Citations

BACKGROUND: Patients with locally advanced rectal cancer face substantial costs related to multimodal therapy. However, the extent of this burden is poorly characterized. OBJECTIVE: To characterize the prevalence and predictors of patient-reported financial toxicity after treatment for locally advanced rectal cancer. DESIGN: Multicenter retrospective cohort study with a cross-sectional survey administered to assess patients’ financial concerns as well as clinicodemographic data. SETTING: Three high-volume tertiary academic centers. PATIENTS: Patients who completed treatment for pathological stage II to III rectal adenocarcinoma between 2000 and 2019 and were alive. MAIN OUTCOME MEASURES: Patient-reported financial toxicity and risk factors associated with financial toxicity. RESULTS: A total of 523 patients were identified, 190 (36.3%) responded to the survey, and 2 were excluded for incomplete surveys. Of the responders, 163 (86.7%) were identified as having financial toxicity related to their cancer diagnosis, and most (96.8%) had insurance. Patients with financial toxicity were less likely to have fully paid medical leave (39.8% vs 75%; p = 0.03) compared to patients without financial toxicity. They also reported increased difficulty paying bills ( p < 0.001) and decreased monthly household income ( p < 0.001) due to their diagnosis. Furthermore, these patients reported increased difficulty paying for transportation to medical appointments ( p = 0.002) and were less likely to be completely satisfied with their insurance coverage ( p = 0.003). Feeling well informed regarding treatment-related costs was associated with decreased odds of financial toxicity (OR 0.14; 95% CI, 0.02–0.78; p = 0.02), whereas taking unpaid leave for treatment was associated with increased odds of financial toxicity (OR 4.71; 95% CI, 1.36–16.34; p = 0.01). LIMITATIONS: Cross-sectional design and moderate response rate may introduce selection and recall bias. CONCLUSIONS: Patients undergoing treatment for locally advanced rectal cancer, including those insured, are at risk for financial toxicity due to direct and indirect costs. Effective communication between these patients and physicians regarding the economic implications of treatment is essential to reducing financial toxicity. See Video Abstract . TOXICIDAD FINANCIERA TRAS EL TRATAMIENTO DEL CÁNCER RECTAL LOCALMENTE AVANZADO ANTECEDENTES: Los pacientes con cáncer de recto localmente avanzado enfrentan costos sustanciales relacionados con la terapia multimodal. Sin embargo, la magnitud de esta carga está poco caracterizada. OBJETIVO: Caracterizar la prevalencia y los predictores de la toxicidad financiera reportada por los pacientes después del tratamiento para el cáncer de recto localmente avanzado. DISEÑO: Estudio de cohorte retrospectivo multicéntrico con una encuesta transversal para evaluar las preocupaciones financieras de los pacientes, así como datos clínico-demográficos. ESCENARIO: Tres centros académicos terciarios de alto volumen. PACIENTES: Pacientes que completaron el tratamiento para el adenocarcinoma de recto en estadio patológico II-III entre 2000 y 2019 y estaban vivos. PRINCIPALES MEDIDAS DE RESULTADOS: Toxicidad financiera reportada por los pacientes y factores de riesgo asociados con la toxicidad financiera. RESULTADOS: Se identificó a un total de 523 pacientes, 190 (36,3%) respondieron a la encuesta y 2 fueron excluidos por encuestas incompletas. De los encuestados, 163 (86,7 %) presentaron toxicidad financiera relacionada con su diagnóstico de cáncer, y la mayoría (96,8 %) contaba con seguro médico. Los pacientes con toxicidad financiera tuvieron menos probabilidades de tener licencia médica con goce de sueldo completo (39,8 % frente a 75 %; p = 0,03) en comparación con los pacientes sin toxicidad financiera. También informaron mayor dificultad para pagar facturas ( p < 0,001) y una disminución de los ingresos familiares mensuales ( p < 0,001) debido a su diagnóstico. Además, estos pacientes informaron mayor dificultad para pagar el transporte a las citas médicas ( p = 0,002) y menor probabilidad de estar completamente satisfechos con su cobertura médica ( p = 0,003). Sentirse bien informado sobre los costos relacionados con el tratamiento se asoció con una menor probabilidad de toxicidad financiera (OR: 0,14; IC del 95 %: 0,02-0,78; p = 0,02), mientras que tomar una licencia sin sueldo para el tratamiento se asoció con una mayor probabilidad de toxicidad financiera (OR: 4,71; IC del 95 %: 1,36-16,34; p = 0,01). LIMITACIONES: El diseño transversal y la tasa de respuesta moderada pueden introducir sesgos de selección y de recuerdo. CONCLUSIONES: Los pacientes en tratamiento para el cáncer de recto localmente avanzado, incluidos los asegurados, corren el riesgo de sufrir toxicidad financiera debido a los costos directos e indirectos. Una comunicación eficaz entre estos pacientes y los médicos sobre las implicaciones económicas del tratamiento es esencial para reducir la toxicidad financiera. ( AI-generated translation )

