Citations

Introduction: Pressure-adjusted heart rate (PAHR) provides an integrated assessment of hemodynamic decompensation in critically ill patients. Research Question: How does PAHR perform in critically ill patients with cardiovascular disease? Aims: We sought to evaluate the prognostic value of PAHR on mortality in patients admitted to the cardiovascular intensive care unit (CICU). Methods: A retrospective cohort of patients admitted to the CICU at a tertiary-care academic institution, between 2007 and 2018, who had a transthoracic echocardiogram (TTE) within one day of admission were evaluated. Heart rate (HR), right atrial pressure (RAP), and mean arterial pressure (MAP), obtained from TTE, were used to calculate PAHR as RAP * HR / MAP. Results: Among 5411 patients included for analysis (median age 70.1 years, 38.6% female, 92.4% White), higher PAHR was associated with greater severity of acute illness, burden of comorbidities, and use of critical care therapies. Median values (25 th percentile, 75 th percentile) for HR were 73.0 (63.0, 87.0) beats per minute (bpm), RAP 10.0 (5.0, 14.0) mm Hg, and MAP 81.3 (72.3, 91.7) mm Hg. Median PAHR was significantly higher among patients who died during hospitalization (14.3 bpm vs 6.8 bpm, p <0.001). In addition, TTE measurements of biventricular function, intracardiac filling pressures, and cardiac output were worse among those with higher PAHR (Table). Adjusted in-hospital mortality increased incrementally with higher PAHR, regardless of admission diagnosis, biventricular function, and critical care therapies (adjusted odds ratio [OR] 1.03 per 1 bpm higher, 95% confidence interval [CI] 1.01-1.05, p = 0.001; adjusted OR per quartile 1.37, 95% CI 1.19-1.59, p <0.001, Figure 1). Similarly, one-year mortality increased incrementally with higher PAHR (adjusted hazard ratio 1.03 per 1 bpm higher, 95% CI 1.02-1.04, p <0.001, Figure 2). When compared to component values, including the modified shock index, which is defined by HR / MAP, PAHR had the highest area under the curve (C-statistic 0.75). Conclusions: PAHR is a readily determinable composite measure of filling pressures and vascular resistance that enhances clinical risk stratification of critically ill patients by TTE. Among a diverse cohort of CICU patients, higher PAHR was associated with greater in-hospital and one-year mortality, regardless of admission diagnosis, biventricular function, or illness severity.

Background: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome in women. Although the role of sex-hormones in the pathogenesis of SCAD is unclear, menopausal hormone therapy (HT) after SCAD is generally dissuaded. This limits management options for women with menopausal symptoms, the burden of which among SCAD patients is unknown. Aims: To quantify the burden of menopausal symptoms among women with a history of SCAD. Methods: We surveyed 1617 participants in the Mayo Clinic SCAD "Virtual" Multi-Center Registry on the topic of menopausal symptoms. Among women who had completed key portions of the survey (N = 846), 666 were identified as being either peri or post-menopausal based on patient report. Results: Menopausal symptom prevalence was high in women with SCAD (Figure). Many women (45%) experienced weight changes in the prior 6 months, and most (75%) never used HT for their menopausal symptoms. Forty-five (6%) women experienced menopause at age 45 or younger, and five (1%) experienced menopause at 40 or younger. At the time of the survey, intravaginal estrogen (11.4%) was the most common HT used, while all other individual HT therapies were used by fewer than 5%. Conclusions: Peri- and postmenopausal women with SCAD experience a high burden of menopausal symptoms, and very few use HT outside of intravaginal estrogen. These findings highlight the need for further exploration of treatment strategies for women with menopausal symptoms following SCAD including assessment of benefits versus harms in the subset of women with premature menopause.

ABSTRACT Suicidality contributes substantially to global morbidity and mortality, yet despite its heritability, its biological etiology remains largely elusive. We conducted multi-ancestry genome-wide association study meta-analyses of suicidal ideation (259,747 cases), suicide attempt (64,993 cases), suicide death (9,197 cases), and suicidal behavior (suicide attempt/ death, 75,300 cases), across 54 cohorts (e.g., the Psychiatric Genomics Consortium, Million Veteran Program, UK Biobank). We identified 77 significant loci across meta-analyses, including 59 previously unreported for suicidality. SNP-based heritability ranged from 2.0-6.7% and there were strong, yet incomplete, genetic correlations between suicidality phenotypes (0.70-0.88). Fine-mapping prioritized putative causal SNPs and 20 credible genes. Enrichment analyses implicated synaptic pathways and neuronal populations predominantly in subcortical brain regions (e.g., amygdala excitatory, medium spiny, hippocampal CA1-3). Together, these findings establish suicidality as a polygenic set of traits with both shared and distinct genetic influences, providing a foundation for future studies of suicide biology and etiology.

