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Abstract Background Flow‐related ghost artifact from a 3D Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence results from unsaturated magnetization of incoming arterial flow. This is especially common on MR scanners equipped with smaller radiofrequency (RF) transmit coils. A high‐performance compact 3T (C3T) scanner features a smaller RF‐transmit coil (inner diameter 37 cm, length 40 cm), leading to a rapid fall‐off of the B1 field below the neck. This configuration results in more intense flow‐related ghost artifacts, especially in younger patients. Purpose The C3T scanner's smaller RF‐transmit coil provides RF field coverage over the brain region, causing bright in‐flow arterial signals and flow‐related artifacts in the conventional 3D‐MPRAGE scans. The purpose of this study is to suppress these artifacts by adding a RF saturation band (RFSB) pulses to the 3D‐MPRAGE sequence. Methods The RFSB was added to the 3D‐MPRAGE sequence as a preparation pulse option. To test the effectiveness, 37 subjects were scanned on the C3T under an IRB‐approved protocol using 3D‐MPRAGE with and without RFSB. Ten of those subjects underwent repeated scans with and without RFSB to evaluate test‐retest reliability. A consensus evaluation by two neuroradiologists was performed on all data to compare signal to noise ratio, image contrast, presence of artifacts, and diagnostic confidence. Quantitative analysis included calculating test‐retest differences by image subtraction and evaluating the variance in flow‐artifact‐induced image intensity between the scans with and without RFSB. Additionally, one subject was scanned on a whole‐body 3T scanner using a transmit/receive (T/R) head coil to demonstrate the method's applicability across different MRI platforms as a proof of concept. Results The Wilcoxon signed‐rank test of the neuroradiologist evaluations showed a significant reduction in artifacts and an improvement in diagnostic confidence in the posterior fossa region with and without RFSB ( p < 0.0001). Test–retest analysis showed that adding RFSB significantly reduced image intensity variability in the cerebellum, even among subjects without visible flow artifacts. The normalized difference decreased from 8.71% to 6.41% ( p = 0.0059), suggesting improved image reliability in regions prone to flow‐related artifacts. Additionally, similar findings were observed in scans on a whole‐body 3T with a T/R head coil, demonstrating the broader applicability of this method. Conclusion Incorporating RFSB into 3D‐MPRAGE scans effectively reduces flow‐related ghost artifact on the C3T scanner, improving image quality and diagnostic confidence. These findings suggest that the proposed method could be widely implemented across MRI systems utilizing a smaller RF‐transmit coil.

BACKGROUND AND OBJECTIVES: Single-session stereotactic radiosurgery (SRS) has limited role for large arteriovenous malformations (AVM). Volume-staged SRS (VS-SRS) is used to optimize outcomes, but studies reporting results are limited. METHODS: This multicenter retrospective cohort of 378 patients from 21 centers reports results of VS-SRS for the entire AVM nidus. We report favorable outcome, obliteration, hemorrhage, and permanent symptomatic adverse radiation effect rates. RESULTS: The median age was 31 years (IQR: 19-44) at the first volume stage, with patients treated in 2–4 stages. The median total nidus volume was 21 cm 3 (IQR: 13.9-30.1 cm 3 ), and a median prescription dose of 17 Gy (IQR: 16-18 Gy) was used. The median radiographic and clinical follow-up were 48 and 55 months, respectively. Seventy-seven patients (20.4%) had a favorable outcome, with the 3-year and 5-year rates being 3.9% and 18%, respectively. 127 patients (33.6%) achieved obliteration, with the 3-year and 5-year rates being 6.8% and 26%, respectively. Obliteration rates of AVMs <15 cm 3 were 81% and 31%, respectively. The latency period hemorrhage incidence rate was 3.02 cases per 100 patient-years; 52 patients (13.8%) had a bleed. Seventy-two patients (19%) had symptomatic adverse radiation effect; in 38 patients (10.1%), these were permanent. Total nidus volume, prescription dose at first stage, diffuse nidus, and prior hemorrhage were all independent affecting outcome rates. CONCLUSION: VS-SRS can be used to treat large AVMs as a standalone treatment. Obliteration rates and favorable outcomes are lower than that with smaller AVMs, and repeat treatment is often required. Optimizing treatment plans, by increasing prescription doses, reducing treatment volume at each stage, and increasing the number of stages, may lead to better outcomes.