Abstract Aim Rectal prolapse is a full‐thickness intussusception of the rectum beyond the anal canal. It is often mistaken for other anorectal pathologies, leading to inaccurate referrals to colorectal surgeons and inappropriate management. However, the frequency of misdiagnosis is not well characterized. We aimed to assess the diagnostic accuracy of rectal prolapse referrals to three tertiary medical centres. Methods This is a retrospective study of patients referred for rectal prolapse to colorectal surgeons at the Mayo Clinic in Rochester, Jacksonville, and Phoenix from 2020 to 2024. The primary outcome is the accuracy of rectal prolapse diagnosis. The secondary outcomes are factors that correlate with diagnostic accuracy. Results Rectal prolapse was inaccurately diagnosed in 38.7% (186/480) of patients. Among misdiagnosed patients, the correct diagnosis was haemorrhoids (68.0%, n = 134), pelvic floor dysfunction (24.3%, n = 48) and rectocele (18.7%, n = 37). A diagnosis of rectal cancer was found in 3 patients (1.5%). The most common presenting symptoms were protrusion (66.3%, n = 345) and bleeding (33.6%, n = 175). Among the referring physicians, only 50.5% ( n = 227) performed an anorectal examination. Overall, there was significant variability in diagnostic accuracy across different specialties, with the highest accuracy from colorectal practices (84.0%) and the lowest from urologists (50.0%). Internal medicine physicians had a lower diagnostic accuracy with anorectal examination than without, though it did not reach statistical significance (44.0% vs. 59.5%, p = 0.2). Conclusion Over one‐third of rectal prolapse referrals were incorrectly diagnosed. This study highlights the opportunity for further training of referring providers on anorectal pathologies to improve diagnostic accuracy which could reduce treatment delays and optimize clinical outcomes.

Abstract INTRODUCTION The tau positron emission tomography (PET) overlap index (OI) has shown promise in maximizing signal‐to‐noise for longitudinal tau PET imaging, particularly for early tau pathology, but requires validation against neuropathology. METHODS Fifty‐seven participants who underwent serial tau PET imaging (flortaucipir) and subsequent autopsy were included. Tau PET OI and standardized uptake value ratios (SUVRs) were compared across neuropathological diagnoses. RESULTS Tau PET OI showed greater concordance with neurofibrillary tangle (NFT) severity in the entorhinal cortex (a key region for Alzheimer's disease [AD] tauopathy) than SUVR, particularly in early Braak tangle stages (positivity: 52.2% for OI vs. 13.0% for SUVR). OI detected overlapping tau voxels that exhibited spatial correspondence with immunohistochemical and autoradiography measures of tau deposition across both AD and non‐AD tauopathies. DISCUSSION These findings demonstrate the enhanced capacity of OI in serial tau PET to robustly detect early and spatially localized tau pathology, supporting its application as a sensitive imaging metric in AD and select non‐AD tauopathies.

