Citations

Outcomes of kidney-alone transplantation (KAT) in former simultaneous liver-kidney (SLK) transplant candidates after liver waitlist delisting are not well defined. Using Scientific Registry of Transplant Recipients (SRTR) data, we identified adult recipients who underwent KAT between 2005 and 2025 after prior SLK listing (RLD-KAT), which was matched 1:5 to primary KAT recipients without liver disease by age, transplant year, and diabetes status. Patient and graft survival were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazards models. We identified 163 RLD-KAT recipients matched to 815 controls. Unadjusted Kaplan-Meier analyses demonstrated lower patient survival in RLD-KAT (p = 0.020), whereas death-censored and overall graft survival were similar (p > 0.05). In multivariable models, death-censored graft survival (HR 0.89; 95% CI 0.51–1.53), overall graft survival (HR 1.00; 95% CI 0.73–1.36), and patient survival (HR 1.07; 95% CI 0.76–1.5) did not differ significantly. Six RLD-KAT recipients (3.7%) subsequently underwent liver transplantation. Kidney-alone transplantation in prior SLK candidates was associated with acceptable patient and graft outcomes and a low incidence of subsequent liver transplantation.

Abstract Identification of gene expression changes in post-mortem brain tissue of Alzheimer’s disease donors compared to controls have implicated numerous biological pathways for Alzheimer’s disease pathophysiology. Nonetheless, there is still limited understanding of how gene expression dysregulation underpins specific proteinopathies core to Alzheimer’s disease. Here we investigate brain transcriptomic changes in a well characterized cohort of Alzheimer’s disease donors to identify genes and networks that associate with Alzheimer’s disease endophenotypes including neuropathology measures (Braak stage, Thal phase and cerebral amyloid angiopathy score) and Alzheimer’s disease-related brain protein levels (Apolipoprotein E, Amyloid-β 40, Amyloid-β 42, tau, and phospho-Tau). Bulk transcriptome measures were collected from the temporal cortex tissue of 477 Alzheimer’s disease donors. Following quality control, transcriptome-wide association studies were performed for each endophenotype. We used weighted gene co-expression network analysis to build co-expression networks and integrated transcriptome with epigenetic and genetic data from the same donors. We detected a total of 5,740 Bonferroni significant temporal cortex gene associations with Alzheimer’s disease endophenotypes, most of which were with brain tau levels. We discovered tau-associated co-expression modules enriched in known and novel Alzheimer’s disease pathways. We found that a beneficial (or neutral) brain biochemical state of higher total tau and lower phospho-Tau are associated with increased levels of synaptic, DNA damage/repair, nucleic acid metabolism and myelin processes. In contrast, in a detrimental state of lower total and higher phospho-Tau, there is upregulation of vascular and immune, and downregulation of mitochondrial and myelin pathways. There are brain gene expression perturbations that are associated with Alzheimer’s disease endophenotypes. While some of these associations are common across multiple endophenotypes, many are distinct for different Alzheimer’s disease-related proteins. Based on these findings, we propose a hypothetical model of dynamic brain gene expression changes that track with progressive Alzheimer’s disease proteostasis. These expression changes hold potential to serve as dynamic, precision biomarkers of brain Alzheimer’s disease progression. This study demonstrates the potential of integrative multiomics and deep Alzheimer’s disease endophenotype analyses in well-characterized brain tissues to uncover with precision the complex biology of Alzheimer’s disease.

