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Background Amyloid plaques and neurofibrillary tangles, the molecular lesions that characterize Alzheimer's disease (AD) and other forms of dementia, are emerging as determinants of proteinopathies 'beyond the brain'. This study aims to establish tau's putative pathophysiological mechanistic roles and potential future therapeutic targeting of tau in heart failure (HF). Methods and results A mouse model of tauopathy and human myocardial and brain tissue from patients with HF, AD, and controls was employed in this study. Tau protein expression was examined together with its distribution, and in vitro tau-related pathophysiological mechanisms were identified using a variety of biochemical, imaging, and functional approaches. A novel tau-targeting immunotherapy was tested to explore tau-targeted therapeutic potential in HF. Tau is expressed in normal and diseased human hearts, in contradistinction to the current oft-cited observation that tau is expressed specifically in the brain. Notably, the main cardiac isoform is high-molecular-weight (HMW) tau (also known as big tau), and hyperphosphorylated tau segregates in aggregates in HF and AD hearts. As previously described for amyloid-beta, the tauopathy phenotype in human myocardium is of diastolic dysfunction. Perturbation in the tubulin code, specifically a loss of tyrosinated microtubules, emerged as a potential mechanism of myocardial tauopathy. Monoclonal anti-tau antibody therapy improved myocardial function and clearance of toxic aggregates in mice, supporting tau as a potential target for novel HF immunotherapy. Conclusion The study presents new mechanistic evidence and potential treatment for the brain–heart tauopathy axis in myocardial and brain degenerative diseases and ageing. [ABSTRACT FROM AUTHOR]

Objective We hypothesize that reoperation rates of spinal cord stimulation (SCS) systems utilizing percutaneous leads are comparable to those utilizing paddle leads. We attempt here to characterize causes for those reoperations and identify any related patient characteristics. Design and Subjects This study is a single-center retrospective chart review of 291 subjects (410 operations) who underwent at least one permanent SCS implantation utilizing percutaneous or paddle leads over a 10-year period at the Medical University of South Carolina. Methods Charts were reviewed for height, weight, body mass index, gender, race, age, stimulator type, type of reoperation, diabetes status, history and type of prior back surgery, top lead location, and number of leads placed. Comparisons of patient and procedural characteristics were conducted using a two-sample t test (continuous variables), chi-square, or Fisher exact approach (categorical variables). Univariate and multivariate Cox regression models were developed, identifying associations between patient characteristics, SCS characteristics, reoperation rates, and time to reoperation. Results Thirty point five eight percent of subjects (89/291), required at least one reoperation. The reoperation rate was 27.84% for percutaneous systems (N = 54/194) and 27.78% for percutaneous systems (N = 60/216). Time to reoperation also did not differ between the two systems (hazard ratio [HR] = 1.06, 95% CI = 0.70–1.60). Of all factors examined, younger age at time of placement was the only factor associated with risk of reoperation (HR = 0.73, 95% CI = 0.62–0.87, P  < 0.001). Conclusions Our data suggest that reoperation rates and time to reoperation between percutaneous and paddle leads are clinically similar; therefore, rates of reoperation should have no bearing on which system to choose. [ABSTRACT FROM AUTHOR]

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