Citations

ABSTRACT Background Sentinel lymph node (SLN) biopsy is a critical staging tool in skin and soft tissue cancers. Although technetium lymphoscintigraphy is the most common adjunct, indocyanine green (ICG) demonstrates a promising alternative in pediatric, adolescent, and young adult (AYA) skin and soft tissue cancers. Methods and Objectives Evaluate the safety and efficacy of ICG in SLN biopsy (SLNB) in diverse pediatric and AYA solid cancers in a multi‐institutional environment. This is a prospective, observational study conducted at 13 member institutions in the Pediatric Surgical Oncology Research Collaborative between 2019 and 2023. Eligible patients underwent SLNB for primary or recurrent solid skin and soft tissue tumors. Peritumoral ICG was administered intraoperatively. Outcomes included SLN detection rates, histopathology of excised specimens, and surgeon‐reported assessment of utility. Safety was assessed through adverse event reporting. Results Forty SLNB procedures yielded 84 specimens: 13 melanoma (32.5%), 12 squamous cell carcinoma (30%), 11 non‐rhabdomyosarcoma soft tissue sarcoma (27.5%), two rhabdomyosarcoma (5%), one Ewing sarcoma (2.5%), and one malignant peripheral nerve sheath tumor (2.5%). Histologic evaluation identified 81 lymph nodes, 75 benign (89.3%) and six malignant (7.1%); three specimens were adipose tissue (3.6%). Of 81 lymph nodes, 76% were ICG‐positive. ICG had a sensitivity of 79.5%, a specificity of 33%, and a positive predictive value of 96%. All malignant nodes were ICG‐avid. There were no adverse reactions to ICG at 30 days. Conclusions ICG is a safe and effective adjunct for SLNB in pediatric and AYA soft tissue and skin malignancies.

Abstract Background Identification of the microorganisms causing infection in children with central nervous system infection is important. Conventional cerebrospinal fluid (CSF) tests may provide limited pathogen detection. CSF metagenomic next-generation sequencing (mNGS) may provide broader pathogen detection in a single assay. Methods Results of CSF mNGS testing performed at Mayo Clinic on patients and nonpatients between January 2024 and June 2025 were retrospectively analyzed. The subcohort of children treated at Mayo Clinic was analyzed to assess test performance as compared with conventional CSF diagnostics and potential clinical impact. Results In total 134 patients (138 CSF mNGS tests) from 22 US states and 2 international sites were included. Overall positivity was 16% with viruses representing most (59%) detections. In the Mayo Clinic subcohort (n = 15), test positivity was 27%: organisms included single detections of Streptococcus mitis group and HIV type 1, as well as 2 detections of Epstein-Barr virus, all confirmed by conventional tests. Positive results were associated with CSF pleocytosis (P = .026). Higher yield was observed in participants whose care was overseen by pediatric infectious diseases (PID) specialists (P = .026) and when a specimen hold strategy was applied (P = .033). Most results (87%) did not alter antimicrobial therapy, with 2 negative results contributing to antimicrobial de-escalation. Conclusions CSF mNGS demonstrated higher diagnostic yield in patients whose specimens showed CSF pleocytosis and in those who had PID consultation. Diagnostic stewardship strategies were applied, including specimen hold approaches and PID consultation.

This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

INTRODUCTION Recent work has identified unique cognitive profiles for early‐onset Alzheimer's disease (EOAD) relative to late‐onset Alzheimer's disease (LOAD), however, examination has been limited in determining whether the association between age and cognitive severity at presentation also differs across conditions. METHODS A series of linear spline regression models was conducted across baseline cognitive data from 325 EOAD and 314 LOAD participants, after accounting for education, sex, and apolipoprotein ε4 status. RESULTS Significant differences existed in the relationship between baseline age and cognitive performance between EOAD and LOAD samples for Processing Speed/Attention, Executive Functioning, and Episodic Immediate Memory. Younger participants from both EOAD and LOAD groups performed disproportionately worse on non‐amnestic cognitive domains, with this occurring to a greater extent in EOAD than LOAD. DISCUSSION In the age of disease‐modifying treatments, results highlight the importance of assessing for cognitive declines in individuals starting much earlier than age 65. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) participants each displayed cognitive impairments relative to same‐aged peers across most domains. Both groups displayed positive relationships between impairment among non‐amnestic cognitive domains and baseline age. This relationship displayed a significantly greater effect in EOAD than LOAD, with domains of Processing Speed/Attention and Executive Functioning skills being the most pronounced. Of those participants developing AD, age displayed a disproportionate impact on their symptom onset.

Introduction: AI-driven software has been recommended as a means of triaging suspected large vessel occlusions (LVOs) on CT angiography (CTA), and different solutions are now commercially available. This study compared the performance of two software packages, Brainomix 360 Triage LVO and Rapid LVO, in prospective, real-world use. Methods: Consecutive patients scanned for suspected stroke at 3 comprehensive stroke centres from May to July 2024 (3 months) were included in the study. CTA, where available, was processed in real time by both Rapid and Brainomix software. Ground truth on vessel occlusion was ascertained using clinical review of electronic medical records. Occlusion location was coded as intracranial internal carotid artery terminus (ICA-T), middle cerebral artery (MCA) M1 or MCA M2. If more than one occlusion was observed, the most proximal of these was taken as the primary vessel affected. Results: There were 561 suspected stroke patients scanned during the study period across the three sites. Of these, CTA was sent for processing by both Rapid LVO and Brainomix 360 Triage LVO for 359 cases. Cases were excluded if no contrast was detected (n=17), leaving 342 cases (Table 1). Of these, proximal LVO (ICA-T or MCA M1) was confirmed in 14 cases and MCA M2 occlusions were present in 6 cases. Table 2 shows the LVO detection results for all cases from the two software packages. For both devices, sensitivity was higher when considering only proximal occlusions (ICA-T or M1). Performance was similar overall, but there was a trend towards differing sensitivity for more distal occlusions. As a composite measure, area under the curve (AUC) was higher for Brainomix than Rapid (Figure 1) but this difference was not significant. The positive predictive value (PPV) was low for both software packages due to the low incidence of LVO in the patient population. Conclusions: This study demonstrated consistent performance of two AI software devices, Brainomix 360 Triage LVO and Rapid LVO, for detection of LVO on CTA imaging, in prospective, real-world use. The low number of positive cases in the dataset (N=21) is a limitation of the study. There was a trend towards different performance for more distal vessel occlusion locations. Overall, the sensitivity observed in this dataset was in line with reports from previous retrospective studies for both software packages and underlines the importance of prospective evaluation to understand real-world performance.

Abstract Optimal dosing of prophylactic enoxaparin for individuals ≥150 kg is unknown due to limited inclusion in previous studies. Estimate an optimal weight-based prophylactic enoxaparin dose for individuals ≥150 kg. This multicenter, retrospective study included ≥150 kg adult patients admitted to the hospital between January 2014 and April 2024, who received twice daily prophylactic enoxaparin (goal peak anti-Xa 0.2–0.4 IU/mL). At least one peak anti-Xa was required, obtained 3 to 5 hours after the 3rd consecutive dose. The primary outcome was the range of dosing that produced goal prophylactic peak anti-Xa following linear regression modeling. Secondary outcomes were hospital and intensive care unit (ICU)/progressive care unit (PCU) length of stay (LOS), in-hospital mortality, and VTE/bleed events within 72 hours after an eligible peak anti-Xa. A total of 311 encounters and 388 peak anti-Xa levels were assessed. Patients were 46 (37–55) years old, 53.1% were male, and weighed 183.3 kg (166.1–204.1) with a BMI of 61.3 kg/m2 (54.8–69.4). Creatinine clearance was 179.6 mL/min (126.5–228.2) and patients received 4 doses (4–6) before peak anti-Xa, with a time between of 249 minutes (227–271). Linear regression modeling revealed a statistically significant correlation (r2 = 0.27) between weight-based dose and peak anti-Xa (p < 0.0001). Enoxaparin 0.34 mg/kg (95% CI 0.33–0.36) twice daily was predicted to achieve a peak anti-Xa of 0.3 IU/mL. Hospital LOS was 8 days (4–15), ICU/PCU LOS was 8 days (4–14, n = 158), and only two patients (0.6%) died during hospitalization. One VTE event was observed. Our results suggest an appropriate empiric weight-based prophylactic enoxaparin dose for hospitalized patients ≥150 kg is 0.34 mg/kg twice daily.

