Citations

Abstract Background Loperamide is a µ-opioid receptor agonist that reduces intestinal peristalsis and is used to treat diarrhea. We previously described significant cross-reactivity of loperamide with 2 fentanyl immunoassays. Since then, new fentanyl immunoassays, including a CLIA-waived point-of-care device, have been approved for clinical use. Methods We evaluated new fentanyl immunoassays for cross-reactivity to loperamide and its major metabolites, N-desmethyl loperamide (dLop) and N-didesmethyl loperamide (ddLop). Previously characterized assays were tested for cross-reactivity to ddLop, which recently became commercially available. Loperamide, dLop, and ddLop were spiked in drug-free urine for analysis by 5 enzyme immunoassays run on automated chemistry analyzers and one lateral flow assay for the detection of fentanyl. Results Loperamide and its metabolites produced positive results in 3 fentanyl immunoassays. The Immunalysis HEIA was previously determined to be reactive to both loperamide and dLop, but it was not reactive to ddLop. The Immunalysis SEFRIA was reactive to loperamide, dLop, and ddLop at minimum concentrations of 14.7 mg/L, 13.1 mg/L, and 17.0 mg/L. The Thermo Fisher DRI was previously determined to be reactive to loperamide and dLop, and it was reactive to ddLop at a minimum concentration of 33.1 mg/L. The Abbott iCassette, ARK Fentanyl II, and Lin-Zhi LZI II fentanyl assays showed no cross-reactivity to loperamide or its metabolites. Conclusions The cross-reactivity of loperamide, dLop, and ddLop in several fentanyl immunoassays has the potential to cause false-positive results during urine drug screening.

Abstract Background Methylation class pleomorphic xanthoastrocytoma (mcPXA) comprises tumors with the DNA methylation signature of classical PXA but with a wider histologic spectrum, including overlap with glioblastoma (GBM). Methods To clarify the histologic and molecular scope of mcPXA and characterize its clinical behavior, a cohort of 469 tumor samples from 458 patients matching to mcPXA by the DKFZ classifier (v12.6 score ≥0.85) was interrogated. Results Patient median age was 23 years (range 1-73 years) with a female predominance (259 female/199 male). CDKN2A/B homozygous deletion was observed in 406 of 469 (87%) samples. In samples tested for BRAF p.V600E mutations (n = 279), 240 (86%) harbored the mutation. A chr7+/chr10− pattern was observed in 103 of 469 (22%) samples. Among samples tested for TERT promoter mutations (n = 143), 32 (22%) harbored the mutation. Progression-free and overall survival of patients with mcPXA were comparable to patients with methylation class IDH-mutant astrocytoma, low grade, but a GBM-like subset (ie, cases with a pre-methylation working diagnosis of GBM) showed shorter survival. Histologic features of high grade, including palisading necrosis and microvascular proliferation, were prognostic in mcPXA. Compared to patients with BRAF p.V600E-altered GBM, patients with mcPXA were younger and had a lower frequency of TERT promoter mutations. Conclusion Tumors in mcPXA share molecular characteristics with histologically defined PXA, and high-grade histologic features can help predict their clinical behavior. The use of an epigenetic classification of PXA reveals that this group of tumors is more common than previously appreciated and warrants in-depth study to identify efficacious therapeutic options.

Abstract Craniopharyngiomas are rare parasellar tumors, and papillary craniopharyngiomas (PCPs) represent 8 to 20% of cases. Interim analysis of retrospective data collected from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). Fourteen U.S.-based academic skull base centers between 2011 and 2023. Patients with PCPs. Demographic, imaging, surgical, and outcome variables. Ninety-nine patients with PCPs were included. The mean age was 51.8 ± 14.7, and 57.6% were male. Most tumors showed mixed cystic/solid components (67.5%), were transinfundibular (50.0%), and were treated with an endoscopic endonasal approach (74.5%), with 51.1% demonstrating gross total resection (GTR). Pituitary stalk was preserved in 51.9%. Permanent arginine vasopressin deficiency was seen in 67.1% and was associated with pituitary stalk sacrifice (p = 0.003). Cerebrospinal fluid leak was the most common nonendocrine postsurgical, 30-day complication (9.1%), reason for return to the operating room (3.1%), and reason for 90-day readmission (8.1%). Most patients (63.9%) received no adjuvant therapy; GTR was associated with decreased radiotherapy use (p = 0.0001). BRAFV600E mutation was detected in 64/69 tumors tested, although only one patient was treated with a BRAF inhibitor. A mean follow-up of 12.3 ± 14.6 months was seen for the group. RAPID consortium enabled the largest real-world clinical information dataset for PCPs. Early findings support that GTR and stalk preservation are important to outcomes. Iterative analysis and discussion of data led to the generation of a framework for future studies to fully leverage the capabilities of multicenter registries.