Abstract Sex differences in cancer outcome, including that of glioblastoma (GBM), are shaped by biological, hormonal, and immunological factors and impact disease progression, treatment responses, survival, and tumor microenvironment (TME) interactions. Platelets regulate the immune responses and tumor progression in many cancers, but it is not clear how they contribute to these sex-based differences by affecting the dynamics of the TME. Here, we show that GBM patients exhibit heightened platelet reactivity driven by PAR4 signaling. In murine GBM models, both pharmacological inhibition of PAR4 using BMS986120 and genetic deletion of PAR4 significantly prolong survival in females but not males. This survival advantage is estrogen dependent: it is preserved in chromosomal male-hormonal female mice within the four-core genotype model and is rescued in ovariectomized mice treated with estrogen. The survival benefit is TME specific and is mediated by platelet-driven enhancement of CD8⁺ T cell infiltration into the tumor. Inhibition of platelet PAR4 signaling increases calcium signaling through an estrogen-dependent interaction between PAR4 and estrogen receptor β (ERβ)—a receptor interaction not previously described. PAR4-activated platelets within the TME suppress CD8⁺ T cell function, and depletion of CD8⁺ T cells abolishes both the tumor-induced platelet reactivity and the survival benefit conferred by PAR4 inhibition. These findings establish platelet-mediated PAR4 signaling as a critical driver of tumor progression and identify sex-specific immune responses as key to therapeutic efficacy.

Abstract The landscape of Alzheimer's disease (AD) and related dementias (ADRD) diagnosis is evolving rapidly, driven by advances in disease understanding, biomarker tools, and disease‐modifying therapies. Modern diagnostic approaches emphasize biological precision, early detection, and dynamic frameworks that adapt to treatment‐induced changes in disease biology. These frameworks enable opportunities for personalized interventions—encompassing pharmacological and non‐pharmacological strategies—and for enhanced clinical trial design. However, implementing these advancements globally is influenced by diverse cultural, infrastructural, and regulatory factors. The 2024 Alzheimer's Association International Conference Advancements: Modernizing Diagnosis, held in Japan, provided a unique platform to explore these global dynamics, particularly from an Asian perspective. This article highlights key discussions from the conference, exploring the role of biomarker‐based diagnostic frameworks in shaping the future of AD/ADRD research, diagnosis, and treatment. We highlight regional challenges and successes and emphasize ethical considerations and practical strategies needed to ensure equitable access to diagnostic and therapeutic innovations. Highlights Advances in biomarkers are reshaping Alzheimer's disease diagnosis and treatment. Modern diagnostic frameworks highlight biological precision, early detection, and dynamic frameworks. The 2024 Alzheimer's Association International Conference Advancements: Modernizing Diagnosis explored challenges and opportunities in global biomarker implementation. The conference explored geographic‐specific impacts, focusing on Asia.

Introduction: Total knee arthroplasty (TKA) is a widely performed elective procedure globally. Periprosthetic joint infection (PJI) remains a serious complication following TKA. Hematogenous seeding from distant infections is a recognized mechanism of PJI. However, to our knowledge, there are no published reports of hematogenous PJI originating from acute epididymo-orchitis. Case Report: A 74-year-old male presented to the emergency department following a ground-level fall on his right knee. He was diagnosed with a knee effusion and discharged for outpatient follow-up. Approximately one week later, the patient presented to his primary care physician with right scrotal swelling and was diagnosed with epididymitis and started on oral antibiotics. The following day, he underwent right knee arthrocentesis which was positive for an acute PJI. The patient then underwent a double debridement, antibiotics and implant retention (DAIR) procedure and was discharged on a six-month course of oral antibiotics. Eight months after the double DAIR, the patient developed right knee swelling and erythema. Right knee aspiration was positive for a persistent PJI, and the patient underwent resection arthroplasty with insertion of an antibiotic spacer. Conclusion: Hematogenous spread of epididymoorchitis resulting in PJI is a rare and underreported complication that has not been fully understood in the literature. In this case, several risk factors—such as the presence of a prosthetic joint, recent trauma, and chronic corticosteroid use—may have increased the patient’s susceptibility to infection. Close monitoring of inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, and white blood cell count can aid in the early detection of septic arthritis and contribute to improved patient outcomes.

Abstract Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. In a multivariable analysis, receipt of ≥3 lines of therapy before tisa-cel (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.13-3.08; P = .015), any-grade cytokine release syndrome (HR, 1.78; 95% CI, 1.17-2.71; P = .007), and lack of neutrophil recovery (HR, 2.63; 95% CI, 1.47-4.69; P = .001) were associated with an increased risk for any infection. Similar associations were observed for bacterial infections, with the addition of younger age as an adverse risk (&lt;6 vs 6-15 years; HR, 2.38; 95% CI, 1.23-4.61; P = .01). Risk factors for viral infections included increasing age (1-year increase; HR, 1.05; 95% CI, 1.01-1.09; P = .016), prior history of any infection (HR, 2.76, 95% CI, 1.40-5.46; P = .004), and prior hematopoietic cell transplant (HR, 2.10; 95% CI, 1.18-3.71; P = .011). D100 infection-related mortality (IRM) rate was low at 0.2% (95% CI, 0.0-0.8). In this multicenter real-world study, we observed a high incidence of infectious complications but a low IRM following tisa-cel for R/R B-ALL.

