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Objectives: This study aims to report otologic manifestations in a cohort of patients with aspirin exacerbated respiratory disease (AERD) to determine if severity of sinonasal inflammation is associated with presence of otologic sequalae (OS)., Methods: All AERD patients treated at a tertiary care center between 2009 and 2016 were included in analysis. Demographics, history of hearing loss, Lund-Mackay (LMK) scores, number of previous sinus procedures, CT findings, and pure tone averages (PTA) were compared between patients with and without OS using chi-square test, Fisher's exact test, and Wilcoxon rank sum test., Results: Of 255 AERD patients, 58.4% were female with a mean age of 48.9 (SD: 13.4) years. The majority (52.2%) had otologic manifestations, most commonly: otitis media requiring antibiotics (n = 89, 34.9%), peripheral vertigo (n = 59, 23.1%), and middle ear effusion (n = 44, 17.3%). A total of 74 patients (29.0%) had hearing loss. PTA ranged from 13.3 to 61.7 dB for the cohort, with no significant difference between those with and without OS. There was no significant difference in LMK in both groups. Patients with OS had a significantly greater number of sinus procedures than those without OS (median = 2.4 and 1.8 respectively; P  = .01)., Conclusions: Otologic manifestations are common in patients with AERD. While there was an increased number of sinonasal surgeries performed in the patients with OS, there was no correlation between sinonasal inflammation, and the presence of OS as measured by LMK score or PTA. Otologic signs and symptoms should be considered in patients with AERD to help mitigate patient morbidity., Level of Evidence: III., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate and compare the readability and quality of patient information generated by Chat-Generative Pre-Trained Transformer-3.5 (ChatGPT) and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) using validated instruments including Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease, DISCERN, and Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P)., Methods: ENTHealth.org and ChatGPT-3.5 were queried for patient information on laryngology topics. ChatGPT-3.5 was queried twice for a given topic to evaluate for reliability. This generated three de-identified text documents for each topic: one from AAO-HNS and two from ChatGPT (ChatGPT Output 1, ChatGPT Output 2). Grade level and reading ease were compared between the three sources using a one-way analysis of variance and Tukey's post hoc test. Independent t-tests were used to compare DISCERN and PEMAT understandability and actionability scores between AAO-HNS and ChatGPT Output 1., Results: Material generated from ChatGPT Output 1 and ChatGPT Output 2 were at least two reading grade levels higher than that of material from AAO-HNS (p < 0.001). Regarding reading ease, ChatGPT Output 1 and ChatGPT Output 2 documents had significantly lower mean scores compared to AAO-HNS (p < 0.001). Moreover, ChatGPT Output 1 material on vocal cord paralysis had a lower PEMAT-P understandability compared to that of AAO-HNS material (p > 0.05)., Conclusion: Patient information on the ENTHealth.org website for select laryngology topics was, on average, of a lower grade level and higher reading ease compared to that produced by ChatGPT, but interestingly with largely no difference in the quality of information provided., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Early in the pandemic, extensive attention was cast on limited inclusion of historically underrepresented patient populations in COVID-19 clinical trials. How diverse representation improved following these initial reports remains unclear., Methods: PubMed, Embase and the Cochrane Library were searched (through April 2024) for US-based COVID-19 trials. Utilizing random-effects, we compared expected proportions of trial participants from racial and ethnic groups and of female sex between trials enrolling primarily in 2020 versus primarily 2021-2022. Meta-regression was performed to assess associations between trial characteristics and group representation., Results: We retrieved 157 studies