Citations

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

Study Design This study is part of the AO Spine Metastatic Tumor Research and Outcomes Network [MTRON], an international multicenter prospective observational registry including patients with spinal metastases. Objectives This study aims to elucidate the incidence of surgical complications, their risk factors and consequent effects on survival outcomes, hospital length of stay, and overall health-related quality of life (HRQOL) parameters in a large cohort of patients affected by spinal metastases who were surgically treated. Methods Available data from February 2017 to July 2023 were analyzed. The primary outcome of this study was the evaluation of the incidence of intraoperative and postoperative adverse events (AEs). The secondary outcomes included the assessment of risk factors for surgery-related AEs and the impact of AEs on survival, length of hospital stay and quality of life. Results Among the 1267 patients analyzed, 6.9% experienced intraoperative AEs and 19.3% experienced at least 1 postoperative AE. Several factors resulted to be associated to the occurrence of postoperative AEs: age, smoking habit, poor Eastern Cooperative Oncology Group (ECOG) Performance status, previous radiation therapy at the index target, duration of surgery, number of instrumented levels, simultaneous anterior and posterior approach, presence of metastases at other sites, multiple spinal metastases. Postoperative AEs were associated with reduced survival rates, increased hospital length of stay and poorer HRQOL outcomes, particularly in domains such as neurological function and mental health. In general, surgery substantially improves HRQOL across multiple domains, with these benefits persisting over time despite the occurrence of AEs. However, patients with preoperative risk factors, including comorbidities, smoking, neurological impairment, and prior radiation therapy, experienced less improvement. Conclusions The negative impact of AEs on overall survival and HRQOL could be associated with the presence of some preoperative parameters of frailty that are detected as risk factors for AEs occurrence. This finding emphasizes the need for personalized preoperative assessments and optimized perioperative care strategies.

Abstract Background The increasing prevalence of dementia poses significant challenges for emergency department (ED) care, as persons living with dementia (PLWD) more frequently experience adverse outcomes such as delirium, prolonged stays, and higher mortality rates. Despite advancements in care strategies, a critical gap remains in understanding how ED interventions impact outcomes in this vulnerable population. This systematic review aims to identify evidence‐based ED care interventions tailored to PLWD to improve outcomes. Methods A systematic review was conducted in Ovid MEDLINE, Cochrane Library (Wiley), Scopus (Elsevier), and ProQuest Dissertations & Theses Global through September 2024. The review protocol was registered on PROSPERO (CRD42024586555). Eligible studies included randomized controlled trials, observational studies, and quality improvement initiatives focused on ED interventions for PLWD. Data extraction and quality assessment were performed independently by two reviewers, with disagreements resolved through discussion. Outcomes included patient satisfaction, ED revisits, functional decline, and mortality. Results From 3305 screened studies, six met the inclusion criteria. Interventions included nonpharmacologic therapies (e.g., music and light therapy), specialized geriatric ED units, and assessment tools, such as for pain. Tailored interventions including geriatric emergency units and community paramedic care transitions were effective in reducing 30‐day ED revisits and hospitalizations. However, heterogeneity in study designs and outcomes precluded meta‐analysis. Risk of bias ranged from low to moderate. Conclusion This review underscores the urgent need for standardized and evidence‐based interventions in ED settings for PLWD. Approaches including multidisciplinary care models and nonpharmacologic therapies demonstrated potential for improving outcomes. Future research should prioritize consistent outcome measures, interdisciplinary collaboration, and person‐centered care strategies to enhance the quality and equity of ED services for PLWD.

