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.

Mpox Keratitis: A Case Report and Review.

PURPOSE: Mpox is a rare infectious disease. Lack of knowledge among eye care professionals regarding mpox keratitis greatly reduces the likelihood of diagnosis and effective management. This report and review seek to increase the knowledge of mpox keratitis among eye care professionals. METHODS: We report a patient with mpox keratitis who underwent successful penetrating keratoplasty, with 20 years of follow-up. A systematic literature search and review of cases of mpox keratitis from 1970 to 2024 was performed. RESULTS: A total of 24 articles and 2 abstracts reporting 35 cases of mpox keratitis were identified. A frequency of 0.5% to 1.0% may be the lower range of mpox keratitis among symptomatic patients with a confirmed mpox diagnosis. Mpox keratitis occurred with and without systemic mpox. Initial misdiagnoses were common (40%). Polymerase chain reaction results aided clinical diagnosis. Corneal disease ranged from mild epitheliopathy to fulminant ulcerative keratitis. Outcomes ranged from 20/20 acuity to no light perception. In the absence of fulminant systemic disease, tecovirimat was associated with clinical improvement of mpox keratitis in almost all cases. Our case is the only known report of successful penetrating keratoplasty for mpox keratitis and the only case whereby monkeypox virus was cultured from the corneal surface. CONCLUSIONS: Mpox keratitis is rare but can result in severe vision loss and blindness. Systemic tecovirimat seems to be effective in treating mpox keratitis, although the low frequency of keratitis precludes clinical trials. Topical steroids may extend virus survival in the cornea. Polymerase chain reaction may help confirm mpox corneal involvement.

Growing pains with kratom: experiences discussed in subreddits contrast with satisfaction expressed in surveys.

Background: "Kratom" refers to an array of bioactive products derived from Mitragyna speciosa, a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences. Methods: We collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types. Results: Codes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information. Conclusion: As in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making.

Selection of Single-Analyte Delta Check Rules with Logistic Regression for Detection of Intravenous Fluid Contamination in a Clinical Chemistry Laboratory.

BACKGROUND: The conventional single-analyte delta check, utilized for identifying intravenous fluid contamination and other preanalytical errors, is known to flag many specimens reflecting true patient status changes. This study aimed to derive delta check rules that more accurately identify contamination. METHODS: Results for calcium, creatinine, glucose, sodium, and potassium were retrieved from 326 103 basic or comprehensive metabolic panels tested between February 2021 and January 2022. In total, 7934 specimens showed substantial result changes, of which 1489 were labeled as either contaminated or non-contaminated based on chart review. These labeled specimens were used to derive logistic regression models and to select the most predictive single-analyte delta checks for 4 common contaminants. Their collective performance was evaluated using a test data set from October 2023 comprising 14 717 specimens. RESULTS: The most predictive single-analyte delta checks included a calcium change by ≤-24% for both saline and Plasma-Lyte A contamination, a potassium increase by ≥3.0 mmol/L for potassium contamination, and a glucose increase by ≥400 mg/dL (22.2 mmol/L) for dextrose contamination. In the training data sets, multi-analyte logistic regression models performed better than single-analyte delta checks. In the test data set, logistic regression models and single-analyte delta checks demonstrated collective alert rates of 0.58% (95% CI, 0.46%-0.71%) and 0.60% (95% CI, 0.49%-0.74%), respectively, along with collective positive predictive values of 79% (95% CI, 70%-89%) and 77% (95% CI, 68%-87%). CONCLUSIONS: Single-analyte delta checks selected by logistic regression demonstrated a low false alert rate.

"Does My Kid Have an Ear Infection?" An Analysis of Pediatric Acute Otitis Media Videos on TikTok.