Abstract Disclosure: A.J. Han: None. S.J. Achenbach: None. B.J. Atkinson: None. I. Bancos: None. Background: The prevalence of adrenal adenomas continues to rise with increased utilization of imaging. However, much remains unknown about what risk factors may predispose individuals to develop adrenal adenomas. In this study, we aimed to identify modifiable and non-modifiable risk factors associated with development of adrenal adenomas. Methods: Historical case-control population study was performed. Patients diagnosed with adrenal adenoma between 2005-2017 with no evidence of overt hormone excess were paired with age- and sex-matched individuals without a diagnosis of adrenal adenoma who had a CT/MRI scan performed within 5 years prior to index date. The prevalence of various social and metabolic risk factors present within 10 years prior to index date (date of adrenal adenoma diagnosis) was compared. Results: Total of 670 patients (median age 63, IQR 53-74 years, 56% women) with adrenal adenomas were identified. At 10 years prior to index date, patients with adrenal adenomas had a higher body mass index (BMI) (median 30.1 vs 28.2 kg/m2, p&lt;0.001), lower socioeconomic status (SES) based on Area Deprivation Index (36.2% with national percentile score &gt;50 vs 30.9%, p=0.037), and more tobacco use (70.2% vs 61.4%, p=0.001), compared to referent subjects. Patients also had a higher prevalence of diabetes (17.5% vs 11.7%, p=0.003) 5-10 years prior to index date, but no difference in prevalence of hypertension, myocardial infarction, chronic kidney disease, atrial fibrillation, stroke, or heart failure was observed between groups. Based on multivariable analysis, increased BMI and tobacco use 10 years prior to index date was associated with increased odds of adrenal adenoma diagnosis with odds ratio (OR) of 1.18 (95% Confidence Interval 1.06-1.32) and 1.41 (1.06-1.87), respectively. Conclusions: Compared to controls, patients with adrenal adenoma were more likely to be obese, have lower SES, endorse tobacco use, and demonstrate evidence of impaired glucose metabolism at least 5-10 years prior to diagnosis. In particular, increased BMI and prior tobacco use was associated with increased odds of adrenal adenoma diagnosis. Further exploration of these intricate relationships may help identify modifiable risk factors for development of adrenal adenomas. Presentation: Saturday, July 12, 2025

Purpose: This study assesses intersurgeon variability in proptosis reduction after orbital decompression for thyroid eye disease. Methods: This multicenter retrospective study included patients with thyroid eye disease who underwent orbital decompression from 1 of 7 surgeons at 7 different institutions between January 2002 and December 2018. Data were included if a single decompression technique was performed on ≥10 patients by ≥2 surgeons. The primary outcome was postoperative change in proptosis with emphasis on comparison among surgeons utilizing similar surgical techniques. Statistical analysis was performed with χ 2 and ANOVA testing, and a multivariable logistic regression model was generated. Results: Six hundred thirty-three orbits that underwent orbital decompression were included. Five different decompression techniques were analyzed: medial wall (n = 29), fat + lateral wall (n = 113), medial wall + floor (n = 123), fat + lateral wall + medial wall (n = 140), and fat + lateral wall + medial wall + floor (n = 228), without significant difference in proptosis reduction among surgeons. Surgeons did not demonstrate significant differences in outcomes at different time points compared with each other or themselves. Outcomes when comparing endoscopic versus open medial wall decompression varied among surgery types. Multivariate modeling revealed a statistically significant association between postoperative change in proptosis with preoperative proptosis ( p < 0.001). Conclusions: Postoperative change in proptosis did not differ significantly between surgeons utilizing similar orbital decompression techniques for patients with thyroid eye disease. This study may strengthen the statistical validity of multicenter clinical trials assessing orbital decompression outcomes performed by surgeons employing uniform surgical techniques, thereby advancing our understanding of optimal surgical management strategies for thyroid eye disease.

