Citations

BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T max (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome ( P <0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.

Background: Patients performing self-triage for chest pain need to pick an algorithm which includes questions pertinent to chest pain to triage accurately. Objective: Our study reviews patient self-triage choices and outcomes for patients who completed an online self-triage encounter before being triaged by a nurse for chest pain. Methods: Patients who underwent telephone nurse triage for chest pain, and also had an online self-triage encounter within the prior 24 hours were reviewed for the frequency with which they chose “chest pain” as their symptom to triage for during self-triage, whether they reported chest pain during the self-triage encounter (if asked as part of the algorithm for their chosen self-triage symptom) and whether the patient had any follow up evaluation within 1 week. Results: There were 70 self-triage and nurse triage dyads during the study period where triage nurses chose “chest pain” as the primary symptom to be triaged for during the telephone triage encounter. Of these, only 5 (7.1%) patients chose the “chest pain” self-triage option during online self-triage. During the self-triage encounter, 50 (71%) reported chest pain, 10 (14%) denied chest pain and 10 chose to self-triage their symptoms with an algorithm that did not include a question on whether chest pain was present. Of the 70 total dyads 59 (84%) had a follow up emergency department (40 patients) or office visit (19 patients) documented. Conclusion: Most patients chosen to be triaged for chest pain by triage nurses did not choose the online self-triage algorithm for chest pain even though the majority did report chest pain during their self-triage encounter (when asked). This is concerning from a safety perspective as a non-chest pain self-triage option chosen by the patient may not always ask about the presence or absence of chest pain and thus could increase the risk of being triaged inaccurately. Implications for improvement of self-triage could include diagrams for patients to choose the symptom area.

Abstract Disclosure: J.R. Hewlett: None. J.G. Sfeir: None. R.A. Wermers: None. J.J. Schmitz: None. Percutaneous ethanol ablation (PEA) is a non-surgical technique used in the management of hyperparathyroidism (HPT) since the 1980s. Previously published cohorts are small and/or focused on patients with primary hyperparathyroidism (PHPT) in the setting of multiple endocrine neoplasia type 1 (MEN1). New randomized controlled trial data suggests similar response rates between parathyroidectomy and PEA (98.5% vs 91.1%) for uniglandular disease, and a previously published cohort of PEA in patients with MEN1 and recurrent multiglandular PHPT at our institution reported post-PEA normocalcemia in 74.5% of patients. This retrospective cohort study examined the treatment response to PEA in those with PHPT (including MEN1) and tertiary HPT (THPT) at a single institution between 1997-2023. Those with secondary hyperparathyroidism or eucalcemic PHPT were excluded. The primary outcome was a serum calcium ≤10.1 mg/dL at 3-6 months and secondary outcomes included number and volume of ethanol injections, time to recurrence of HPT, and complications of PEA. A total of 83 patients were included. Most were women (62.7%) and the median age at diagnosis of HPT was 40 years. The majority had PHPT (90.4%), and many (86.7%) had previously undergone surgery. The most common indications for PEA were risk for hypoparathyroidism with additional surgery (72.3%) poor surgical candidacy (16.9%), and patient preference (8.4%). The mean calcium was 10.7 mg/dL (95% CI 10.56-10.85) and the mean PTH was 164 pg/mL (95% CI 120.6-208.3) prior to PEA. The mean number of ethanol injections was 3.0 (95% CI 2.6 – 3.4) and the cumulative volume of ethanol was 1.2 mL (95% CI 1.0-1.4). At 3-6 months, 68.3% of treated patients had calcium ≤10.1 mg/dL with a mean value of 9.4 mg/dL (95% CI 9.1-9.6). Of those, 42% did not have recurrence at most recent follow-up. Of those with recurrence, a post-PEA calcium ≤10.1 mg/dL at 3-6 months was associated with a longer time to recurrence than those without (36.9 months versus 3.75 months; P=0.0009). There was no significant difference between the number of times (P=0.56) or the volume (P=0.41) of ethanol injected between those with calcium of ≤10.1 mg/dL at 3-6 months and those without. Hypocalcemia was observed in 8 (9.6%; transient in 75%), hypoparathyroidism in 3 (3.6%; transient in 66.7%), laryngeal nerve injury in 2 (2.4%; transient in 50%), and hoarseness in 9 (10.8%; transient in 100%) patients. This is the largest North American cohort of patients who received PEA for HPT and represents a broader review of HPT than previously published. Our rate of post-PEA eucalcemia is lower than previously reported, however this cohort was complex with a high proportion of multiglandular disease (80.7%), MEN1 (39.8%) and prior surgeries (mean 1.7 per person; 95% CI 1.5-1.9). PEA remains a safe and effective treatment for patients with recurrent HPT, especially those at high risk of post-surgical hypoparathyroidism. Presentation: Monday, July 14, 2025

