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Evgenii Belykh,1 Arpan A Patel,1 Eric J Miller,1 Baran Bozkurt,1 Kaan Yağmurlu,1 Eric C Woolf,2 Adrienne C Scheck,2 Jennifer M Eschbacher,3 Peter Nakaji,1 Mark C Preul1 1Department of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA; 2Neuro-Oncology Research, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA; 3Department of Neuropathology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA Background: Confocal laser endomicroscopy (CLE) is used during fluorescence-guided brain tumor surgery for intraoperative microscopy of tumor tissue with cellular resolution. CLE could augment and expedite intraoperative decision-making and potentially aid in diagnosis and removal of tumor tissue.Objective: To describe an extension of CLE imaging modality that produces Z-stack images and three-dimensional (3D) pseudocolored volumetric images.Materials and methods: Hand-held probe-based CLE was used to collect images from GL261-luc2 gliomas in C57BL/6 mice and from human brain tumor biopsies. The mice were injected with fluorescein sodium (FNa) before imaging. Patients received FNa intraoperatively, and biopsies were imaged immediately in the operating room. Some specimens were counterstained with acridine orange, acriflavine, or Hoechst and imaged on a benchtop confocal microscope. CLE images at various depths were acquired automatically, compiled, rendered into 3D volumes using Fiji software and reviewed by a neuropathologist and neurosurgeons.Results: CLE imaging, Z-stack acquisition, and 3D image rendering were performed using 19 mouse gliomas and 31 human tumors, including meningiomas, gliomas, and pituitary adenomas. Volumetric images and Z-stacks provided additional information about fluorescence signal distribution, cytoarchitecture, and the course of abnormal vasculature.Conclusion: 3D and Z-stack CLE imaging is a unique new option for live intraoperative endomicroscopy of brain tumors. The 3D images afford an increased spatial understanding of tumor cellular architecture and visualization of related structures compared with two-dimensional images. Future application of specific fluorescent probes could benefit from this rapid in vivo imaging technology for interrogation of brain tumor tissue. Keywords: 3D microscopy, confocal laser endomicroscopy, fluorescein sodium, fluorescence-guided brain tumor resection, glioma, brain tumor, volumetric imaging

Introduction: For decades, first-line treatment for advanced/metastatic urothelial cancer has been platinum-based chemotherapy. However, many patients do not respond to platinum-based chemotherapy alone, and the vast majority do not have durable responses. While immune checkpoint blockade has demonstrated benefit in this setting, initial trials of concurrent chemotherapy and immune checkpoint blockade did not demonstrate improvements in overall survival., Areas Covered: The recent CheckMate 901 trial compared gemcitabine, cisplatin, plus nivolumab to gemcitabine and cisplatin alone for first-line treatment of advanced/metastatic urothelial cancer. This was the first trial to demonstrate significant benefit in the combined chemotherapy and immune checkpoint blockade arm in advanced/metastatic urothelial cancer, most significantly showing an improvement in the primary outcomes of progression-free survival and overall survival, and the exploratory outcomes of objective response rate, complete response rate, and duration of complete response., Expert Opinion: The combination of gemcitabine, cisplatin, plus nivolumab represents a new first-line treatment option for metastatic urothelial cancer. This article details the clinical benefit observed and how this establishes proof-of-concept for prior hypotheses related to the importance of the specific chemotherapy regimen combined with immune checkpoint blockade, revolving around immunomodulatory mechanisms of action of cisplatin, and synergy of these mechanisms with immunotherapy.