ABSTRACT Despite remarkable interest in the biomarker potential of urinary extracellular vesicles (uEVs) and the identification of numerous promising candidates, their clinical translation still presents multiple challenges. The opportunities for successful translation are obvious, yet the main roadblocks on the way have hardly been systematically considered and more coordinated approaches are needed to overcome them. In the present review article, we have identified the most relevant roadblocks of clinical translation of urinary EV‐based biomarkers and discuss possible solutions to overcome them. These roadblocks are categorized as fundamental and technical but also related to development of novel biomarker assays and clinical acceptance. In addition, hurdles within the regulatory approval process are discussed. It is clear that various roadblocks to clinical translation of urinary EV biomarkers exist; however, they are addressable by promoting rigor and reproducibility as well as collaboration between basic and clinical scientists, clinicians, industry and regulatory bodies. Moreover, knowledge of obstacles for assay development and regulatory requirements should already be considered when developing a new biomarker to maximize the chance of successful translation. This review presents not only a status quo, but also a roadmap for the further development of the field.

AbstractDocumentation burden contributes to health professional burnout and negatively impacts health professional well-being and patient care quality. Yet, there is a gap in the literature regarding an effective measure to assess the perceived documentation burden of health professionals in a wide range of care settings over time.We developed and administered a pulse survey to trend, with subsequent administrations, the perceived documentation burden of health professionals in all care settings in the United States over time.A multimethods approach was used which included conducting a scoping review of the literature to identify and then curate a set of potential survey items based on scoping review results. Next, a modified Delphi approach was used with clinical informatics experts for consensus-driven item selection and pulse survey development. Finally, we administered the pulse survey nationally using snowball sampling through professional listservs and networks of organizations.The scoping review helped to identify constructs and items to include on the pulse survey. After four iterations of the modified Delphi approach, consensus was reached on five final items for the pulse survey, labeled “TrendBurden.” The first administration of “TrendBurden” was completed by 1,253 healthcare professionals in April 2024. Most respondents (73.26%) disagreed that the time and effort spent documenting patient care is appropriate, with 77.42% reporting finishing work later or needing to work from home due to excessive documentation tasks. Seventy-four point three-eight percent agreed that the effort or time required to complete documentation tasks impedes patient care, and less than one-third (31.76%) agreed that the EHR is easy to use.The “TrendBurden” Pulse Survey was developed through a scoping review of the literature and expert consensus. The resulting five-question pulse survey was administered nationally and provided insight into current perceptions of documentation burden among healthcare professionals.

