Scharf, Eugene

The study included 1,738 Mayo Clinic Study of Aging participants (≥50 years old; 1,460 cognitively unimpaired and 278 with mild cognitive impairment (MCI)) and examined the cross-sectional association between cerebrovascular (CVD) imaging biomarkers (e.g., white matter hyperintensities (WMH), infarctions) and Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) scores, as well as their association with MCI. High (abnormal) WMH burden was significantly associated with having BDI-II>13 and BAI > 7 scores, and both (CVD imaging biomarkers and depression/anxiety) were significantly associated with MCI when included simultaneously in the model, suggesting that both were independently associated with the odds of MCI.

Introduction: Embolic stroke of undetermined source (ESUS) is a clinical paradigm that helps to classify and lead investigations into cryptogenic stroke. Diagnostic evaluation of ESUS involves investigating several potential etiologies of stroke. One such etiology includes antiphospholipid syndrome (APLS), a syndrome known to cause hypercoagulability. Clinical characteristics of primary APLS in ESUS have not been described. Methods: This is an IRB approved, retrospective study including patients from 2015-2020 who were seen at Mayo Clinic, were diagnosed with ESUS, and had APLS testing (anti-cardiolipin, beta-2 glycoprotein, or lupus anticoagulant). Baseline characteristics and radiographic features were collected and compared between patients who were and were not diagnosed with APLS, as well as between patients who were and were not APLS antibody positive. Results: Our study included 206 patients. Positive APLS antibody testing was seen in 21 (10%) patients. Of those patients, 8 (4%) received a formal diagnosis of APLS. Compared to controls, patients with positive APLS antibodies as well as those diagnosed with APLS were more likely to have a history of cancer (20 [11%] APLS antibody negative vs 7 [33%] APLS antibody positive p=0.004) (23 [12%] APLS diagnosis negative vs 4 [50%] APLS diagnosis p=0.002). Mean age in primary APLS was greater, 57 years old APLS antibody negative vs 69 years old APLS antibody positive (p<0.001) and 58 years old APLS diagnosis negative vs 75 years old APLS diagnosis (p=0.001) (Table 1). Regressions analyses examining infarct topography and rate of hemorrhagic transformation were non-significant between groups (p>0.1) Conclusion: APLS presenting as ESUS is associated with older age and history of malignancy. We speculate this finding may underscore the need to consider hypercoagulable conditions more broadly in stroke evaluations of older populations. Larger cohorts and longer follow up will be required to validate this observation.

Background Computed tomography (CT) angiography collateral score (CTA-CS) is an important clinical outcome predictor following mechanical thrombectomy for ischemic stroke with large vessel occlusion (LVO). The present multireader study aimed to evaluate the performance of e-CTA software for automated assistance in CTA-CS scoring. Materials and Methods Brain CTA images of 56 patients with anterior LVO were retrospectively processed. Twelve readers of various clinical training, including junior neuroradiologists, senior neuroradiologists, and neurologists graded collateral flow using visual CTA-CS scale in two sessions separated by a washout period. Reference standard was the consensus of three expert readers. Duration of reading time, inter-rater reliability, and statistical comparison of readers’ performance metrics were analyzed between the e-CTA assisted and unassisted sessions. Results e-CTA assistance resulted in significant increase in mean accuracy (58.6% to 67.5%, p = 0.003), mean F1 score (0.574 to 0.676, p = 0.002), mean precision (58.8% to 68%, p = 0.007), and mean recall (58.7% to 69.9%, p = 0.002), especially with slight filling deficit (CTA-CS 2 and 3). Mean reading time was reduced across all readers (103.4 to 59.7 s, p = 0.001), and inter-rater agreement in CTA-CS assessment was increased (Krippendorff's alpha 0.366 to 0.676). Optimized occlusion laterality detection was also noted with mean accuracy (92.9% to 96.8%, p = 0.009). Conclusion Automated assistance for CTA-CS using e-CTA software provided helpful decision support for readers in terms of improving scoring accuracy and reading efficiency for physicians with a range of experience and training backgrounds and leading to significant improvements in inter-rater agreement.

(1) Background: Chronic inflammation and insulin resistance are associated with cardiometabolic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Therapeutic water-only fasting and whole-plant-food refeeding was previously shown to improve markers of cardiometabolic risk and may be an effective preventative treatment but sustained outcomes are unknown. We conducted a single-arm, open-label, observational study with a six-week post-treatment follow-up visit to assess the effects of water-only fasting and refeeding on markers of cardiometabolic risk. (2) Methods: Patients who had voluntarily elected and were approved to complete a water-only fast were recruited from a single-center residential medical facility. The primary endpoint was to describe changes to Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores between the end-of-refeed visit and the six-week follow-up visit. Additionally, we report on changes in anthropometric measures, blood lipids, high-sensitivity C-reactive protein (hsCRP), and fatty liver index (FLI). Observations were made at baseline, end-of-fast (EOF), end-of-refeed (EOR), and six-week follow-up (FU). (3) Results: The study enrolled 40 overweight/obese non-diabetic participants, of which 33 completed the full study protocol. Median fasting, refeeding, and follow-up lengths were 14, 6, and 45 days, respectively. At the FU visit, body weight (BW), body mass index (BMI), abdominal circumference (AC), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein (LDL), hsCRP, and FLI were significantly decreased from baseline. Triglycerides (TG) and HOMA-IR scores, which had increased at EOR, returned to baseline values at the FU visit. (4) Conclusion: Water-only fasting and whole-plant-food refeeding demonstrate potential for long-term improvements in markers of cardiovascular risk including BW, BMI, AC, SBP, DBP, blood lipids, FLI, and hsCRP.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Introduction: Cerebrovascular disease (CVD) and neuropsychiatric symptoms (NPS) are common in older adults and are independently associated with cognitive impairment. In addition, vascular depression (a late-life depression) is hypothesized to be associated with cerebrovascular pathology. Hypothesis: CVD pathology imaging biomarkers (e.g., white matter hyperintensities (WMH), infarctions) are associated with depression and anxiety, and both (depression/anxiety and CVD imaging biomarkers) are independently associated with mild cognitive impairment (MCI). Methods: This cross-sectional study included 1739 Mayo Clinic Study of Aging participants (≥50 years old) without dementia, with comprehensive cognitive evaluations and available data on the Beck Depression Inventory II (BDI), the Beck Anxiety Inventory (BAI) and imaging CVD biomarkers via FLAIR-MRI (i.e., WMH% of total intracranial volume (TIV) and brain infarctions). We used linear and logistic regression models to examine the associations adjusting for age, sex, education, and apolipoprotein E ε4 status. Results: Participants’ mean age (SD) was 71.11 (10.61) years (53.3% males). Higher WMH% TIV burden was significantly associated with higher BDI (b= 0.082, 95%CI: 0.031, 0.133), p=0.002) and BAI scores (b= 0.088, 95%CI: 0.037, 0.140), p=0.001); the presence of infarctions was also associated with a higher BDI score. Both WMH %TIV burden (OR: 1.20 (95%CI:1.05, 1.38), p=0.008) and BDI score (OR: 1.38 (95%CI:1.21, 1.57), p<0.001) were significantly associated with MCI when included simultaneously in the model. We observed similar associations for CVD biomarkers and BAI score with MCI. Conclusions: CVD imaging biomarkers and NPS, as measured by BDI and BAI scores, could represent two distinct processes associated with cognitive impairment. Studies are ongoing to further examine these associations and delineate how CVD, NPS, and other pathophysiology processes (e.g., Alzheimer’s disease) interact and are associated with cognitive impairment.