Race, Ethnicity, and Sex in Pediatric Eye Disease Investigator Group Clinical Studies.

Importance: Racial, ethnic, and sex disparities exist in US clinical study enrollment, and the prevalence of these disparities in Pediatric Eye Disease Investigator Group (PEDIG) clinical studies has not been thoroughly assessed. Objective: To evaluate racial, ethnic, and sex representation in PEDIG clinical studies compared with the 2010 US Census pediatric population. Design, Setting, and Participants: This cross-sectional analysis examined PEDIG clinical studies based in the US from December 1, 1997 to September 12, 2022, 41 of which met inclusion criteria of a completed study, a study population younger than 18 years, and 1 or more accompanying publication. Data analysis was performed between November 2023 and February 2024. Exposure: Study participant race, ethnicity, and sex for each clinical study, as collected from peer-reviewed publications, patient-enrollment datasets, and ClinicalTrials.gov. Main Outcomes and Measures: Median enrollment percentages of female, White, Black, Hispanic, Asian, and other race participants were calculated and compared with the 2010 US Census pediatric population using a 1-sample Wilcoxon rank test. Proportionate enrollment was defined as no difference on a 1-sample Wilcoxon rank test if P ≥ .05. If P < .05, we determined if the median enrollment percentage was greater than or less than 2010 US Census proportion to determine if enrollees were underrepresented or overrepresented. To calculate the magnitude of overrepresentation or underrepresentation, enrollment-census difference (ECD) was defined as the difference between groups' median enrollment percentage and percentage representation in the 2010 US Census. Compound annual growth rate (CAGR) was used to measure temporal trends in enrollment, and logistic regression analysis was used to analyze factors that may have contributed to proportionate representation outcomes. Results: A total of 11 658 study participants in 41 clinical studies were included; mean (SD) participant age was 5.9 (2.8) years and 5918 study participants (50.8%) were female. In clinical studies meeting inclusion criteria, White participants were overrepresented (ECD, 0.19; 95% CI, 0.10-0.28; P < .001). Black participants (ECD, -0.07; 95% CI, -0.10 to -0.03; P < .001), Asian participants (ECD, -0.03; 95% CI, -0.04 to -0.02; P < .001), and Hispanic participants (ECD, -0.09; 95% CI, -0.13 to -0.05; P < .001) were underrepresented. Female participants were represented proportionately (ECD, 0.004; 95% CI, -0.036 to 0.045; P = .21). White and Asian participants demonstrated a decreasing trend in study enrollment from 1997 to 2022 (White: CAGR, -1.5%; 95% CI, -2.3% to -0.6%; Asian: CAGR, -1.7%; 95% CI, -2.0% to -1.4%), while Hispanic participants demonstrated an increasing enrollment trend (CAGR, 7.2%; 95% CI, 3.7%-10.7%). Conclusions and Relevance: In this retrospective cross-sectional study of PEDIG clinical studies from December 1, 1997 to September 12, 2022, Black, Hispanic, and Asian participants were underrepresented, White participants were overrepresented, and female participants were represented proportionally. Trends suggested increasing enrollment of Hispanic participants and decreasing enrollment of White participants over time. This study demonstrates an opportunity to advocate for increased enrollment of underrepresented groups in pediatric ophthalmology clinical studies.

Large language models: a new frontier in paediatric cataract patient education.

BACKGROUND/AIMS: This was a cross-sectional comparative study. We evaluated the ability of three large language models (LLMs) (ChatGPT-3.5, ChatGPT-4, and Google Bard) to generate novel patient education materials (PEMs) and improve the readability of existing PEMs on paediatric cataract. METHODS: We compared LLMs' responses to three prompts. Prompt A requested they write a handout on paediatric cataract that was 'easily understandable by an average American.' Prompt B modified prompt A and requested the handout be written at a 'sixth-grade reading level, using the Simple Measure of Gobbledygook (SMOG) readability formula.' Prompt C rewrote existing PEMs on paediatric cataract 'to a sixth-grade reading level using the SMOG readability formula'. Responses were compared on their quality (DISCERN; 1 (low quality) to 5 (high quality)), understandability and actionability (Patient Education Materials Assessment Tool (≥70%: understandable, ≥70%: actionable)), accuracy (Likert misinformation; 1 (no misinformation) to 5 (high misinformation) and readability (SMOG, Flesch-Kincaid Grade Level (FKGL); grade level <7: highly readable). RESULTS: All LLM-generated responses were of high-quality (median DISCERN ≥4), understandability (≥70%), and accuracy (Likert=1). All LLM-generated responses were not actionable (<70%). ChatGPT-3.5 and ChatGPT-4 prompt B responses were more readable than prompt A responses (p<0.001). ChatGPT-4 generated more readable responses (lower SMOG and FKGL scores; 5.59±0.5 and 4.31±0.7, respectively) than the other two LLMs (p<0.001) and consistently rewrote them to or below the specified sixth-grade reading level (SMOG: 5.14±0.3). CONCLUSION: LLMs, particularly ChatGPT-4, proved valuable in generating high-quality, readable, accurate PEMs and in improving the readability of existing materials on paediatric cataract.

