Jeffrey Liles

Dysregulation of Tissue Factor, Thrombin-Activatable Fibrinolysis Inhibitor, and Fibrinogen in Patients Undergoing Total Joint Arthroplasty

Total joint arthroplasty (TJA) of the hip or knee (THA, TKA) has become an increasingly common procedure. While TJA is a successful treatment for individuals experiencing degenerative joint diseases, it is well known that one of the most common perioperative complications of TJA is deep venous thrombosis (DVT). To profile tissue factor (TF), microparticle-tissue factor (MP-TF), thrombin-activatable fibrinolysis inhibitor (TAFI), and fibrinogen levels in patients undergoing TJA to determine potential preexisting Hemostatic dysregulation. De-identified blood samples were obtained from patients undergoing TJA 1 day pre- and 1 day postprocedure. Plasma samples were analyzed using enzyme-linked immunosorbent assay kits for fibrinogen, TAFI, TF, and MP-TF; fibrinogen levels were also assessed using a clot-based activity assay. In comparison with healthy controls, there were significant increases of fibrinogen and MP-TF levels, while there were significant decreases in TF and TAFI levels in the preoperative and postoperative patients. Comparing the pre versus postoperative patients, no significant differences were found; interestingly, however, surgical intervention exacerbated the changes found in the preoperative samples compared to the controls. The results of this study confirm that patients undergoing TJA have preexisting alterations in the fibrinolytic system. Surgical intervention tended to exacerbate these changes. The alterations observed in this study may provide insight as to why TJA is associated with higher rates of DVT and thromboembolism.

Increased Level of Thrombotic Biomarkers in Patients with Atrial Fibrillation Despite Traditional and New Anticoagulant Therapy.

The aim of this study was to examine the effect of the traditional oral anticoagulant, warfarin (W), and new anticoagulants, apixaban (A) and rivaroxaban (R), on the level of thrombotic biomarkers in patients with atrial fibrillation (AF). Circulating plasma levels of von Willebrand factor (vWF), prothrombin fragment 1.2 (F1.2), microparticle tissue factor (MP-TF), and plasminogen activator inhibitor (PAI-1) were analyzed as potential markers of clot formation in 30 patients with AF prior to ablation surgery. Patients with AF were divided into 2 groups based on their usage (n = 21) and nonusage (n = 9) of any oral anticoagulant. Furthermore, those on anticoagulants were divided based on their use of newer (R and A, 16) or traditional (W, 4) anticoagulants. A statistical increase (P < .05) in the levels of vWF, MP-TF, and PAI-1 were seen in anticoagulated patients with AF, whereas F1.2 and PAI-1 were increased in nonanticoagulated patients with AF compared to normal. There was no statistical difference (P > .05) in levels of any thrombotic biomarker between patients treated with the traditional anticoagulant, W, and those treated with new anticoagulants, R and A. Our data suggest that, despite the use of traditional or newer anticoagulants, prothrombotic biomarkers are still generated at increased levels in patients with AF. Further studies to confirm these findings are warranted.

Biomarkers of Inflammation, Thrombogenesis, and Collagen Turnover in Patients With Atrial Fibrillation

The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF. Baseline plasma was collected from patients with AF prior to ablation surgery at Loyola University Medical Center. Individuals with AF had statistically significantly increased levels of PAI-1, CD40-L, and nucleosomes, when compared to the normal population (P < .0001). Additionally, there was a statistically significant increase in the CRP (P = .01), PIIINP (P = .04), and PIIICP (P = .0008) when compared to normal individuals. From this study, it is concluded that the prothrombotic, inflammatory, and collagen turnover biomarkers PAI-1, CD40-L, nucleosomes, CRP, PIIICP, and PIIINP are elevated in AF.

Hearing Loss following Posterior Fossa Microvascular Decompression: A Systematic Review.

