Citations

Purpose: There are reported barriers to implementation of esophageal screening during the videofluoroscopic swallow study (VFSS) completed by the speech-language pathologist (SLP). Often, patients referred to the SLP for a VFSS have an esophageal component that may explain their complaint. In this article, authors explore roadblocks to esophageal screening and potential roadmaps to improve patient care through standardization of esophageal screening procedures. Conclusions: A strong body of literature supports physiologic, anatomic, and disease state relationships of the oropharynx and esophagus. Despite this, the assessment of the oropharynx and esophagus is dichotomized. There remain billing limitations for same-day esophagram and VFSS, and the well-documented esophageal screen provides a view of bolus flow in an upright, typical eating position with consideration of oropharyngeal function to provide a comprehensive view of the continuous process of swallowing from mouth to stomach. The continued practice of evaluating the oropharynx without consideration of the esophagus poses a threat to patient safety and may delay care. A collaborative, multidisciplinary effort among healthcare professionals to create streamlined practice parameters, update position statements, and enhance education parameters will allow for cohesive practices among professionals. Assessment of the swallow mechanism is incomplete without consideration of the entire continuum.

Background: Biobanks often lack standard mechanisms to keep donors connected to their biospecimens, reflecting a broken feedback loop that compromises trust, engagement, and scientific progress. Decentralized biobanking empowers patients to track their donations throughout the research journey, supporting personalized feedback and research collaboration via a privacy-preserving blockchain network. This case study explores operational feasibility of implementing decentralized biobanking for a large breast cancer biobank at a US academic medical center. Methods: A mixed-methods case study of the groundwork, implementation, and stakeholder feedback for a real-world decentralized biobanking app pilot was conducted. Biobank members were recruited from February to April 2023. Operational feasibility was assessed via analysis of institutional stakeholder perspectives, pilot engagement, and de-bi app activity. Findings: Physicians and other biobank stakeholders surfaced challenges surrounding managing expectations, balancing empowerment with clinical and research workflows, and navigating power dynamics between patients, physicians, scientists, and leadership. A total of 1080 participants enrolled over 10 weeks, including nearly 10% of the biobank with about 4000 biospecimens. During the pilot, biobank enrollment increased 65% versus the prior year, and there were no biobank withdrawals during or within 1 year following the pilot ( p < 0.001 for both). The app, which facilitated biospecimen tracking and research engagement, was downloaded by 405 users. A total of 140 users tested the blockchain component, with 89% successfully claiming a nonfungible token representing their unique, immutable connection and access to donated biospecimens. Feedback was solicited to inform potential process improvements and risk assessments related to public relations, systems infrastructure, and ethical governance, illuminating next steps. Conclusions: We established operational feasibility for the first step toward decentralized biobanking, informed by requirements to manage expectations, workflows, and power dynamics. Our technical solution demonstrated robust participant engagement and compatibility with established biobanks, suggesting potential to build trust and align incentives and identifying next steps for communications, sustainability, and governance.

Goals: This study aimed to assess perspectives and practices among expert gastroenterologists regarding the screening, diagnosis, and management of BE. Background: Significant variability in the management of Barrett’s esophagus (BE) persists among physicians despite the development and dissemination of several clinical practice guidelines. Study: An online survey was conducted with 38 expert gastroenterologists specializing in BE management. The 38-question survey evaluated demographics, medical management, and attitudes toward endoscopic treatment, with responses analyzed for trends and variations. Results: Of the 38 experts, 34 (89%) responded. Respondents were primarily male (85%), with 82% affiliated with academic hospitals and 53% clinically focused on BE. Half discussed BE risks during initial consultations for gastroesophageal reflux disease (GERD). Most (61.8%) agreed BE should be considered in women with chronic GERD, and 88.2% regularly used narrow-band imaging (NBI). However, 44% were neutral or disagreed with diagnosing BE based solely on community gastroenterologist biopsies, and acceptance of Wide-Area Transepithelial Sampling with 3D Analysis (WATS-3D) for Barrett’s esophagus diagnosis and surveillance was limited. Fifty-three percent recommended ablation for nondysplastic BE. Fifty-two percent recommended indefinite daily PPI therapy after complete eradication of intestinal metaplasia (CEIM), regardless of symptoms. When encountering cardia intestinal metaplasia after endoscopic eradication, 38% recommended ablation, while 47% continued surveillance. Conclusion: This study highlights substantial variations in the management of BE among expert gastroenterologists, despite the existence of updated guidelines. Identifying these discrepancies is crucial for optimizing care. Further efforts are needed to standardize practices and enhance the implementation of evidence-based guidelines in clinical settings.