Abstract Early-onset Alzheimer’s disease (EOAD) and Late-onset AD (LOAD) differ in clinical presentations and rates of progression. We aimed to compare baseline and longitudinal tau PET burden, and their relationship with clinical variables in amyloid-PET positive, cognitively impaired participants from the Longitudinal Early-Onset Alzheimer’s Disease Study (EOAD; n=390) and Alzheimer’s Disease Neuroimaging Initiative (LOAD; n=211). Patients with EOAD showed higher baseline tau PET retention, broader neuroanatomical involvement and faster accumulation rates over time compared to LOAD, after adjusting for amyloid load and clinical stage. Tau PET showed stronger correlations with baseline amyloid burden and clinical measures of global cognition and function in EOAD than LOAD. We conclude that earlier age of onset in AD is linked to a more aggressive tauopathy, which in turn is a primary driver of clinical decline. These findings suggest that optimal therapeutic targets and strategies may differ between EOAD and LOAD. One Sentence Summary Younger patients with Alzheimer’s disease show more aggressive tau spread, suggesting age of onset defines distinct disease pathways with key clinical implications.

PURPOSE There is growing scientific interest in incorporating patient-reported outcomes (PROs) in early phase dose-finding oncology trials (DFOTs) to assess tolerability, inform dose selection, and guide later stage trial design. However, research indicates that PRO objectives in DFOTs are often unclear. The Incorporating Patient-Reported Outcomes in Dose-Finding Trials-Research Objectives Recommendations (OPTIMISE-ROR) project was established to support trialists to effectively incorporate PROs into DFOTs. METHODS Using the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework, guideline development included the following: (1) a methodological review of published DFOTs incorporating PROs; (2) candidate item generation, refined through expert consultation; (3) a two-round international multistakeholder Delphi survey (N = 109 in Round 1 [October 2024]; N = 96 in Round 2 [December 2024]); and (4) an independently chaired virtual consensus meeting (N = 31; January 2025) where multidisciplinary, international experts reviewed and voted to finalize items for inclusion. RESULTS Consensus was reached on six recommendations emphasizing three core PRO tolerability concepts: overall side effect impact, symptomatic adverse events, and overall health-related quality of life. The integration of PROs to inform final dose recommendations in dose escalation and optimization trials should be considered, regardless of trial design. The recommendations highlight the importance of PRO data analysis over time and across dose levels, defining PRO research objectives as descriptive or statistically powered, and assessing PRO-related end points to guide end point selection for subsequent studies. CONCLUSION This foundational guidance outlines key PRO research objectives in DFOTs. By facilitating the systematic integration of PROs, this guidance supports the utilization of patient-centered evidence for the tolerability and efficacy assessment of therapies to inform dose escalation, optimization, and regulatory evaluation—ultimately contributing to the development of safer, more effective therapies.

Abstract INTRODUCTION Understanding neuroinflammation across the Alzheimer's disease (AD) spectrum is essential to elucidate disease mechanisms and individualize therapy. METHODS Human microglial translocator protein (TSPO) expression under inflammatory stimuli was assessed by immunoblot experiments. Ninety‐six participants were enrolled across four groups: cognitively unimpaired amyloid (CU A) + and −, mild cognitive impaired (MCI) A+, and Alzheimer's disease dementia (ADD) A+. Neuroinflammation using 11 C‐ER176 TSPO positron emission tomography (PET) was compared to amyloid and tau PET. Correlations between neuroinflammation, amyloid, and tau pathology were examined across disease stages. RESULTS TSPO was upregulated in human microglia under AD‐like inflammatory conditions. Neuroinflammation, defined by PET TSPO, increased in CU A+ participants and became more widespread with increasing disease severity, aligning with worsening amyloid and tau pathology. Associations with tau were particularly extensive in temporal and parietal regions. DISCUSSION These findings suggest probable amyloid association with early microglial activation, while tau pathology is closely tied to wider distribution of neuroinflammation. Highlights TSPO expression increases in human microglia under AD‐like inflammation. 11 C‐ER176 PET shows stage‐dependent neuroinflammation across the AD spectrum. Neuroinflammation overlaps with tau and is more widespread in amyloid‐positive individuals. Activity peaks in MCI, stabilizes later, and relates to vascular and neurodegenerative changes.