Background and Aims: The diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) requires advanced imaging, precluding large-scale pre-clinical testing. Artificial intelligence (AI)-enabled transthoracic echocardiography (TTE) and electrocardiography (ECG) may provide a scalable strategy for pre-clinical monitoring., Methods: This was a retrospective analysis of individuals referred for nuclear cardiac amyloid testing at Yale-New Haven Health System (YNHHS, internal cohort) and Houston Methodist Hospitals (HMH, external cohort). Deep learning models trained to discriminate ATTR-CM from age/sex-matched controls on TTE videos (AI-Echo) and ECG images (AI-ECG) were deployed to generate study-level ATTR-CM probabilities (0-100%). Longitudinal trends in AI-derived probabilities were examined using age/sex-adjusted linear mixed models, and their discrimination of future disease was evaluated across preclinical stages., Results: Among 984 participants at YNHHS (median age 74 years, 44.3% female) and 806 at HMH (69 years, 34.5% female), 112 (11.4%) and 174 (21.6%) tested positive for ATTR-CM, respectively. Across cohorts and modalities, AI-derived ATTR-CM probabilities from 7,352 TTEs and 32,205 ECGs diverged as early as 3 years before diagnosis in cases versus controls ( p time(x)group interaction ≤ 0.004). Among those with both AI-Echo and AI-ECG available one-to-three years before nuclear testing (n=433 [YNHHS] and 174 [HMH]), a double-negative screen at a 0.05 threshold (164 [37.9%] and 66 [37.9%], vs all else) had 90.9% and 85.7% sensitivity (specificity of 40.3% and 41.2%), whereas a double-positive screen (78 [18.0%] and 26 [14.9%], vs all else) had 85.5% and 88.9% specificity (sensitivity of 60.6% and 42.9%)., Conclusions: AI-enabled echocardiography and electrocardiography may enable scalable risk stratification of ATTR-CM during its pre-clinical course.

Background: Estimation of coronary artery calcification (CAC) can provide important prognostic information in patients with suspected coronary artery disease., Objectives: The authors aimed to investigate whether CAC evaluation offers additional insight into the association of stress electrocardiographic (ECG) changes with adverse outcomes in patients undergoing myocardial perfusion imaging (MPI)., Methods: Twelve thousand two hundred sixty-five patients (47% female, median: 64 (56-73) years, body mass index: 29 ± 7 kg/m 2 ) who underwent exercise treadmill or regadenoson single-photon emission computed tomography/computed tomography (CT) MPI during June 2016 to May 2022 at a large academic center were retrospectively studied., Results: During the median follow-up of 1.6 (IQR: 0.5-3.0) years, the primary outcome (3-year composite of death, myocardial infarction, or coronary revascularization, major adverse cardiac event [MACE]) occurred in 1,422 patients. Within participants with normal perfusion, MACE rate was the highest in patients with CAC with or without ischemic stress ECG (9.6% and 7%, respectively), and low event rates were observed in patients without CAC with or without ischemic stress ECG (0.5% and 1.9% respectively). In a subgroup analysis, all CAC grades (mild, moderate, severe) were independently associated with worse 3-year composite endpoint rates. In multivariable analysis, the presence of CAC was associated with MACE independent of ischemic ECG changes in both the overall cohort (P < 0.001) and when restricting the analysis to patients with normal perfusion (P < 0.05)., Conclusions: In patients with normal single-photon emission computed tomography/CT MPI, CAC is strongly associated with adverse outcomes independent of ischemic ECG changes with low event rates in patients without CAC on attenuation CT irrespective of ischemic stress ECG changes., Competing Interests: Funding support and author disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

We previously demonstrated that a deep learning (DL) model of myocardial perfusion SPECT imaging improved accuracy for detection of obstructive coronary artery disease (CAD). We aimed to improve the clinical translatability of this artificial intelligence (AI) approach using the results to derive enhanced total perfusion deficit (TPD) and 17-segment summed scores. Methods: We used a cohort of patients undergoing myocardial perfusion imaging within 180 d of invasive coronary angiography. Obstructive CAD was defined as any stenosis of at least 70% or at least 50% in the left main coronary artery. We used per-vessel DL predictions to modulate polar map pixel scores. These transformed polar maps were then used to derive TPD-DL and summed stress score-DL. We compared diagnostic performance using area under the receiver operating characteristic curve (AUC). Results: In the 555 patients held out for testing, the median age was 65 y (interquartile range, 57-73 y), and 381 (69%) were male. Obstructive CAD was present in 329 (59%) patients. The prediction performance for obstructive CAD of stress TPD-DL (AUC, 0.837; 95% CI, 0.804-0.870) was higher than AI prediction alone (AUC, 0.795; 95% CI, 0.758-0.831; P = 0.005) and traditional