Citations

Background Rapid stroke type identification is essential for time‐sensitive interventions, yet timely neuroimaging remains limited, especially in pre‐hospital and resource‐constrained settings. The EMVision emu™ Brain Scanner is a portable neurodiagnostic device using non‐ionizing electromagnetic signals to distinguish stroke subtypes. In an Australian prevalidation study enrolling 277 suspected stroke patients, it demonstrated diagnostic accuracy with sensitivity and specificity of 92% and 85% for hemorrhagic and 95% and 80% for ischemic strokes, respectively. Case studies and image reconstructions provided (figures 1 and 2). This follow‐up study aims to validate the diagnostic performance of emu™ for detecting intracranial hemorrhage in an international cohort, targeting ≥80% sensitivity and specificity. Methods A prospective, multi‐center, international, paired diagnostic accuracy study, with 4 US sites and 2 Australian sites. It will enroll 300 patients presenting within 12 hours of stroke onset. Patients will be stratified into two arms: intracranial hemorrhage, and ischemic stroke, TIA, or stroke mimic. Participants will undergo standard imaging, followed by non‐invasive scan by the emu™ device. Ground‐truth diagnoses will be adjudicated by a blinded expert panel. The primary endpoints are the sensitivity and specificity of the emu™ device for detecting hemorrhage, calculated against the reference standard. Statistical inference will rely on whether the lower bound of the 95% confidence interval for sensitivity and specificity exceeds 80%. Results First Australian and US enrollments occurred on June 11, 2025, and July 3, 2025, respectively. Latest progress in the study will be presented at the time of conference. Conclusion This is the first international validation study of a portable electromagnetic brain scanner for intracranial hemorrhage detection; a novel, non‐ionizing, diagnostic tool that can revolutionize acute stroke triage, enabling earlier treatment decisions, improved workflows, and equitable access to neuroimaging. image image

OBJECTIVE Objective values on procedural risk are essential to facilitate informed consent and optimize clinical decision-making in patients with unruptured intracranial aneurysms (UIAs). While robust heuristics, such as the PHASES (population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage, and site of aneurysm) score, are established for predicting rupture risk, contemporary and granular benchmarks for procedural safety remain scarce. The multinational Prediction of Adverse Events After Microsurgery for Intracranial Unruptured Aneurysms (PRAEMIUM) study aims to comprehensively characterize contemporary adverse event rates following microsurgical treatment at high-volume expert centers, stratified by aneurysm location, morphology, and complexity factors to better inform individual risk/benefit analyses. METHODS A cohort study among 20 participating expert centers from 9 countries was established. Patients treated microsurgically for UIAs were included. The authors describe the epidemiology of treated patients and UIAs and a comprehensive adverse event profile using 3 outcomes measured at hospital discharge: 1) poor neurological outcome (modified Rankin Scale score ≥ 3), 2) new sensorimotor neurological deficits, and 3) all-cause adverse events (Clavien-Dindo grade ≥ 1). Subgroup reports were given for aneurysm location, morphology, and complexity factors (prior aneurysm treatment, calcifications, complex angioanatomy involving critical branch vessels or perforators, and thrombosis). The authors purposely chose discharge as the time point to capture early postoperative risks and complications in patients with asymptomatic UIAs, for whom preserving neurological function is paramount. RESULTS The cohort included 3705 patients (mean age 56 [SD 12] years, 28% male). Overall, at discharge 13.9% of patients (95% CI 12.8%–15.0%) had poor neurological functional outcomes, 14.4% (95% CI 13.3%–15.5%) had new sensorimotor deficits, and 24.1% (95% CI 22.8%–25.5%) experienced all-cause adverse events. Poor neurological outcomes ranged from 8.5% (M1 aneurysms) to 37.4% (posterior circulation aneurysms), neurological deficits from 9.3% (distal anterior cerebral artery [ACA] aneurysms) to 34.2% (posterior circulation aneurysms), and all-cause adverse events from 21.2% (distal ACA aneurysms) to 31.3% (posterior circulation aneurysms). Dissecting and fusiform aneurysms showed notably high rates of poor neurological outcomes (22.0%–33.3%), new deficits (25.4%–26.7%), and adverse events (26.7%–37.0%). Complexity factors significantly influenced outcomes, with prior treatment (22.9%, 19.7%, and 30.1%), calcification (16.3%, 18.1%, and 30.5%), complex angioanatomy (13.1%, 15.9%, and 26.9%), and thrombosis (19.6%, 23.9%, and 39.6%) notably increasing the risks for poor neurological outcomes, deficits, and adverse events, respectively. CONCLUSIONS This large international cohort provides contemporary benchmarks for microsurgical treatment of UIAs, emphasizing variability in outcomes based on aneurysm location, morphology, and complexity. The presented granular and quotable adverse event rates support informed patient counseling and individualized risk/benefit assessments in comparable high-volume centers.

