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Abstract INTRODUCTION Multi‐omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP‐AD) expanded brain multi‐omics profiling to multi‐ethnic donors. RESULTS We generated multi‐omics data and curated and harmonized phenotypic data from BA ( n = 306), LA ( n = 326), or BA and LA ( n = 4) brain donors plus non‐Hispanic White ( n = 252) and other ( n = 20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION The inclusion of traditionally underrepresented groups in multi‐omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD. Highlights Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi‐ethnic populations. Brain multi‐omics data is generated from Black American, Latin American, and non‐Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.

ImportanceAsymmetric oropharynx uptake on positron emission tomography (PET)/computed tomography (CT) is a common incidental finding and often prompts otolaryngology referral to rule out malignancy; however, the true risk of malignancy based on this finding is unknown.ObjectiveTo identify the incidence of oropharynx cancer in patients with incidental asymmetric oropharynx PET uptake.Design, Setting, and ParticipantsIn this retrospective cohort study, patients 18 years and older undergoing PET/CT scans at Mayo Clinic between January 2001 and December 2018 were included. Patients with a history or pretest suspicion of oropharynx cancer were excluded. Data were analyzed from March 2021 to December 2023.ExposureBlinded radiologic review of imaging studies, including measurement of maximum standardized uptake values (SUVmax) of the ipsilateral side of concern and contralateral side. Retrospective medical record review for associated clinical data.Main Outcomes and MeasuresThe primary study outcome was the incidence of oropharynx cancer diagnosis in patients with asymmetric oropharynx PET uptake. The primary outcome was formulated before data collection.ResultsOf the 1854 patients identified with asymmetric oropharynx PET uptake, 327 (17.6%) met inclusion criteria. Of these, 173 (52.9%) were male, and the median (range) age was 65.0 (24.8-90.7) years. The mean (SD) follow-up interval was 52.1 (43.4) months. A total of 18 of 327 patients (5.5%) were newly diagnosed with oropharynx cancer. The most common diagnosis was squamous cell carcinoma (n = 9), followed by lymphoma (n = 8), and sarcoma (n = 1). Patients with an incidental diagnosis of oropharynx cancer had higher mean (SD) ipsilateral SUVmax (8.7 [3.7] vs 5.3 [1.9]) and SUVmax ratio (3.0 [1.6] vs 1.6 [0.6]) compared with patients with normal examination findings. SUVmax ratio and difference were found to be good discriminators of oropharynx cancer, with areas under the receiver operating characteristic curve of 86.3% (95% CI, 76.4-94.6) and 85.8% (95% CI, 74.8-94.6), respectively. Patients with a new diagnosis of oropharynx cancer were more likely to have a corresponding CT abnormality than those with normal examination findings (6 of 18 [33%] vs 24 of 295 [8.1%]). Patients with concerning lesions on oropharynx palpation by an otolaryngology health care professional were significantly more likely to be diagnosed with oropharynx cancer compared with patients with normal examination findings (odds ratio, 28.4; 95% CI, 6.6-145.8).Conclusions and RelevanceIn this cohort study, while incidental asymmetric oropharynx PET uptake was common, a new diagnosis of oropharynx cancer was not and potentially results in a large volume of unnecessary referrals and work-up. Using SUVmax ratio, SUVmax difference, and CT correlation may increase the benefit of referral. Patients with a palpable oropharynx lesion and asymmetric oropharynx PET uptake should undergo confirmatory biopsy.

Background: Hip arthroscopy has seen a significant surge in utilization, but complications remain, and optimal functional outcomes are not guaranteed. Artificial intelligence (AI) has emerged as an effective supportive decision-making tool for surgeons. The purpose of this systematic review was to characterize the outcomes, performance, and validity (generalizability) of AI-based prediction models for hip arthroscopy in current literature. Methods: Two reviewers independently completed structured searches using PubMed/MEDLINE and Embase databases on August 10, 2022. The search query used the terms as follows: (artificial intelligence OR machine learning OR deep learning) AND (hip arthroscopy). Studies that investigated AI-based risk prediction models in hip arthroscopy were included. The primary outcomes of interest were the variable(s) predicted by the models, best model performance achieved (primarily based on area under the curve, but also accuracy, etc), and whether the model(s) had been externally validated (generalizable). Results: Seventy-seven studies were identified from the primary search. Thirteen studies were included in the final analysis. Six studies (n = 6,568) applied AI for predicting the achievement of minimal clinically important difference for various patient-reported outcome measures such as the visual analog scale and the International Hip Outcome Tool 12-Item Questionnaire, with area under a receiver-operating characteristic curve (AUC) values ranging from 0.572 to 0.94. Three studies used AI for predicting repeat hip surgery with AUC values between 0.67 and 0.848. Four studies focused on predicting other risks, such as prolonged postoperative opioid use, with AUC values ranging from 0.71 to 0.76. None of the 13 studies assessed the generalizability of their models through external validation. Conclusion: AI is being investigated for predicting clinical outcomes after hip arthroscopy. However, the performance of AI models varies widely, with AUC values ranging from 0.572 to 0.94. Critically, none of the models have undergone external validation, limiting their clinical applicability. Further research is needed to improve model performance and ensure generalizability before these tools can be reliably integrated into patient care. Level of Evidence: Level IV . See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVE Patients with cervical spondylotic myelopathy (CSM) experience progressive neurological impairment. Surgical intervention is often pursued to halt neurological symptom progression and allow for recovery of function. In this paper, the authors explore predictors of patient satisfaction following surgical intervention for CSM. METHODS This is a retrospective review of prospectively collected data from the multicenter Quality Outcomes Database. Patients who underwent surgical intervention for CSM with a minimum follow-up of 2 years were included. Patient-reported satisfaction was defined as a North American Spine Society (NASS) satisfaction score of 1 or 2. Patient demographics, surgical parameters, and outcomes were assessed as related to patient satisfaction. Patient quality of life scores were measured at baseline and 24-month time points. Univariate regression analyses were performed using the chi-square test or Student t-test to assess patient satisfaction measures. Multivariate logistic regression analysis was conducted to assess for factors predictive of postoperative satisfaction at 24 months. RESULTS A total of 1140 patients at 14 institutions with CSM who underwent surgical intervention were included, and 944 completed a patient satisfaction survey at 24 months postoperatively. The baseline modified Japanese Orthopaedic Association (mJOA) score was 12.0 ± 2.8. A total of 793 (84.0%) patients reported satisfaction (NASS score 1 or 2) after 2 years. Male and female patients reported similar satisfaction rates (female sex: 47.0% not satisfied vs 48.5% satisfied, p = 0.73). Black race was associated with less satisfaction (26.5% not satisfied vs 13.2% satisfied, p < 0.01). Baseline psychiatric comorbidities, obesity, and length of stay did not correlate with 24-month satisfaction. Crossing the cervicothoracic junction did not affect satisfactory scores (p = 0.19), and minimally invasive approaches were not associated with increased patient satisfaction (p = 0.14). Lower baseline numeric rating scale neck pain scores (5.03 vs 5.61, p = 0.04) and higher baseline mJOA scores (12.28 vs 11.66, p = 0.01) were associated with higher satisfaction rates. CONCLUSIONS Surgical treatment of CSM results in a high rate of patient satisfaction (84.0%) at the 2-year follow-up. Patients with milder myelopathy report higher satisfaction rates, suggesting that intervention earlier in the disease process may result in greater long-term satisfaction.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