Abstract Molecular profiling reveals that up to 40% of advanced biliary tract cancers (BTCs) harbor actionable genomic alterations amenable to matched targeted therapies. However, conventional trial designs typically evaluate these agents in pretreated populations, resulting in approvals for later-line use. Notably, 25–44% of patients with advanced BTC may become ineligible for treatment after first-line therapy due to disease progression or functional decline, thus the real-world survival outcomes with matched therapies remains poorly characterized. This international collaborative study includes data from Mayo Clinic, Duke Cancer Institute, and National Cancer Center East (Japan), as well as a combined dataset from the SCRUM-Japan GOZILA, MONSTAR-SCREEN-1, and MONSTAR-SCREEN-2 projects. We assessed overall survival (OS) of patients based on the presence of actionable alterations and the receipt of matched therapy. To adjust for confounding, we applied propensity score weighting with inverse probability of treatment and multivariate Cox regression modeling, controlling for age, sex, tumor location, prior resection, and mutational subgroup. Among 1,049 patients that were analyzed, 358 (34.1%) harbored actionable alterations, with 160 (44.7%) receiving matched targeted therapy. The matched group (patients with actionable tumors who received a matched therapy) were significantly associated with longer median OS (23.3 months; 95% CI: 19.5–30.4) compared to the unmatched group (14.7 months; 95% CI: 12.8–17.9) and those with non-actionable tumors (17.1 months; 95% CI: 15.5–18.7; HR 0.57, 95% CI: 0.46–0.71; p < 0.0001). The unmatched group also was associated with the lowest three-year OS rate (13% vs. 35% in matched and 19% in actionable groups, respectively; p<0.0001). On multivariable analysis with patients who received ≥2 lines of therapy, receipt of matched therapy remained an independent predictor of improved OS (HR 0.62; 95% CI 0.43–0.90). These findings support the early integration of targeted therapies in BTC management and underscore the need to overcome systemic barriers to treatment access.

Abstract Background The Freelite serum free light chain (FLC) assay has been widely used for detecting and monitoring monoclonal gammopathies. Reference intervals (RIs) established by Katzmann et al. in 2002 have served as the standard values for interpreting kappa/lambda FLC ratios. However, multiple reports suggested an assay drift and clinical laboratories started to move towards locally established RIs given the challenge in verifying original RIs. The assay drift over time increased kappa concentration measurements and was attributed to an interaction between the kappa FLC calibrator and serum proteins, including alpha-1-antitrypsin. A stabilized calibrator was developed to improve consistency of results with original RI. The objective of this study was to assess whether the new updated kappa calibrator would warrant a RI update. Methods Healthy adult donors’ serum samples were selected from the institution quality unit. Exclusion criteria included autoimmune diseases, cancers and renal disease. FLC measurements were obtained on the Optilite by turbidimetry using routine reagents for kappa (old lot); the new lot of reformulated kappa calibrator, and a single measurement for lambda FLC. FLC ratios were calculated with the old lot and new lot. All samples were tested by MASS-FIX to confirm absence of a monoclonal protein. Bootstrap resampling (10,000 replicates) estimated standard errors, with statistical significance defined as p &lt; 0.05. Clinical significance was assessed per CLSI EP28-A3 guidelines. A RI was considered for partitioning by sex if the mean difference between males and females exceeded 25% of the RI width or if &gt;4% of either sex had values beyond RI limits. Similar tests were applied to age groups (&lt;60 and =60 years). Results 465 donors (48.2% male, 51.8% female) aged 30-89 years were used. Sixteen donors with incidental monoclonal proteins identified by MASS-FIX were excluded, for a final n=449. No clinically significant relationships of results were found with sex or age. The updated kappa calibrator resulted in a measurable shift down in FLC values with the new lot of reagents. The kappa FLC concentration and corresponding FLC ratio decreased by a median -12.1%, see table 1 for absolute values When reviewing Optilite results of the new lot, 98/449 samples were outside the kappa concentration original RI (21%). Lambda concentration RI was shifted up on Optilite when compared to original RI but passes verification (1.6% of samples, acceptance criteria &lt; or =10%). 19 samples (4.2%) were outside the original RI for the FLC ratio of 0.26 to 1.65 (all &gt;1.65), which was originally established as a 100% diagnostic range. The calibrator reformulation, while decreasing test results by &gt;10%, was not sufficient to verify the original RI for kappa and still left a few cases outside the original diagnostic range for the FLC ratio. Conclusion This study assessed the impact of the stabilized calibrator on RIs for the Optilite Freelite assay. These findings suggest revisiting existing RIs to ensure continued accuracy in clinical interpretation and should be further evaluated with additional lots of reagents for robustness.