stress TPD (AUC, 0.737; 95% CI, 0.696-0.778; P < 0.001). Summed stress score-DL had the second highest prediction performance (AUC, 0.822; 95% CI, 0.788-0.857) and higher AUC than traditional quantitative summed stress score (AUC, 0.728; 95% CI, 0.686-0.769; P < 0.001). At a threshold of 5%, the sensitivity and specificity of TPD rose from 72% to 79% and from 62% to 70%, respectively. Conclusion: Integrating AI predictions with traditional quantitative approaches leads to a simplified AI approach, presenting clinicians with familiar measures but operating with higher accuracy than traditional quantitative scoring. This approach may facilitate integration of new AI methods into clinical practice., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Transthyretin cardiac amyloidosis (ATTR-CA) is disproportionately diagnosed in older men. However, studies suggest that the true prevalence of ATTR-CA in women may be greater than previously reported. The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study uses nuclear scintigraphy to identify ATTR-CA in self-identified Black and Caribbean Hispanic participants ≥60 years old with heart failure and left ventricular hypertrophy. We characterized the sex distribution and phenotypic characteristics of ATTR-CA in this active ascertainment cohort in comparison with a population of patients with ATTR-CA who were referred to a tertiary care academic center outpatient clinic. The active ascertainment SCAN-MP cohort had a greater proportion of women than did the referral clinic cohort (31.3% vs 13.3%, p = 0.016). This was mainly attributed to the greater proportion of women with wild-type ATTR-CA (27.8% vs 7.1%, p = 0.012). Women with ATTR-CA in the active ascertainment cohort exhibited higher left ventricular ejection fraction than did those in the referral cohort (61% vs 50%, p = 0.011), lower left ventricular mass index (110 vs 148 g/m 2 , p = 0.014), and smaller posterior wall thickness (1.4 vs 1.6 cm, p = 0.01). An active ascertainment strategy for ATTR-CA identification showed a greater proportion of women than did a referral cohort, driven predominantly by the greater proportion of women with wild-type ATTR-CA, and echocardiographic evidence of a less severe phenotype. In conclusion, efforts for early identification of ATTR-CA in women are critical for reducing sex disparities in this clinically treatable disease., Competing Interests: Declaration of competing interest Dr. Einstein is supported by National Institutes of Health (NIH) R01 HL139671, and reports receiving a speaker's fee from Ionetix, consulting fees from W. L. Gore & Associates and Artrya, authorship fees from Wolters Kluwer Healthcare—UpToDate, and serving on a scientific advisory board for Canon Medical Systems USA; his institution has grants/grants pending from Attralus, BridgeBio, Canon Medical Systems USA, GE HealthCare, Intellia Therapeutics, Ionis Pharmaceuticals, Neovasc, Pfizer, Roche Medical Systems, and W. L. Gore & Associates. Dr. Miller is a consultant for Eidos, Pfizer, Siemens, Alnylam, and Roivant; and has received grant support from Eidos, Pfizer, and Argospect. Dr. Ruberg is supported by NIH R01 HL139671 and acknowledges institutional research grant support from Akcea/Ionis Therapeutics, Anumana, Alnylam Pharmaceuticals, and Pfizer, and consulting fees from AstraZeneca and Attralus. Dr. Maurer has grant support from NIH R01 HL139671 and R01 AG 081582; consulting income from BridgeBio, Astra Zeneca, Novo Noridisk, Roche, Attralus, Ionis, Alnylam, and Intellia; and institutional support in the form of clinical trial funding from Attralus, Intellia, Pfizer, Alexion, Ionis, Eidos, and Alnylam. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Traumatic brachial plexus injury (BPI) results in significant disability, often hindering functionality in the patient's daily life. Post- surgery, muscle strength recovery can take up to two years, with 40% of patients requiring even longer. A powered elbow orthosis can enhance functionality during activities of daily living (ADLs). This study tested a novel powered myoelectric elbow orthosis (PMEO) during ADLs. Subjects with BPI were fitted with the PMEO and divided into two groups: more impaired (Manual Muscle Test (MMT) < 3, N = 5) and less impaired (MMT ≥ 3, N = 4). They performed four ADLs involving full elbow motion, including an activity requiring the subjects to lift a basket with weights. Upper extremity kinematics, electromyographic activity, weight lifted, and subject feedback on the device's form and fit were collected and analyzed. Results showed that the PMEO significantly improved elbow range of motion in the more impaired group (14 ± 23 degrees, p = 0.019) without any additional compensatory motions in the shoulder or trunk. More impaired subjects lifted an average of 1.1 ± 0.6 kg with the PMEO, whereas they could not do so without it (p = 0.011). Subjects appreciated the PMEO's weight, fit, and form. All could don and doff the device with minimal assistance. These findings demonstrate that the PMEO is a viable option to enhance ADL function for patients with BPI.

