Lung Cancer Adoptive Cell Therapy: Inspiring TIL ACT Comes Center Stage.

Schoenfeld and colleagues report, in this issue, a measurable objective response rate in 6/28 (21.4%) of patients with advanced non-small cell lung cancer treated with lifileucel, a cell therapy product based on autologous tumor-infiltrating lymphocytes (TIL). Extending solid evidence in advanced melanoma that led to FDA approval of lifileucel, this new evidence bodes well for treating patients with other common tumor histologies, justifying important efforts by a large number of academic and biotechnology companies engaged in improving the TIL process. See related article by Schoenfeld et al., p. 1389 (1).

Fully Automated MRI-based Analysis of the Locus Coeruleus in Aging and Alzheimer's Disease Dementia using ELSI-Net.

INTRODUCTION: The Locus Coeruleus (LC) is linked to the development and pathophysiology of neurodegenerative diseases such as Alzheimer's Disease (AD). Magnetic Resonance Imaging based LC features have shown potential to assess LC integrity in vivo. METHODS: We present a Deep Learning based LC segmentation and feature extraction method: ELSI-Net and apply it to healthy aging and AD dementia datasets. Agreement to expert raters and previously published LC atlases were assessed. We aimed to reproduce previously reported differences in LC integrity in aging and AD dementia and correlate extracted features to cerebrospinal fluid (CSF) biomarkers of AD pathology. RESULTS: ELSI-Net demonstrated high agreement to expert raters and published atlases. Previously reported group differences in LC integrity were detected and correlations to CSF biomarkers were found. DISCUSSION: Although we found excellent performance, further evaluations on more diverse datasets from clinical cohorts are required for a conclusive assessment of ELSI-Nets general applicability. Highlights: thorough evaluation of a fully automatic LC segmentation method termed ELSI-Net in aging and AD dementiaELSI-Net outperforms previous work and shows high agreement with manual ratings and previously published LC atlasesELSI-Net replicates previously shown LC group differences in aging and ADELSI-Net's LC volume correlates with CSF biomarkers of AD pathology. RESEARCH IN CONTEXT: Systematic Review: The authors reviewed the literature using traditional sources (e.g. Pubmed, Google Scholar). Although there are several publications introducing semi-automatic methods for LC segmentation, the application of Deep Learning methods is underexplored. To the best of our knowledge, this is the first paper using a Deep Learning based approach for automated LC segmentation in AD dementia. Interpretation: Our work introduces and evaluates an improved automatic, Deep Learning based LC segmentation and analysis approach. The results suggest a very high potential for practical applicability, e.g. in large-scale clinical studies for neurodegenerative diseases. Future Directions: ELSI-Net can be used to assess LC integrity on large- or small-scale studies in Alzheimer's Disease dementia. To ensure robust performance, ELSI-Net should be further evaluated in larger, more diverse datasets comprising varying LC MRI protocols and clinical populations.

Safety and tolerability of pooled human immune globulins after topical ophthalmic administration in New Zealand White rabbits.

PURPOSE: To evaluate the safety and tolerability of pooled human immune globulins, Flebogamma® 5% DIF and Flebogamma® 10% DIF, administered by topical ophthalmic instillation to New Zealand White (NZW) rabbits. METHODS: Male NZW rabbits were used in this study. In the acute single dose tolerability study, rabbits (n = 12) received a single topical dose of Flebogamma® 5% DIF. In the two-week repeated-dose tolerability study, rabbits (n = 5 for each group) were administered either Flebogamma® 5% DIF or Flebogamma® 10% DIF by topical bilateral administration four times daily (q.i.d.) between 8 am and 6 pm for a period of two weeks. Full ophthalmic examinations were conducted to evaluate ocular tolerability at baseline, Day 7, and Day 14. RESULTS: In the acute single dose study, mild hyperaemia was observed in 1 out of 4 eyes at each 4 h and 24 h post-instillation of Flebogamma® 5% DIF. In the repeated dose study, no ocular signs were detected after q.i.d. topical instillation of Flebogamma® 5% DIF, while Flebogamma® 10% DIF resulted in mild hyperaemia in 8 out of 10 eyes on Day 7, and 5 out of 10 eyes on Day 14. No positive corneal fluorescein staining was detected. Schirmer tear test results were unremarkable. No other ocular signs were observed. Administration of immune globulins had no effect on intraocular pressure. CONCLUSIONS: Flebogamma® 5% DIF and Flebogamma® 10% DIF were well-tolerated by NZW rabbits following single and repeat dose topical ophthalmic administration, supporting the future development of topical pooled human immune globulins for the treatment of ocular surface disease.