INTRODUCTION: With the rise of social media, online platforms have become a common way to access healthcare information. This study examines the quality of pediatric acute otitis media (AOM) videos on TikTok, a popular short-form video social media platform. METHODS: A TikTok search was conducted between 8/18 and 8/19/2023 using pediatric AOM hashtags: #pediatric acute otitis media management, #kid ear infections remedy, #child ear infections treatment, and #kid ear infection. Data collected include number of views/shares per day, uploader type (nonmedical influencer, lay individual, and medical professional), and content categories. The Patient Education Materials Assessment Tool for Audiovisual Material (PEMAT-AV) and DISCERN questionnaire measured understandability, actionability, and quality of videos. Multivariable linear regression models were used (significance set at ≤0.05). RESULTS: Of 166 videos, 38.6% (64) of uploaders were medical professionals, and 32.5% (54) were nonmedical influencers. Nonmedical influencer videos were viewed and shared significantly more than those by medical professionals (p < 0.05). Controlling for covariates, physicians were more likely to produce more beneficial and higher quality videos as compared with nonmedical influencers (ß = 2.4 and 1.3, p < 0.01, respectively). However, physicians did not have significantly different ratings for understandability compared with nonmedical influencers (ß = 0.45, p > 0.05). DISCUSSION: AOM content on TikTok is often geared toward caretakers of symptomatic children. Although physician-created AOM content was significantly higher quality, these videos reached a statistically smaller audience than those from nonmedical influencers. Addressing misinformation on social media platforms requires physicians to reach larger audiences by producing more actionable and understandable content. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

The effect of pleural drainage on pulse oximetry in a post-operative thoracic surgery population.

BACKGROUND: Pleural effusions in post-operative thoracic surgery patients are common. Effusions can result in prolonged hospitalizations or readmissions, with prior studies suggesting mixed effects of pleural drainage on hypoxia. We aimed to define the impact of pleural drainage on pulse oximetry (SpO2) in post-thoracic surgery patients. METHODS: A retrospective study of post-operative thoracic surgery patients undergoing pleural drainage was performed. SpO2 and supplemental oxygen (FiO2) values were recorded at pre- and post-procedure. The primary outcome was difference in pre-procedural and post-procedural SpO2. RESULTS: We identified 95 patients with a mean age of 65 (SD - 13.8) years undergoing 122 pleural drainage procedures. Mean drainage volume was 619 (SD-423) mL and the majority of procedures (88.5 %) included a drainage of <1000 mL. SpO2 was associated with an increase from 94.0 % (SD-2.6) to 97.3 % (SD-2.0) at 24-h (p < 0.0001). FiO2 was associated with a decrease from 0.31 (SD-0.15) to 0.29 (SD-0.12) at 24-h (p = 0.0081). SpO2/FiO2 was associated with an increase from 344.5 (SD-99.0) to 371.9 (SD-94.7) at 24-h post-procedure (p < 0.0001). CONCLUSIONS: Pleural drainage within post-operative thoracic surgery patients offers statistically significant improvements in oxygen saturation by peripheral pulse oximetry and oxygen supplementation; however the clinical significance of these changes remains unclear. Pleural drainage itself may be requested for numerous reasons, including diagnostic (fevers, leukocytosis, etc.) or therapeutic (worsening dyspnea) evaluation. However, pleural drainage may offer minimal clinical impact on pulse oximetry in post-operative thoracic surgery patients.

Evaluating ChatGPT's moral competence in health care-related ethical problems.