The vitreous humor undergoes liquefaction with age, resulting in complications that may require a vitrectomy, or surgical removal of the vitreous from the eye. Silicone oil, a common vitreous substitute, lacks properties similar to the natural vitreous. In particular, it lacks antioxidants that may be necessary to reduce oxidative stress in the eye. The purpose of this study was to evaluate antioxidant-loaded hydrogel vitreous substitutes in a pilot in vivo study. Ascorbic acid and glutathione were loaded into synthesized PEGDA hydrogels. Following vitrectomy, experimental antioxidant hydrogels or silicone oil were injected into one eye of rabbits, while the other eye served as untreated or sham control. Ophthalmic assessments, including electroretinography, were performed. Levels of glutathione and ascorbic acid were higher in the eyes treated with the antioxidant-loaded hydrogel vitreous substitute, although this was not found to be significant after 28 days. There were no statistically significant differences between groups with respect to clinical examination, and ocular health scores, electroretinograms, and histology were normal. These results indicate minimal concerns for the hydrogel formulation or high levels of antioxidants. Future research will assess the capability of vitreous substitutes to prolong antioxidant release, with the goal of minimizing cataract after vitrectomy., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Background and Hypothesis: Schizophrenia spectrum disorders (SSD) are associated with face perception impairments. It is unclear whether impairments are equal across aspects of face perception or larger-indicating a differential impairment-for perceiving emotions relative to other characteristics (eg, identity, age). While many studies have attempted to compare emotion and non-emotion face perception in SSD, they have varied in design and produced conflicting findings. Additionally, prior meta-analyses on this topic were not designed to disentangle differential emotion impairments from broader impairments in face perception or cognition. We hypothesize that SSD-related impairments are larger for emotion than non-emotion face perception, but study characteristics moderate this differential impairment., Study Design: We meta-analyzed 313 effect sizes from 104 articles to investigate if SSD-related impairments are significantly greater for emotion than non-emotion face perception. We tested whether key study characteristics moderated these impairments, including SSD severity, sample intelligence matching, task difficulty, and task memory dependency., Study Results: We found significantly greater impairments for emotion (Cohen's d = 0.74) than non-emotion face perception (d = 0.55) in SSD relative to control samples, regardless of SSD severity, intelligence matching, or task difficulty. Importantly, this effect was obscured when non-emotion tasks used a memory-dependent design., Conclusions: This is the first meta-analysis to demonstrate a differential emotion impairment in SSD that cannot be explained by broader impairments in face perception or cognition. The findings also underscore the critical role of task matching in studies of face perception impairments; to prevent confounding influences from memory-dependent task designs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Observational data have suggested that patients with moderate to severe ischemia benefit from revascularization. However, this was not confirmed in a large, randomized trial., Objectives: Using a contemporary, multicenter registry, the authors evaluated differences in the association between quantitative ischemia, revascularization, and outcomes across important subgroups., Methods: Patients who underwent myocardial perfusion imaging in 12 centers were included in this retrospective analysis. The population was divided into original (2009-2014) and recent (2014-2021) registry sites. Early revascularization was defined as any revascularization within 90 days of myocardial perfusion imaging. A propensity score was developed to adjust for nonrandomization. Propensity score-adjusted survival analyses were used to evaluate the associations between quantitative ischemia, early revascularization, and death or myocardial infarction (MI) to identify at what severity of ischemia the HR for early revascularization crosses 1 (threshold for potential benefit)., Results: Overall, 40,449 patients were included with a median follow-up of 3.5 (IQR: 2.4-4.6) years, during which death or MI