Context.— Clinical laboratories are increasingly implementing pharmacogenomic (PGx) testing. Although PGx is similar to genetic testing for other indications, there are unique aspects that laboratories should consider. Objective.— To aid clinical laboratories that are implementing clinical PGx testing by describing characteristics of PGx test design and validation, as well as approaches to reporting. Resources that are useful for clinical laboratories performing PGx testing will be highlighted. Design.— The College of American Pathologists formed a workgroup composed of laboratorians with expertise in clinical PGx testing. The workgroup included representatives from the Association for Molecular Pathology and the American College of Medical Genetics and Genomics. The workgroup reviewed pertinent literature, as well as experience from proficiency testing and from members’ laboratories. Results.— The workgroup recommends that laboratories implementing PGx consider the following concepts: testing platform, test design (ie, selection of pharmacogenes and variants/alleles), use of reference materials during test development and as controls during clinical runs, star allele and standard nomenclature systems, translations from genotype to predicted phenotype, and considerations for result reporting including making medication recommendations. The workgroup provides considerations when using report vendors, emphasizing the clinical laboratory’s role and responsibility when implementing such reporting tools from vendors. Conclusions.— Clinical laboratories should be familiar with the fundamentals of PGx, ensure that PGx testing meets the applicable regulatory requirements for all aspects of the clinical laboratory testing process, and follow recommendations for standardization of nomenclature and reporting.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented. Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair. Study Design: Prospective cohort study; Level of evidence, 2. Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 were selected. Six-year follow-up was obtained to determine whether any subsequent surgery had occurred since their initial revision ACLR. If so, operative reports were obtained, whenever possible, to verify pathological condition and treatment. Results: In total, 221 patients from 1234 revision ACLRs underwent concurrent primary meniscal repairs (18% of the cohort). There were 238 repairs performed: 173 medial and 65 lateral. The majority of these repairs (n = 181; 76%) were performed with an all-inside technique. Six-year surgical follow-up was obtained in 77% (171/221) of the cohort, or 189 of 238 (79%) of the repairs (136 medial, 53 lateral). The meniscal repair failure rate, defined as reoperation, was 16% (31/189) at 6 years. Of the 31 failures, 28 were medial (24 all-inside, 4 inside-out; 28/136 = 20.6% failure rate) and 3 were lateral (2 all-inside, 1 inside-out; 3/53 = 5.7% failure rate). Three medial failures were treated in conjunction with a subsequent repeat revision ACLR. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears (20.6% vs 5.7%; P = .01) and had a significantly shorter survival time compared with lateral tears ( P = .02). No difference was found between the failure and nonfailure groups when it came to tear type, tear length, repair technique utilized, suture/implant type, or number of sutures used between the 2 groups. Conclusion: Meniscal repair in the revision ACLR setting has a 16% failure rate at 6 years. Failure rates for medial tears (20.6%) were found to be higher than that for lateral tears (5.7%), which aligns with previous studies in both the revision and primary ACLR setting.

Abstract INTRODUCTION Brigatinib is an oral ALK inhibitor that inhibits multiple tyrosine kinases. We previously published outcomes of patients with NF2-related schwannomatosis treated with brigatinib for a median of 10.4 months. We report updated results of these patients with extended follow-up. METHODS This multicenter, phase II, open-label study included participants ≥12 years with NF2-SWN and progressive target tumors (baskets: VS, NVS, meningioma, or ependymoma). Patients were treated with brigatinib 180 mg daily. Patients discontinued treatment upon progression of target tumors but could continue treatment with isolated progression of non-target tumors if deemed clinically acceptable by the treating team and patient. One target and up to 5 non-target tumors were followed in each participant. Tumor response was evaluated by MRI every 3 months in year 1 and every 6 months thereafter with radiographic response (RR) defined as ≥20% decrease in volume compared to baseline. RESULTS Forty participants were treated for a median of 23 months (range, 3-40 months). Updated imaging data is available on 162 tumors (45 VS, 59 non-VS, 53 meningiomas, and 5 ependymomas). RR rate for all tumors was 28% and was 31% for non-VS, 28% for meningioma, 22% for VS, and 60% for ependymomas. The 12-month freedom from tumor progression was 77.1% for all tumors, 81.5% for non-VS, 78.1% for meningioma, 69.2% for VS, and 100.0% for ependymoma. The 24-month freedom from tumor progression was 73% for all tumors, 81.3% for non-VS, 72.4% for meningioma, 62.4% for VS, and 100.0% for ependymoma. There were no grade 4/5 treatment-related adverse events (AEs). The most common AEs were diarrhea (65%), nausea (40%), muscle cramps (40%), hypertension (35%), increased LDH (35%), increased AST (33%), and increased ALT (25%). CONCLUSION Brigatinib treatment was associated with high rates of tumor stability at 24 months across multiple tumor types in patients with NF2-related schwannomatosis.