Abstract Disclosure: S.R. Chacko: None. C.A. Villavicencio Torres: None. K. Yu: None. S.G. Waguespack: None. L. Lu: None. Z. Belaya: None. T. Bandgar: None. A. Sada: None. O. Ragnarsson: None. B. Altieri: None. A. Newman: None. P. Vibhatavata: None. M. Tóth: None. E.V. Varlamov: None. C. Badiu: None. A. Paissan: None. M. St-Jean: None. H. Falhammar: None. N. Imamudeen: None. L. Haberbosch: None. M. Bobrowicz: None. A. Tabarin: None. R. Shah: None. M.R. Gadelha: None. A. Peersen: None. W.F. Young: None. J. Kaplan: None. J. Varghese: None. M.A. Habra: None. O. Golounina: None. G.A. Melnichenko: None. A.R. Lila: None. C. Yamichannaiah: None. I. Bancos: None. Context: Cushing syndrome (CS) due to ectopic ACTH secretion (EAS) is a rare condition, associated with severe hypercortisolism and consequent morbidity and mortality. Its varied and often emergent presentation make diagnosis and treatment challenging. Objectives: 1.Characterize clinical and biochemical presentation of EAS. 2.Describe the scope of hypercortisolism-related complications, overall and CS-specific mortality. 3.Identify factors associated with CS-specific mortality. Methods: We conducted a multicenter retrospective cohort study in patients with EAS at 37 centers. Outcomes were clinical/biochemical severity scores, complications, overall and CS-specific mortality. Results: In 1053 patients [median age at diagnosis 52 years (IQR 37-64), 57% women], metastatic disease was present at diagnosis in 585 (56%). The most common sources of EAS were bronchial neuroendocrine neoplasm (NEN) (304, 29%), pancreatic NEN (114, 11%) and small cell lung carcinoma (114, 11%), with the source of EAS being occult in 192 (18%). Clinical and biochemical severity scores were severe in 475 (45%) and 873 patients (92%) respectively. Hypokalemia was present in 819 patients (78%) in the year prior to diagnosis. Of 342 patients (32%) who had IPSS, 301 (88%) suggested an ectopic source, 7 (2%) a pituitary source, and 23 (7%) were non-diagnostic. Of 595 patients who had both functional and cross-sectional imaging, discordant findings were seen in 122 (21%), concordant lesion was seen on both in 326 (55%), and no lesion in 147 (25%). Of those with discordant results, cross-sectional imaging was accurate in 66 (54%) and functional imaging in 56 (46%).Management included medical therapy alone in 237 (23%), surgical excision of the source of EAS in 158 (15%), bilateral adrenalectomy in 77 (7%) and multimodal therapies in 498 patients (47%). Complications within 5 years after diagnosis included hospitalization related to CS or its therapy in 351 (33%), infection in 337 (32%), thromboembolic event in 102 (10%), cardiovascular event in 83 (8%) and cerebrovascular event in 27 (3%). During a median follow-up of 35 months (IQR 20-122) from CS diagnosis, death occurred in 462 patients (44%), with the cause of death related to CS in 149 (14%). CS-specific mortality was higher in metastatic compared with non-metastatic disease (19% vs. 7%, P&lt;0.001). On multivariable analysis of age, sex, clinical and biochemical severity, older age (HR 1.03, 95% CI: 1.02-1.04) and lower clinical severity score (HR 0.97, 95% CI: 0.94-0.99), were associated with higher CS-specific mortality. Conclusion: Our interim analysis, the largest worldwide, found that most patients with EAS had severe hypercortisolism and hypokalemia. Metastatic disease was present in 56%, and the source of EAS was occult in 18%. CS-related death occurred in 14%, emphasizing the need for urgent management. Presentation: Monday, July 14, 2025

Adolescents and young adults (AYA; ages 15–39) with acute leukemia have significant unmet supportive care needs. This pilot study integrated same-day palliative care (PC) into an AYA leukemia clinic, measuring symptom burden (SB) with validated symptom assessment tools at baseline, 3, and 6 months. Among 31 patients, moderate-severe symptoms included tiredness, anxiety, and poor appetite. AYAs experienced high SB and psychological distress, regardless of care phase or sociodemographics. With PC integration, tiredness and depression improved significantly; no symptoms worsened. Half of the PC visits led to management changes. Early integration of symptom-focused PC was feasible, value-adding, and well-received by patients.

