Citations

Abstract Obesity accelerates the onset and progression of age-related conditions. In preclinical models, obesity drives cellular senescence, a cell fate that compromises tissue health and function, in part through a robust and diverse secretome. In humans, components of the secretome have been used as senescence biomarkers that are predictive of age-related disease, disability, and mortality. Here, using biospecimens and clinical data from two large and independent cohorts of older adults, we tested the hypothesis that the circulating concentrations of senescence biomarkers are influenced by body mass index. After adjusting for age, sex, and race, we observed significant increases in activin A, Fas, MDC, PAI1, PARC, TNFR1, and VEGFA, and a significant decrease in RAGE, from normal weight, to overweight, to obesity body mass index categories by linear regression in both cohorts (all p < .05). These results highlight the influence of body mass index on circulating concentrations of senescence biomarkers.

Importance Despite the unmet need for donor organs, organ use from donation after circulatory determination of death (DCD) donors has been limited by inferior transplant outcomes. Normothermic regional perfusion (NRP) improves recipient outcomes and organ utilization from DCD donors. There is variability in NRP policies and experience among US organ procurement organizations (OPOs). Objectives To determine OPO experience, identify operational inconsistencies, and explore needs related to NRP. Design, Setting, and Participants This survey study included 55 OPOs in the US that had recovered DCD organs and completed a survey on operational, administrative, and educational components related to NRP in November to December 2023. Data analysis was performed from February to April 2024. Main Outcome and Measures The primary outcome was the number of OPOs participating in and/or anticipating NRP participation. Secondary outcomes were NRP implementation barriers, OPO education practices, and future needs regarding consensus NRP recommendations and standards. Results Of 55 respondents, 11 (20%) were chief executive officers, 8 (15%) were chief operating officers, and 36 (65%) were medical directors or chief clinical officers. Forty-nine OPOs facilitated NRP cases: 26 OPOs (53%) facilitated both thoracoabdominal NRP (TA-NRP) and abdominal NRP (A-NRP) cases, 16 OPOs (33%) facilitated only TA-NRP, and 7 OPOs (14%) facilitated only A-NRP. OPOs reported 606 NRP cases (421 TA-NRP [69%], 185 A-NRP [31%]); median (range) case experience was 8 (1-52). Fifty-two of 55 OPOs (95%) thought standardized guidance documents would be helpful. All 49 OPOs facilitated NRP at a transplant center’s request; 39 (80%) had NRP initiated by a nonlocal transplant center. Twenty-three of 49 OPOs (47%) participated in NRP without a policy and without a policy pending approval. Positive donor hospital feedback was received by 29 OPOs (59%), primarily focused on increased organs transplanted and prerecovery communication. Allocation challenges were experienced by 21 OPOs (43%); their median (range) case volume was higher than those with no reported allocation challenges (11 [3-52] vs 6.5 [1-29]; P = .03). Eleven OPOs (22%) had incorporated NRP into general donor hospital education. Conclusions In this survey study of US OPOs, wide variation existed with respect to NRP experience and practice. Allocation challenges occurred more frequently with increased NRP experience. NRP guidelines and standardization were desired by most OPOs to decrease allocation challenges and maximize the gift of organ donation.

Abstract BACKGROUND [ 18 F] flortaucipir (FTP) binding to paired helical filament (PHF) tau in Alzheimer's disease (AD) is well accepted. Binding to 3R and 4R tau in frontotemporal lobar degeneration (FTLD) is controversial. We aimed to investigate whether an FTP fluorescent analog (T726) can help shed light on this controversy. METHOD We assessed T726 binding to amyloid beta (Aβ) and different tau isoforms in nine subjects (one control, three with Alzheimer's disease [AD], and five with FTLD) with different 3R and 4R tauopathies using fluorescence confocal microscopy. RESULTS T726 did not colocalize with Aβ but showed significant co‐localization with PHF tau in AD. We also observed some, albeit limited, co‐localization of T726 with 3R and 4R tau lesions in FTLD. DISCUSSION This study's findings support FTP binding to some 3R and 4R tau lesions in FTLD. Further studies are needed to understand the biology of why FTP binds some but not all FTLD tau lesions. Highlights Flortaucipir analog (T726) showed significant co‐localization with paired helical filament (PHF) tau in Alzheimer's disease (AD). Colocalization between T726 with 3R and 4R tau lesions was observed in frontotemporal lobar degeneration (FTLD). Not all 4R tau lesions bind to T726 across different FTLD brain regions.

People living with dementia have high rates of hospitalizations. Identifying factors that influence hospitalization is important. This study examines the influence of physical activity levels on risk of hospitalization and emergency department (ED) use among older people living with mild cognitive impairment (MCI) or dementia followed in our primary care practice in Rochester, Minnesota, United States. We included those age 55 years and older, who had a clinic visit between June 1, 2019 and June 30, 2021 and completed a social determinants of health questionnaire about physical activity levels ( n = 3090). Physical activity was classified as sufficiently active, insufficiently active, or physically inactive. Risk of hospitalization and ED visits by physical activity levels were examined. People who were physically inactive were at higher risk of hospitalization and ED visits ( p < .001) compared with those who were sufficiently active. This highlights an area for health promotion in people living with MCI and dementia.

Introduction/Objectives: We aimed to investigate the effect of family structure on depression program outcomes for adolescents enrolled in a depression-focused, primary care-based collaborative care program. Methods: This was a retrospective study of primary care patients ages 12 to 18 years seen at a Midwestern academic center with data obtained by medical record review. We used logistic regression models to assess the effect of family structure on program graduation and achievement of a single Patient Health Questionnaire 9–Modified for Adolescents (PHQ-9M) score <5 at any time while enrolled. Results: Adolescents were divided into 2 groups, Both Parents in Household (n = 179) and Parents Not Together (n = 161). The Both Parents in Household group had higher rates of graduation (38.0% vs 23.6%, P = .005) and achieving single PHQ-9M scores <5 (64.1% vs 46.2%, P = .002) than the Parents Not Together group. Discussion: Youth residing with both parents had higher rates of successful outcomes in a depression-focused collaborative care program.

ABSTRACTApheresis is performed worldwide for an increasing number of indications. The development of common data elements (CDE) for apheresis related areas may facilitate conduct of new research, enhance quality initiatives including benchmarking, and improve patient care. This report describes the systematic development of the Uniform Apheresis Case Report Form (UACRF) as part of the Apheresis in the United States (ApheresUS) program. A consensus panel of 17 diverse experts in apheresis, related specialties, and electronic case report form (eCRF), and database development was assembled. The panel met via online conferencing from November 17, 2020 to December 1, 2021. A draft document was posted online for public comment from October 11, 2021 to November 10, 2021. Feedback was collected using an online survey tool. The consensus panel revised the UACRF. This version was converted to an eCRF with additional changes made to improve usability in this format. The final version of the UACRF was created on August 24, 2023. The UACRF contains 16 modules: procedure and subject eligibility, patient demographics, general procedure information, laboratory parameters, vascular access, common procedure elements, eight procedure specific modules (mononuclear cell collection and seven therapeutic modalities), outcomes, and site information. A total of 137 data elements were created, including 57 with one or more subelements. The UACRF is the first systematic attempt to develop CDE for therapeutic apheresis and white blood cell collections. Further validation of the UACRF is necessary to confirm the tool's ability to collect the relevant data elements and determine the usability of the form.