Background Transcatheter edge‐to‐edge repair (TEER) and replacement (TTVR) have emerged as new modalities to treat patients with symptomatic significant tricuspid regurgitation. This study aimed to compare invasive hemodynamic and right ventricular (RV) changes and symptom improvement over 1 year. Methods Patients who underwent TEER/TTVR at Mayo Clinic (Rochester, MN, 2017–2024) were included. Hemodynamic profiles were described before and immediately after intervention, in addition to RV enlargement/dysfunction ≥moderate at 30 days and change in symptoms over time. Results Of 100 patients included (50 per group, median age 81 versus 80 years and female 62% versus 42%, in TTVR and TEER, respectively), all had ≥ moderate–severe symptomatic tricuspid regurgitation. Post intervention, mean right atrial pressure decreased in TEER (16 to 14 mm Hg, P <0.001), V wave decreased in both groups (to 16 mm Hg, P <0.001). RV enlargement was less prevalent in both cohorts at 30 days (60%–40% in TEER, P =0.01, and 72 to 58% in TTVR, P =0.07), yet prevalence of RV dysfunction decreased only in TEER (26 to 15%, P =0.17) as opposed to TTVR (31 to 44%, P =0.13). TTVR resulted in a higher stroke volume index and more complete tricuspid regurgitation elimination at 30 days. Both groups resulted in similar improvements in New York Heart Association class, with overall similar survival. Conclusions TEER was associated with a greater reduction in right atrial pressure and more favorable RV remodeling at 30 days, as opposed to TTVR, which achieved more complete and sustained elimination of tricuspid regurgitation with higher forward stroke volume.

Abstract Background. Cardiovascular disease is a leading cause of death among women with breast cancer, and the 2026 ACC/AHA dyslipidemia guideline endorses coronary artery calcium (CAC) scoring to guide statin therapy before cardiotoxic treatment. Breast cancer patients routinely undergo staging 18 F-fluorodeoxyglucose PET/CT, whose low- dose CT visualizes the coronary arteries, thus enabling CAC quantification at no additional cost or radiation. Methods In this single-center retrospective study, consecutive women with newly diagnosed breast cancer undergoing staging 18 F-FDG PET/CT (2009–2021) had semi- automated Agatston CAC scoring performed on the low-dose CT and were stratified by CAC presence (CAC-P) versus absence (CAC-A). We assessed a composite of cardiac diagnostic testing (stress testing, coronary CT angiography, invasive angiography), clinical events, and reclassification of statin eligibility per ACC/AHA guideline thresholds in a prevention-eligible subgroup. Results Among 276 women (mean age 55.5 years; median follow-up 7.1 years), CAC was present in 68 (25%) but was clinically reported in only 5.4%. CAC-P was associated with more cardiac testing (34% vs 12%; age-adjusted hazard ratio 2.75, 95% CI 1.43–5.28) and, though underpowered, with more atherosclerotic events (7.4% vs 1.4%), but not with the all-cause composite. In the prevention-eligible subgroup (n=39), CAC scoring would have changed statin eligibility in 64%, initiating therapy in 62% of CAC-P women and supporting de-prescribing in 67% of CAC-A women. Conclusions CAC can be feasibly quantified from staging PET/CT in women with breast cancer and would frequently reclassify statin eligibility at no additional cost or radiation, yet is rarely reported.

Abstract T-cell immune tolerance is established in part through the activity of the autoimmune regulator (AIRE) transcription factor in medullary thymic epithelial cells (mTEC) of the thymus. AIRE induces expression of peripheral tissue–specific self-antigens for presentation to naïve T cells to promote activation/deletion of autoreactive T cells. This traditional role of AIRE in mTECs is to prevent autoimmunity. Herein, we demonstrate that tumors mimic the role of AIRE in mTECs to evade immune rejection. We found that AIRE induced a profile of “selfness” at the RNA and protein levels which, when presented on major histocompatibility complexes (MHC), shielded the tumor from inherently self-tolerized T cells. Moreover, we describe an in vivo immunotherapy in which engineered changes in AIRE expression in tumor cells altered their profile of selfness, exposing both AIRE-modified and parental unmodified tumor cells to T-cell attack. Therefore, by resetting the immunologic selfness of cancer cells, this AIRE-mediated immunotherapy (i) converted a highly tolerized T-cell compartment into a tumor-reactive T-cell population; (ii) conferred upon nonimmunogenic tumors de novo sensitivity to immune checkpoint blockade; (iii) removed the need to identify potentially immunogenic tumor-associated antigens as targets for generation of T-cell responses; and (iv) lead to potent T cell–mediated rejection of aggressive, immunologically cold, nonimmunogenic tumors. Patient RNA sequencing data showed that the expression of AIRE predicted response to immune therapies with a strong correlation between AIRE expression and markers of T-cell receptor signaling, suggesting that our studies have therapeutic translational value.