occurred in 2,797 (6.9%). Early revascularization was associated with reduced death or MI in patients with >9.0% myocardial ischemia (95% upper CI: 11.2%, interaction P  < 0.001). The threshold for ischemia, above which patients may benefit from revascularization, was higher in more recent patients (14.0% vs 6.5%), but similar in female (>10.0%) and male patients (>8.6%)., Conclusions: Early revascularization was associated with reduced risk in patients with a higher burden of quantitative ischemia in more recent populations. These findings suggest that methods integrating more factors than just ischemia are needed to improve patient selection for revascularization., Competing Interests: This research was supported in part by the National Heart, Lung, and Blood Institute at the National Institutes of Health (grant numbers R01HL089765, R35HL161195) to Dr Slomka The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Robert Miller received consulting fees and research support from Pfizer. Drs Berman and Slomka participate in software royalties for QPS software at Cedars-Sinai Medical Center. Dr Slomka has received research grant support from Siemens Medical Systems and consulting fees for Synektik, SA. Drs Berman, Dorbala, Einstein, and Edward Miller have served or currently serve as consultants for GE Healthcare. Dr Einstein has received speaker fees from Ionetix; has received consulting fees from W. L. Gore & Associates; has received authorship fees from Wolters Kluwer Healthcare–UpToDate; and has received grants to his institution from Attralus, Canon Medical Systems, Eidos Therapeutics, Pfizer, Roche Medical Systems, W. L. Gore & Associates, and XyloCor Therapeutics. Dr Dorbala has served as a consultant to Bracco Diagnostics; her institution has received grant support from Astellas. Dr Di Carli has received research grant support from Spectrum Dynamics and consulting honoraria from Sanofi and GE Healthcare. Dr Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: Compared to estimated population prevalence rates, relatively few patients at risk are diagnosed with and treated for transthyretin cardiac amyloidosis (ATTR-CA). Where along the clinical pathway patient drop-off occurs, as well as the association of drop-off with patient sociodemographic characteristics, remains unknown., Methods: Using data from a healthcare system-wide cardiovascular imaging repository and specialty pharmacy, we characterized the clinical pathway from diagnosis with pyrophosphate scintigraphy (PYP) to tafamidis prescription, initiation, and adherence. Standardized differences (d values of ≥0.20, indicating at least a small effect size) were used to compare sociodemographics (age, sex, race, Area Deprivation Index) among patients with PYP-identified ATTR-CA by tafamidis prescription status and among patients prescribed tafamidis by initiation status. Tafamidis adherence was measured with the proportion of days covered (PDC)., Results: Of 97 patients with ATTR-CA, 58.8% were prescribed tafamidis, with 80.7% of those initiating therapy. Patients with ATTR-CA prescribed tafamidis were younger than those not prescribed tafamidis (d = -0.30). Utilization of a specialty pharmacy resulted in enrichment of treatment in subgroups traditionally undertreated in cardiovascular medicine, with higher rates of tafamidis initiation among women (100% initiation), patients of Black/African American race (d = 0.40), and those living in more economically disadvantaged areas (d ≥ 0.30). Adherence was high (PDC of >80%) in 88.4% of those initiating tafamidis., Conclusion: These findings highlight the tremendous opportunity for more robust ATTR-CA clinical programs, identifying potential patient subgroups that should be targeted to reduce disparities. For patients diagnosed with ATTR-CA, utilization of a specialty pharmacy process appears to ensure equitable provision of tafamidis therapy., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Traumatic adult brachial plexus injury is a debilitating injury. Myoelectric exoskeletons are functional tools for restoring elbow flexion. Electromyography signals are used for exoskeleton control, but a characterization specific to the traumatic adult brachial plexus injury population has yet to be performed. This study evaluated if adult patients with traumatic brachial plexus injury and a reconstructed elbow flexor can control a myoelectric exoskeleton. Adult patients who underwent surgical intervention to restore elbow flexion with traumatic brachial plexus injury were recruited