Objectives: Artificial intelligence tools such as Chat Generative Pre-trained Transformer (ChatGPT) have been used for many health care-related applications; however, there is a lack of research on their capabilities for evaluating morally and/or ethically complex medical decisions. The objective of this study was to assess the moral competence of ChatGPT. Materials and methods: This cross-sectional study was performed between May 2023 and July 2023 using scenarios from the Moral Competence Test (MCT). Numerical responses were collected from ChatGPT 3.5 and 4.0 to assess individual and overall stage scores, including C-index and overall moral stage preference. Descriptive analysis and 2-sided Student's t-test were used for all continuous data. Results: A total of 100 iterations of the MCT were performed and moral preference was found to be higher in the latter Kohlberg-derived arguments. ChatGPT 4.0 was found to have a higher overall moral stage preference (2.325 versus 1.755) when compared to ChatGPT 3.5. ChatGPT 4.0 was also found to have a statistically higher C-index score in comparison to ChatGPT 3.5 (29.03 ± 11.10 versus 19.32 ± 10.95, P =.0000275). Discussion: ChatGPT 3.5 and 4.0 trended towards higher moral preference for the latter stages of Kohlberg's theory for both dilemmas with C-indices suggesting medium moral competence. However, both models showed moderate variation in C-index scores indicating inconsistency and further training is recommended. Conclusion: ChatGPT demonstrates medium moral competence and can evaluate arguments based on Kohlberg's theory of moral development. These findings suggest that future revisions of ChatGPT and other large language models could assist physicians in the decision-making process when encountering complex ethical scenarios.

Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

AIMS: To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol-1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol-1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6-week interventions: (1) exercise training (EX; 70%-75% maximum heart rate; four sessions/week; n = 13) or (2) non-exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA-IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin-18 (CK18) M65, among others. RESULTS: In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA-IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = -0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). CONCLUSIONS: Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate-intensity exercise training.

Biomarker profiles associated with reverse ventricular remodelling in patients with heart failure and a reduced ejection fraction: Insights from the echocardiographic substudy of the VICTORIA trial.

AIMS: Reverse ventricular remodelling, defined as a decrease in left ventricular end-systolic volume indexed to body surface area (LVESVI) or an increase in left ventricular ejection fraction (LVEF), is associated with improved clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, the underlying pathophysiological mechanisms remain unclear. METHODS AND RESULTS: We evaluated paired core-lab assessed echocardiograms and measurements of 92 biomarkers at baseline and 8 months thereafter in 419 participants with HFrEF. Reverse ventricular remodelling was defined as a >5% LVEF increase or >15% LVESVI relative decrease between baseline and 8 months. We evaluated the association between baseline biomarkers and their changes with reverse ventricular remodelling in the prospectively randomized controlled VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) trial. Of 419 patients (median age 66 [interquartile range 57-74] years, 27.4% women), 206 (49.2%) had reverse ventricular remodelling (either a 5% LVEF increase or a 15% LVESVI decrease). There were no differences in baseline biomarker concentrations between patients with versus those without reverse ventricular remodelling on follow-up. However, in patients with reverse ventricular remodelling there were significant decreases in biomarkers relating to inflammation and cardiac metabolism; particularly the tumour necrosis factor superfamily member 13B (ratio 0.82, 95% confidence interval [CI] 0.77-0.88), growth differentiation factor-15 (ratio 0.74, 95% CI 0.66-0.84), and insulin-like growth factor binding protein 7 (ratio 0.80, 95% CI 0.73-0.88). CONCLUSIONS: Reverse ventricular remodelling in patients with HFrEF is associated with a decrease of biomarkers related to inflammation and cardiac metabolism.

Challenges and advances in device-related thrombus in left atrial appendage occlusion.

Oral anticoagulation therapy (OAC) is a mainstay for mitigating stroke and other embolic events in patients with atrial fibrillation (AF). Despite the demonstrated efficacy of OAC in reducing events, many patients are unable to tolerate OAC due to bleeding risks. Left atrial appendage occlusion (LAAO) devices were developed as implantable technologies to moderate stroke risk in patients with intolerance to OAC. Despite clinical data supporting near-comparable protection against thromboembolic events with OAC, device-related thrombus formation has emerged as a critical complication following LAAO that remains a potential limitation to the safety and efficacy of LAAO. Improved biocompatibility of LAAO devices with fluoropolymers, a well-established stent-coating technology used to reduce thrombus formation and promote endothelialization, may optimize outcomes after LAAO.

[Box: see text].

Changes in Registered Nurse Employment Plans and Workplace Assessments.

