Citations

Abstract A novel stationary tomographic Ultra-Fast Molecular Breast Imaging (UFMBI) technology was developed to reduce acquisition time and radiation dose of Molecular Breast Imaging (MBI), enabling its wider acceptance for supplemental dense breast screening. The system combines a stationary dual-head gamma camera made of CZT detectors with densely packed multi-pinhole collimators and novel de-multiplexing reconstruction methods, exploiting the ultra-high 3D position resolution of CZT detectors and their excellent energy resolution. A small field-of-view prototype (132 mm × 88 mm) was designed, built and calibrated. Raw detector data were processed using a machine-learning model providing 10×10 subpixelisation of 2 mm pixels in 5 mm thick CZT detectors and depth-of-interaction (DOI) estimation from anode signals alone. Tomographic images were reconstructed using an OSEM algorithm, including de-multiplexing and corrections for attenuation and collimator response. The prototype was evaluated using a 99mTc-filled phantom with lesions of different sizes and uniform background acquired separately. Prototype performance was compared with a clinical planar MBI system by imaging 99mTc-infused gel phantoms, with lesion detectability assessed via contrast-to-noise ratio (CNR). The results from the spheres’ phantom indicated that 5-7 mm diameter lesions with tumour-to-background ratios of 10-20:1 were detectable even with a dose/time reduction factor (DRF) of 8 relative to current MBI clinical practice. The gel phantom experiments showed that, with equal activity concentration and scanning time (DRF=1), the UFMBI prototype provided 2.5 to 3.9-fold CNR of the clinical planar system depending on the lesion activity and position within the field-of-view; with DRF of 6, UFMBI provided 1.6 to 2.4-fold CNR of the clinical system, improving to 2.5 to 3.4-fold with application of non-local means noise filtering. These results demonstrate the feasibility of UFMBI as a low-dose, high throughput approach and support its further development toward cancer screening of dense breasts and image-guided biopsy applications.

ABSTRACT Background To consolidate into a single review more than forty non‐cancer‐related factors that have been found to elevate or reduce prostate‐specific antigen (PSA) levels in the peer‐reviewed literature, emphasizing their contribution to false‐positive and false‐negative clinical interpretations. Materials and Methods A narrative literature review was conducted using PubMed, focusing on human studies describing benign physiologic, infectious, inflammatory, iatrogenic, hormonal, pharmacologic, and laboratory‐related factors that influence PSA values. The review emphasizes contemporary studies but incorporates earlier foundational literature where relevant. Results Forty‐five non‐cancer‐related factors were identified that influence PSA values through biologic, mechanical, pharmacologic, or analytic mechanisms. Thirty factors were associated with transient or persistent PSA elevation, whereas fifteen were associated with PSA reduction. Some factors varied substantially in the strength, magnitude, and consistency of reported PSA effects across studies. PSA elevations were reported in association with prostatic inflammation or infection, urinary retention, ejaculation, non‐instrumental prostatic physical stimulation, urologic instrumentation, and systemic inflammatory conditions. PSA reductions were observed with medications including 5‐alpha‐reductase inhibitors, nonsteroidal anti‐inflammatory drugs, statins, thiazide diuretics, metformin, and certain lifestyle factors. Inter‐assay and inter‐laboratory variability alone has been reported to result in PSA differences exceeding 20%. Tables summarizing the approximate magnitude and duration of PSA change for each modifier were developed, along with a patient questionnaire intended to support, not replace, clinician judgment. Conclusion PSA interpretation must incorporate awareness of more than forty influencers that can alter PSA independent of any malignancy. Accounting for these PSA level‐altering variables can improve PSA test result specificity and enhance confidence in prostate cancer risk assessment. Use of a structured patient questionnaire, a thorough consideration of benign factors that can alter PSA, repeat testing when transient factors are present, and consistent blood assay methodology can reduce unnecessary imaging, unneeded biopsies, and missed malignancies.