Abstract In comparative effectiveness research (CER), ensuring internal, construct, and external validity is crucial. Internal validity determines whether observed outcomes are causally linked to an intervention; construct validity assesses whether a study measures what it intends to; and external validity relates to generalizability in routine practice. Double-blind randomized trials optimize internal validity by minimizing bias and confounding, while construct validity is strengthened through pre-specified protocols and standardized data collection. However, controlled conditions limit external validity. Pragmatic RCTs improve generalizability but may compromise internal validity due to open-label designs. Observational CER studies—including observational studies following the target trial emulation framework—offer broader external validity and feasibility in less time and at lower cost. However, due to lack of random assignment, these studies are susceptible to measured and unmeasured confounding. Several techniques help mitigate these concerns, including a detailed pre-specified protocol, tools such as propensity score matching to balance measured confounders, falsification endpoint testing for assessing the presence of unmeasured confounders, and quasi-experimental designs (including instrumental variable analysis), which may be able to address both. Pre-specified sensitivity analyses and triangulation with complementary data sources further enhance robustness. Construct validity in observational CER depends on accurate patient profiling and validated computational phenotypes for identifying patients, exposures, and outcomes. Thoughtful study design and analytic rigor are essential for balancing these validity considerations. This brief review highlights these issues with examples from thrombosis research.

Abstract Endoscopic mucosal resection (EMR) techniques for large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) have expanded with the introduction of ablation and cold EMR. This study assessed adverse events (AEs) for the newer EMR techniques, including cold EMR, compared with hot EMR. We conducted a secondary analysis of four prospective multicenter studies of consecutive patients with LNPCPs undergoing EMR from 2019 to 2024. The primary outcome was serious AEs (SAEs) with cold and hot EMR. Secondary outcomes included SAEs in the hot EMR subgroups (no ablation [hEMR], margin ablation [hEMR-m], margin and base ablation [hEMR-mb]). 1762 patients (mean age 65.8; 1890 LNPCPs) were included: 522 cold and 1368 hot EMRs (368 hEMR, 770 hEMR-m, 230 hEMR-mb). SAEs were higher with hot EMR (4.7%, 95%CI 3.6%–5.9%) vs. cold EMR (1.9%, 95%CI 0.9%–3.5%), also for the subgroups of hEMR (6.0%, 95%CI 3.8%–8.9%), hEMR-m (3.9%, 95%CI 2.6%–5.5%), and hEMR-mb (5.2%, 95%CI 2.7%–8.9%). Serious postendoscopic bleeding (PEB) was numerically higher with hot EMR (2.3%, 95%CI 1.6%–3.3%) vs. cold EMR (1.3%, 95%CI 0.5%–2.7%), also for the subgroups of hEMR (3.0%, 95%CI 1.5%–5.3%), hEMR-m (1.9%, 95%CI 1.1%–3.2%), and hEMR-mb (2.6%, 95%CI 1.0%–5.6%). Perforation, intraprocedural and post-procedural, was numerically higher with hot EMR (1.2%, 95%CI 0.7%–2.0%) vs. cold EMR (0.2%, 95%CI 0.0%–1.1%). hEMR-m and hEMR-mb with clipping had lower rates of serious and overall PEB than no clipping. Cold EMR demonstrated lower rates of SAEs, serious PEB, and perforation compared with hot EMR. Perforation and mortality occurred almost exclusively after hot EMR. Hot EMR with margin +/− base ablation did not increase SAEs compared with hot EMR without ablation.

Background: Proximal pole scaphoid fracture nonunions are challenging conditions to treat. When significant comminution of the proximal pole and avascular necrosis is present, scaphoid proximal pole reconstructive options are considered. The proximal pole of the hamate is a local autograft option; however, little has been described on the outcomes of this procedure. Methods: Patients who underwent proximal pole scaphoid reconstruction using proximal hamate autograft at 3 tertiary care centers were retrospectively reviewed. Radiographic union was classified by greater than 50% bony trabeculae across the reconstruction site on computed tomography scan. Results: Ten patients were included. Average age at the time of surgery was 27.9 years, and 60% were men. Average length of proximal hamate autograft harvested was 10 mm. All patients healed at an average of 14.3 weeks following surgery. At final follow-up, 3 patients reported no pain, 3 reported mild occasional pain, 2 reported moderate tolerable pain (1 at the hamate graft site), and 2 had no reports on their pain level. Conclusions: In small proximal pole scaphoid nonunions with fragmentation and avascular necrosis, ipsilateral proximal hamate autograft reconstruction of the scaphoid proximal pole is a viable and reproducible option with high rates of union and patient satisfaction.

Abstract Background: Understanding of the diagnosis and treatment of adults with community-acquired pneumonia (CAP) has evolved thanks to new evidence, experience, and emerging technologies. This document updates evidence-based clinical practice guidelines on four key questions for the diagnosis and management of adult patients with CAP. Methods: A multidisciplinary panel integrated systematic reviews of comparative evidence with other relevant research and clinical experience, then applied Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology to produce recommendations using the Evidence to Decision Framework. Results: The panel formulated clinical recommendations that address questions related to CAP, including lung ultrasound for diagnosis, empiric antibacterial therapy if a test for a respiratory virus is positive, antibiotic duration, and the use of systemic corticosteroids. Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with CAP.