Importance: The US registered nurse (RN) workforce is in flux, with high rates of burnout, intention to leave, and vacancies. Rapid, repeated assessments of the nursing workforce can help hospital executives and policymakers enact effective recruitment and retention strategies. Objective: To identify changes in practicing RNs' employment plans and workplace assessments between the 2022 and 2023 surveys. Design, Setting, and Participants: This survey study compared data collected from the Michigan Nurses' Study at 2 time points: February 22 to March 1, 2022, and May 17 to June 1, 2023. Practicing RNs with an active, unrestricted license in Michigan and a valid individual email address were included. Main Outcome and Measures: The primary outcome was nurses' intention to leave their current position within 1 year. In the 2023 survey, nurses who planned to leave were queried on their next career step and the primary reason for their planned departure. Workplace assessments included questions about abusive or violent workplace events, emotional exhaustion, job satisfaction, the practice environment's delivery of high-quality care, and the clinical setting's safety rating. Regression analysis was used to examine workplace assessments and personal factors associated with planned departures. Results: This study obtained data on 9150 nurses (6495 females [71.0%]) and 7059 nurses (5134 females [72.7%]) responding to the 2022 (response rate, 8.3%) and 2023 (response rate, 7.4%) surveys, respectively. In the 2023 survey, 32.0% (2259) of nurses planned to leave their position, compared with 39.1% (3576) in the 2022 survey. Of these nurses, 957 (41.8%) planned to leave their current employer but remain in nursing, with workloads as the most frequently cited reason (29.4% [672]). Compared with the 2022 cohort, nurses in the 2023 sample reported less workplace abuse or violence (4591 [50.2%] vs 3063 [43.4%]; P < .001), fewer understaffed shifts (4407 [48.2%] vs 2898 [41.0%]; P < .001), and less frequent use of mandatory overtime (1709 [18.7%] vs 824 [11.7%]; P < .001). Factors associated with increased likelihood for planned departures included workplace abuse or violence (odds ratio [OR], 1.39; 95% CI, 1.05-1.82) and higher emotional exhaustion scores (OR, 3.05; 95% CI, 2.38-3.91). Favorable practice environments (OR, 0.37; 95% CI, 0.22-0.62) and excellent clinical setting safety ratings (OR, 0.28; 95% CI, 0.14-0.56) were associated with lower likelihood of planned departure. Conclusions and Relevance: Results of this study showed that nurses reported improved workplace conditions in the 2023 vs the 2022 survey; however, planned departure rates, abusive or violent events, and unsafe conditions remained high, and understaffing remained a primary concern for most nurses. Health system leaders and policymakers should prioritize initiatives that support nurse retention and reduce potential workforce instability.

Parkinsonian Tremor as Unstable Feedback in a Physiologically Consistent Control Framework.

Parkinson's disease (PD) is characterized by decreased dopamine in the basal ganglia that causes excessive tonic inhibition of the thalamus. This excessive inhibition seems to explain inhibitory motor symptoms in PD, but the source of tremor remains unclear. This paper investigates how neural inhibition may change the closed-loop characteristics of the human motor control system to determine how this established pathophysiology could produce tremor. The rate-coding model of neural signals suggests increased inhibition decreases signal amplitude, which could create a mismatch between the closed-loop dynamics and the internal models that overcome proprioceptive feedback delays. This paper aims to identify a candidate model structure with decreased-amplitude-induced tremor in PD that also agrees with previously recorded movements of healthy and cerebellar patients. The optimal feedback control theory of human motor control forms the basis of the model. Key additional elements include gating of undesired movements via the basal ganglia-thalamus-motor cortex circuit and the treatment of the efferent copy of the control input as a measurement in the state estimator. Simulations confirm the model's ability to capture tremor in PD and also demonstrate how disease progression could affect tremor and other motor symptoms, providing insight into the existence of tremor and non-tremor phenotypes. Altogether, the physiological underpinnings of the model structure and the agreement of model predictions with clinical observations provides support for the hypothesis that unstable feedback produces parkinsonian tremor. Consequently, these results also support the associated framework for the neuroanatomy of human motor control.