ImportanceIdentifying factors associated with resilience during the COVID-19 pandemic can inform targeted interventions and resource allocation for groups disproportionately affected by systemic inequities.ObjectiveTo examine factors associated with self-reported resilience during the COVID-19 pandemic in racially and ethnically diverse, community-dwelling US adults.Design, Setting, and ParticipantsThis cross-sectional study was conducted as part of the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) study, which assessed the associations of the pandemic with self-reported resilience of participants from 14 established US prospective cohorts since January 2021. This report includes participants who responded to the self-reported resilience question on C4R questionnaires. Data was initially analyzed from October 2023 to May 2024, with updated analyses performed from August 2024 to April 2025.ExposureRace and ethnicity, behavior factors, health conditions, and social determinants of health measurements accessed before and during the COVID-19 pandemic through cohort visits and C4R questionnaires.Main Outcomes and MeasuresSelf-reported resilience was collected via 1 question (from the Brief Resilience Scale) in C4R questionnaires, “I tend to bounce back quickly after hard times.” Participants who answered agree or strongly agree were classified as resilient, and those who reported neutral, disagree, or strongly disagree were classified as not resilient. Modified Poisson regression was performed to estimate prevalence ratios (PRs) and access multivariable-adjusted associations with resilience.ResultsOf 31 045 participants (18 672 [60%] women; 10 746 [34.6%] aged <65 years), 1185 (3.8%) identified as American Indian, 6728 (21.7%) as Black, 293 (0.9%) as East Asian, 6311 (20.3%) as Hispanic, 565 (1.8%) as South Asian, and 15 961 (51.3%) as White; a total of 23 103 participants (74.4%) self-identified as resilient. Compared with White participants, Black and Hispanic participants had higher prevalence of self-reported resilience (adjusted PR [aPR], 1.04; 95% CI, 1.02-1.06; aPR, 1.08; 95% CI, 1.06-1.11; respectively) and American Indian and East Asian participants had lower prevalence (aPR, 0.90; 95% CI, 0.86-0.94; aPR, 0.76; 95% CI, 0.68-0.84; respectively). Higher education, being married or living as married, higher income, and overweight were also associated with higher prevalence of resilience. Being female, having diabetes, and being unemployed were associated with lower prevalence of self-reported resilience. Compared with participants with public insurance only, participants with private insurance had higher prevalence of resilience (aPR, 1.07; 95% CI, 1.03-1.10). COVID-19 vaccination and infection statuses were not significantly associated with resilience. Modification analyses showed important racial and ethnic differences in how factors such as hypertension, marital status, and insurance status were associated with resilience.Conclusions and RelevanceIn this cross-sectional study of 31 045 adults, self-reported resilience varied by race, ethnicity, and sociodemographic factors. These findings highlight the complex interplay of individual and social factors in shaping the perception of resilience.

BACKGROUND AND OBJECTIVE: In skull base surgery, endoscopic endonasal approaches require precise evaluation of the area of exposure and the maneuverability provided by each approach. Current neuroanatomical methodologies for quantifying these parameters primarily rely on computed tomography (CT) scans and neuronavigation systems, which entail significant financial investment. The aim of this study was to develop and validate an innovative, cost-effective methodology using an endoscopic photogrammetric model to measure the exposure area and maneuverability in endoscopic endonasal approaches, offering an accessible alternative to existing techniques. METHODS: Six cadaveric specimens were used to validate the accuracy of endoscopic photogrammetric measurements by comparing them with direct measurements. Subsequently, the exposure area, angle of attack, and surgical freedom were analyzed for 3 endoscopic approaches to the parasellar region: contralateral transmaxillary, single-nostril, and double-nostril approaches. RESULTS: Photogrammetric measurements demonstrated a high level of concordance with direct cadaveric measurements, with a mean difference of 0.02 mm as shown in the Bland-Altman plot. In addition, measurements obtained in comparative analysis describing the exposure area and maneuverability of 3 endoscopic approaches were congruent with those reported in existing literature derived using CT scans and neuronavigation systems. CONCLUSION: To our knowledge, this study is the first to validate endoscopic photogrammetric models as a measurement tool in neuroanatomy. Performing direct measurements on 3D models might eliminate the necessity of expensive CT and neuronavigation systems for volumetric quantification. Our cost-effective methodology allows for the widespread democratization of anatomical quantification within skull base neuroanatomy.

Abstract Epcoritamab and glofitamab are CD20-directed bispecific antibodies (BsAbs) approved in the United States for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Limited data exist for patients treated outside of trials. Patients with R/R DLBCL receiving commercial epcoritamab or glofitamab between 1 January 2023 and 15 October 2024 were collected from 21 United States institutions. Among 245 patients, 156 received epcoritamab and 89 received glofitamab, 113 were refractory to front-line therapy, 40 had MYC and BCL2 and/or BCL6 rearrangements, 147 received prior chimeric antigen receptor T-cell therapy, and 174 patients would have been ineligible for registrational trials. The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median progression-free survival (PFS) was 2.6 months (95% confidence interval [CI], 2.0-3.8 months), and median overall survival (OS) was 7.8 months (95% CI, 6.2-11.0 months). The 6-month PFS was 36% (95% CI, 30-44) and the 6-month OS was 60% (95% CI, 54-67). Both trial ineligibility and undetectable CD20 pre-BsAbs portended shorter PFS and OS. Of 17 individuals with paired biopsies, 15 (88.2%) lost CD20 expression after BsAbs with a median time to progression of 3.7 months. This analysis including patients with R/R DLBCL shows the ORR to CD3/CD20 BsAbs was comparable to pivotal trials, although PFS and OS were lower. Baseline undetectable levels of CD20 were associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL, and underscore the importance of target antigen expression.