for this cross-sectional study. The processed elbow flexor muscle signal and activation thresholds were used to evaluate criteria for exoskeleton control algorithm development. A single activation threshold can be utilized for exoskeleton control, but the calibration routine should consider the resting signal for both extended and flexed elbow positions. The data indicated a 'settle-time' following contraction is needed to prevent unintentional movement of the exoskeleton. All patients activated their elbow flexor above the activation threshold in the supported, flexed position. However, there were different abilities to generate multiple, discrete signals. These results were not specific to surgery, nerve implemented for reconstruction, or post-operative recovery time. Patients with a brachial plexus injury and a reconstructed elbow flexor demonstrated subject-specific capabilities for exoskeleton control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study explores the genetic and epidemiologic correlates of long-term photoplethysmography-derived pulse rate variability (PRV) measurements with anxiety disorders. Individuals with whole-genome sequencing, Fitbit, and electronic health record data (N = 920; 61,333 data points) were selected from the All of Us Research Program. Anxiety polygenic risk scores (PRS) were derived with PRS-CS after meta-analyzing anxiety genome-wide association studies from three major cohorts- UK Biobank, FinnGen, and the Million Veterans Program (N Total =364,550). PRV was estimated as the standard deviation of average five-minute pulse wave intervals over full 24-hour pulse rate measurements (SDANN). Antidepressant exposure was defined as an active antidepressant prescription at the time of the PRV measurement in the EHR. Anxiety PRS and antidepressant use were tested for association with daily SDANN. The potential causal effect of anxiety on PRV was assessed with one-sample Mendelian randomization (MR). Anxiety PRS was independently associated with reduced SDANN (beta = -0.08; p = 0.003). Of the eight antidepressant medications and four classes tested, venlafaxine (beta = -0.12, p = 0.002) and bupropion (beta = -0.071, p = 0.01), tricyclic antidepressants (beta = -0.177, p = 0.0008), selective serotonin reuptake inhibitors (beta = -0.069; p = 0.0008) and serotonin and norepinephrine reuptake inhibitors (beta = -0.16; p = 2×10 -6 ) were associated with decreased SDANN. One-sample MR indicated an inverse effect of anxiety on SDANN (beta = -2.22, p = 0.03). Anxiety and antidepressants are independently associated with decreased PRV, and anxiety appears to exert a causal effect on reduced PRV. Those observational findings provide insights into the impact of anxiety on PRV., Competing Interests: Competing interests RP reported receiving personal fees for editorial work on the journal Complex Psychiatry from Karger Publishers and a research grant from Alkermes outside the submitted work. MBS reported consulting for Acadia Pharmaceuticals Inc., Aptinyx Inc., ATAI Life Sciences, Biogen Inc., Bionomics, BigHealth, BioXcel Therapeutics Inc, Boehringer Ingelheim, Clexio Biosciences Ltd, Eisai Co Ltd, EmpowerPharm, Engrail Therapeutics, Janssen Pharmaceuticals, Jazz Pharmaceuticals, NeuroTrauma Sciences LLC, PureTech Health, Sage Therapeutics, Sumitomo Pharma Co Ltd, and Roche-Genentech; and receiving stock options from Oxeia Biopharmaceuticals Inc and EpiVario outside the submitted work; serving as editor in chief for Depression and Anxiety, deputy editor for Biological Psychiatry, and co-editor in chief for Psychiatry for UpToDate for compensation. RL reported receiving speaker honoraria, advisory board fees, and research funding from Medtronic; speaker honoraria and research funding from Abbott/St Jude; and research funding from Boston Scientific. EJM reported consulting for Eidos, Pfizer, Siemens, Alnylam, and Roivant and receiving research funding from Eidos, Pfizer, and Argospect. No other disclosures were reported., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations study seeks to determine the prevalence of transthyretin cardiac amyloidosis (ATTR-CA) among older Black or Caribbean Hispanic individuals with heart failure and an increased wall thickness. We noticed varied recruitment percentages across the recruiting sites and sought to determine the factors associated with greater percentage enrollment of eligible participants., Methods: The percentage of enrolled to eligible participants was calculated across study sites. Baseline demographic