HappiGenius is a mindfulness-based social–emotional learning (SEL) program developed and initially deployed in the context of COVID-19. Novel features of the HappiGenius program include the use of behavioral practice and activities to enhance traditional classroom-based learning, the capability to teach in a remote setting, and a focus on internalizing behaviors in addition to traditionally targeted externalizing behaviors. A pilot study of four third-grade classrooms completed in the previous academic year showed promising results for improvements in students’ experience of positive affect, self-compassion, total difficulties, and prosocial behaviors. This quasi-experimental case-control study was conducted in 14 third-grade classrooms across four schools in a midsize Midwestern US city. We hypothesized that HappiGenius would lead to improvements in positive affect, self-compassion, and mindfulness, in addition to other social behaviors measured by quantitative standardized scales. We used qualitative methodology to determine whether HappiGenius was feasible and acceptable to teachers for use in the classroom. While there was no statistically significant change in positive affect, self-compassion, or mindfulness, there was meaningful improvement in student internalizing problems and peer problems. Analysis of qualitative data showed the importance of timing during the year to maximize classroom benefits like establishing behavioral expectations early and reducing problem behaviors. The study represents a step in the direction of evaluating the implementation and outcomes of a new social–emotional learning program developed with deliberate attention to internalizing problems alongside traditionally studied externalizing problems.

Key Points Robotic ultrasound performed favorably compared with magnetic resonance imaging for evaluating total kidney volume. Collagen evaluation by two novel methods of picrosirius red imaging were more informative than the standard method by brightfield imaging. Findings can improve research by increasing speed and access to total kidney volume determination and sensitivity of collagen assessment. Background 3D imaging and histology are critical tools for assessing polycystic kidney disease (PKD) in patients and animal models. Magnetic resonance (MR) imaging provides micron resolution but is time consuming and expensive, and access to equipment and expertise is limited. Robotic ultrasound (US) imaging has lower spatial resolution but is faster, more cost-effective, and accessible. Similarly, picrosirius red (PSR) staining and brightfield microscopy are commonly used to assess fibrosis; however, alternative methods have been shown in non-kidney tissues to provide greater sensitivity and more detailed structural characterization. Methods In this study, we evaluated the utility of robotic US and alternative methods of quantifying PSR staining for PKD research. We compared longitudinal total kidney volume measurements using US and MR imaging. We additionally compared PSR imaging and quantification using standard brightfield microscopy with that by circularly polarized light with hue analysis and fluorescence imaging analyzed using curvelet transform fiber extraction software for automatic detection of individual collagen fibers. Results Increased total kidney volume was detected by US in Pkd1 RC/RC versus wild-type (WT) at time points spanning from early to established disease. US interobserver variability was greater but allowed scanning in 2–5 minutes/mouse, whereas MR imaging required 20–30 minutes/mouse. While no change in fibrotic index was detected in this cohort of relatively mild disease using brightfield microscopy, polarized light showed fibers skewed thinner in Pkd1 RC/RC versus WT. Fluorescence imaging showed a higher density of collagen fibers in Pkd1 RC/RC versus WT, and fibers were thinner and curvier with no change in length. In addition, fiber density was higher in both glomeruli and tubules in Pkd1 RC/RC , and glomeruli had a higher fiber density than tubules in Pkd1 RC/RC and trended higher in WT. Conclusions These studies show robotic US is a rigorous imaging tool for preclinical PKD research. In addition, they demonstrate the increased sensitivity of polarized and fluorescence analysis of PSR-stained collagen.

Abstract With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group–European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (&lt;10 g/dL for women and &lt;11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.

PURPOSE Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients. MATERIALS AND METHODS A prospective, single-institution, institutional review board–approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months. RESULTS Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2–, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM. CONCLUSION A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.