Abstract Background The use of autonomous mobile robots (AMRs) to move materials/supplies is long-standing in manufacturing/warehouse settings and is expanding into hospitals and clinical laboratories. The recently launched Proxie robot (Collaborative Robotics i.e. Cobot) is an AMR that can autonomously move existing carts between defined locations. However, AMRs pose new challenges compared to traditional lab automation. The aims of this study were to: i) perform functional validation to verify Proxie*s manufacturer performance specifications within the laboratory, ii) assess the risk of using Proxie to deliver laboratory specimens, and iii) pilot the use of the Proxie robot to autonomously deliver loaded carts from the Pathology case intake area to the sorting station at Mayo Clinic Laboratories. Methods Functional validation of Proxie consisted of verifying manufacturer’s performance specifications for the following robot parameters (5 test runs): maximum speed, emergency-stop, and ability to maintain localization, travel autonomously, stop and/or avoid moving/fixed objects, and park/unpark. Risk assessment for the robotic use case was performed by a multi-disciplinary team utilizing an AMR risk assessment tool developed by the institutional robotics group. Hazards were categorized as mechanical, electrical, noise, ergonomic, environmental, material/substance or combination risks. Injury severity, exposure(frequency), and avoidance scores were assigned to each hazard to determine negligible-, low-, medium-, high- or very high-risk levels. Proxie’s workstream was evaluated weekly over four weeks by measuring number of cart deliveries, total time/miles traveled, % autonomous deliveries(goal &gt;80%), % on-time deliveries, average±standard deviation(SD) time (min:sec±min:sec) for delivery/return trips, and dwell times at intake/sorting stations. Results Manufacturer’s performance specifications were verified in 100% of test runs. Proxie traveled at human walking speed, stopped within 1 second of emergency stop being enabled, maintained localization, and traveled autonomously for =5 consecutive workflow cycles. Proxie navigated through spaces =4’ wide along fixed pathways and stopped safely when encountering obstacles. Proxie navigated around people and carts in the main 6’ hallway if they were blocking &lt;2’ hallway width. For objects blocking &gt;2’, Proxie stopped and resumed motion after the object moved. After task completion, Proxie side-shifted into the AMR parking space stopping no closer than 7.8” from any object. Twenty-four potential hazards were identified through the risk assessment tool with all risk levels scored as negligible or low. Proxie completed 304 cart deliveries/returns operating 17:35 hours and traveling 11.5 miles during the pilot. The % autonomous deliveries for week 1-4 was 82%,88%,91% and 88%, respectively with =99% on-time deliveries. Delivery from pathology case intake to sorting station averaged 5:43±0:25 min and return trips averaged 3:32±0:34. Proxie dwell times were 13:10±0:33 and 37:34±0:23 min at the pathology intake and sorting stations, respectively. Conclusions The Proxie AMR was capable of successfully and autonomously moving carts with laboratory specimens between the pathology intake and sorting stations of the laboratory during the pilot study. Adding Proxie to this workstream translated to eliminating 5,800 steps and 4 hours 24 min of human cart-pushing per week. Incorporating Proxie into laboratory operations as a cart-moving AMR would increase efficiency and allow laboratory staff to focus on technical, non-repetitive work.

Abstract Background Cryoglobulins are immunoglobulins that precipitate at cold temperatures. They are associated with plasma cell disorders, infectious and autoimmune diseases. Laboratory testing is manual and requires strict temperature control, from keeping the blood sample warm from the moment of draw until processing in the laboratory. Serum samples are transferred to Kolmer glass graduated tubes upon arrival, and kept on ice for visualization of a precipitate for up to 7 days. Because of the temperature variation samples are subjected to, positive sample identification is important. The Kolmer glass tubes are not disposable, and undergo several steps of deidentification and cleaning for reuse. The goal of this project was to improve patient safety and label adherence in cryoglobulin testing by using the Managing for Daily Improvement (MDI) method to monitor and implement changes effectively. Methods During a Plan Do Study Act (PDSA) initiative, it was discovered that labels were not being secured on both ends with tape due to safety concerns when using a box cutter to remove the label prior to cleaning. This practice led to an increase in labels detaching from the glass tubes. To address this issue, we employed the MDI method and established a Key Performance Indicator (KPI) to monitor and evaluate potential changes aimed at improving label adherence. The MDI method facilitates problem-solving through daily visual indicators and discussions by empowering technologists to identify and address issues affecting daily operations. This approach encourages open communication and collaborative problem-solving, allowing the entire team to share insights and solutions in real time. Results A PDSA initiative via MDI uncovered the label adherence challenges. A KPI was developed to monitor interventions to improve the process. First, removable tape was used to secure both sides of the label. Initial results were worse than the original method but slight improvement occurred at about 3 weeks. A Just Do It (JDI) approach was initiated to leave additional space between samples. No improvements were observed and the practice discontinued within &lt; 2 weeks. A second JDI was trialed with a different tool to remove labels post-use. The entire sample identification process was reviewed and the original identification process resumed, by adding scotch tape securing both sides of the labels and using a ceramic box cutter to remove the labels. Significant improvements to labels adherence was observed, from about 60% of labels coming off to zero, while the new tool was also safer for the team. Another PDSA was initiated to investigate if plastic, disposable tubes were a viable option for testing, and a full method validation of the new plastic tubes followed, finally eliminating the challenges with the larger process or reusing glass tubes. Conclusion MDI helped recognize a problem from the front-line and find real time solutions that benefited end-to-end operations. Visual daily indicators clearly showed effectiveness of interventions. Identifying real issues, even if they appear small, can lead to improved patient and staff safety, and empowerment to initiate meaningful change.