and clinical characteristics, health literacy, trust in providers, perceived discrimination, area deprivation index (ADI) and English proficiency were compared by site using Kruskal-Wallis's test or one-way ANOVA for continuous variables and the Chi-Square test or Fisher's exact test for categorical variables. Wilcoxon rank sum and Chi-Square tests, with multiple comparisons correction using the false discovery rate (FDR) method, were used as post-hoc analysis when results were statistically significant., Results: Among the four recruiting sites, Boston Medical Center, Columbia University Irving Medical Center, Harlem Hospital and Yale University, which employed different recruitment approaches, the percentage of participants enrolled among eligible participants differed, with the highest rate at Harlem Hospital (n=149 of 310, 48%), followed by Yale University (n=27 of 67, 40%), Boston University (n=247 of 655, 38%), and Columbia University (n=137of 442, 32%), p <0.01. Direct recruitment by the primary cardiovascular care team providing clinical care was associated with higher percent enrolled across sites as were higher education levels and English proficiency. Enrollment differences across sites were not associated with the number of chronic diseases, physician trust, perceived discrimination, or health literacy., Conclusions: Recruitment of eligible under-represented minorities (URMs) in SCAN-MP was associated with approaches employed in recruitment, including direct initial contact by the primary cardiovascular care team providing the potential participant's clinical care. Such data may help improve approaches to more successful recruitment of URMs in clinical research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Registry of Fast Myocardial Perfusion Imaging with Next-Generation SPECT (REFINE SPECT) has been expanded to include more patients and CT attenuation correction imaging. We present the design and initial results from the updated registry. Methods: The updated REFINE SPECT is a multicenter, international registry with clinical data and image files. SPECT images were processed by quantitative software and CT images by deep learning software detecting coronary artery calcium (CAC). Patients were followed for major adverse cardiovascular events (MACEs) (death, myocardial infarction, unstable angina, late revascularization). Results: The registry included scans from 45,252 patients from 13 centers (55.9% male, 64.7 ± 11.8 y). Correlating invasive coronary angiography was available for 3,786 (8.4%) patients. CT attenuation correction imaging was available for 13,405 patients. MACEs occurred in 6,514 (14.4%) patients during a median follow-up of 3.6 y (interquartile range, 2.5-4.8 y). Patients with a stress total perfusion deficit of 5% to less than 10% (unadjusted hazard ratio [HR], 2.42; 95% CI, 2.23-2.62) and a stress total perfusion deficit of at least 10% (unadjusted HR, 3.85; 95% CI, 3.56-4.16) were more likely to experience MACEs. Patients with a deep learning CAC score of 101-400 (unadjusted HR, 3.09; 95% CI, 2.57-3.72) and a CAC of more than 400 (unadjusted HR, 5.17; 95% CI, 4.41-6.05) were at increased risk of MACEs. Conclusion: The REFINE SPECT registry contains a comprehensive set of imaging and clinical variables. It will aid in understanding the value of SPECT myocardial perfusion imaging, leverage hybrid imaging, and facilitate validation of new artificial intelligence tools for improving prediction of adverse outcomes incorporating multimodality imaging., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Inherently limited by poor bioavailability, antiviral agent tenofovir (TFV) is administered to people living with HIV in prodrug form. However, current prodrugs are prematurely metabolized, compromising access to HIV-infected cells and inducing toxicity. Inspired by lipid conjugate TFV exalidex (TXL), we recently disclosed TXL analogs with potent activity and robust hepatic stability in vitro, as well as attractive oral PK profiles in vivo. In parallel, we discovered the equipotent and equally stable hexadecylthiopropyl (HTP) derivative of TXL ( 2a ). Reported herein are the synthetic and bioanalytic efforts that led to potent, safe, and hepatically stable HTP derivatives. While HTP analog 16h showed the most attractive PK profile in mice (55% F) discrepancies in translating in vitro cell-based results to in vivo PK data, for certain prodrugs, indicated that further in vitro/in vivo optimization is required for continued advancement of this program.