New and known predictors of the postthrombotic syndrome: A subanalysis of the ATTRACT trial

Introduction: Postthrombotic syndrome (PTS) remains associated with significant clinical and economic burden. This study aimed to investigate known and novel predictors of the development of PTS in participants of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal With Adjunctive Catheter-Directed Thrombolysis) trial. Methods: We used multivariable logistic regression to identify baseline and postbaseline factors that were predictive of the development of PTS during study follow-up, as defined by a Villalta score of 5 or greater or the development of a venous ulcer from 6 to 24 months after enrollment. Results: Among 691 patients in the study cohort (all had proximal deep vein thrombosis [DVT] that extended above the popliteal vein, of which 57% had iliofemoral DVT), 47% developed PTS. Further, we identified that Villalta score at baseline (odds ratio [OR], 1.09 [95% confidence interval [CI], 1.05-1.13] per one-unit increase) and employment status (unemployed due to disability: OR, 3.31 [95% CI, 1.72-6.35] vs. employed more than 35 hours per week) were predictive of PTS. In terms of postbaseline predictors, leg pain severity at day 10 (OR, 1.28 [95% CI, 1.13-1.45] per 1-point increase in a 7-point scale) predicted PTS. Also, patients receiving rivaroxaban on day 10 following randomization had lower rates of PTS (OR, 0.53 [95% CI, 0.33-0.86]) than patients on warfarin. Conclusions: Novel predictors for PTS identified in our study include baseline Villalta score, leg pain severity at 10 days, and unemployed due to disability. Our findings also suggest that the initial choice of anticoagulant to treat DVT may have an impact on the development of PTS

Exploring the Villalta scale to capture postthrombotic syndrome using alternative approaches: A subanalysis of the ATTRACT trial

BACKGROUND: Clinical trials that evaluated interventions to prevent postthrombotic syndrome (PTS) used the Villalta scale (VS) to define PTS, but there is a lack of consistency in its use. OBJECTIVES: This study aimed to improve the ability to identify patients with clinically meaningful PTS after DVT in participants of the ATTRACT trial. METHODS: We conducted a post hoc exploratory analysis of 691 patients from the ATTRACT study, a randomized trial evaluating the effectiveness of pharmacomechanical thrombolysis to prevent PTS in proximal deep vein thrombosis. We compared 8 VS approaches to classify patients with or without PTS in terms of their ability to discriminate between those with poorer vs better venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL]) between 6- and 24-months follow-up. The difference in the average area under the fitted curve of VEINES-QOL scores between PTS and no PTS ( RESULTS: For any PTS (a single VS score ≥5), approaches 1 to 3 had similar CONCLUSION: A single VS score of ≥ 5 reliably distinguishes patients with clinically meaningful PTS as assessed by impact on QOL and is preferred because of greater convenience (only one assessment needed). Alternative methods to define PTS (ie, adjusting for CVI) do not improve the scale\u27s ability to identify clinically meaningful PTS

Positron Emission Tomography-Computed Tomography Compared with Invasive Mediastinal Staging in Non-small Cell Lung Cancer: Results of Mediastinal Staging in the Early Lung Positron Emission Tomography Trial

IntroductionPatients with non-small cell lung cancer (NSCLC) require careful preoperative staging to define resectability for potential cure. 18Fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG PET-CT) is widely used to stage NSCLC. If the mediastinum is positive on PET-CT examination, some practitioners conclude that the patient is inoperable and refer the patient for nonsurgical treatment.MethodsIn this analysis of a previously reported trial comparing PET-CT with conventional imaging in the diagnostic work-up of patients with clinical stage I, II, or IIIA NSCLC, we determined the accuracy of PET-CT in mediastinal staging compared with invasive mediastinal staging either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy.ResultsAll 149 patients had mediastinal nodal staging at mediastinoscopy alone (14), thoracotomy alone (64), or both (71). The sensitivity of PET-CT was 70% (95% confidence interval [CI], 48–85%), and specificity was 94% (95% CI, 88–97%). Of 22 patients with a PET-CT interpreted as positive for mediastinal nodes, 8 did not have tumor. The positive predictive value and negative predictive value were 64% (95% CI, 43–80%) and 95% (95% CI, 90–98%), respectively. Based on PET-CT alone, eight patients would have been denied potentially curative surgery if the mediastinal abnormalities detected by PET-CT had not been evaluated with an invasive mediastinal procedure.ConclusionsPET-CT assessment of the mediastinum is associated with a clinically relevant false-positive result. Our study confirms the need for pathologic confirmation of mediastinal lymph node abnormalities detected by PET-CT

Noncommutative Geometry Inspired Entropic Inflation

Recently Verlinde proposed that gravity can be described as an emergent phenomena arising from changes in the information associated with the positions of material bodies. By using noncommutative geometry as a way to describe the microscopic, microstructure of quantum spacetime, we derive modified Friedmann equation in this setup and study the entropic force modifications to the inflationary dynamics of early universe.Comment: 14 pages, 5 figuers, Accepted for Publication in Phys. Lett.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter pharmacomechanical thrombolysis ) rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P CONCLUSIONS: Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .)

A Systematic Molecular Pathology Study of a Laboratory Confirmed H5N1 Human Case

Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo