Citations

We examined outcomes of a quality improvement (QI) culture implemented through Mayo Clinic Quality Academy by retrospectively reviewing data from QI projects credited from 2019 to 2024. Data analyzed included roles, member count, region, project details, priorities, financial outcomes, methodologies, and lessons learned. During the study period, Mayo Clinic Quality Academy credited 1106 projects involving 10 063 members (median, 8 members per project). Physicians participated in 52.4% of projects, allied health professionals in 83.6%, and nurses in 55.2%. Among all projects, teamwork (54.0%) and efficiency (52.8%) were the most common organizational priorities; among National Academy of Medicine priorities, efficiency was the most common (32.2%), followed by safety (20.7%) and patient-centeredness (18.9%). Model for improvement was the most prevalent QI methodology (29.2%). Most participants (93%) believed the QI project changed the way they work. Cultivating a QI culture influences health care delivery by emphasizing efficiency, teamwork, operational performance, patient outcomes, satisfaction, and financial benefits.

Abstract Background: Tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager (TCE) is FDA approved in patients (pts) with extensive stage small cell lung cancer (ES-SCLC), after progression on frontline chemoimmunotherapy. We aimed to evaluate the immune cell profile in pts who received this therapy in standard-of-care (SOC) practice with progression free survival (PFS) less than and greater than two months (mo). Methods: Patients who received tarlatamab at Mayo Clinic Rochester and consented to immuno phenotyping of blood are included in the present study. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Microsoft Excel and PRISM. Results: Eighteen patients with median age 64 (range 37-79) were included in the study. 66% of our cohort were women and 83% had present or past history of smoking, with an average of 40 pack years (range 26-60). With a median follow-up of 2 months, the median PFS for the cohort was 1.5 mo (range 0.33-2.76 months). 61% (13/18) of patients had PFS <2mo. 39% (5/18) had PFS>2mo and of which, three patients had partial response with one maintaining stable disease and one patient with mixed response. At baseline (BL), there were no difference in T cell, CD4 or CD8 cell count between patients in the PFS<2mo and PFS>2mo groups. Patients with PFS<2mo had higher exhausted CD8 T cells compared to those in the PFS>2mo group (CD8+PD1+TIGIT+CD57+, PFS<3mo vs >3mo, cells/mL: 7.14±4.28, 1.58±1.37, p=0.009). Additionally, when analyzing the B-cell population, the PFS<2mo group had lower percentage of B cells compared to the group with PFS>2mo at baseline (6.0±7.5, 10.4±14, p=0.02). At day 7, the group with PFS<2mo had lower Treg compared to the group with PFS>2mo (2.88±1.38, 4.60±1.47, p=0.02). Also, the PFS<2mo group had an increase of B cells compared to the group with PFS>2mo at day 7(<2mo vs >2mo: 10.0±14, 4.37±3.07, p=0.04). Finally, the group with PFS>2mo had decrease in total monocytes (mono), classical mono, and immunosuppressive cells (PFS<2mo vs >2mo, Mono: 340±347, 253±106, p=0.04. Classical mono: 305±283, 155±109, p=0.02. CD14+HLA-DRneg: 105.8±96, 12±39, p=0.03) compared to the group with PFS<2mo by day 7. While no changes were seen between BL and day 7 for intermediate mono in PFS<2mo group, PFS>2mo group had decreased post treatment intermediate monocytes (BL vs day 7, cells/mL, intermed mono: 32.5±15,17.7±6.2, p=0.03). Conclusion: In this study investigating the SOC outcomes of tarlatamab, early progression was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at AACR meeting. Citation Format: Dhauna Karam Prasad, Andre De Menezes Silva Corraes, Malvika Gupta, Audrey Ma, Chen Wu, Zuoyi Shao, Kevin Reagan, Rayaan Kamal, Ashley Potter, Abdullah Al-Ajmi, Syeda Mina, Sykler J. Taylor, Antonious Hazim, Anastasios Dimou, Kaushal Parikh, Mohammed Shanshal, Ailsa Luce, Anna Schwecke, Julian Molina, Aaron Mansfield, Katherine Smith, Lucy Holmes, Haidong Dong, Yi Lin, Konstantinos Leventakos. Immune cell profile changes in patients treated with tarlatamab for extensive stage small cell lung cancer in real world practice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3931.

Variants in TMEM106B and GRN , which encode lysosomal proteins, interact through unknown mechanisms to increase the risk of age-related cognitive decline and neurodegeneration. Here, we show that these variants converge on a single molecular intermediate: the cleaved intra-lysosomal fibril core of TMEM106B, a precursor to amyloid fibrils that accumulate in the aging brain. A protein-coding TMEM106B risk variant (p.T185) drives fibril core accumulation by impairing its degradation and GRN risk variants amplify this effect. Mice over-expressing the fibril core develop hallmarks of neurodegeneration, and cryo-electron tomography reveals intra-lysosomal fibrils in cultured neurons, mice, and diseased human brain. In GRN -mutation carriers, in whom fibril burden is greatest, fibrils extrude through ruptured lysosomal membranes. These findings identify intra-lysosomal TMEM106B fibrillization as a convergent neurodegeneration mechanism and potential therapeutic target.

ABSTRACT Electrocardiography (ECG) is a critical diagnostic tool for identifying cardiac conditions. While standard lead positions are widely used to ensure diagnostic accuracy, alternative lead placements have been developed to address specific clinical scenarios. These alternative configurations can overcome physical or technical challenges, enhance rhythm assessment, improve signal quality, and provide greater specificity for certain conditions, ultimately enabling more personalized diagnostic strategies. This paper examines the clinical significance of alternative ECG lead positions, highlighting their advantages, limitations, and potential applications in various clinical settings.

Precis: This retrospective multicentre study of 77 NTG eyes undergoing phacoemulsification and Hydrus implantation showed a sustained reduction in medication burden, while maintaining IOP levels. Complications were rare and nonsight-threatening. Purpose: To evaluate 36-month outcomes of combined phacoemulsification and Hydrus Microstent implantation (Phaco-Hydrus) in eyes with normal tension glaucoma (NTG). Methods: This multicentre retrospective study included 77 NTG eyes from Singapore and Canada that underwent Phaco-Hydrus between 2014 and 2023. Primary outcomes were changes in intraocular pressure (IOP) and medication burden, and cumulative success probabilities from Kaplan-Meier (KM) analyses. Longitudinal changes were analysed using generalized estimating equations. Results: Of 77 eyes, 31 completed 36 months of follow-up. Mean baseline IOP and medications was 13.5±2.5 mm Hg and 1.7±0.9, respectively. No significant reductions in IOP were observed. A sustained reduction in medication use was observed at all follow-up timepoints ( P ≤0.001). At 36 months, medication use decreased by −0.7±0.2 [adjusted mean difference±SE of the mean [SEM]]. Proportion of medication-free eyes increased from 7.8% (n=6/77) at baseline to 45.2% (n=14/31) at 36 months. Cumulative success probabilities varied widely based on definitions. When defined as a decrease in ≥1 medication from baseline without an increase in IOP, or IOP ≤15 mm Hg and reduced ≥20% from baseline while medication-free, and no additional laser or incisional glaucoma surgery, this was 40.7% at 36 months. No visual field mean deviation progression was detected. Adverse events were infrequent and nonsight-threatening. Conclusion: In eyes with NTG, Phaco-Hydrus may offer a greater role in medication reduction or achieving a medication-free status over 36 months, rather than absolute IOP reduction.

Abstract The transition from internship to residency represents an important period for trainees. However, little is known about self-assessed preparedness among physiatry trainees. This national cross-sectional exploratory survey of United States postgraduate year 2–4 physiatry residents aimed to examine self-reported preparedness at the start of postgraduate year 2. A total of 109 postgraduate year 2–4 residents completed this survey, with 57.8% (63/109) reporting feeling prepared to assume patient care responsibilities at the start of postgraduate year 2 and 42.2% (46/109) reporting feeling unprepared to do so. Specific internship experiences (e.g., developing comfort handling overnight calls and rapid responses), but not type of intern year (e.g., transitional year, preliminary internal medicine or surgery year, intern year included in a categorical physiatry residency program) may be associated with self-reported clinical preparedness. Further research is warranted to explore in more detail factors identified as potentially associated with self-assessed clinical preparedness, as well as opportunities to identify and address physiatry trainee needs.

