Research Spotlight

McCullough, P. A., A. Vasudevan, M. Sathyamoorthy, J. M. Schussler, C. E. Velasco, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and T. Bottiglieri (2017). “Urinary 11-Dehydro-Thromboxane B2 and Mortality in Patients With Stable Coronary Artery Disease.” Am J Cardiol 119(7): 972-977.

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Antiplatelet therapy with aspirin has been shown to reduce adverse outcomes in patients with coronary artery disease (CAD). Aspirin irreversibly inhibits platelet cyclooxygenase-1 and attenuates thromboxane A2 (TXA2)-mediated platelet aggregation, but there is variable suppression of cyclooxygenase-1. From a cohort of patients with stable CAD, we performed blinded, detailed chart abstraction, and measured urinary 11-dehydro-thromboxane B2 (11dhTxB2), an inactive metabolite of TxA2 from frozen samples. There were 327 men (73%) and 122 women (27%) with a mean age (+/-SD) of 67 +/- 10 and 65 +/- 10 years, respectively. A positive linear trend for age was observed among tertiles of 11dhTxB2 (p trend = 0.01). Higher proportions of women (p = 0.001), chronic obstructive pulmonary disease (p trend = 0.0003), and heart failure (p trend = 0.003) were observed in the upper tertile of 11dhTxB2. Sixty-seven patients (14.9%) died over a median follow-up of 1,149 days and 87.5% of the deaths were due to cardiovascular causes. Twenty-six nonsurvivors (38.8%) were treated with P2Y12 receptor antagonists versus 161 survivors (42.2%; p = 0.61). By stepwise Cox proportional hazards analysis, we identified that patients in the middle (hazard ratio 7.14; 95% CI 2.46 to 20.68) and upper tertiles (hazard ratio 9.91; 95% CI 3.45 to 28.50) had higher risks for mortality after adjusting for age and co-morbidities. In conclusion, urinary concentration of 11dhTxB2 was a strong independent risk factor for all-cause mortality among patients with stable CAD on aspirin therapy and may be a marker for patients with CAD who require more intensive secondary prevention measures.

McCullough, P. A., A. Rios and B. Smith (2017). “Dialysis fistulas and heart failure.” Eur Heart J: 2017 Mar [Epub ahead of print].

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Defining the optimal care for patients reaching end-stage renal disease (ESRD) requiring haemodialysis continues to be a challenge for nephrologists, cardiologists, and vascular surgeons. It has been acutely recognized that temporary dialysis catheters used in ∼82% of those who start dialysis can be a nidus for intravascular infection and are associated with early mortality in ESRD.1 Accordingly, there has been a large emphasis on ‘fistula first’ or, in other words, having a permanent surgically created dialysis access conduit [arteriovenous fistula (AVF) or shunt with graft (AVG) material] and thus reducing the exposure to and the length of time with dialysis catheters.2 Permanent vascular access brings a new set of issues to the patient and physician, with complications such as low flow, clotting, infection, and need for revision.3,4 In this issue of the journal, Reddy and colleagues present data from 137 ESRD patients who underwent echocardiographic examinations before and 2.6 years after AVF/AVG creation.5 While there were modest improvements in left ventricular hypertrophy, access creation was associated with multiple adverse changes in right ventricular structure and function without a measurable increase in cardiac output.

Magombedze, G., T. Shiri, S. Eda and J. R. Stabel (2017). “Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data.” Sci Rep 7: 44765.

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Available diagnostic assays for Mycobacterium avium subsp. paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN-gamma, ELISA-antibody and fecal shedding experimental sensitivity scores for MAP infection detection and disease progression. We used both statistical methods and dynamic mathematical models to (i) evaluate the empirical assays (ii) infer and explain biological mechanisms that affect the time evolution of the biomarkers, and (iii) predict disease stages of 57 animals that were naturally infected with MAP. This analysis confirms that the fecal test is the best marker for disease progression and illustrates that Th1/Th2 (IFN-gamma/ELISA antibodies) assays are important for infection detection, but cannot reliably predict persistent infections. Our results show that the theoretical simulated macrophage-based assay is a potential good diagnostic marker for MAP persistent infections and predictor of disease specific stages. We therefore recommend specifically designed experiments to test the use of a based assay in the diagnosis of MAP infections.