ABSTRACT BACKGROUND Opioids prescribed for acute pain frequently remain unused, creating opportunities for unintended use, accidental ingestion, or diversion. Little is known about counseling patients receive from prescribers or pharmacists on storage and disposal of opioids. OBJECTIVE To characterize clinician counseling on opioid disposal and patient-reported storage, use, and disposal practices among opioid-naïve patients prescribed opioids for acute pain. DESIGN Multicenter prospective cohort study with participant recruitment between September 2020 and March 2023. PARTICIPANTS Opioid-naïve patients prescribed opioids for acute pain in emergency departments, primary care or urgent care clinics, inpatient settings, and dental practices. MAIN MEASURES Patient-reported receipt of counseling on the importance of opioid disposal and appropriate disposal methods; opioid storage practices; use and disposition of prescribed opioids; disposal methods; and reasons for keeping or disposing of leftover opioids. KEY RESULTS Among 1708 participants, the median age was 38 years (IQR, 28-52); most were recruited from emergency departments (n=915; 53.6%) and primary care or urgent care clinics (n=307; 18.0%). Among 1233 participants who answered the question on counseling about the importance of opioid disposal, 811 (65.8%) reported receiving no counseling. Among 1220 participants who answered the question on counseling about appropriate disposal methods, 832 (68.2%) reported receiving no counseling. Among 812 participants who answered the question about storing opioids in a locked location, 610 (75.1%) reported never doing so. Among 929 participants providing information on opioid leftovers and disposition, 618 (66.5%) did not use all prescribed opioids. Among these 618 participants, 258 (42.8%) kept leftover opioids and 345 (57.2%) disposed of them. Among 256 participants who reported reasons for keeping leftover opioids, 159 (62.1%) wanted medication available for the same condition, 70 (27.3%) wanted medication available for a different condition, and 36 (14.1%) did not know how to properly dispose of the medication. CONCLUSIONS Among opioid-naïve patients prescribed opioids for acute pain, counseling about opioid disposal was uncommon, secure storage was infrequent, and leftover opioids were frequent, with many patients keeping leftover opioids for possible future use. These findings suggest opportunities to improve counseling on opioid storage and disposal and encourage safe disposal of unused opioids after acute pain treatment.

Abstract INTRODUCTION Combining Alzheimer's disease blood biomarkers may improve prediction of amyloid positivity (A+) compared with single biomarkers. METHODS Logistic regression models using plasma phosphorylated tau 217 (p‐tau217), amyloid beta (Aβ) 42, and Aβ40 were developed in cognitively impaired (CI) participants from Mayo Clinic Rochester (MCR) and validated in Alzheimer's Disease Neuroimaging Initiative (ADNI) and Mayo Clinic Florida (MCF) cohorts. Performance was measured by area under the curve (AUC) and Probability of Amyloid Positivity Score (PAPS). RESULTS Plasma p‐tau217 alone showed high AUC (95% confidence intervals) across cohorts MCR, 0.928 (0.900–0.953); ADNI, 0.938 (0.915–0.959); MCF, 0.935 (0.893–0.970). Adding Aβ42 to regression models yielded marginal model improvement MCR, 0.940 (0.915–0.963); ADNI, 0.945 (0.922–0.965); MCF, 0.960 (0.925–0.986). Utilization of two cutpoints (≥ 90% sensitivity and specificity), yielded ≤ 10% intermediate results for p‐tau217, and ≤ 8% for p‐tau217+Aβ42. Addition of Aβ40 did not improve models’ performance. DISCUSSION An immunoassay‐based p‐tau217 PAPS model accurately predicted amyloid positivity across independent CI cohorts and achieved confirmatory‐test performance with two cutpoints. The added value of Aβ42 was modest and cohort dependent, supporting the potential of use of p‐tau217–based PAPS in clinical workflows.

Purpose Immune checkpoint inhibitors (ICIs) are integral to first-line treatment of metastatic non–small cell lung cancer (NSCLC). Circadian biology may influence antitumor immunity, raising the hypothesis that time-of-day of ICI administration could affect outcomes. We evaluated the association between initial and cumulative ICI administration time-of-day and clinical outcomes in metastatic NSCLC. Materials and Methods We conducted a retrospective cohort study of 778 patients with metastatic NSCLC treated with first-line ICI-containing therapy across Mayo Clinic sites between January 2021 and March 2024. Patients were stratified by time-of-day of first ICI administration: early (0700-1200) versus late (1201-2400). Primary end points were overall survival (OS) and progression-free survival (PFS); the secondary end point was immune-related toxicity. Multivariable Cox proportional hazards models adjusted for clinically relevant covariates. Exploratory analyses evaluated cumulative infusion time-of-day and alternative administration-time thresholds using spline and cut-point analyses. Results Of 778 patients, 277 received early and 501 received late initial ICI administration. Median OS was 1.33 versus 1.48 versus years and median PFS was 0.65 versus 0.67 years in the late and early groups, respectively. Time-of-day of initial ICI administration was not associated with OS (HR, 1.01 [95% CI, 0.85 to 1.20]) or PFS (HR, 1.03 [95% CI, 0.88 to 1.21]). Findings were unchanged after multivariable adjustment. Immune-related toxicity occurred in 26.9% and 24.2% of patients in the late and early groups, respectively ( P = .40). Cumulative infusion time-of-day was not associated with OS or PFS, and spline analyses identified no significant administration-time threshold associated with outcomes. Conclusion In this large real-world cohort of patients with metastatic NSCLC, neither initial nor cumulative ICI administration time-of-day was associated with survival or immune-related toxicity. Prospective studies incorporating chronotype and circadian biomarkers are warranted to further define the role of chronotherapy in immuno-oncology.