Global prevalence of nonalcoholic fatty liver disease: an updated meta-analysis on 78 million population over 38 countries.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global health challenge, with a rising rate in line with other metabolic diseases. We aimed to assess the global prevalence of NAFLD in adult and pediatric populations. METHODS: PubMed, Scopus and Web of Science databases were systematically searched up to May 2023. Heterogeneity was assessed using Cochran's Q test and I2 statistics, and random-effects model was used for meta-analysis. Analyses were performed using STATA version 18. RESULTS: A total of 479 studies with 78,001,755 participants from 38 countries were finally included. The global prevalence of NAFLD was estimated to be 30.2% (95% CI: 28.7-31.7%). Regionally, the prevalence of NAFLD was as follows: Asia 30.9% (95% CI: 29.2-32.6%), Australia 16.1% (95% CI: 9.0-24.8%), Europe 30.2% (95% CI: 25.6-35.0%), North America 29% (95% CI: 25.8-32.3%), and South America 34% (95% CI: 16.9-53.5%). Countries with a higher human development index (HDI) had significantly lower prevalence of NAFLD (coefficient = -0.523, p = 0.005). Globally, the prevalence of NAFLD in men and women was 36.6% (95% CI: 34.7-38.4%) and 25.5% (95% CI: 23.9-27.1%), respectively. The prevalence of NAFLD in adults, adults with obesity, children, and children with obesity was 30.2% (95% CI: 28.8-31.7%), 57.5% (95% CI: 43.6-70.9%), 14.3% (95% CI: 10.3-18.8%), and 38.0% (95% CI: 31.5-44.7%), respectively. CONCLUSION: The prevalence of NAFLD is remarkably high, particularly in countries with lower HDI. This substantial prevalence in both adults and children underscores the need for disease management protocols to reduce the burden.

Co-observation of germline pathogenic variants in breast cancer predisposition genes: Results from analysis of the BRIDGES sequencing dataset.

Co-observation of a gene variant with a pathogenic variant in another gene that explains the disease presentation has been designated as evidence against pathogenicity for commonly used variant classification guidelines. Multiple variant curation expert panels have specified, from consensus opinion, that this evidence type is not applicable for the classification of breast cancer predisposition gene variants. Statistical analysis of sequence data for 55,815 individuals diagnosed with breast cancer from the BRIDGES sequencing project was undertaken to formally assess the utility of co-observation data for germline variant classification. Our analysis included expected loss-of-function variants in 11 breast cancer predisposition genes and pathogenic missense variants in BRCA1, BRCA2, and TP53. We assessed whether co-observation of pathogenic variants in two different genes occurred more or less often than expected under the assumption of independence. Co-observation of pathogenic variants in each of BRCA1, BRCA2, and PALB2 with the remaining genes was less frequent than expected. This evidence for depletion remained after adjustment for age at diagnosis, study design (familial versus population-based), and country. Co-observation of a variant of uncertain significance in BRCA1, BRCA2, or PALB2 with a pathogenic variant in another breast cancer gene equated to supporting evidence against pathogenicity following criterion strength assignment based on the likelihood ratio and showed utility in reclassification of missense BRCA1 and BRCA2 variants identified in BRIDGES. Our approach has applicability for assessing the value of co-observation as a predictor of variant pathogenicity in other clinical contexts, including for gene-specific guidelines developed by ClinGen Variant Curation Expert Panels.