Utility of pan-bacterial and pan-fungal PCR in endophthalmitis: case report and review of the literature.

BACKGROUND: Endophthalmitis is a clinical diagnosis but identification of the disease-causing agent or agents allows for a more tailored treatment. This is routinely done through intraocular fluid cultures and staining. However, culture-negative endophthalmitis is a relatively common occurrence, and a causative organism cannot be identified. Thus, further diagnostic testing, such as pan-bacterial and pan-fungal polymerase chain reactions (PCRs), may be required. BODY: There are now newer, other testing modalities, specifically pan-bacterial and pan-fungal PCRs, that may allow ophthalmologists to isolate a causative agent when quantitative PCRs and cultures remain negative. We present a case report in which pan-fungal PCR was the only test, amongst quantitative PCRs, cultures, and biopsies, that was able to identify a pathogen in endophthalmitis. Pan-PCR has unique advantages over quantitative PCR in that it does not have a propensity for false-positive results due to contamination. Conversely, pan-PCR has drawbacks, including its inability to detect viruses and parasites and its increased turnaround time and cost. Based on two large retrospective studies, pan-PCR was determined not to be recommended in routine cases of systemic infection as it does not typically add value to the diagnostic workup and does not change the treatment course in most cases. However, in cases like the one presented, pan-bacterial and pan-fungal PCRs may be considered if empiric treatment fails or if the infective organism cannot be isolated. If pan-PCR remains negative or endophthalmitis continues to persist, an even newer form of testing, next-generation sequencing, may aid in the diagnostic workup of culture-negative endophthalmitis. CONCLUSION: Pan-bacterial and pan-fungal PCR testing is a relatively new diagnostic tool with unique advantages and drawbacks compared to traditional culturing and PCR methods. Similar to the tests' use in non-ophthalmic systemic infections, pan-bacterial and pan-fungal PCRs are unlikely to become the initial diagnosis test and completely replace culture methods. However, they can provide useful diagnostic information if an infectious agent is unable to be identified with traditional methods or if empiric treatment of endophthalmitis continues to fail.

Comparative Effects of GLP-1 Receptor Agonists and Metformin on Glaucoma Risk in Type 2 Diabetes Patients.

PURPOSE: To compare effects of glucagon-like peptide-1 (GLP-1) receptor agonists and metformin on the risk of primary open-angle glaucoma (POAG), ocular hypertension, and the need for first-line glaucoma treatments in patients with type 2 diabetes. DESIGN: A retrospective cohort study was conducted using electronic medical records (EMR) data from the from an international electronic health record network, covering a period from May 2006 to May 2024. PARTICIPANTS: Patients diagnosed with type 2 diabetes mellitus (T2DM) who were treated with either GLP-1 receptor agonists or metformin. METHODS: Data from 120 healthcare organizations across 17 countries were analyzed. Patient outcomes were assessed at 1, 2, and 3 years. Propensity score matching (PSM) was used to balance covariates such as demographics, comorbidities, and medication usage. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. MAIN OUTCOME MEASURES: Incidence of POAG, ocular hypertension, and the need for first-line treatments including beta-blockers, prostaglandin analogues, brimonidine, brinzolamide, dorzolamide, netarsudil, and laser trabeculoplasty. RESULTS: After PSM, both groups included 61,998 patients at the 1-year follow-up, 27,414 at the 2-year follow-up, and 14,100 at the 3-year follow-up. Patients treated with GLP-1 receptor agonists had a significantly decreased risk of developing POAG compared to those on metformin at 1 year (RR 0.59, 95% CI 0.39-0.88), 2 years (RR 0.50, 95% CI 0.32-0.78), and 3 years (RR 0.59, 95% CI 0.37-0.94). Similar protective effects were observed for ocular hypertension with risk reductions of 56% at 1 year (RR 0.44, 95% CI 0.31-0.62), 57% at 2 years (RR 0.43, 95% CI 0.30-0.62), and 49% at 3 years (RR 0.51, 95% CI 0.34-0.75). The risk of first-line therapy initiation was also lower in the GLP-1 receptor agonists group at 1 year (RR 0.63, 95% CI 0.53-0.74), 2 years (RR 0.71, 95% CI 0.59-0.85), and 3 years (RR 0.75, 95% CI 0.62-0.91). CONCLUSIONS: GLP-1 receptor agonists are associated with a significantly lower incidence of POAG, ocular hypertension, and the need for first-line glaucoma treatments compared to metformin in patients with type 2 diabetes. These findings highlight the potential ocular benefits of GLP-1 receptor agonists and their expanding role in the clinical management of diabetic patients.