OBJECTIVE Multisegmental pathological autofusion is a hallmark feature of ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), creating a rigid, brittle spine highly susceptible to three-column fractures and devastating neurological injury. This study aimed to evaluate survival outcomes in this patient population and identify clinical and demographic predictors of mortality. METHODS Adults with DISH or AS who sustained a fracture and were admitted to a single tertiary care center for spinal fracture were retrospectively identified using ICD-10 diagnostic codes. Data were extracted on demographics, clinical presentation, fracture characteristics, and details of treatment. RESULTS A total of 383 patients (median age 78 years, 75.2% male) were included. Over a median follow-up of 17.3 months, overall mortality was 38.1%, in-hospital mortality was 5.2%, 30-day mortality was 5.7%, and 1-year mortality was 18.0%. Initial treatment consisted of external orthosis in 220 (57.4%) and surgery in 144 (37.6%), while 19 (5.0%) were left untreated. Patients who died were older (median 83 vs 74 years, p < 0.001), had a lower BMI (29.4 vs 32.3 kg/m 2 , p < 0.001), had higher frailty on the 5-item modified frailty index (mFI-5), and more commonly had congestive heart failure (CHF), cancer, functional dependency, and chronic kidney disease (CKD) (all p < 0.01). Mortality was not associated with fracture location, mechanism of injury, fracture number, or the presence of neurological deficits. Univariable time-to-event analysis showed that decreased survival was predicted by older age (HR 1.08, p < 0.0001), lower BMI (HR per kg/m 2 0.93, p < 0.0001), functional dependency (HR 2.05, p < 0.001), cancer (HR 1.55 p = 0.01), CKD (HR 1.48, p = 0.019), CHF (HR 2.18, p < 0.001), and higher mFI-5 score (HR per point 1.34, p < 0.001). On multivariable analysis, older age (HR 1.06 per year, p < 0.001), lower BMI (HR per kg/m 2 0.95, p < 0.001), and mFI-5 score (HR per patient 1.37, p < 0.001) remained significant independent predictors of mortality. Treatment modality did not predict mortality. CONCLUSIONS AS- or DISH-associated spinal fractures have a high associated mortality, regardless of mechanism or severity. Treatment modality did not affect odds of survival, suggesting that nonoperative management with an external orthosis may be an appropriate option, particularly in older and medically complex patients.

Abstract Purpose The devastation and impact of a new cancer diagnosis can be compounded by psychosocial challenges that can significantly affect patient outcomes. Historically at Mayo Clinic Florida, social work contact with newly diagnosed hematology oncology patients occurred at various and inconsistent times during treatment. Baseline data revealed that 2.16% of these patients received social work contact ranging from 2 to 43 days after diagnosis. Referrals were typically initiated following elevated distress screening or provider-identified needs. This quality improvement initiative explored the impact of embedding early clinical social work services to increase timely social work support for patients and awareness of the role of social work and resources. Methods All patients newly diagnosed with hematological malignancy were scheduled for first contact with social work within two weeks of meeting with their medical provider. During the first social work appointment, psychosocial screening was performed and social work role and resource education was provided. A follow-up consultation was scheduled if needs were identified. Results 96 out of 122 (78.6%) newly diagnosed patients had social work contact for an initial screen during this quality improvement project. There was a 76.44% increase from baseline in the number of patients receiving social work support as a result of this initiative. 52.08% of the newly diagnosed patients proceeded from this initial screening to a scheduled social worker consult. Conclusion Early and proactive social work outreach through a Responsive Practical Proactive (RPP) approach improved access to psychosocial care and helped address gaps between distress screening and timely intervention.