Human in vivo baseline intrarenal pressure, peristaltic activity and response to ureteric stenting.

OBJECTIVES: To assess human in vivo intrarenal pressure (IRP) and peristaltic activity at baseline and after ureteric stent placement, using a narrow calibre pressure guidewire placed retrogradely in the renal pelvis. PATIENTS AND METHODS: A prospective, multi-institutional study recruiting consenting patients undergoing ureteroscopy was designed with ethical approval. Prior to ureteroscopy, the urinary bladder was emptied and the COMET™ II pressure guidewire (Boston Scientific) was advanced retrogradely via the ureteric orifice to the renal pelvis. Baseline IRPs were recorded for 1-2 min. At procedure completion, following ureteric stent insertion, IRPs were recorded for another 1-2 min. Statistical analysis of mean baseline IRP, peristaltic waveforms and frequency of peristaltic contractions was performed, thereby analysing the influence of patient variables and ureteric stenting. RESULTS: A total of 100 patients were included. Baseline mean (±SD) IRP was 16.76 (6.4) mmHg in the renal pelvis, with maximum peristaltic IRP peaks reaching a mean (SD) of 25.75 (17.9) mmHg. Peristaltic activity generally occurred in a rhythmic, coordinated fashion, with a mean (SD) interval of 5.63 (3.08) s between peaks. On univariate analysis, higher baseline IRP was observed with male sex, preoperative hydronephrosis, and preoperative ureteric stenting. On linear regression, male sex was no longer statistically significant, whilst the latter two variables remained significant (P = 0.004; P < 0.001). The mean (SD) baseline IRP in the non-hydronephrotic, unstented cohort was 14.19 (4.39) mmHg. Age, α-blockers and calcium channel blockers did not significantly influence IRP, and no measured variables influenced peristaltic activity. Immediately after ureteric stent insertion, IRP decreased (mean [SD] 15.18 [5.28] vs 16.76 [6.4] mmHg, P = 0.004), whilst peristaltic activity was maintained. CONCLUSIONS: Human in vivo mean (SD) baseline IRP is 14.19 (4.39) mmHg in normal kidneys and increases with both hydronephrosis and preoperative ureteric stenting. Mean (SD) peristaltic peak IRP values of 25.75 (17.9) mmHg are reached in the renal pelvis every 3-7 s and maintained in the early post-stent period.

Ocular findings in Jansen metaphyseal chondrodysplasia.

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous PTHR1 variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical coherence tomography (OCT), visual field testing, and craniofacial CT scans. Five of 6 patients had good visual acuity. All patients had widely spaced eyes; 5/6 had downslanted palpebral fissures. One patient had proptosis, and another had bilateral ptosis. Two patients had incomplete closure of the eyelids (lagophthalmos), one had a history of progressive right facial nerve palsy with profuse epiphora, while the second had advanced optic nerve atrophy with corresponding retinal nerve fiber layer (RNFL) thinning on OCT and significant bilateral optic canal narrowing on CT scan. Additionally, this patient also had central visual field defects and abnormal color vision. A third patient had normal visual acuity, subtle temporal pallor of the optic nerve head, normal average RNFL, but decreased temporal RNFL and retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4/6 patients indicating a subclinical optic nerve atrophic process. None of the patients had glaucoma or high myopia. These data represent the first comprehensive report of ophthalmic findings in JMC. Patients with JMC have significant eye findings associated with optic canal narrowing due to extensive skull base dysplastic bone overgrowth that appear to be more prevalent and pronounced with age. Progressive optic neuropathy from optic canal narrowing may be a feature of JMC, and OCT GCA can serve as a useful biomarker for progression in the setting of optic canal narrowing. We suggest that patients with JMC should undergo regular ophthalmic examination including color vision, OCT, visual field testing, orbital, and craniofacial imaging.