Zirconium Hydride Catalysis Initiated by Tetrabutylammonium Fluoride.

In our drug discovery campaigns to target the oncogenic drivers of cancers, the demand for a chemoselective, stereoselective and economical synthesis of chiral benzylamines drove the development of a catalytic zirconium hydride reduction. This methodology uses the inexpensive, bench stable zirconocene dichloride, and a novel tetrabutylammonium fluoride activation tactic to catalytically generate a metal hydride under ambient conditions. The diastereo- and chemoselectivity of this reaction was tested with the preparation of key intermediates from our discovery programs and in the scope of sulfinyl ketimines and carbonyls relevant to medicinal chemistry and natural product synthesis. A preliminary mechanistic investigation conducted into the role of tetrabutylammonium fluoride indicates that formation of a zirconocene fluoride occurs to initiate catalysis. The implications of this convenient activation approach may provide expanded roles for zirconium hydrides in catalytic transformations.

Effects of Antioxidant Dietary Supplement Use upon Response to Cancer Treatment: A Scoping Review of Available Evidence.

INTRODUCTION: The effects of antioxidant dietary supplements on response to biological therapies for cancer is unknown. We conducted a scoping review of the available systematic review evidence on this question. METHODS AND ANALYSIS: We searched six databases from inception to August 19, 2022 for systematic reviews of randomized controlled trials of antioxidant dietary supplements used by patients receiving curative chemotherapy, radiotherapy, or other biological therapy for cancer and assessing the impact of supplements on survival, treatment response, or disease progression. We focused on results from reviews at high or moderate AMSTAR-2 quality. Records were selected, data extracted, and AMSTAR-2 ratings assessed independently by two authors. RESULTS: We found 24 systematic reviews with relevant evidence. Reviews were heterogenous in cancers, treatments, and antioxidant dietary supplements assessed. Conclusions across reviews were mixed, ranging from negative to no apparent difference to positive, but always with caveats about the limited size and quality of the evidence. One review was rated 'moderate' on AMSTAR-2; it included one small trial of vitamin C and formed no firm conclusions. CONCLUSIONS: We did not find reliable systematic review evidence on the effects of antioxidant dietary supplements upon therapies for cancer. More research is necessary to inform clinical recommendations.

The Utilization of Systematic Reviews and Meta-Analyses in Stroke Guidelines.

BACKGROUND: Stroke guideline statements are important references for clinicians due to the rapidly evolving nature of treatments. Guideline statements should be informed by up-to-date systematic reviews (SRs) and meta-analyses (MAs) because they provide the highest level of evidence. To investigate the utilization of SRs/MAs in stroke management guidelines, we conducted a literature review of guidelines and extracted relevant information regarding SRs/MAs. METHODS: A literature review was conducted in PubMed with supplementation using the Trip medical database with the term "stroke" as the target population, followed by using the filter "guidelines". We extracted the number of included SRs/MAs, the years of publication, the country of origin, and other characteristics of interest. Descriptive statistics were generated using the R software version 4.2.1. RESULTS: We included 27 guideline statements. The median number of overall SRs or MAs within the guidelines was 4.0 (interquartile range [IQR] = 2-9). For MAs only, the median number included in the guidelines was 3.0 (IQR = 2.0-5.5). Canadian guidelines had the oldest citations, with a median gap of 12.0 (IQR = 5.2-18.0) years for the oldest citation, followed by European (median = 12; IQR = 9.5-13.5) and US (median = 10.0; IQR = 5.2-16) guidelines. CONCLUSIONS: Stroke guideline writing groups and issuing bodies should devote greater effort to the inclusion of up-to-date SRs/MAs in their guideline statements so that clinicians can reference recent data with the highest level of evidence.

Hypoxic Memory Mediates Prolonged Tumor Intrinsic Type I Interferon Suppression to Promote Breast Cancer Progression.