Abstract Understanding tumor cell dynamics can improve prognosis and treatment but remains limited for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA sequencing data from 684 NS-LUAD cases and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histologic data further characterized the subtypes. “Steady,” marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver gene alterations, is linked to prolonged survival and low immune evasion. “Proliferative” shows high proliferation markers, TP53 mutations, and gene fusions. “Chaotic,” with high epithelial-to-mesenchymal transition markers, has the worst prognosis, even within stage I tumors. Lacking known molecular or histologic characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the classification and predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving early-stage NS-LUAD prognostication in clinical settings. Significance: The transcriptome of 684 NS-LUAD identifies three subtypes with different cellular dynamics and genomic and morphologic features. A 60-gene signature accurately stratifies subjects for mortality risk, even in stage I, offering a potential clinically applicable tool for treatment decision-making in patients with NS-LUAD. See related commentary by Azizi et al., p. 423

Abstract Disclosure: P. Hopmann: None. S. Lund: None. T. Foster: None. B. Dy: None. T. McKenzie: None. G. Johnson: None. R.A. Wermers: None. M. Lyden: None. Background: Previous studies have demonstrated that C11 choline positron emission tomography/computed tomography (Choline-PET/CT) can localize abnormal parathyroid glands in the re-operative setting. This study assesses a large volume of patients with primary hyperparathyroidism (1HPT) who underwent Choline-PET/CT to confirm its utility in the setting of negative or equivocal conventional imaging. Methods: All patients who underwent Choline-PET/CT for evaluation of 1HPT from July 2017 to July 2024 at a single institution were reviewed. Inclusion criteria were patients who underwent parathyroidectomy and had lab testing to assess for cure (defined as >50% drop from baseline PTH and into normal range, or resolution of hypercalcemia at follow-up). Sensitivity, positive predictive value (PPV), false negative rate (FNR), and accuracy were compared to conventional imaging (neck ultrasound, parathyroid scan, and parathyroid four-dimensional CT (4D-CT)). Subgroup analysis was conducted comparing sensitivity of modalities among index operations, and separately in re-operations. Results: 176 patients were identified. 85 underwent parathyroidectomy, 1 patient was excluded due to lacking data to evaluate for cure. Of 91 patients who did not undergo parathyroidectomy, 45 were non-localizing on all imaging, and 46 had positive Choline-PET/CT findings but opted against surgery due to mild disease or prohibitive re-operative risk. Of the included 84 parathyroidectomy patients, 61 failed to localize on at least one conventional modality, and 15 failed to localize on all conventional studies. 67 patients (80%) achieved cure, of whom 53 were re-operations (range of 1-4 prior operations, average 1.5). Choline-PET/CT outperformed conventional modalities across sensitivity, PPV, FNR, and accuracy. Among index operations, Choline-PET/CT had significantly higher sensitivity than conventional modalities (100% vs 27% for ultrasound, 30% for parathyroid scan, 29% for 4D-CT; p values ≤0.01). This was also true in re-operations (95% for Choline-PET/CT vs 13% for ultrasound, 30% for parathyroid scan, 32% for 4D-CT; p values <0.01). Conclusion: C11 choline-PET/CT is a valuable imaging modality in the re-operative setting and demonstrates utility for index operations. It provides localization when other modalities fail and allows for a high surgical cure rate. Further investigation into its utility as a primary imaging modality is warranted. Presentation: Monday, July 14, 2025

PURPOSE Older patients with ALL receiving conventional chemotherapy have poor survival due to toxic death and relapse. We hypothesized that a chemotherapy-free, targeted regimen using the anti-CD22 antibody-calicheamicin conjugate inotuzumab ozogamicin followed by the bispecific anti-CD19/CD3 T-cell engager blinatumomab would reduce toxic death and yield high rates of prolonged remission and survival. METHODS Eligible patients were age 60 years and older with untreated, Philadelphia chromosome (Ph)–negative, CD22-positive, B-cell ALL. Patients received up to two cycles of inotuzumab ozogamicin followed by four or five cycles of blinatumomab with intrathecal methotrexate CNS prophylaxis. The primary end point was 1-year event-free survival (EFS). RESULTS The 33 eligible patients had a median age of 71 years (range, 60-84) and a median CD22 expression of 92% (range, 21%-100%). Eight (24%) had previous chemotherapy or radiation for other cancers, six for multiple myeloma. The composite complete remission rate was 85% after two cycles of inotuzumab ozogamicin and 97% by the end of two cycles of blinatumomab. At a median follow-up of 30 months, the 1-year EFS and overall survival were 75% (95% CI, 61 to 92) and 85% (95% CI, 73 to 98), respectively. EFS was shorter with lower CD22 expression or detectable measurable residual disease at any time point. CONCLUSION Inotuzumab ozogamicin then blinatumomab without maintenance chemotherapy in older patients with untreated, Ph-negative, CD22-positive, B-cell ALL yields a high remission rate and excellent EFS. Given the lack of standard, safe, and effective therapies in this population, the regimen should be considered a standard treatment option.

ABSTRACT Objectives To characterize practice patterns and outcomes in the management of low‐ and intermediate‐grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods Analysis of a registry of patients who underwent parotid and submandibular gland resections for low‐and intermediate‐grade carcinomas between 2010 and 2019. Results Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial ( n = 384, 53%) or total ( n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50–0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22–0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy ( RT ) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively ( RR 0.74, 95% CI 0.61–0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates ( RR 0.52, 95% CI 0.26–1.04, p = 0.06) or regional control rates ( RR 0.75, 95% CI 0.26–2.13, p = 0.58). Conclusions Management of low‐ and intermediate‐grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence 2b.