Abstract Chromosome 5p15.33 harbors several independent association signals which demonstrate antagonistic pleiotropy across cancer types, with causal mechanisms largely unresolved. To identify functional variants and enhancer elements at this locus, we performed statistical fine-mapping followed by massively parallel reporter assays (MPRA) and proliferation based CRISPRi screens. This approach identified eight multi-cancer functional variants (MCFVs) across three GWAS signals. Targeting rs421629 (part of the CLPTM1L signal marked by rs465498) with CRISPRi revealed opposing effects on TERT expression in pancreatic versus lung cancer cells, consistent with the antagonistic pleiotropy observed for this signal. Furthermore, CRISPRi nominated an intronic CLPTM1L variable number tandem repeat (VNTR) as a potent enhancer. Long-read sequencing established VNTR polymorphisms as potential causal variants for the rs465498 signal. We showed that Hippo-pathway transcription factors mediate VNTR enhancer activity in lung and pancreatic cancer cells. Together, these findings indicate that cancer susceptibility at 5p15.33 may be mediated by both SNPs and VNTRs and provide an integrated framework for resolving complex pleiotropic loci.

382 Background: Androgen receptor signaling drives prostate cancer (PC) progression, and genes involved in androgen production, uptake, and conversion (APUC) are key therapeutic targets. We previously defined a 6-APUC gene set ( HSD3B1, HSD3B2, CYP3A43, CYP11A1, CYP11B1, and CYP17A1 ), that identified metastatic PC with favorable prognosis and predict docetaxel benefit. However, the expression landscape and clinical relevance of APUC genes have not been interrogated in localized PC. Methods: We analyzed the expression of 21 APUC genes in 55,329 radical prostatectomy tumor samples that underwent Decipher prostate genomic classifier (GC) testing (Veracyte Inc) between 2016-2024. Baseline clinical/pathologic factors were retrieved from Decipher GRID database (NCT02609269). Associations between gene expression quartiles with PathoGenomic Risk Factors (PGRF) including Very High Decipher score >0.85 (VHD), Grade Group (GG) 4-5, LNI and SVI were examined. Associations with distant metastatic (DM) outcomes and metastasis free survival (MFS) were evaluated using logistic regression in Mayo545 and Cox regression in Meta855 RP cohorts, respectively. Results: High expression of SRD5A2 was associated with favorable PGRF (lower odds ratio (OR), p<0.0001), lower rate of development of DM (OR 0.36, p<0.05), and longer MFS (Hazard ratio (HR) 0.51, p<0.05). HSD17B6 showed similar results for PGRF (lower OR, p<0.0001), DM (OR 0.58, p<0.05) and longer MFS (HR 0.39, p<0.05) despite being associated with GG4-5 and SVI+ in samples with VHD. In contrast, high expression of SRD5A3 and HSD17B10 had high OR for PGRFs (p<0.0001). High expression of SLCO2B1 , an androgen uptake gene, had the strongest association with GG4-5 and SVI/LNI (p<0.001 for both). We noted that SRD5A2 lacked correlation with SRD5A1 and SRD5A3 , which instead correlated with each other. Compared to all APUC genes, SRD5A2 had limited correlations with almost all APUC genes, including ones that exhibited robust cross correlation with each other . Similar to our prior finding, most APUC genes demonstrated negative correlation with AR expression and AR activity signatures. Key outcomes were validated based on transcriptomic data from 492 samples from TCGA database. Conclusions: Comprehensive analysis of 21 APUC genes in over 55,000 PC identified distinct, context-dependent associations with metastatic outcomes and clinical and molecular risk factors. Notably, high SRD5A2 expression was associated with lower odds of high-risk features and metastatic outcomes, whereas SRD5A1 and SRD5A3 linked to adverse outcomes, suggesting critical yet divergent roles among 5-alpha-reductase family members. These findings underscoring androgen-metabolic heterogeneity and highlighting SRD5A2 as a potential biomarker of indolent biology in localized prostate cancer.