Al-Moraissi, E. A. and L. M. Wolford (2017). “Does temporomandibular joint pathology with or without surgical management affect the stability of counterclockwise rotation of the maxillomandibular complex in orthognathic surgery? A systematic review and meta-analysis.” J Oral Maxillofac Surg 75(4): 805-821.

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PURPOSE: This study was designed to determine the stability of counterclockwise rotation (CCWR) of the maxillomandibular complex (MMC) in orthognathic surgery with or without surgical correction of coexisting temporomandibular joint (TMJ) pathology. MATERIALS AND METHODS: The authors implemented a systematic review and meta-analysis. A search of major databases through PubMed, EMBASE, and Cochrane CENTRAL was performed. Inclusion criteria were studies that analyzed CCWR of the MMC in regard to skeletal stability after orthognathic surgery in patients with or without pre-existing TMJ pathology that was or was not surgically corrected concomitantly. The predictor variables were patients who underwent CCWR of the MMC in the following subgroups: 1) healthy TMJs (presumed healthy based on history, clinical evaluation, and radiographic analysis but without magnetic resonance imaging [MRI] confirmation), 2) no TMJ assessment, 3) untreated TMJ disc displacement (confirmed by MRI), 4) TMJ disc displacement (confirmed by MRI) repositioned using Mitek anchors, and 5) reconstruction with TMJ total joint prosthesis. Outcome variables were surgical relapse for angular and linear measurements. Postsurgical mean changes for the occlusal plane (OP) and linear measurements using a fixed-effects model with a 95% confidence interval were analyzed. RESULTS: A total of 345 patients enrolled in 12 studies were included in this study. There was significant OP relapse and horizontal relapse at the B point and menton for studies with untreated TMJ disc displacement and studies without TMJ assessment (P < .005). There was significant horizontal relapse at the A point for studies with healthy TMJs, without assessment of the TMJs, and with TMJ reconstruction with total joint prostheses (P < .005). There was no significant vertical relapse at the B and A points for all subgroup analyses (P < .005). CONCLUSION: The result of the meta-analysis suggests that CCWR of the MMC is a stable procedure for patients with healthy TMJs, patients undergoing concomitant TMJ disc repositioning with Mitek anchors, and patients with TMJ patient-fitted total joint prostheses but unstable in the presence of untreated TMJ disc displacements and when TMJ status is not assessed.

Lindner, P., A. Miloff, W. Hamilton, L. Reuterskiold, G. Andersson, M. B. Powers and P. Carlbring (2017). “Creating state of the art, next-generation Virtual Reality exposure therapies for anxiety disorders using consumer hardware platforms: design considerations and future directions.” Cogn Behav Ther: 1-17.

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Decades of research and more than 20 randomized controlled trials show that Virtual Reality exposure therapy (VRET) is effective in reducing fear and anxiety. Unfortunately, few providers or patients have had access to the costly and technical equipment previously required. Recent technological advances in the form of consumer Virtual Reality (VR) systems (e.g. Oculus Rift and Samsung Gear), however, now make widespread use of VRET in clinical settings and as self-help applications possible. In this literature review, we detail the current state of VR technology and discuss important therapeutic considerations in designing self-help and clinician-led VRETs, such as platform choice, exposure progression design, inhibitory learning strategies, stimuli tailoring, gamification, virtual social learning and more. We illustrate how these therapeutic components can be incorporated and utilized in VRET applications, taking full advantage of the unique capabilities of virtual environments, and showcase some of these features by describing the development of a consumer-ready, gamified self-help VRET application for low-cost commercially available VR hardware. We also raise and discuss challenges in the planning, development, evaluation, and dissemination of VRET applications, including the need for more high-quality research. We conclude by discussing how new technology (e.g. eye-tracking) can be incorporated into future VRETs and how widespread use of VRET self-help applications will enable collection of naturalistic “Big Data” that promises to inform learning theory and behavioral therapy in general.