Abstract Background Ultra‐high‐field 7 Tesla (7T) magnetic resonance imaging (MRI) provides improved resolution and signal‐to‐noise ratio (SNR) over standard clinical field strengths (1.5T, 3T). However, 7T scanners are costly, scarce, and introduce additional challenges such as susceptibility artifacts. Purpose We propose an efficient transformer‐based model (7T‐Restormer) to synthesize 7T‐like MRI (quantitative T1 MP2RAGE maps) from routine 1.5T or 3T T1‐weighted (T1W) images. Methods The proposed method leverages an efficient restoration transformer backbone and spatial attention layers to capture long‐range dependencies and generate high‐quality 7T‐like images. Our model was validated on an institutional dataset, comprised of 35 1.5T and 108 3T T1w MRI paired with corresponding 7T T1 maps of patients with confirmed multiple sclerosis (MS). A total of 141 patient cases (32 128 slices) were randomly divided into 105 (25 1.5T and 80 3T) training cases (19 204 slices), 19 (5 1.5T and 14 3T) validation cases (3476 slices), and 17 (5 1.5T and 12 3T) test cases (3145 slices). The synthetic 7T T1 maps were evaluated by comparing their similarity to the ground truth volumes using peak signal‐to‐noise ratio (PSNR), structural similarity index measure (SSIM), and normalized mean squared error (NMSE), and were compared against ResViT and ResShift. In addition, a blinded reader study was performed in which three clinicians scored the diagnostic image quality of each method on a 5‐point Likert scale (1 = non‐acceptable, 5 = excellent). Statistical significance ( α = 0.05) was assessed using two‐sided paired t ‐tests with Holm correction for multiple comparisons and Wilcoxon signed‐rank tests with Holm correction for reader scores. Effect sizes (Cohen's for paired data) were also computed to quantify practical significance. We interpreted and as small, medium, and large effects. Results For 1.5T inputs, 7T‐Restormer achieved an NMSE of 0.018 ± 0.003, PSNR of 25.0 ± 0.6 dB, and SSIM of 0.870 ± 0.019; for 3T inputs, the corresponding values were 0.019 ± 0.006, 24.5 ± 1.2 dB, and 0.874 ± 0.027. Across both field strengths, 7T‐Restormer provided the lowest NMSE and highest PSNR and SSIM among the three methods, reducing NMSE by approximately 5% and 25% relative to ResShift and ResViT at 1.5T and by 14% and 24% at 3T, respectively, and increasing PSNR by 0.5–1.5 dB (Holm‐adjusted p < 0.05, paired Cohen's = 1.37–6.84). Training on mixed 1.5T+3T data improved performance for 1.5T inputs compared with 1.5T‐only training (e.g., NMSE 0.018 vs. 0.019; p = 0.001, ), without degrading performance for 3T inputs ( p = 0.630, for NMSE). In the blinded reader study, 7T‐Restormer received higher diagnostic quality scores (3.50 ± 0.28) than ResShift (3.00 ± 0.27) and ResViT (2.33 ± 0.27), corresponding to mean improvements of 0.5–1.2 points on the 5‐point scale (Holm‐adjusted p = 0.014 and 0.004; paired Cohen's and 3.24, respectively). Conclusion We propose a novel method for predicting quantitative 7T MP2RAGE maps from 1.5T and 3T T1W scans with higher quality than existing state‐of‐the‐art methods. Future development and application of our approach may enhance diagnostic accuracy, treatment planning, and facilitate downstream tasks by making the benefits of 7T MRI more accessible to standard clinical workflows.
Irreversible electroporation associated with improved overall survival vs standard of care for stage 3 pancreatic ductal adenocarcinoma
Abstract Background Emerging evidence suggests irreversible electroporation (IRE) with standard-of-care (SOC) chemotherapy may improve survival in patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) when compared to SOC alone. This study evaluates the overall survival (OS) and progression-free survival (PFS) of Stage 3 PDAC patients treated with SOC plus IRE with the NanoKnife System versus SOC alone. Methods This prospective, multicenter study included two cohorts from the DIRECT registry: an IRE cohort from sites offering IRE as part of clinical care, and a comparator SOC cohort of prospectively enrolled and contemporaneous retrospective patients. Enrollment spanned 08/05/2019 to 02/05/2023, with follow-up through at least 24 months, death, or loss to follow-up. Included were 137 patients (99 IRE; 38 SOC), aged ≥18 years with Stage 3 PDAC and no progression after three months of SOC therapy. Results Median (interquartile range) time from diagnosis to enrollment was 8 (6-10) months for IRE and 4 (3-6) for SOC (p<0.0001). Median OS and PSF from enrollment were 18 (95% confidence interval [CI]: 15-24) months and 9 (95% CI: 7-12) months for IRE, and 10 (95% CI: 8-14) months and 6 (5-8) months for SOC, respectively (p<0.0001 and p=0.009). Adverse events occurred in 80% (79/99) of IRE patients and 95% (36/38) of SOC patients; 29% (29/99) of the IRE cohort experiencing an IRE-related adverse event. Conclusions IRE was associated with improved OS versus SOC alone and may be an effective consolidative treatment for Stage 3 PDAC after three months of induction chemotherapy.