Abstract Aberrant DNA methylation and copy-number alterations (CNA) drive Barrett’s esophagus progression to esophageal adenocarcinoma; however, their combined utility for early detection is unclear. We aimed to identify and validate methylated DNA markers (MDM) and CNAs to distinguish esophageal adenocarcinoma/high-grade dysplasia (HGD) from nondysplastic Barrett’s esophagus (NDBE). In this multiphase, multicenter study, we discovered and validated MDMs and quantified CNAs utilizing whole-genome methylation sequencing of esophageal brushings. DNA biomarkers identified from discovery were further validated in independent patients with paired esophageal brushing and swallowed capsule sponge samples. MDMs were filtered against a reduced representation bisulfite sequencing dataset obtained from independent tissue samples to advance only concordant candidates. CNA burden was quantified using ichorCNA-derived aneuploidy scores (AS). Two hundred MDMs discovered in HGD (N = 18) and esophageal adenocarcinoma (N = 18) versus NDBE brushing samples (N = 18) were tested in independent samples (N = 146). A 52-MDM panel achieved a cross-validated AUC of 0.88 [95% confidence interval (CI), 0.82–0.95]; the addition of AS improved discrimination of HGD/esophageal adenocarcinoma from NDBE to 0.91 (95% CI, 0.86–0.97) AUC. At 80% specificity, the combined model detected 93% of esophageal adenocarcinoma and 88% of HGD cases. In paired capsule sponge samples, a 58-MDM panel achieved a cross-validated AUC of 0.77 (95% CI, 0.66–0.88); a combined 58-MDM and AS model achieved AUC 0.80 (95% CI, 0.7–0.9). MDMs and AS discerned HGD/esophageal adenocarcinoma from normal esophagus/NDBE in endoscopic brushing and capsule sponge samples. This approach may improve Barrett’s esophagus surveillance. Prevention Relevance: This study demonstrates that combining epigenetic and genomic biomarkers across minimally invasive sampling methods can accurately distinguish HGD/esophageal adenocarcinoma from nondysplastic Barrett’s esophagus, offering promising, less invasive strategies to improve BE surveillance and enable endoscopic therapy for esophageal adenocarcinoma prevention and treatment.

Abstract Medical imaging is undergoing a transformation driven by the advent of new, highly effective, machine learning techniques paired with increases in computational capabilities (Cheng et al. 2021; Gilson et al. 2023; Almeida et al. 2024; Krishna et al. 2024). These advanced algorithms have the potential to improve disease detection, diagnosis, prognosis, and treatment outcomes. However, the complexity of machine learning models, the large amounts of curated and annotated data required by some methods, and the potential for bias and error make it challenging for individuals to safely and effectively leverage these methods (Lin et al. 2024; Guo et al. 2024; Xu et al. 2024; Linguraru et al. 2024; Wood et al. 2019). To address these challenges, the American Association of Physicists in Medicine (AAPM), American College of Radiology (ACR), Radiological Society of North America (RSNA), and Society for Imaging Informatics in Medicine (SIIM) have worked together to develop a syllabus detailing a recommended set of competencies for medical imaging professionals interacting with these systems. This guide is aimed at four different personas: users of AI systems, purchasers of AI systems, individuals who provide clinical expertise during the development of AI systems (“clinical collaborators”), and developers of AI systems.1 This is a syllabus, not a curriculum, and is intentional in this scope. Recognizing that individuals may benefit from different presentations of the same material, this work enumerates a series of relevant competencies but does not prescribe, nor offer, a method of instruction (Schuur, Rezazade Mehrizi, and Ranschaert 2021; Garin et al. 2023). By addressing the task‐specific demands of each role, this guide will enable medical imaging professionals to utilize machine learning systems more safely and effectively, ultimately improving patient care and outcomes.

Abstract Objectives Neurofilament light (NfL) is an established biofluid marker of neuroaxonal injury for neurological diseases. Several high-throughput and sensitive immunoassays have been developed to quantify NfL in blood and cerebrospinal fluid (CSF), facilitating the use of NfL as a biomarker in research and clinical practice. However, because of the lack of rigorous comparisons of assays, it has been difficult to determine whether data are comparable and whether assay performance differs. Here, we compared the performance of five NfL immunoassays. Methods To assess the five NfL immunoassays (Fujirebio, ProteinSimple, Quanterix, Roche and Siemens), we used pooled plasma or pooled CSF, as well as unique samples from 20 healthy controls and 20 individuals with El Escorial defined probable or definite amyotrophic lateral sclerosis (ALS), to evaluate precision, parallelism and/or bias. We also examined correlations between plasma and CSF NfL concentrations within and across assays and evaluated their ability to differentiate healthy controls from individuals with ALS. Results Four of the five assays demonstrated exemplary performance based on our analyses of precision and parallelism. Across the five assays, NfL concentrations were lower in plasma than in CSF, although they displayed a high degree of correlation. We noted bias across assays; plasma NfL concentrations were lowest for the Roche assay and highest for the ProteinSimple assay. In addition, all assays reliably distinguished healthy controls from individuals with ALS using plasma or CSF NfL. Conclusions Four NfL assays demonstrated similar analytic performance. Alongside performance, other factors such as costs, accessibility, usability, footprint, and intended use, should be considered.

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

OBJECTIVE In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control. RESEARCH DESIGN AND METHODS In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%–11.5% [58–102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300–900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety. RESULTS Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was −1.32% (95% CI −1.81 to −0.83; P &lt; 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of −5.12 kg [95% CI −8.20 to −2.03] and −5.1 cm [−8.23 to −1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (&gt;10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone’s known tolerability profile. Increases in blood pressure also occurred. CONCLUSIONS In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.