The COVID-19 pandemic caused unprecedented disruption of social networks and negatively impacted social determinants of health (SDoH, e.g., economic stability, mental health, health care access) among African Americans. The FAITH! (Fostering African-American Improvement in Total Health!) Program, an academic-community partnership with African American churches, pivoted to pandemic-related impacts on health behaviors of African Americans. This exploratory, cross-sectional study examined associations between multilevel factors influencing difficulty maintaining a healthy lifestyle during the early pandemic phase, including mental/emotional health and COVID-19 hardships (e.g., job/food/housing insecurity, paying utilities). An online survey was distributed via FAITH!-affiliated churches and social media. Logistic regression (odds ratios [ORs], adjusted for age/gender) and associated 95% confidence intervals [CIs]) examined associations between difficulty maintaining a healthy lifestyle and multilevel factors. Greater than half of respondents reported difficulty maintaining a healthy lifestyle (N = 169, 54% [91/169]). Adjusted odds of having difficulty maintaining a healthy lifestyle were greater for those reporting mental/emotional health issues (high-stress OR 4.0; 95% CI [1.9,8.9], p < .001); occasional symptoms of depression (OR 3.7; 95% CI [01.9,7.7]; p < .001); anger (OR 2.5; 95% CI [1.2,5.4]; p = .044), and anxiety (OR 2.8; 95% CI [1.4,6.0]; p = .008)). COVID-19 hardships of job insecurity (OR 1.4.; 95% CI [0.7, 2,8]; p = .015), difficulty paying rent (OR 4.4; 95% CI [2.1,9.9]; p < .001) or difficulty paying for food/utilities (OR 5.4; 95% CI [2.6,11.7]; p < .001) were associated with difficulty maintaining a healthy lifestyle. Our study revealed the negative impact of mental/emotional health and COVID-19 hardships on maintaining a healthy lifestyle among African Americans. This could inform SDoH-focused lifestyle interventions during future public health crises.

Abstract Korpinen, M, Magee, M, Dulak-Sigler, C, Fields, JB, Jagim, AR, King, E, Burke, A, and Jones, MT. Seasonal changes in neuromuscular performance across a training year in women collegiate lacrosse athletes. J Strength Cond Res 39(11): 1186–1193, 2025—Body composition and athlete load management are vital to adequate training stimuli and to mitigate neuromuscular (NM) fatigue. Research is limited regarding NM performance (NMP) in women lacrosse athletes. Therefore, the purpose of this study was to investigate changes in NMP in women lacrosse athletes across a training year. Collegiate women lacrosse athletes ( n = 9, mean ± SD ; age = 19.1 ± 0.9 years, height = 168.4 ± 6.8 cm, body mass = 68.0 ± 8.1 kg) completed countermovement jump (CMJ) and isokinetic strength (IS) testing of dominant and nondominant legs 4 times throughout the season: preseason start, preseason end, in-season end, and off-season end to assess NMP. Measures included (a) CMJ output variables of reactive strength index modified (RSImod), jump height, relative values of braking force, peak power, peak propulsive force, impulse; (b) CMJ strategy variables of time-to-takeoff, eccentric duration, concentric duration, relative braking time, CMJ depth; and (c) IS relative peak torques of quadriceps and hamstrings musculature. Secondary measures including body composition variables of body mass, % body fat (%BF), and fat-free mass. Repeated measures ANOVA with Bonferroni post hoc analysis assessed changes in CMJ and IS parameters to determine patterns in NMP ( p < 0.05). Changes observed from preseason start to offseason end included increased CMJ depth ( p = 0.019), relative braking time ( p = 0.009), and %BF ( p = 0.01). The IS variables increased throughout the training year, except for a decrease during preseason, perhaps indicative of overreaching. Negative changes in alternative CMJ variables and body composition reduced NMP, which highlights the importance of off-season program design and implementation to elicit desired training adaptations.