comprising 198,012 participants. White (2020: 63.1% [95% CI, 60.8%-67.3%]; 2021-2022: 73.8% [95% CI, 71.5%-76.0%]) and female representation (2020: 46.1% [95% CI, 44.7%-47.4%)]; 2021-2022: 51.1% [95% CI, 49.3%-52.8%) increased across enrollment periods. Industry-sponsored trials were associated with higher White (coefficient, 0.10 [95% CI, 0.03-0.18]) and Hispanic or Latinx representation (coefficient, 0.16 [95% CI, 0.08-0.25]) and lower Asian (coefficient, -0.03 [95% CI, -0.06- -0.003]) and female representation (coefficient, -0.03 [95% CI, -0.07- -0.002]). Outpatient trials were associated with higher White (coefficient, 0.20 [95% CI, 0.13-0.26]) and female representation (coefficient, 0.16 [95% CI, 0.13-0.18]), and lower Black representation (coefficient, -0.10 [95% CI, -0.10- -0.08])., Conclusions: Despite improved female representation in COVID-19 trials over time, there was no clear increase in non-White representation. Trial characteristics such as primary sponsor, clinical setting, and intervention type correlate with representation of specific demographic groups and should be considered in future efforts to improve participant diversity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Clinical trials for coronavirus disease 2019 (COVID-19) have struggled to achieve diverse patient enrollment, despite underrepresented groups bearing the largest burden of the disease and, presumably, being most in need of the treatments under investigation., Methods: To assess the willingness of patients to enroll into inpatient COVID-19 clinical trials when invited, we conducted a cross-sectional analysis of adults hospitalized with COVID-19 who were approached regarding enrollment. Associations between patient and temporal factors and enrollment were assessed by multivariable logistic regression analysis., Results: A total of 926 patients were included in this analysis. Overall, Hispanic/Latinx ethnicity was associated with a nearly half-fold decrease in the likelihood to enroll (adjusted odds ratio [aOR], 0.60 [95% confidence interval {CI}, .41-.88]). Greater baseline disease severity (aOR, 1.09 [95% CI, 1.02-1.17]), age 40-64 years (aOR, 1.83 [95% CI, 1.03-3.25]), and age ≥65 years (aOR, 1.92 [95% CI, 1.08-3.42]) were each independently associated with higher likelihood to enroll. Over the course of the pandemic, patients were less likely to enroll during the summer 2021 wave in COVID-19-related hospitalizations (aOR, 0.14 [95% CI, .10-.19]) compared with patients from the first wave in winter 2020., Conclusions: The decision to enroll into clinical trials is multifactorial. Amid a pandemic disproportionately affecting vulnerable groups, Hispanic/Latinx patients were less likely to participate when invited, whereas older adults were more likely. Future recruitment strategies must consider the nuanced perceptions and needs of diverse patient populations to ensure equitable trial participation that advances the quality of healthcare for all., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Thymosin-α-1 (Tα1) may be a treatment option for coronavirus disease 2019 (COVID-19), but efficacy and safety data remain limited., Methods: Prospective, open-label, randomized trial assessing preliminary efficacy and safety of thymalfasin (synthetic form of Tα1), compared with the standard of care, among hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19., Results: A total of 49 patients were included in this analysis. Compared with control patients, the incidence of clinical recovery was higher for treated patients with either baseline low-flow oxygen (subdistribution hazard ratio, 1.48 [95% confidence interval, .68-3.25]) or baseline high-flow oxygen (1.28 [.35-4.63]), although neither difference was significant. Among patients with baseline low-flow oxygen, treated patients, compared with control patients, had an average difference of 3.84 times more CD4+ T cells on day 5 than on day 1 (P = .01). Nine serious adverse events among treated patients were deemed not related to Tα1., Conclusions: Tα1 increases CD4+ T-cell count among patients with baseline low-flow oxygen support faster than the standard of care and may have a role in the management of hospitalized patients with hypoxemia and lymphocytopenia due to COVID-19., Clinical Trials Registration: NCT04487444., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