PURPOSE Neoadjuvant immunotherapy (IO) has become the standard of care for early-stage triple-negative breast cancer (TNBC), but not yet for other subtypes. We previously developed a clinical-grade mRNA-based immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the response predictive subtypes. We report the performance of ImPrint in hormone receptor–positive and human epidermal growth factor receptor 2–negative (HR+HER2–) patients from five IO arms. METHODS A total of 204 HR+HER2– (MammaPrint high-risk) patients from five IO arms (anti–PD-1, anti–PD-L1/poly [ADP-ribose] polymerase inhibitor combination, anti–PD-1/toll-like receptor 9 dual-IO combination, and anti–PD-1 ± lymphocyte activation gene 3 dual-IO combination) and 191 patients from the chemotherapy-only control arm were included in this analysis. Patients were classified as ImPrint+ (likely sensitive) versus ImPrint– (likely resistant), using pretreatment mRNA. Performance of ImPrint for predicting pathologic complete response (pCR) to IO-containing arms was characterized and compared with tumor grade (III), MammaPrint (ultra) High2 risk (MP2), and estrogen receptor (ER)-low (ER ≤ 10%). RESULTS Overall, the pCR rate across the five IO arms was 33%. 26% of HR+HER2– patients were ImPrint+, and pCR rates with IO were 75% in ImPrint+ versus 17% in ImPrint–, with the highest pCR rate >90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint–. Tumor grade (III), MP2, and ER-low showed pCR rates in IO of 45%, 56%, and 63%, respectively, with lower pCR odds ratios (OR < 7.5) compared with ImPrint (OR = 14.5). CONCLUSION Using an accurate selection strategy, HR+HER2– patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (ie, pCR rate >65%-70%). ImPrint, an Food and Drug Administration IDE-enabled assay, may represent a way to identify HR+HER2– patients for IO that best balances likely benefit versus risk of serious immune-related adverse events.

Abstract Background: Classic metaphyseal lesions (CMLs) are considered specific for child abuse, but the reliability of radiologists in distinguishing CMLs from metaphyseal variations is unclear. Objective: To evaluate whether radiologists can differentiate between CMLs and metaphyseal variations in the knees. Materials and Methods: We performed a retrospective review of distal femur and proximal tibia radiographs in children under two years of age who underwent skeletal surveys for suspected child abuse. The CML group included children diagnosed with abuse and reported CMLs. The metaphyseal variation group included children not diagnosed with abuse, with reported metaphyseal variations and either no fractures or an isolated skull fracture. Radiographs were trimmed to exclude other injuries. Four pediatric and four general radiologists reviewed anonymized studies and categorized each case as CML, metaphyseal variation, normal, or indeterminate, with confidence levels (high, moderate, low). We analyzed diagnoses with moderate or high confidence. Interobserver agreement was assessed using kappa statistics. Results: There were 48 children with CMLs (40 initial, 38 follow-up) and 27 with metaphyseal variations (20 initial, 12 follow-up). Metaphyseal fragmentation was the most common variation, identified in 259 of 356 femurs (72.8%) and 69 of 83 tibias (83.1%). Fragmentations were most frequently located in the posterior or medial metaphysis, or both, in 257 of 259 femurs (99.2%) (257/259) and 68 of 69 tibias (98.6%). In the CML group, 34 of 115 initial CML diagnoses (29.4%) were read on follow-up as either metaphyseal variation (n=17) or normal (n=17). In contrast, in the metaphyseal variation group, only one follow-up case was diagnosed as a CML; the remainder were diagnosed as metaphyseal variation (n=22) or normal (n=2). Diagnostic performance for CML demonstrated high specificity (90.7%) and positive predictive value (94.9%), with moderate accuracy (76.1%), sensitivity (70.2%), and negative predictive value (55.2%). Interobserver agreement was substantial, with a mean kappa of 0.61. Conclusion: Radiologists demonstrated substantial agreement and high specificity in distinguishing CMLs from metaphyseal variations. Metaphyseal fragmentation was the most common variation and was uncommonly diagnosed as CML on follow-up.

This review describes approaches for encapsulation of pluripotent stem cells, the biomaterials used, strategies for differentiation into hepatocytes and β cells, and the impact of microencapsulation on cellular therapy.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.