Abstract Background Head and neck cancer represents the seventh most common cancer diagnosis globally. Maintaining sufficient nutrition is important for preventing malnutrition (undernutrition) and muscle wasting, which contribute to worse outcomes, although many patients are unable to maintain adequate oral intake throughout treatment. This guideline provides practice guidance on nutrition care for patients with head and neck cancer. Methods An interdisciplinary team developed key questions and scanned results from a systematic search of the PubMed, EMBASE, CINAHL, and Cochrane Central databases back to 2001. Recommendations were created for key questions concerning timing and duration of nutrition support (early vs delayed enteral nutrition [EN], postoperative feeding, and perioperative dietitian intervention), frequency of dietitian and speech pathology consultations, nutrition screening and assessment, macronutrient requirements, enteral access devices, adjunctive strategies (appetite stimulants and continuation of oral intake alongside EN), specialized nutrients (arginine, glutamine, ω‐3, and immunonutrition), and interdisciplinary care. Results Ninety‐two studies were included. Recommendations were made supporting early initiation of EN when oral intake is inadequate, nutrition within 24 h after surgery, weekly consultation with a dietitian during radiotherapy, malnutrition screening and assessment with validated tools, interdisciplinary models of care, dietitian involvement before and after surgery, and when to consider use of specialized nutrients. Recommendations are also provided for protein intake (1.2–1.5 g/kg/day) and energy intake (≥30 kcal/kg/day). Conclusion This guideline provides guidance for the nutrition care of patients with head and neck cancer, identifies research gaps, and calls for standardized outcome reporting to further the state of the evidence. This paper was approved by the ASPEN Board of Directors.

ABSTRACT Background Primary lateral sclerosis (PLS) is an ultrarare upper motor neuron syndrome with a prognosis unique from classical ALS. The study of PLS is complicated by its rarity and the difficulty distinguishing PLS from ALS. We present data from a 1‐year prospective follow‐up study on PLS and efforts to distinguish it from ALS. Methods Seventy‐six PLS participants enrolled in this prospective natural history study. EMG studies, blood neurofilament light chain levels (NfLs), and demographic characteristics were obtained at baseline. At 1‐year follow‐up, repeat EMG studies were conducted to determine which participants fulfilled criteria for ALS. Baseline characteristics were then compared to determine features that predict reclassification. Results Seventy participants completed 1‐year follow‐up. Five of the 70 were reclassified to ALS (7.1%). Those reclassified had higher trends in baseline blood NfL levels (91.4 vs. 34.0 pg/mL, p = 0.13) and shorter symptom duration (39 vs. 69 months in the PLS group, p = 0.15). Reclassification was noted in both probable and definite PLS participants. All cases with a symptomatic duration of less than 2 years retained the PLS phenotype (5 of 5). NfL levels over 90 pg/mL predicted reclassification with 94% specificity and 60% sensitivity. No other features predicted reclassification to ALS. Conclusions In our population, reclassification of PLS to ALS occurred at a low frequency at 1 year follow‐up (7.1%). Baseline NfL was the strongest predictor in differentiating UMN dominant ALS from PLS at 1‐year follow‐up. Based on our data, we propose EMG and NfL criteria for enrollment in future PLS trials.

ABSTRACT The COVID‐19 pandemic underscored the critical need to strengthen healthcare systems and optimize resource allocation planning during times of disruption and crisis. This retrospective, single‐center, cross‐sectional study included 33,158 admissions for patients ≤ 17 years old admitted to the Children's Hospital (CH) between January 1, 2017, and December 31, 2021. Data was abstracted using Vizient Clinical Data Base and the internal data warehouse. A Poisson regression model was implemented to compare admission diagnosis patterns during the pre‐ and intra‐pandemic phases. CH SARS‐CoV‐2 prevalence rate was 0.1% in 2020 and 0.5% in 2021. There was a decrease in overall admissions to the CH ( p < 0.01) and PICU ( p < 0.01) at the onset of the pandemic. There were significant and variable differences in admission patterns for certain infectious and seizure‐related diagnoses. The CH experienced an increase in certain specific mental health diagnoses. Seasonality was noted for viral bronchiolitis during the pre‐pandemic phase, but was disrupted during the intra‐pandemic phase. The COVID‐19 pandemic had a significant impact on the number and pattern of admissions, despite low prevalence of SARS‐CoV‐2 in our hospital. These changes may be secondary to COVID‐19 community mitigation strategies. Results can inform anticipated patterns during future pandemics.