(1) Background: Respiratory co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses are common, but data on clinical outcomes and laboratory biomarkers indicative of disease severity are limited. We aimed to compare clinical outcomes and laboratory biomarkers of patients with SARS-CoV-2 alone to those of patients with SARS-CoV-2 and either rhinovirus or adenovirus. (2) Methods: Hospitalized patients co-infected with SARS-CoV-2 and rhinovirus and patients co-infected with SARS-CoV-2 and adenovirus were matched to patients infected with SARS-CoV-2 alone. Outcomes of interest were the cumulative incidences of mechanical ventilation use, intensive care unit (ICU) admission, 30-day all-cause mortality, and 30-day all-cause readmission from the day of discharge. We also assessed differences in laboratory biomarkers from the day of specimen collection. (3) Results: Patients co-infected with SARS-CoV-2 and rhinovirus, compared with patients infected with SARS-CoV-2, had significantly greater 30-day all-cause mortality (8/23 (34.8%) vs. 8/69 (11.6%), p = 0.02). Additionally, median alanine transaminase (13 IU/L vs. 24 IU/L, p = 0.03), aspartate transaminase (25 IU/L vs. 36 IU/L, p = 0.04), and C-reactive protein (34.86 mg/L vs. 94.68 mg/L, p = 0.02) on day of specimen collection were significantly lower in patients co-infected with SARS-CoV-2 and rhinovirus in comparison to patients infected with SARS-CoV-2 alone. Clinical outcomes and laboratory markers did not differ significantly between patients with SARS-CoV-2 and adenovirus co-infection and patients with SARS-CoV-2 mono-infection. (4) Conclusion: SARS-CoV-2 and rhinovirus co-infection, compared with SARS-CoV-2 mono-infection alone, is positively associated with 30-day all-cause mortality among hospitalized patients. However, our lack of significant findings in our analysis of patients with SARS-CoV-2 and adenovirus co-infection may suggest that SARS-CoV-2 co-infections have variable significance, and further study is warranted.

Background: Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections. Aims: Provide a pooled estimate of the cumulative incidence for infections that fulfilled the criteria associated with severe infectious adverse events for grade 3 or higher (including pneumonia, febrile neutropenia and sepsis) in patients who receive targeted therapies. Methods: We searched PubMed and EMBASE for randomized controlled trials (RCT) that included patients with CLL/SLL who received targeted therapies and performed a random-effects meta-analysis to estimate the cumulative incidence of infections. Results: Of 2,914 studies screened, we retrieved 31 which evaluated 11,660 patients. The pooled cumulative incidence of infections for patients who received treatment regimens based on a BTK inhibitors was 19.86%. For patients who received treatment based on rituximab and second generation anti-CD20 monoclonal antibodies, the pooled cumulative incidence of infections was 19.85 and 13.46%, respectively. Regarding PI3K inhibitor-based regimens the cumulative incidence of severe infections was 30.89%. BCL-2 inhibitors had a cumulative incidence of infections of 17.49% while lenalidomide and alemtuzumab had an incidence of 13.33 and 45.09%, respectively. The cumulative incidence of pneumonia ranged from 3.01 to 8.45% while febrile neutropenia ranged from 2.68 to 10.80%. Regarding sepsis, the cumulative incidence ranged from 0.9 to 4.48%. Conclusion: Patients with CLL/SLL who receive targeted therapies may develop severe infections at significant rates that, in addition to disease stage and other complications, depend on the mechanism of action of the used drug. Surveillance for infections and development of effective prophylactic strategies are critical for patients with CLL/SLL who receive targeted therapies. Systematic Review Registration: [https://systematicreview.gov/], identifier [registration number]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vassilopoulos, Shehadeh, Kalligeros, Tran, Schiffman and Mylonakis.)

Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized by disease progression and increased mortality. We reveal Pf, a bacteriophage produced by Pa that delays healing of chronically infected wounds in human subjects and animal models of disease. Interestingly, impairment of wound closure by Pf is independent of its effects on Pa pathogenesis. Rather, Pf impedes keratinocyte migration, which is essential for wound healing, through direct inhibition of CXCL1 signaling. In support of these findings, a prospective cohort study of 36 human patients with chronic Pa wound infections reveals that wounds infected with Pf-positive strains of Pa are more likely to progress in size compared with wounds infected with Pf-negative strains. Together, these data implicate Pf phage in the delayed wound healing associated with Pa infection through direct manipulation of mammalian cells. These findings suggest Pf may have potential as a biomarker and therapeutic target in chronic wounds., Competing Interests: Declaration of interests G.A.S. received grants and has an equity and royalty-bearing know-how agreement with Adaptive Phage Therapeutics (APT) and is a principal investigator for clinical trials with APT and Phagelux. The other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: Clostridioides difficile infection (CDI) is associated with a high recurrence rate, and a significant proportion of patients with CDI are readmitted following discharge. We aimed to identify the risk factors for CDI-related readmission within 90 days following an index hospital stay for CDI. (2) Methods: We analyzed the electronic medical data of admitted patients in our health system over a two-year period. A multivariate logistic regression model, supplemented with bias-corrected and accelerated confidence intervals (BCa-CI), was implemented to assess the risk factors. (3) Results: A total of 1253 adult CDI index cases were included in the analysis. The readmission rate for CDI within 90 days of discharge was 11% (140/1253). The risk factors for CDI-related readmission were fluoroquinolone exposure within 90 days before the day of index CDI diagnosis (aOR: 1.58, 95% CI: 1.05-2.37), higher Elixhauser comorbidity score (aOR: 1.05, 95% CI: 1.02-1.07), and being discharged home (aOR: 1.64, 95% CI: 1.06-2.54). In contrast, a longer length of index stay (aOR: 0.97, 95% BCa-CI: 0.95-0.99) was associated with reduced odds of readmission for CDI. (4) Conclusion: More than 1 out of 10 patients were readmitted for CDI following an index hospital stay for CDI. Patients with recent previous fluoroquinolone exposure, greater overall comorbidity burden, and those discharged home are at higher risk of readmission for CDI.

A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find that 4MU treatment reduces pericellular hyaluronan, destabilizes interactions between DC and T-cells, and prevents T-cell proliferation in vitro and in vivo. These effects were observed only when 4MU was added prior to initial antigen presentation but not later, consistent with 4MU-mediated inhibition of de novo antigenic responses. Building on these findings, we find that 4MU delays rejection of allogeneic pancreatic islet transplant and allogeneic cardiac transplants in mice and suppresses allogeneic T-cell activation in human mixed lymphocyte reactions. We conclude that 4MU, an approved drug, may have benefit as an adjunctive agent to delay transplantation rejection., Competing Interests: Declaration of Competing Interest The authors have no competing financial interests. N.N., P.L.M., and P.L.B. are listed as inventors of the patent (PCT/US2019/019310) filed by the Board of Trustees of the Leland Stanford Junior University., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Theoretical models and preceding studies have described age-related alterations in neuronal activation of frontoparietal regions in a working memory (WM) load-dependent manner. However, to date, underlying neuronal mechanisms of these WM load-dependent activation changes in aging remain poorly understood. The aim of this study was to investigate these mechanisms in terms of effective connectivity by application of dynamic causal modeling with Bayesian Model Selection. Eighteen healthy younger (age: 20-32 years) and 32 older (60-75 years) participants performed an n-back task with 3 WM load levels during functional magnetic resonance imaging (fMRI). Behavioral and conventional fMRI results replicated age group by WM load interactions. Importantly, the analysis of effective connectivity derived from dynamic causal modeling, indicated an age- and performance-related reduction in WM load-dependent modulation of connectivity from dorsolateral prefrontal cortex to inferior parietal lobule. This finding provides evidence for the proposal that age-related WM decline manifests as deficient WM load-dependent modulation of neuronal top-down control and can integrate implications from theoretical models and previous studies of functional changes in the aging brain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Previous studies on working memory training have indicated that transfer to non-trained tasks of other cognitive domains may be possible. The aim of this study is to compare working memory training and transfer effects between younger and older adults (n = 60). A novel approach to adaptive n-back training (12 sessions) was implemented by varying the working memory load and the presentation speed. All participants completed a neuropsychological battery of tests before and after the training. On average, younger training participants achieved difficulty level 12 after training, while older training participants only reached difficulty level 5. In younger participants, transfer to Verbal Fluency and Digit Symbol Substitution test was found. In older participants, we observed a transfer to Digit Span Forward, CERAD Delayed Recall, and Digit Symbol Substitution test. Results suggest that working memory training may be a beneficial intervention for maintaining and improving cognitive functioning in old age.