Clinical Outcomes of Transcatheter Aortic Valve Replacement (TAVR) vs Surgical Aortic Valve Replacement (SAVR) in Patients With Sarcoidosis.

Introduction Data regarding clinical outcomes after transcatheter aortic valve replacement (TAVR) vs surgical aortic valve replacement (SAVR) in patients with sarcoidosis is lacking. This study aims to clarify the clinical outcomes of TAVR vs SAVR in patients with sarcoidosis. Methods Data was collected from the National Inpatient Sample database from 2016-2019 using validated ICD-10-CM codes for sarcoidosis, TAVR, and SAVR. Patients were divided into two cohorts: those who underwent TAVR and those who underwent SAVR. Statistical analysis was performed using Pearson's chi-squared test to determine clinical outcomes of TAVR vs SAVR in patients with sarcoidosis. Results The prevalence of sarcoidosis was 0.23% among total study patients (n=142,420,378). After exclusions, the prevalence of TAVR was 650 (49%) and SAVR was 675 (51%) in patients with sarcoidosis. Patients who underwent TAVR were on average older (74 vs 65 years old, p=0.001), and more likely to be female (57 vs 40%, p<0.001) compared to patients who underwent SAVR. The TAVR cohort had higher rates of congestive heart failure (CHF) (77.7 vs 42.2%, p=0.001), chronic kidney disease (CKD) (42.3 vs 24.4% p=0.001), anemia (5.4 vs 2.2%, p=0.004), percutaneous coronary intervention (PCI) (1.5 vs 0%, p=0.004), and hypothyroidism (31.5 vs 16.3%, p=0.001) compared to the SAVR cohort. Inpatient mortality post-procedure was higher in the SAVR cohort compared to the TAVR cohort (15 vs 0, p=0.001). Regarding post-procedure complications, respiratory complications were more common in the SAVR cohort (4.4 vs 0%, p=0.001), while TAVR was associated with a higher incidence of permanent pacemaker (PPM) insertion (2.15 vs 0.8%, p=0.001). There was no statistical difference in the development of acute kidney injury (AKI) (0.8 vs 1.5%, p=0.33), AKI requiring hemodialysis (0 vs. 0.7%, p=0.08), or stroke (0.8 vs 0.7, p=1) post-procedure between the two cohorts. Conclusion This study found that in the sarcoidosis population, TAVR was associated with reduced mortality, shorter hospital length of stay, and lower hospitalization costs in comparison to SAVR.

Compulsive digital use: the risk and link of loneliness among adolescents.

PURPOSE OF REVIEW: The current rise of digital technologies is causing adolescents to spend more time on their digital devices, especially since the lockdown period of the pandemic. Adolescents are among those who are affected by lifestyle changes and are at risk of digital addiction due to the overuse of digital technologies. This opinion paper discusses the possible risk of loneliness among adolescents due to the overuse of digital devices. In this article, we would like to propose the concept of digital abuse and its risk of loneliness, as well as discuss some proposed solutions by referring to recent statistics and research evidence to reduce digital abuse among adolescents. RECENT FINDINGS: Evidence from previous studies highlights the association between digital addiction and loneliness among adolescents. Overusing digital devices among adolescents is also associated with various physical and psychological side effects. SUMMARY: Recent findings support the rapid rise of digital device usage among adolescents and its contributions to digital use. More research is needed to support existing interventions, provide early screening, and combat digital addiction to protect adolescents from the risks of loneliness due to the overuse of digital devices.