Hypoxia is a common feature of many solid tumors due to aberrant proliferation and angiogenesis that is associated with tumor progression and metastasis. Most of the well-known hypoxia effects are mediated through hypoxia-inducible factors (HIFs). Identification of the long-lasting effects of hypoxia beyond the immediate HIF-induced alterations could provide a better understanding of hypoxia-driven metastasis and potential strategies to circumvent it. Here, we uncovered a hypoxia-induced mechanism that exerts a prolonged effect to promote metastasis. In breast cancer patient-derived circulating tumor cell (CTC) lines and common breast cancer cell lines, hypoxia downregulated tumor intrinsic type I interferon (IFN) signaling and its downstream antigen presentation (AP) machinery in luminal breast cancer cells, via both HIF-dependent and HIF-independent mechanisms. Hypoxia induced durable IFN/AP suppression in certain cell types that was sustained after returning to normoxic conditions, presenting a "hypoxic memory" phenotype. Hypoxic memory of IFN/AP downregulation was established by specific hypoxic priming, and cells with hypoxic memory had an enhanced ability for tumorigenesis and metastasis. Overexpression of IRF3 enhanced IFN signaling and reduced tumor growth in normoxic, but not hypoxic, conditions. The histone deacetylase inhibitor (HDACi) entinostat upregulated IFN targets and erased the hypoxic memory. These results point to a mechanism by which hypoxia facilitates tumor progression through a long-lasting memory that provides advantages for CTCs during the metastatic cascade.

Evaluating Lab-Based Eligibility Criteria by Race/Ethnicity in Clinical Trials of Diffuse Large B-Cell Lymphoma.

Underrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy (IC) would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 lab-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Utilizing data from the prospectively enrolled Lymphoma Epidemiology Outcomes (LEO) Cohort study, with demographics broadly similar to the U.S. patients diagnosed with lymphoma, we evaluated the impact of laboratory eligibility criteria from recent first-line DLBCL trials across various racial and ethnic backgrounds. There were significant differences in the baseline lab values by race/ethnicity with Black/African American (AA) patients having the lowest mean hemoglobin and highest creatinine clearance. Based on recent clinical trial eligibility criteria, AA and Hispanic patients had higher rates of lab-based ineligibility compared to Non-Hispanic Whites. The largest gap in the clinical outcomes between eligible (ref) and non-eligible patients was noted within AA patients with an overall survival hazard ratio based on POLARIX clinical trial criteria of 4.09, 95% CI: 1.83-9.14. A thoughtful approach to the utility of each criterion and cut offs for eligibility needs to be evaluated in the context of its differential impact across various racial/ethnic groups.

A scoping review of geriatric emergency medicine research transparency in diversity, equity, and inclusion reporting.

INTRODUCTION: The intersection of ageism and racism is underexplored in geriatric emergency medicine (GEM) research. METHODS: We performed a scoping review of research published between January 2016 and December 2021. We included original emergency department-based research focused on falls, delirium/dementia, medication safety, and elder abuse. We excluded manuscripts that did not include (1) original research data pertaining to the four core topics, (2) older adults, (3) subjects from the United States, and (4) for which full text publication could not be obtained. The primary objective was to qualitatively describe reporting about older adults' social identities in GEM research. Secondary objectives were to describe (1) the extent of inclusion of minoritized older adults in GEM research, (2) GEM research about health equity, and (3) feasible approaches to improve the status quo of GEM research reporting. RESULTS: After duplicates were removed, 3277 citations remained and 883 full-text articles were reviewed, of which 222 met inclusion criteria. Four findings emerged. First, race and ethnicity reporting was inconsistent. Second, research rarely provided a rationale for an age threshold used to define geriatric patients. Third, GEM research more commonly reported sex than gender. Fourth, research commonly excluded older adults with cognitive impairment and speakers of non-English primary languages. CONCLUSION: Meaningful assessment of GEM research inclusivity is limited by inconsistent reporting of sociodemographic characteristics, specifically race and ethnicity. Reporting of sociodemographic characteristics should be standardized across different study designs. Strategies are needed to include in GEM research older adults with cognitive impairment and non-English primary languages.