GLP-1 Receptor Agonist Use Is Associated With Lower Risk of Intracranial Aneurysm Rupture and Rupture Severity
BACKGROUND: Unruptured intracranial aneurysms (UIAs) affect up to 5% of the population, and rupture can lead to devastating subarachnoid hemorrhage. GLP-1RAs (glucagon-like peptide-1 receptor agonists) have anti-inflammatory and vasculoprotective effects, but their impact on aneurysm stability and subarachnoid hemorrhage outcomes is unexplored. This study evaluated whether GLP-1RA use is associated with reduced rupture risk and attenuated severity in the event of a rupture. METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2016–2024). Cohort 1 included patients with newly diagnosed, untreated UIA; cohort 2 included those who suffered aneurysm rupture. GLP-1RA exposure was defined as use before or within 3 months of UIA diagnosis (cohort 1) or before rupture (cohort 2). The primary outcome was aneurysm rupture risk in cohort 1. Secondary outcomes include presentation severity, vasospasm, and mortality in cohort 2. Propensity score matching balanced demographics, comorbidities, and medications. RESULTS: After propensity score match, cohort 1 of patients with untreated UIA included 8088 GLP-1RA users and 8088 nonusers. GLP-1RA use was associated with significantly lower probabilities of aneurysm rupture at 1-year (0.65% versus 1.51%; P <0.001), 3-year (1.18% versus 1.85%; P <0.001), and 5-year (1.49% versus 2.10%; P <0.001) timepoints, representing a 48% decrease in hazards (hazard ratio, 0.52 [95% CI, 0.38–0.69]). Among patients who suffered aneurysm rupture (cohort 2, N=298 after propensity score match), prerupture GLP-1RA use (n=149) was associated with lower rates of intraparenchymal hemorrhage (17.4% versus 33.6%; P <0.001), intraventricular hemorrhage (10.1% versus 23.5%; P <0.001), and clinically significant vasospasm (10.7% versus 24.2%; P =0.002), as well as numerically lower rates of 30-day mortality (9.4% versus 14.1%; P =0.21). CONCLUSIONS: For patients with untreated UIA, GLP-1RA use was associated with a 48% reduction in aneurysm rupture risk and, among those who suffered aneurysm rupture, milder clinical and radiographic severity. These findings suggest possible neuroprotective and vascular stabilizing effects of GLP-1RAs for patients with UIA.
Role of the Emergency Medicine Pharmacist in the Management of Boarding Patients: An Opinion of the Emergency Medicine Practice and Research Network of the American College of Clinical Pharmacy Endorsed by the SAEM Academy of Emergency Medicine Pharmacists
ABSTRACT As emergency department (ED) crowding and patient boarding reach critical levels nationwide, the role of the emergency medicine pharmacist (EMP) must be both defined and safeguarded. While EMPs are increasingly valued for their contributions to acute care, their responsibilities often unintentionally expand during periods of operational strain, particularly when admitted patients remain in the ED for prolonged durations. EMPs should ideally be resourced to remain focused on time‐sensitive, high‐risk medication management where their expertise is most impactful and not be used as default providers for all pharmacotherapy needs during ED boarding. This perspective outlines our position on the ideal scope of EMP practice during times of congestion, advocating for clearly defined role boundaries, strategic collaboration with other pharmacy team members, and system‐level support to prevent dilution of emergency care. EMPs must be empowered to prioritize critical ED workflows, support resuscitations, and lead initiatives in education, protocol development, and patient safety, without being overextended by responsibilities that can be absorbed by other team members.
