Citations

Background: Cerebral microbleeds (CMBs) are associated with incident dementia, but the impact of specific CMB patterns is unclear. CMBs in lobar regions suggest cerebral amyloid angiopathy (CAA), which is sometimes accompanied by superficial siderosis (SS), while subcortical CMBs indicate hypertensive origins. This study investigates the association between CMB patterns and dementia risk in the community-based longitudinal Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Methods: All ARIC-NCS participants with a 3T research MRI at visit 5 (2011-13; aged 67-90) without intracerebral hemorrhage or dementia were included. CMB and SS presence and location were coded from T2* GRE sequences. Individuals were classified into one of four patterns: no CMBs, only subcortical, mixed (lobar and/or SS + subcortical), and only lobar and/or SS. Incident dementia diagnoses were defined by cognitive testing (in-person and telephone), informant interviews, and hospital discharge codes or death certificates. Cox proportional-hazards models assessed the association between the presence, patterns, and frequency of CMBs (0,1,2,3+), presence of SS, and incident dementia from visit 5 through 2020. Model covariates included demographics, vascular risk factors, and imaging markers of small vessel disease. Results: Among 1609 participants, 364 had CMBs (Table 1). Participants with CMBs tended to be older and female compared to those without CMBs. Compared to individuals with no CMBs, presence of any CMBs was associated with an increased risk of dementia (Table 2). Compared to individuals without CMBs, individuals with only lobar CMBs and/or SS had an increased risk of incident dementia, as did individuals with mixed CMBs, but individuals with subcortical-only did not. Participants with ≥3 CMBs of any variant had an increased risk of incident dementia vs no CMBs. Although SS was infrequent, its presence (vs no SS) was associated with an elevated risk of dementia. Conclusion: CMBs, particularly in a mixed or lobar and/or SS-only pattern, are linked to an increased risk of incident dementia. The number of recurrent CMBs and any SS also showed an increased dementia risk. These data support that dementia risk is high in individuals with a CAA-type CMB pattern, but also emphasize that a mixed pattern, not typical of CAA alone, is associated with a high risk of dementia. Further studies should evaluate mechanisms by which these different patterns contribute to dementia.

Abstract Background The COVID-19 pandemic has underscored challenges with patient adherence to medical directives, particularly vaccine acceptance. While sociodemographic factors have been linked to non-COVID-19 vaccine hesitancy, the relationships between patient experience, the COVID-19 pandemic, and adherence to routine vaccinations are uncertain.Figure 1:Yearly influenza vaccine refusal, influenza vaccine administrations, and overall patient satisfaction since establishing care with a primary care provider from 2017-2023.Panel A (Influenza Refusals): the number of vaccine refusals among individuals who are Intermittently Vaccinated and Never Vaccinated for seasonal influenza since establishing care with a primary care provider over time.Panel B (Influenza Vaccinations): the number of vaccines administered over time since establishing care with a primary care provider among those who are Always Vaccinated and Intermittently Vaccinated for seasonal influenza.Panel C (Overall Satisfaction): the number of patients who indicated that they were maximally satisfied with their overall care following any interaction with the healthcare system over time. Methods We retrospectively analyzed influenza vaccination records of adult primary care patients in Olmsted County, Minnesota. Vaccination history was examined during two phases: Pre-Pandemic (1/1/2017—2/28/2020) and Pandemic-Plus (3/1/2020—12/31/2023). Vaccination status was defined as “always vaccinated” (AV), “never vaccinated” (NV), or “intermittently missed years of vaccinations” (IV) for seasonal influenza. Patient dissatisfaction was determined if patients negatively ranked their overall quality of care on standard patient experience surveys. We explored the relationship between influenza vaccination rates, healthcare engagement, and patient satisfaction.Figure 2:Multinomial logistic regression of patient satisfaction on vaccination status across the phases of the COVID-19 Pandemic, adjusted for engagement in the health care system, participation, and area of deprivation index (ADI) for patients that were (A) intermittently vaccinated compared to always vaccinated and (B) never vaccinated comparted to always vaccinated. The “Pre-pandemic phase” refers to influenza immunization data and patient satisfaction data prior to March 2020. The “Pandemic-plus phase” refers to immunization data and patient satisfaction data from March 2020 to January 2024. Low ADI ranking refers to areas with a low level of deprivation, whereas high ADI ranking refers to areas with a high level of deprivation. Individuals were considered low if they came from an area with a state ADI ranking from 1 to 5 and were considered high if they came from an area with a state ADI ranking from 6 to 10. Results From 1/1/2017 to 12/31/2023, 21% of individuals were AV (n=36,632), 52% were IV (n=90,776), and 27% were NV (n=46,418) for seasonal influenza. Post-pandemic onset, 7% (n=3,556) of the Pre-Pandemic AV and 32% (n=16,710) of the Pre-Pandemic IV never received another influenza vaccine. In the Pandemic-Plus phase, the IV and NV had a higher likelihood of disengagement with the healthcare system [odds ratio (OR) (95% CI): 1.59 (1.55, 1.64); 4.21 (4.09, 4.33)], residing in areas of greater deprivation [1.58 (1.53, 1.62); 1.99 (1.94, 2.05)], and self-identifying their race as Black [2.29 (2.09, 2.51); 3.29 (3.01, 3.60)] compared to the AV. After adjusting for healthcare engagement and area of deprivation, dissatisfaction OR increased from 1.03 (0.99,1.07) Pre-Pandemic to 1.07 (1.03,1.12) in the Pandemic-Plus phase among IV compared to AV. Similarly, the OR of dissatisfaction rose from 1.11 (1.05, 1.18) Pre-Pandemic to 1.16 (1.09, 1.24) in the Pandemic-Plus phase among those who were NV compared to those AV. Conclusion Higher healthcare dissatisfaction was observed among those inconsistently adherent to vaccination recommendations. Targeted efforts to enhance patient satisfaction may boost vaccination rates. Disclosures All Authors: No reported disclosures

