Background Lymph node metastasis (LN+) is a prognostic factor in appendiceal cancers, but predictors and outcomes for LN+ in mucinous appendiceal adenocarcinoma (MAC) remain poorly defined. Methods Patients were identified from the 2010 to 2016 NCDB who underwent surgical resection as first‐line management for Stage I‐III mucinous appendiceal cancer. A LN+ risk‐score model was developed using multivariable regression on a training data set and internally validated using a testing data set. Three‐year overall survival (OS) was analyzed by Cox proportional hazards regression. Results Of 1158 patients, LN+ (N = 244, 21.1%) patients were more likely to have higher pT group and grade of disease, lymphovascular invasion (LVI), and positive margins on univariate analyses. Predictive factors associated with LN+ on multivariable analysis included positive surgical margins (odds ratio [OR] 3.00, P <.0001), higher grade (moderately differentiated: OR, 2.16, P < .0001; poorly or undifferentiated: OR, 3.07, P < .0001), and LVI (OR, 7.28, P < .0001). A validated risk‐score model using these factors was developed with good performance (AUC 0.749). LN+ patients had a worse 3‐year OS compared with LN− patients (17.4% vs 82.6%, hazard ratio 1.96, P = .001). Conclusions LN+ is associated with worse survival in patients with MAC. A risk‐score model using margin status, LVI, and grade can accurately risk stratify patients for LN+.
Spontaneous pseudoaneurysm is extremely uncommon. Apparently the first case of a deep femoral artery pseudoaneurysm, caused by acute trunk and hip torsion during a golf swing, is reported. The lesion was documented by computed tomography, arteriography and surgical investigation. The present report is aimed at making known the possibility of such a complication following this and similar types of physical activity in order to enable prompt assessment and treatment of the lesion.
OBJECTIVES/SPECIFIC AIMS: The primary aim is to assess differences in therapeutic effect between MSC and EPC EVs on acute ischemic rat hearts through delivery in a biocompatible and shear-thinning hydrogel. Primary outcomes for therapeutic assessment include an in-vitro angiogenesis assay and in-vivo hemodynamic analysis, mainly identifying differences in ejection fraction and contractility. Secondary hemodynamic outcomes include cardiac output, stroke volume, and end-diastolic pressure volume relationship (EDPVR). Secondary structural outcomes include post-mortem scar analysis and immunohistochemistry (IHC) staining for angiomyogenesis. METHODS/STUDY POPULATION: MSCs and EPCs will be cultured according to previously published protocols. EVs will be isolated from cultured cell lines through precipitation methods with polyethylene glycol. EVs will be qualitatively analyzed with nanoparticle tracking analysis (NTA) and flow cytometry. The shear thinning hydrogel (STG) will be constructed using a hyaluronic backbone conjugated to adamantane or beta-cyclodextrin, ultimately facilitating guest-host interactions with shear thinning properties. Controls and treatment groups mixed with the hydrogel will be injected into the border zone of infarcted Wistar rat hearts immediately following a left anterior descending artery ligation. Hemodynamic assessment will be performed at four weeks through left ventricular catheter based pressure-volume recordings. Ex-vivo analysis will include scar thickness assessment using Masson collagen staining and IHC stain for vessel (anti-vonWillebrand factor; anti-Isolectin) and myocyte formation (anti-cardiac Troponin I). RESULTS/ANTICIPATED RESULTS: We hypothesize that, in-vitro, MSC-EVs will demonstrate non-inferior angiogenic potential as compared to EPC-EVs. We posit that MSC-EVs will demonstrate superior therapeutic effect to EPC-EVs in-vivo as measured by functional hemodynamics and structural assessment. We have successfully isolated MSC and EPC EVs and have validated uniformity across EV populations (Figure 1). Preliminary data from the angiogenesis assay (n=3) demonstrated that MSC-EV and EPC-EV produce non-significantly different angiogenic potential as measured by number of vascular meshing extremes (p=0.144) and length of master vascular segment (p=0.193), with significant differences compared to either positive or negative controls. DISCUSSION/SIGNIFICANCE OF IMPACT: Novel regenerative therapies are needed for patients with a history of AMI given current limitations to therapy and sequelae of ischemic heart disease. Delivery of extracellular vesicles through a shear-thinning gel is a novel “off-the-shelf” translational approach to address the current clinical need.
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