Diverse PFAS produce unique transcriptomic changes linked to developmental toxicity in zebrafish.

Per- and polyfluoroalkyl substances (PFAS) are a widespread and persistent class of contaminants posing significant environmental and human health concerns. Comprehensive understanding of the modes of action underlying toxicity among structurally diverse PFAS is mostly lacking. To address this need, we recently reported on our application of developing zebrafish to evaluate a large library of PFAS for developmental toxicity. In the present study, we prioritized 15 bioactive PFAS that induced significant morphological effects and performed RNA-sequencing to characterize early transcriptional responses at a single timepoint (48 h post fertilization) after early developmental exposures (8 h post fertilization). Internal concentrations of 5 of the 15 PFAS were measured from pooled whole fish samples across multiple timepoints between 24-120 h post fertilization, and additional temporal transcriptomics at several timepoints (48-96 h post fertilization) were conducted for Nafion byproduct 2. A broad range of differentially expressed gene counts were identified across the PFAS exposures. Most PFAS that elicited robust transcriptomic changes affected biological processes of the brain and nervous system development. While PFAS disrupted unique processes, we also found that similarities in some functional head groups of PFAS were associated with the disruption in expression of similar gene sets. Body burdens after early developmental exposures to select sulfonic acid PFAS, including Nafion byproduct 2, increased from the 24-96 h post fertilization sampling timepoints and were greater than those of sulfonamide PFAS of similar chain lengths. In parallel, the Nafion byproduct 2-induced transcriptional responses increased between 48 and 96 h post fertilization. PFAS characteristics based on toxicity, transcriptomic effects, and modes of action will contribute to further prioritization of PFAS structures for testing and informed hazard assessment.

Targeting α1- and α2-Adrenergic Receptors as a Countermeasure for Fentanyl-Induced Locomotor and Ventilatory Depression.

This study assessed the ability of α1 and α2-adrenergic drugs to decrease fentanyl-induced locomotor and ventilatory depression. Rats were given saline or fentanyl, following by: (1) naltrexone, (2) naloxone, (3) nalmefene, (4) α1 agonist phenylephrine, (5) α1 antagonist prazosin, (6) α1D antagonist BMY-7378, (7) α2 agonist clonidine, (8) α2 antagonist yohimbine or (9) vehicle. All µ-opioid antagonists dose-dependently reversed fentanyl-induced locomotor and ventilatory depression. While the α1 drugs did not alter the effects of fentanyl, clonidine dose-dependently decreased locomotion and respiration with and without fentanyl. Conversely, yohimbine given at a low dose (0.3-1mg/kg) stimulated ventilation when given alone and higher doses (>1mg/kg) partially reversed (~50%) fentanyl-induced ventilatory depression, but not locomotor depression. High doses of yohimbine in combination with a suboptimal dose of naltrexone reversed fentanyl-induced ventilatory depression, suggestive of additivity. Yohimbine may serve as an effective adjunctive countermeasure agent combined with naltrexone to rescue fentanyl-induced ventilatory depression.

Arborized pattern of MRI enhancement in spinal cord schistosomiasis: A report of 2 successful case outcomes.

This case report describes 2 patients with spinal cord schistosomiasis diagnosed based on a magnetic resonance imaging finding of a unique arborized type of postcontrast enhancement. Both patients presented with back pain and lower limb weakness, and prompt treatment with an anti-schistomal agent and steroid resulted in significant neurological and radiological improvement. The report emphasizes the role of imaging in the early diagnosis of spinal cord schistosomiasis, as well as the importance of early treatment for the best clinical outcomes.

The Annual Cost of Cancer Screening in the United States.