Background: It has been demonstrated that an athlete’s psychological readiness contributes to one’s ability to successfully return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction. However, the effect of graft choice on psychological readiness is not yet understood. Purpose/Hypothesis: The purpose of this study was to evaluate the association between graft choice and an athlete’s psychological readiness to RTS. It was hypothesized that similar ACL-Return to Sport after Injury (ACL-RSI) scores would be achieved among patients who underwent ACL reconstruction with quadriceps autograft (QA), hamstring tendon autograft (HA), and bone–patellar tendon–bone (BTB) autograft. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary ACL reconstruction at a single institution between January 2017 and December 2018 were placed into separate cohorts depending on graft type (HA, BTB, or QA; n = 30 patients in each group), and the ACL-RSI, International Knee Documentation Committee subjective form, and Lysholm scores were compared between the different graft cohorts at 6 months postoperatively, at RTS, and at 2 years postoperatively. Also, the rate of patients who achieved an ACL-RSI score of ≥65 (predictive of return to preinjury sport at 2 years postoperatively) was calculated, as was the RTS rate and time. Results: The QA group demonstrated significantly higher ACL-RSI scores than both the HA and BTB groups at 6 months postoperatively ( P < .0001) and RTS ( P = .011). The QA group also had a higher rate of achieving ≥65 on ACL-RSI than the other groups at 6 months postoperatively ( P = .002) and RTS ( P = .024). There was no significant difference in the RTS rate between the 3 groups, although the QA group demonstrated a significantly quicker return (QA, 8.1 months; BTB, 9.6 months; HA, 10.5 months; P < .001). Conclusion: Athletes undergoing primary ACL reconstruction with QA achieved a higher mean ACL-RSI score and more often achieved a score of ≥65 at the 6-month and RTS time points compared with the HA and BTB groups. QA may afford an advantage over other grafts in terms of improved psychological readiness to RTS.

Importance Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. Objective To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). Design, Setting, and Participants This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. Exposure DBD and DCD livers preserved on NMP or SCS. Main Outcomes and Measures The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. Results A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) ( P &amp;lt; .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P &amp;lt; .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P &amp;lt; .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) ( P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P &amp;lt; .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P &amp;lt; .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). Conclusions and Relevance In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Background Mild cognitive impairment (MCI) represents a stage between cognitively normal and Alzheimer's disease. Despite much published research on MCI, there continues to be a knowledge gap of volumetric brain changes in MCI versus cognitively normal (CN) in racially diverse, community-based samples. Objective The study aimed to understand differences in volume of selected brain regions in individuals with MCI versus those who are cognitively normal. Methods This was a cross-sectional study with 1835 participants, which sampled all cognitively impaired participants (n = 667) and a subsample of cognitively normal participants from the ARIC neurocognitive study (ARIC-NCS). All individuals underwent a brain MRI. Two models (5 versus 22 regions of interest [ROI]) were built to analyze differences in brain volume between cognitively normal and MCI, and among 3 cognitive domains (memory, language, executive function). Using previous visits data, we estimated the standard deviations of 20-year cognitive decline equivalent to the difference in brain volume between MCI and CN. Results Every lobe was significantly smaller in individuals with MCI, with the largest difference observed in the temporal lobe. Moreover, there was a significant difference between MCI and CN in every subregion within the temporal lobe. The difference in volume between CN and MCI was equivalent to the total brain volume difference associated with a 1.24 standard deviation greater long-term cognitive decline. Conclusions Loss of volume in all cortical lobes, but particularly in the temporal lobe, was associated with MCI. Additionally, significant volume differences were observed in the temporal lobe in all three cognitive domains.

Abstract INTRODUCTION We aimed to compare gait between individuals with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and cognitively unimpaired (CU) individuals and to evaluate the association between gait and regional amyloid beta (Aβ) burden in AD and DLB. METHODS We included 420 participants (70 AD, 70 DLB, 280 CU) in the Mayo Clinic Study of Aging (MCSA). Gait was assessed using a pressure‐sensor walkway. Aβ deposition was analyzed with Pittsburgh compound B (PiB) positron emission topography (PET). RESULTS The DLB group had reduced stride velocity, step length, and stride width variability, as well as increased double support percentage (%DS) and variability in step length, swing time, and step time compared to the AD and CU groups. Aβ burden was not associated with any gait outcomes. DISCUSSION This study provides additional evidence that gait differs between AD and DLB. Larger studies are needed to investigate associations between Aβ burden and gait outcomes in dementia. Highlights Gait was more impaired in dementia than in cognitively unimpaired (CU) controls. Compared with Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) had more impaired pace, variability, and postural control. Step length and double support (%) distinguished DLB and AD with moderate accuracy.