Mutational profiling links biologically relevant variants to multisystemic Rosai-Dorfman disease
OBJECTIVE The objective was to evaluate the trajectories of hematoma resolution and functional improvement after middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH), model the temporal pattern of cSDH resolution, and identify factors associated with favorable outcomes. METHODS This real-world multicenter retrospective study included cSDH patients treated with MMAE at 24 centers between 2019 and 2024. Hematoma thickness was measured at baseline and at follow-up intervals (1–4 weeks, 1–3 months, 3–6 months, 6–12 months, and > 12 months after embolization). Resolution patterns were modeled using exponential decay functions. Modified Rankin Scale (mRS) scores assessed functional outcomes. Good functional outcome was defined as mRS score ≤ 2. Resolution patterns were modeled using exponential decay functions to estimate time to 50% and 80% reduction. Patients were categorized as complete resolution (≥ 99%) or by quartile of the remaining distribution (substantial [73%–98%], moderate [53%–73%], partial [27%–53%], minimal [< 27%]). The primary outcome was good functional status (mRS score ≤ 2). RESULTS The authors analyzed a total of 1781 patients with 2295 cSDHs who underwent MMAE. The mean ± SD age was 72.8 ± 12.4 years and 68.1% of patients were male. The initial mean hematoma thickness was 15.31 ± 6.53 mm, decreasing to 5.24 ± 5.91 mm at final follow-up (mean reduction 64.3% ± 42.1%). Resolution followed an exponential decay pattern, with an estimated time to 50% reduction of 1.8 months and to 80% reduction of 8.9 months. Complete resolution occurred in 1031 of 2224 patients (46.4%) with complete follow-up. The median (IQR) mRS score improved from 1 (0–3) at baseline to 0 (0–2) at > 12 months. Good functional outcomes were more common in patients with complete versus minimal resolution (68.9% vs 35.0%, p < 0.001). Achieving ≥ 73% resolution within 90 days was associated with better outcomes (good outcome in 76.9% of those with ≥ 73% resolution vs 67.3% in those without, p < 0.001). Neurological deterioration was the strongest predictor of lack of good outcome (23.7% in patients with neurological deterioration vs 82.4% without, p < 0.001). CONCLUSIONS After MMAE for cSDH, reduction in hematoma thickness follows a predictable exponential decay pattern. Greater extent (≥ 80%) and faster timing (within 90 days) of resolution are valuable prognostic indicators. Functional outcomes improve progressively through 6–12 months after the procedure. The relationship between resolution extent and functional outcomes provides quantitative benchmarks for evaluating treatment response.
Deprescribing Levothyroxine in Older Adults: Time to Challenge the “Lifelong” Dogma?
ABSTRACT Background In chronic liver disease, fat and fibroinflammatory changes often coexist. However, their biomarkers, proton density fat fraction (PDFF) and T 1 , are typically assessed separately. Their reproducibility under mutual confounding remains unclear. Purpose To assess multicenter, multi‐vendor reproducibility of confounder‐corrected chemical shift‐encoded (CSE)‐MRI‐based PDFF mapping and MOLLI‐based T 1 mapping using a combined PDFF‐T 1 phantom. Study Type Prospective phantom study. Phantom Commercial PDFF‐T 1 Phantom (Model 725) with varying PDFF (0%–30%) and T 1 (200–1400 ms) values. Field Strength/Sequence 1.5 T and 3 T multi‐echo, three‐dimensional spoiled‐gradient‐echo (SGRE) sequence for PDFF mapping, and MOLLI sequence (5(3)3 acquisition scheme) using two‐dimensional SGRE readouts for T 1 mapping across four centers and vendors. Assessment PDFF and T 1 maps were acquired using standardized protocols. PDFF maps were reconstructed locally, while T 1 maps were generated using a centralized algorithm. All maps were quantitatively analyzed by a single radiologist using standardized region‐of‐interest placement. Phantom temporal stability was assessed at one center across five sessions over 9 months (baseline, retest, 1 week, 6 and 9 months). Statistical Tests Intraclass correlation coefficients (ICC), reproducibility coefficients (RDC), and linear regression analysis were used. A p value < 0.05 was considered statistically significant. Results PDFF showed overall excellent reproducibility (ICC = 0.987, RDC = 3.7%), with increased variability at higher T 1 values (RDC up to 7.9% at T 1 = 1400 ms). T 1 mapping showed good reproducibility in the absence of fat (RDC 16–161 ms at PDFF = 0%), but moderate to poor reproducibility in the presence of fat, with RDC increasing up to 1553 ms at PDFF 30%. Temporal stability was excellent ICC ≥ 0.998 for both PDFF and T 1 , and RDC of 1.1%–1.3% for PDFF and 52–57 ms for T 1 . Data Conclusion This phantom study demonstrated high reproducibility of PDFF, whereas T 1 reproducibility deteriorated at higher fat and T 1 levels, underscoring the need for fat‐corrected T 1 mapping for reliable assessment of fibroinflammatory changes. Evidence Level N/A. Technical Efficacy Stage 1.