BACKGROUND AND OBJECTIVES: Surgery for cervical spondylotic myelopathy improves quality of life but remains expensive. We conducted a cost-effectiveness analysis of patients treated with anterior cervical diskectomy/fusion (ACDF), posterior cervical decompression/fusion (PCDF), and laminoplasty (LP) in the Cervical Spondylotic Myelopathy Surgical (CSM-S) Trial, a randomized trial comparing surgical approaches for cervical spondylotic myelopathy. METHODS: In the trial, patients were randomized (2:3) to anterior (ACDF) or posterior surgery (LP or PCDF, at surgeon's discretion). A cost-effectiveness analysis was performed from a societal perspective with a 1-year time horizon, including only US patients as-treated. Cumulative costs were estimated using patient data on utilization and lost productivity using a human capital approach. Direct costs were calculated using 2022 Medicare rates for professional fees and cost-to-charge ratios for hospital services. Quality-adjusted life-years (QALYs) were calculated from patient responses to the EuroQol-5-Dimensions instrument at baseline and 3, 6, and 12 months postoperatively. Incremental cost-effectiveness ratio analysis was performed with bootstrapping to address uncertainty. RESULTS: Of 163 total patients enrolled in the CSM-S Trial, 153 from the United States (mean age, 62 years; 80 (52%) female) were included as-treated (ACDF = 61, PCDF = 64, LP = 28) in a cost-effectiveness analysis. Economic data were not available for 9 patients. The remaining 144 patients treated (ACDF = 55, PCDF = 61, LP = 28) had cost data through a 1-year follow-up. Mean hospitalization costs were higher after PCDF than ACDF and LP ($33 410 vs $26 468 vs $25 550; P < .001). Mean total costs were higher after PCDF than ACDF and LP ($62 383 vs $53 074 vs $47 426; P = .017). LP yielded greater QALY gains than ACDF (0.792 vs 0.732; P = .08) and PCDF (0.792 vs 0.698; P = .01). At a willingness-to-pay threshold of $150 000/QALY-gained, the probability that LP was cost-effective compared with PCDF was 99.7% and the probability compared with ACDF was 96%. CONCLUSION: In the CSM-S Trial, LP yielded greater 1-year quality-of-life improvements at lower costs than PCDF and ACDF.

Background Sudden cardiac death (SCD) is the leading cause of duty‐related death among firefighters. Understanding postmortem cardiovascular abnormalities associated with SCD is critical to guiding fire service cardiovascular disease screening and prevention programs. Methods This study included US firefighters who had a duty‐related death over a 16‐year period (1999–2014) with available postmortem reports (autopsy/medical examiner reports). Cases were systematically reviewed to identify cases of SCD. For each SCD case, the primary etiology of SCD was adjudicated by experts in sports cardiology and cardiovascular pathology. Results Postmortem evaluations were available for 794 of 2100 (37.8%) on‐duty firefighter deaths over the study period (average age, 44±13 years; age range, 17–82 years; 4.0% women). A total of 312 of 794 (39.3%) firefighter deaths were adjudicated as SCD. A total of 255 of 312 (81.8%) SCD events were attributable to coronary artery disease/ischemic heart disease or hypertensive heart disease, which both are associated with traditional cardiovascular risk factors. The leading etiology of SCD among young firefighters (aged <40 years) was also coronary artery disease/ischemic heart disease (24/50 [48.0%]). Of firefighters who had an exertional SCD event thought to be secondary to coronary artery disease (n=97), a total of 62 of 91 (68.1%) had severe fixed coronary stenosis, while 29 of 91 (31.9%) demonstrated acute plaque rupture/thrombosis. Conclusions More than 80% of on‐duty SCD events among US firefighters are due to coronary artery disease and hypertensive heart disease that may be prevented by early disease identification and risk factor modification. Future studies should assess the efficacy of more rigorous firefighter cardiovascular disease screening and management practices.

ABSTRACT Artificial intelligence (AI) has emerged as a transformative technology in the fields of medicine and ophthalmology. Recent advances in machine learning, deep learning and convolutional neural networks have significantly improved cataract detection and grading, intraocular lens power calculations, surgical decision‐making, risk prediction and patient education. Intraoperative AI‐assisted surgical phase recognition, workflow analysis, real‐time guidance, robotic technologies and femtosecond laser integration can improve surgical precision, efficiency and safety. AI has shown promise in predicting visual outcomes, detecting postoperative complications and facilitating telemedicine follow‐up. Though challenges with AI include transparency, data diversity, regulatory oversight and clinical validation, continued advances are expected to further personalise cataract surgery, support clinical decision‐making, optimise surgical performance and improve patient outcomes. This narrative summarises the current and emerging applications of AI in preoperative, intraoperative and postoperative management of cataracts.