Abstract Background We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn’s disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content. Methods Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers. Circulating CD64, extracellular matrix protein 1 (ECM1), GM-CSF autoantibodies (GM-CSF Ab), and fecal calprotectin were measured by ELISA. Ileal 3-dimensional magnetization transfer ratio (3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, diffusion-weighted intravoxel incoherent motion (IVIM), and the simplified magnetic resonance index of activity (sMaRIA) were measured by MRI. Ileal resection specimen acute inflammation was graded, and collagen content was measured quantitatively using second harmonic imaging microscopy. Associations between biomarkers and ileal collagen content were tested. Results Median (interquartile range [IQR]) age was 19.5 (16-33) years. We observed an inverse relationship between ileal acute inflammation and collagen content (r = −0.39 [95% confidence interval {CI}: −0.61, −0.10], P = .008). Most patients (33 [66%]) received biologics, with no variation in collagen content with treatment exposures. In the univariate analysis, CD64, GM-CSF Ab, fecal calprotectin, and sMaRIA were positively associated with acute inflammation and negatively associated with collagen content (P &lt; .1). The multivariable model for ileal collagen content (R2 = 0.31 [95% CI: 0.11, 0.52]) included log CD64 (β = −.27; P = .19), log ECM1 (β = .47; P = .06), log GM-CSF Ab (β = −.15; P = .01), IVIM f (β = .29, P = .10), and IVIM D* (β = 1.69, P = .13). Conclusions Clinically available and exploratory circulating and MRI biomarkers are associated with the degree of inflammation versus fibrosis in CD ileal resections. With further validation, these biomarkers may be used to guide medical and surgical decision-making for refractory CD.

Purpose To compare the surgical outcomes of anterior cruciate ligament (ACL) reconstruction using hamstring autograft (HA) plus lateral extra‐articular tenodesis (LET), isolated all‐soft tissue quadriceps autograft (QA), and isolated HA. Methods A retrospective review was performed comparing high‐risk patients undergoing ACL reconstruction with isolated HA, isolated QA, or HA + LET from August 2013 to January 2023. High‐risk patients, as determined by high‐grade pivot shift or generalized ligament laxity, with at least a 2‐year follow‐up, were included. Lysholm and International Knee Documentation Committee scores were compared at 3, 6, 12, and 24 months postoperatively. Retear rate, postoperative pivot‐shift grade, return to sport, and complications were recorded. Results In total, 159 patients (56 HA, 47 HA + LET, and 56 QA) were included. At 6 months postoperatively, the HA International Knee Documentation Committee score was significantly lower than that of the HA + LET and QA groups ( P < .0001). Similarly, the Lysholm score was significantly lower in the HA cohort at 6 months, 1 year, and 2 years postoperatively ( P < .0001‐.02). There was no difference in the rate of achieving the minimally important clinical difference between the cohorts for either of these outcome scores. The retear rate was significantly higher in the HA group (17.9%) compared to the HA + LET (4.3%) and QA (1.8%) cohorts ( P = .01). The rate of postoperative pivot shift of grade 2 or more was also higher in the isolated HA group ( P = .04). Conclusions The use of an all‐soft tissue QA or HA + LET for ACL reconstruction resulted in a lower retear rate and postoperative pivot‐shift grade compared to an isolated HA graft in high‐risk patients at 2 years postoperatively. There was no difference in the rate of achieving the minimal clinically important difference between the cohorts. The QA and HA + LET reconstruction options may improve stability and decrease the failure rate compared with HA reconstruction alone. Level of Evidence Level III, retrospective cohort study.

Abstract Approximately 50% of prostate cancer (PCa) patients harbor fusions involving the TMPRSS2 and ERG genes. Despite this, tailored therapies targeting the fused gene, tERG , remain undeveloped. Our study analyzed biopsy samples from two clinical trials assessing the efficacies of androgen receptor (AR) signaling inhibitors (ARSIs). The results revealed that tERG promotes resistance to ARSIs and is associated with elevated levels of the glucocorticoid receptor (GR). Subsequent assays showed that GR directly interacts with tERG, alleviates allosteric autoinhibition and prevents chemotherapy-induced tERG degradation. In PCa models, either inhibiting GR or lowering cortisol levels suppressed tumor growth in tERG-positive models, but not in fusion-negative models. In addition, patient-derived fusion-positive xenografts displayed enhanced sensitivity to combined GR and AR inhibitors. Collectively, these findings highlight TMPRSS2-ERG as a new biomarker and propose that simultaneous inhibition of GR and AR may specifically benefit tERG -positine patients. However, GR stimulatory corticosteroid therapies may not be advisable for this patient subgroup.