Abstract Current assessments of brain permeability rely predominantly on drug delivery to contrast-enhancing tumor regions. However, substantial portions of central nervous system (CNS) tumors reside within non-enhancing brain (NEB), where drug concentrations frequently remain subtherapeutic. This collaborative Adult Brain Tumor Consortium and Food and Drug Administration workshop aimed to identify criteria for defining NEB permeability to accomplish 2 critical objectives: (1) allocate clinical trial resources toward agents achieving therapeutic NEB concentrations and (2) minimize systemic toxicity when CNS benefit is improbable. The workshop systematically evaluated permeability assessment modalities, including drug physicochemical properties, in vitro blood-brain barrier models, and penetration into cerebrospinal fluid and normal rodent brain. Methodological approaches to determine requisite NEB drug concentrations and approaches to measuring NEB pharmacokinetics and pharmacodynamics were examined. This culminated in developing the Non-Enhancing Brain Permeability Index (NEBPI), which assigns therapeutic agents to 3 categories: sufficiently permeable, insufficiently permeable, or impermeable. The NEBPI provides a standardized framework to assist investigators and regulatory agencies to evaluate NEB penetration before human efficacy studies are initiated for agents that require direct tumor contact. Assessing NEB drug penetration is critical to improving outcomes in CNS tumors and reducing the incidence of brain metastases in systemic malignancies.

Abstract Objectives Diagnosing adult T-cell leukemia/lymphoma (ATLL) remains challenging due to its clinical and histopathologic heterogeneity. While HTLV-1 serology is a key diagnostic criterion, it is often unavailable at the time of diagnosis and does not confirm viral integration in tumor cells. The HTLV-1–encoded HBZ RNA is a reliable diagnostic biomarker for ATLL. We evaluated the diagnostic performance of RNAscope in situ hybridization (ISH) for HBZ RNA in formalin-fixed, paraffin-embedded (FFPE) tissues to distinguish ATLL from other T-cell lymphomas. Methods HBZ ISH was evaluated in 72 cases, including 52 ATLLs and 20 non-ATLL T-cell lymphomas, to determine diagnostic sensitivity and specificity, interobserver agreement, interlaboratory reproducibility, and comparison with digital gene expression. Results This assay demonstrated 86.5% sensitivity and 100% specificity, with sensitivity improving to 97% when excluding bone marrow clot sections and FFPE blocks older than 5 years. Interobserver agreement among 3 pathologists was excellent (κ = 0.92, percent agreement: 94%). Interlaboratory reproducibility of HBZ ISH was high, with 93% to 95% concordance across these Clinical Laboratory Improvement Amendments–certified laboratories. HBZ RNA ISH–positive cases demonstrated significantly higher HBZ gene expression levels by digital gene expression profiling. Conclusions We established HBZ ISH as a reliable tissue-based surrogate for HTLV-1 infection in ATLL. This assay will enhance diagnostic accuracy, expedite definitive diagnosis, and improve patient selection for targeted therapies and clinical trials, particularly in regions with a high prevalence of HTLV-1.

Abstract Objectives Traditional laboratory regulatory frameworks provide robust guidance for conventional clinical testing but lack requirements for data documentation for artificial intelligence and machine learning (AI/ML) solutions. This gap creates significant risks since AI solutions directly inherit patterns, biases, and limitations from their training data. Here, we describe the development and implementation of a comprehensive data documentation checklist with accompanying data lineage for use within an AI lifecycle framework for clinical laboratories. Methods Building on the previously established Clinical AI Readiness Evaluator (CARE) framework, we developed a comprehensive data checklist and data lineage methodology through a multiphase process, including (1) comprehensive review of existing AI/ML data documentation frameworks, (2) focused meetings with 3 institutional AI operations teams, and (3) 3 rounds of iterative refinement by our multidisciplinary team. The checklist’s effectiveness was then assessed using 3 diverse AI/ML projects moving through the CARE framework. Results The CARE Data Checklist and Data Lineage provide a structured approach to documenting critical aspects of datasets used in AI/ML projects, including data composition, demographics, collection methods, labeling processes, usage constraints, maintenance requirements, and a data readiness assessment. The checklist addresses unique data-centric challenges of AI/ML applications, facilitating transparency, reproducibility, and regulatory compliance. Conclusions The CARE Data Checklist and Data Lineage serve as both a technical guide and a communication tool bridging gaps between technical and clinical stakeholders. By working on these documents early in the AI lifecycle, laboratories can anticipate and address data-related challenges, ultimately saving time, optimizing resources, and improving the reliability of AI-augmented laboratory solutions.