Objectives (1) Determine the prevalence of hearing loss following microvascular decompression (MVD) for trigeminal neuralgia (TN) and hemifacial spasm (HFS). (2) Demonstrate factors that affect postoperative hearing outcomes after MVD. Data Sources PubMed-NCBI, Scopus, CINAHL, and PsycINFO databases from 1981 to 2016. Review Methods Systematic review of prospective cohort studies and retrospective reviews in which any type of hearing loss was recorded after MVD for TN or HFS. Three researchers extracted data regarding operative indications, procedures performed, and diagnostic tests employed. Discrepancies were resolved by mutual consensus. Results Sixty-nine references with 18,233 operations met inclusion criteria. There were 7093 patients treated for TN and 11,140 for HFS. The overall reported prevalence of hearing loss after MVD for TN and HFS was 5.58% and 8.25%, respectively. However, many of these studies relied on subjective measures of reporting hearing loss. In 23 studies with consistent perioperative audiograms, prevalence of hearing loss was 13.47% for TN and 13.39% for HFS, with no significant difference between indications (P = .95). Studies using intraoperative brainstem auditory evoked potential monitoring were more likely to report hearing loss for TN (relative risk [RR], 2.28; P < .001) but not with HFS (RR, 0.88; P = .056). Conclusion Conductive and sensorineural hearing loss are important complications following posterior fossa MVD. Many studies have reported on hearing loss using either subjective measures and/or inconsistent audiometric testing. Routine perioperative audiogram protocols improve the detection of hearing loss and may more accurately represent the true risk of hearing loss after MVD for TN and HFS.

Levels of Matrix-Degrading Enzymes and Lubricin in Patients With Degenerative Joint Disease Requiring Arthroplasty:

Total joint arthroplasty (TJA) of the hip or knee (THA and TKA) is the primary surgical intervention for individuals with degenerative joint disease (DJD). Although it is commonly thought that shear force on the joint causes the degradation of articular cartilage, it is possible that there are other factors that contribute to the progression of DJD. It is plausible that specific enzymes that degrade the joint are upregulated, or conversely, there is downregulation of enzymes critical for joint lubrication. The aim of this study is to profile collagenase-1, elastase, heparanase, and lubricin levels in patients undergoing TJA in order to determine potential preexisting dysregulation that contributes to the pathogenesis of DJD. Deidentified blood samples were obtained from patients undergoing TJA 1 day pre- and 1 day postoperatively. Plasma samples were analyzed using enzyme-linked immunosorbent assay kits for elastase, collagenase-1, heparanase, and lubricin. In comparison to healthy controls, there were significant increases in circulating collagenase-1, elastase, and lubricin levels in both the preoperative and postoperative samples. There were no significant differences in heparanase levels in the preoperative or postoperative samples. Comparing the preoperative versus postoperative patient samples, only lubricin demonstrated a significant change. The results of this study confirm that patients undergoing TJA have preexisting alterations in the levels of matrix-degrading enzymes and lubricin. The alterations observed in this study may provide insight into the pathogenesis of DJD.

Fibrinolytic Deficit and Platelet Activation in Atrial Fibrillation and Their Postablation Modulation

This study aims to examine the effects of atrial fibrillation (AF) on the expression of the cellular mediators plasminogen activator inhibitor 1 (PAI-1) and CD40 ligand (CD40-L). Additionally, the effect of catheter ablation on the levels of the aforementioned biomarkers was also examined. In this prospective study, plasma samples were collected from patients with AF at baseline prior to ablation and at 1 and 3 months postablation. There was a statistically significant increase in CD40-L at baseline in patients with AF compared to control (P = .0034). There was a statistically significant decrease in CD40-L levels postablation at both 1 month (P < .0001) and 3 months (P < .0001) compared to baseline. Baseline levels of PAI-1 were elevated compared to the control group (mean 19.55 ± 2.17 ng/mL vs 4.85 ± 0.41 ng/mL) and a statistically significant decrease in circulating PAI-1 levels 1 month postablation (P = .05) was noted compared to preablation levels. These data suggest that inflammation plays an important role in the pathogenesis of AF and that these cellular mediators are modulated by catheter ablation.