Abstract Background Sickle cell disease (SCD) is a hemoglobinopathy with limited treatment options. Genetic modification of the patient's own hematopoietic stem cells (HSCs) offers an avenue to curative therapy using the patient's own cells. Many challenges exist in collecting sufficient numbers of starting material for manufacturing, beginning with the pre‐mobilization optimization of the patient to the mobilization, collection, and post‐collection phases. Study Design and Methods A working group within the Cellular Therapy Subcommittee of the American Society for Apheresis Clinical Applications Committee describes the challenges associated with apheresis collection of the starting material for gene therapy (GT) product manufacturing for patients with SCD and discusses potential strategies for overcoming these challenges. Results and Discussion Patients must undergo automated red blood cell exchange (RCE) to lower hemoglobin S in a relatively short window of time before apheresis collection of HSCs. The risks and benefits of transfusion as well as the logistics of providing adequate and appropriate blood products must be considered. Limited agents are available for mobilization of HSCs into the peripheral blood for collection and the timing of administration is short. Each collection cycle consists of RCE followed by at least three mobilization and apheresis collection events in addition to collecting backup cells. More than one cycle is typically needed to collect enough cells for GT drug product manufacturing. Optimization of patient factors and apheresis instrument parameters leads to better collection yields. Early and frequent ongoing coordination with all stakeholders involved is critical to developing personalized treatment plans for patients.

Importance The effect of cornea donor diabetes on endothelial cell density (ECD) and morphometry after Descemet membrane endothelial keratoplasty (DMEK) is not known. Objective To determine whether endothelial cell loss (ECL) and morphometric changes 1 year after successful DMEK are related to cornea donor’s diabetes status. Design, Setting, and Participants This was a multicenter, double-masked, randomized clinical trial conducted from February 2022 to July 2024 at 28 US clinical sites (46 surgeons) and 13 eye banks. Included in the trial were the eyes of recipients (some of whom received tissue from donors without diabetes and others who received tissue from donors with diabetes) who underwent successful DMEK, primarily for Fuchs endothelial corneal dystrophy, and had at least 1 analyzable postoperative endothelial image. Intervention DMEK performed with a cornea from a donor without or with diabetes, assigned using a minimization procedure to achieve an approximate 2:1 distribution. Main Outcomes and Measures ECD, ECL, coefficient of variation in cell area (CV), and percentage of hexagonal cells (HEX) at 1 year from eye bank and postoperative specular central endothelial images. Results A total 1274 eyes of 982 recipients (mean [SD] age, 70 [8] years; 569 female [57.9%]; 816 [64.1%] with tissue from donors without diabetes and 458 [35.9%] with tissue from donors with diabetes) were included in the study. Preoperatively, mean (SD) central ECD in tissue from donors without diabetes and with diabetes were 2676 (290) cells/mm 2 and 2671 (286) cells/mm 2 , respectively. At 1 year, mean (SD) ECL was 28.3% (16.1%) and 28.0% (17.0%), in the donor groups without and with diabetes, respectively (adjusted mean difference = −0.4%; 95% CI, −2.3% to 1.4%), resulting in a mean (SD) 1-year ECD of 1927 (498) cells/mm 2 and 1920 (496) cells/mm 2 , respectively (adjusted mean difference = 10 cells/mm 2 ; 95% CI, −36 to 56; P = .95). No difference in ECD at 1 year associated with diabetes severity was noted ( P = .97). Mean (SD) CV did not differ at 1 year between the 2 groups of eyes (31.5% [4.1%] vs 31.4% [4.1%]; adjusted mean difference = −0.4%; 95% CI, −0.9% to 0.1%; P = .51), and mean (SD) HEX did not differ at 1 year between the 2 groups of eyes (57.7% [5.8%] vs 57.2% [5.8%]; adjusted mean difference = 0.1%, 95% CI, −0.8% to 0.9%; P = .33). Conclusions and Relevance This randomized clinical trial found that ECL and morphometry 1 year after DMEK were not affected by cornea donor diabetes status. With comparable 1-year graft success with tissue from donors with and without diabetes demonstrated in this trial, these findings support the use of corneas from donors with diabetes for endothelial keratoplasty procedures. Trial Registration ClinicalTrials.gov Identifier: NCT05134480