC) of four clot burden scores were analyzed. Seventy patients were enrolled, including 17 in high-/intermediate-high risk and 53 in low-/intermediate-low risk. Clot burden was related to the risk stratification of APE. Among four clot burden scores, clot ratio had the highest AUC (0.719, 95% CI: 0.569-0.868) to predict patients with higher risk. In the patients with hemodynamically stable APE, only clot ratio presented statistical difference (P=0.046). Clot ratio is a new imaging marker of clot burden which correlates with the risk stratification of patients with APE. Higher clot ratio may indicate higher risk and acute right ventricular dysfunction in patients with hemodynamically stable status.