BACKGROUND: Cancer has substantial health, quality-of-life, and economic impacts. Screening may decrease cancer mortality and treatment costs, but the cost of screening in the United States is unknown. OBJECTIVE: To estimate the annual cost of initial cancer screening (that is, screening without follow-up costs) in the United States in 2021. DESIGN: Model using national health care survey and cost resources data. SETTING: U.S. health care systems and institutions. PARTICIPANTS: People eligible for breast, cervical, colorectal, lung, and prostate cancer screening with available data. MEASUREMENTS: The number of people screened and associated health care system costs by insurance status in 2021 dollars. RESULTS: Total health care system costs for initial cancer screenings in the United States in 2021 were estimated at $43 billion. Approximately 88.3% of costs were attributable to private insurance; 8.5% to Medicare; and 3.2% to Medicaid, other government programs, and uninsured persons. Screening for colorectal cancer represented approximately 64% of the total cost; screening colonoscopy represented about 55% of the total. Facility costs (amounts paid to facilities where testing occurred) were major drivers of the total estimated costs of screening. LIMITATIONS: All data on receipt of cancer screening are based on self-report from national health care surveys. Estimates do not include costs of follow-up for positive or abnormal screening results. Variations in costs based on geography and provider or health care organization are not fully captured. CONCLUSION: The $43 billion estimated annual cost for initial cancer screening in the United States in 2021 is less than the reported annual cost of cancer treatment in the United States in the first 12 months after diagnosis. Identification of cancer screening costs and their drivers is critical to help inform policy and develop programmatic priorities, particularly for enhancing access to recommended cancer screening services. PRIMARY FUNDING SOURCE: None.

A point-of-care tenofovir urine test improves accuracy of self-reported PrEP adherence and increases condomless sex reporting among young women.

OBJECTIVES: We evaluated a recently developed and validated point-of-care urine tenofovir (POC TFV) test to determine whether its use improves the accuracy of self-reported adherence to pre-exposure prophylaxis (PrEP) and sexual behavior. DESIGN: We enrolled sexually active HIV-negative women ages 16-25 years in Kampala, Uganda. METHODS: Women were followed quarterly for 24 months with HIV prevention counseling, PrEP dispensation, and adherence counseling. Midway through the study, the POC TFV test was introduced as part of routine study procedures. We examined changes in self-reported PrEP adherence, sexual behavior, and accuracy of self-reported PrEP adherence before and after the introduction of the POC TFV test. RESULTS: A total of 146 women receiving PrEP refills had ≥1 visit with a POC TFV test administered before the study exit. At baseline, the median age was 19 years (interquartile range [IQR]: 18-21) and the majority (76%) reported having condomless sex within the last three months. Participants more frequently self-reported low PrEP adherence (OR: 2.96, 95% confidence interval [CI]: 1.89-4.67, p = 0.001) and condomless sex (OR: 1.47, 95% CI: 1.04-2.06, p = 0.03) during visits using the test compared to visits without the test. The accuracy of self-reported PrEP adherence (determined by concordance with TFV-diphosphate levels) was greater when the test was used (61% versus 24%, OR: 4.86, 95% CI: 2.85-8.30, p < 0.001). CONCLUSIONS: When the POC TFV test was used, we observed greater reporting of condomless sex, low PrEP adherence, and more accurate reports of PrEP adherence. The test could facilitate honest conversations between clients and providers and warrant further investigation.

Impact of systemic disease on CNS disease control after stereotactic radiosurgery to breast cancer brain metastases (The SYBRA Study).

The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS [LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46-6.83, p = 0.0034; LM2: 5.32, 2.33-12.15, p = <0.0001] and shorter OS (LM1: HR with 95% CI 4.28, 1.98-9.12, p = 0.0002; LM2: 7.40, 3.10-17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.

A comprehensive overview of liquid biopsy applications in pediatric solid tumors.

Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field are reported, these mainly focus on dedicated items such as a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best of our knowledge, a comprehensive overview is lacking. Here, we review the current state of liquid biopsy research for the most common non-central nervous system pediatric solid tumors. These include neuroblastoma, renal tumors, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, and liver tumors. Within this selection, we discuss the most important or recent studies involving liquid biopsy-based biomarkers, anticipated clinical applications, and the current challenges for success. Furthermore, we provide an overview of liquid biopsy-based biomarker publication output for each tumor type based on a comprehensive literature search between 1989 and 2023. Per study identified, we list the relevant liquid biopsy-based biomarkers, matrices (e.g., peripheral blood, bone marrow, or cerebrospinal fluid), analytes (e.g., circulating cell-free and tumor DNA, microRNAs, and circulating tumor cells), methods (e.g., digital droplet PCR and next-generation sequencing), the involved pediatric patient cohort, and proposed applications. As such, we identified 344 unique publications. Taken together, while the liquid biopsy field in pediatric oncology is still behind adult oncology, potentially relevant publications have increased over the last decade. Importantly, steps towards clinical implementation are rapidly gaining ground, notably through validation of liquid biopsy-based biomarkers in pediatric clinical trials.

The clinical potential of radiomics to predict hematoma expansion in spontaneous intracerebral hemorrhage: a narrative review.

Spontaneous intracerebral hemorrhage (sICH) is associated with significant morbidity and mortality, with subsequent hematoma expansion (HE) linked to worse neurologic outcomes. Accurate, real-time predictions of the risk of HE could enable tailoring management-including blood pressure control or surgery-based on individual patient risk. Although multiple radiographic markers of HE have been proposed based on standard imaging, their clinical utility remains limited by a reliance on subjective interpretation of often ambiguous findings and a poor overall predictive power. Radiomics refers to the quantitative analysis of medical images that can be combined with machine-learning algorithms to identify predictive features for a chosen clinical outcome with a granularity beyond human limitations. Emerging data have supported the potential utility of radiomics in the prediction of HE after sICH. In this review, we discuss the current clinical management of sICH, the impact of HE and standard imaging predictors, and finally, the current data and potential future role of radiomics in HE prediction and management of patients with sICH.

A Postmortem Case Report involving Fentanyl, Desalkylgidazepam and Bromazolam.

The emergence of new psychoactive substances (NPS) and the number of new chemically diverse substances in the global illicit drug market have significantly increased over the last few years. Designer benzodiazepines are some of the most misused NPS worldwide, contributing to both nonfatal and fatal drug overdose cases. The use of desalkylgidazepam and bromazolam has recently emerged, and their prevalence has been internationally reported. In this study, we quantified desalkylgidazepam and bromazolam using gas chromatography coupled with mass spectrometry (GC-MS) in the postmortem specimens of a subject found deceased due to suspected drug overdose. A 24-year-old white male with a history of drug use was found unresponsive and not breathing in his home with drug paraphernalia nearby. A yellow powdery substance and prescription tablets were also found at the scene. The GC-MS analysis of the postmortem blood and urine samples confirmed the presence of fentanyl, desalkylgidazepam, and bromazolam. The desalkylgidazepam concentration was 1100 ng/mL in the blood, which was higher than previous reports in the literature, and estimated to be 89 ng/mL in the urine. The bromazolam concentration was 352 ng/mL in the blood and estimated to be 398 ng/mL in the urine. Additionally, fentanyl was detected in the blood (11 ng/mL) and fentanyl, norfentanyl, and gabapentin were detected in the urine. The present study aims to provide the toxicological community with information regarding a fit-for-purpose analysis of two NPS benzodiazepines.

Features of Importance in Nasal Endoscopy: Deriving a Meaningful Framework.

OBJECTIVE: Critical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies. STUDY DESIGN: A consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations. SETTING: An online questionnaire was distributed in July 2023. METHODS: The questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W-NASs) to represent the perceived importance of each feature, scaled from 0 to 1. RESULTS: General concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W-NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W-NAS, 0.67). Similar analyses were performed for features in each case. CONCLUSION: The implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision-making during nasal endoscopy.