Ontogeny and Natural History of Therapy‐Related Clonal Hematopoiesis From a Multidisciplinary
CHIP
Clinic
ABSTRACT Age‐related changes in human hematopoietic stem cells (HSCs) often form the basis for clonal hematopoiesis (CH), which presages the development of overt myeloid neoplasm with variable risk. CH can also arise after exposure to chemotherapy, radiotherapy, or immune interventions. In this study, we performed clinico‐genomic profiling of therapy‐related CH (t‐CH) ( n = 67) versus de novo CH ( n = 123) from a multidisciplinary CHIP Clinic. The most enriched mutations in t‐CH were TET2 (26.2%), DNMT3A (22.4%), and TP53 (8.4%). Median latency period from the time of initial exposure to the diagnosis of t‐CH was 6.96 ± 1.10 years. Patients with t‐CH had inferior event‐free survival compared to de novo CH (median 29.9 months versus 122.1 months, p = 0.0045). Overall survival was also shorter in t‐CH versus de novo CH (median 55.3 months vs. 129.2 months, p = 0.043). Genes that imparted significantly increased risk for progression from t‐CH to overt therapy‐related myeloid neoplasm (t‐MN) included JAK2 (relative risk (RR) 9.42, p = 0.0001), RUNX1 (RR 7.11, p = 0.001), EZH2 (RR 7.11, p = 0.001), and TET2 (RR 13.4, p = 0.01). Clonal dynamic modeling of patients with t‐CH who progressed to overt t‐MN showed an increase in the relative clonal fraction and new clonal outgrowth. In the t‐CH cohort, higher mean variant allele frequency was observed in progressors versus non‐progressors (77.1% vs. 30.6%, p = 0.017). This study sheds light onto outcomes for CH based on differing clinical ontogeny and has implications for previvorship for secondary malignancies.
Opportunistic CT Attenuation Biomarkers of Anemia Are Associated With Impaired Myocardial Flow Reserve and Cardiovascular Outcomes
ABSTRACT Background Anemia is an established marker of cardiovascular disease severity and risk which leads to elevations in resting myocardial blood flow (MBF) and impaired myocardial flow reserve (MFR) in patients without obstructive coronary artery disease (CAD). Anemia can potentially be detected opportunistically from blood pool density changes on computed tomography (CT) imaging. Objectives We evaluated relationships between chamber density measurements with hemoglobin, positron emission tomography (PET) findings, and cardiovascular events. Methods We included 33460 patients from 13 sites in the REFINE-PET who underwent PET and 24368 patients undergoing lung cancer screening chest CT. A deep learning model segmented cardiac chambers from CT images, then quantified chamber density. We evaluated the relationship between chamber density measures with resting MBF and MFR, as well as associations with death or myocardial infarction (MI). Results We included a total of 57,828 patients. A higher density in myocardium compared to left ventricle blood pool was associated with reduced MFR (adjusted odds ratio 3.02 per SD increase, 95% confidence interval[CI] 2.72 – 3.38) and an increased risk of death or MI in (adjusted hazard ratio[HR] 1.38 per SD increase, 95% CI 1.26-1.51). Having myocardial density higher than blood pool density was also associated with cardiovascular death in patients undergoing low-dose chest CT (adjusted HR 1.73, 95% CI 1.20-2.52). Conclusions In a large multimodality dataset, lower cardiac chamber density is associated with impaired MFR and independently associated with cardiovascular events. These biomarkers can be automatically extracted from CT to provide physiologic insights and potentially guide patient care. CONDENSED ABSTRACT Anemia is an important marker of cardiovascular disease severity and predictor of cardiovascular events. We utilized deep learning to measure cardiac chamber density on computed tomography imaging as a surrogate for anemia in 57,828 patients from two large multicenter studies. A higher density in myocardium compared to left ventricle blood pool was associated with reduced MFR and an increased risk of death or MI in patients undergoing positron emission tomography, and an increased risk of cardiovascular death in patients undergoing low-dose computed tomography. These biomarkers can provide additionally physiologic insights which could be used to guide patient care.