Anesthesia Techniques for Vitreoretinal Surgery in the United States: A Report from the Multicenter Perioperative Outcomes Group Research Consortium.

PURPOSE: To explore the patterns of anesthesia use and their determinants during vitreoretinal (VR) surgeries in academic and community hospitals across the US, using data from the Multicenter Perioperative Outcomes Group (MPOG). DESIGN: A retrospective, multicenter, cohort study. METHODS: We queried the MPOG database of 107,066 patients undergoing VR surgeries. Patients (≥18 years) undergoing VR surgery with monitored anesthesia care (MAC) or general anesthesia (GA) from January 1, 2015 to December 31, 2021 were included. Patient-level, case-based, and institutional-level covariates were collected. We performed multivariable mixed-effects models to determine predictors of anesthesia type use. The primary outcome was the type of anesthesia (MAC or GA) used during VR surgeries. As a secondary outcome, MAC cases were further classified based on the additional use of sedation into MAC with or without sedation. RESULTS: We found that 67.45% of VR surgery cases received MAC, and 73.63% of institutions administered MAC to more than half of cases. Random effect modeling revealed that 47.76% of the variation in MAC use was attributed to institutions. A trend toward increased use of MAC with increasing age was observed. Patients diagnosed with chronic pulmonary disease, liver disease, or a history of drug abuse were less likely to receive MAC. Conversely, we found that patients with reported alcohol abuse disorder, diabetes with complications, and those with American Society of Anesthesiologists (ASA) physical status of 4 (vs. 1, 2, or 3) were more likely to use MAC. Compared to non-complex VR surgeries, there was a notably decreased likelihood of MAC use in complex PPV (P = .004), PPV + scleral buckle (SB) for retinal detachment (P < .0001), and primary SB surgery (P < .0001). CONCLUSIONS: Approximately 2/3 of VR anesthesia is under MAC, but GA is still preferred for SBs, complex vitrectomy, and younger patients. We show that large interinstitutional variation for using MAC in practice exists.

Contemporary trends of leadless pacemaker implantation in the United States.

INTRODUCTION: Leadless pacemakers (LPM) have established themselves as the important therapeutic modality in management of selected patients with symptomatic bradycardia. To determine real-world utilization and in-hospital outcomes of LPM implantation since its approval by the Food and Drug Administration in 2016. METHODS: For this retrospective cohort study, data were extracted from the National Inpatient Sample database from the years 2016-2020. The outcomes analyzed in our study included implantation trends of LPM over study years, mortality, major complications (defined as pericardial effusion requiring intervention, any vascular complication, or acute kidney injury), length of stay, and cost of hospitalization. Implantation trends of LPM were assessed using linear regression. Using years 2016-2017 as a reference, adjusted outcomes of mortality, major complications, prolonged length of stay (defined as >6 days), and increased hospitalization cost (defined as median cost >34 098$) were analyzed for subsequent years using a multivariable logistic regression model. RESULTS: There was a gradual increased trend of LPM implantation over our study years (3230 devices in years 2016-2017 to 11 815 devices in year 2020, p for trend <.01). The adjusted mortality improved significantly after LPM implantation in subsequent years compared to the reference years 2016-2017 (aOR for the year 2018: 0.61, 95% CI: 0.51-0.73; aOR for the year 2019: 0.49, 95% CI: 0.41-0.59; and aOR for the year 2020: 0.52, 95% CI: 0.44-0.62). No differences in adjusted rates of major complications were demonstrated over the subsequent years. The adjusted cost of hospitalization was higher for the years 2019 (aOR: 1.33, 95% CI: 1.22-1.46) and 2020 (aOR: 1.69, 95% CI: 1.55-1.84). CONCLUSION: The contemporary US practice has shown significantly increased implantation rates of LPM since its approval with reduced rates of inpatient mortality.

Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic caused global health, economic, and population loss. Variants of the coronavirus contributed to the severity of the disease and persistent rise in infections. This study aimed to identify potential drug candidates from fifteen approved antiviral drugs against SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike protein (6M0J) using virtual screening and pharmacokinetics to gain insights into COVID-19 therapeutics. METHODOLOGY: We employed drug repurposing approach to analyze binding performance of fifteen clinically approved antiviral drugs against the main protease of SARS-CoV-2 (6LU7), SARS-CoV (5B6O), and SARS-CoV-2 spike proteins bound to ACE-2 receptor (6M0J), to provide an insight into the therapeutics of COVID-19. AutoDock Vina was used for docking studies. The binding affinities were calculated, and 2-3D structures of protein-ligand interactions were drawn. RESULTS: Rutin, hesperidin, and nelfinavir are clinically approved antiviral drugs with high binding affinity to proteins 6LU7, 5B6O, and 6M0J. These ligands have excellent pharmacokinetics, ensuring efficient absorption, metabolism, excretion, and digestibility. Hesperidin showed the most potent interaction with spike protein 6M0J, forming four H-bonds. Nelfinavir had a high human intestinal absorption (HIA) score of 0.93, indicating maximum absorption in the body and promising interactions with 6LU7. CONCLUSIONS: Our results indicated that rutin, hesperidin, and nelfinavir had the highest binding results against the proposed drug targets. The computational approach effectively identified SARS-CoV-2 inhibitors. COVID-19 is still a recurrent threat globally and predictive analysis using natural compounds might serve as a starting point for new drug development against SARS-CoV-2 and related viruses.

The Association of Sickle-Cell Disorders With Diabetic Retinopathy: A Large Database Study.

Purpose: To evaluate the association of sickle-cell disease (SCD) and sickle-cell trait (SCT) disease with diabetic retinopathy (DR) in patients with diabetes mellitus (DM). Design: Population-based, retrospective cohort study utilizing data from the TriNetX Research Network, including 119 million patients across 80 health care organizations worldwide. Participants: Diabetes mellitus patients (type 1 [T1DM] or 2 [T2DM]), with or without SCD and SCT, were included. Three cohorts were analyzed, including (1) DM patients without SCD, SCT, or sickle-cell/hemoglobin-C; (2) DM with SCD; and (3) DM with SCT. Methods: All patients with DM were categorized into 3 cohorts based on the presence of SCD and SCT. Each cohort underwent 1:1 propensity score matching for demographics, blood glucose levels, hemoglobin A1C, and other relevant comorbidities. Main Outcome Measures: Risk of DR in DM patients with and without SCD or SCT. Results: There was no significant difference in the risk of any T1DR between those with and without SCD. However, for those with SCT, there was a notable twofold increased risk for T1-proliferative DR (PDR) (relative risk [RR]: 2.03; 95% confidence interval [CI]: 1.33-3.01). In contrast, there was an elevated risk for any T2DR in patients with SCD (RR: 1.50; 95% CI: 1.19-1.88), particularly due to higher PDR risks in T2DM patients (RR: 1.83; 95% CI: 1.29-2.60). The risk of mild to moderate T2DM non-PDR was also found to be higher in patients with SCT. Conclusions: The risk of any DR was increased in T2DM patients with SCD or SCT, with increased risks for PDR in patients with SCT and T1DM. This indicates there may be a potential role of sickle-cell disorders in diabetic eye disease progression. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Posterior Segment Manifestations of Syphilis and Correlation With Serologic Markers of Infection.

BACKGROUND AND OBJECTIVE: Retrospective analysis correlating serologic titers of ocular syphilis with posterior segment manifestations. PATIENTS AND METHODS: This study consisted of 40 patients (80 eyes imaged, 68 affected) with positive rapid plasma reagin (RPR) and Treponema Pallidum immunoglobulin G. We collected demographic and presentation data including HIV status, absolute CD4 count, RPR, cerebrospinal fluid-venereal disease research laboratory (CSF-VDRL) test, and retinal zone. We categorized imaging into syphilitic outer retinopathy (SOR), acute syphilitic posterior placoid chorioretinopathy, retinitis/chorioretinitis (RC), and papillitis. Multivariate analysis correlated HIV status, RPR, and VDRL titers with posterior segment findings and zone. RESULTS: Mean age of 42.8 ± 10.7 years, with 70% male patients. Presenting visual acuity (logMAR) 0.66 ± 0.74 did not correlate with RPR, nor was it associated with papillitis, RC, or acute syphilitic posterior placoid chorioretinopathy. Higher RPR (≥ 1:128) positively associated with SOR (P = 0.031) and zone 1 (odds ratio [OR], 1.62; P = 0.02), but negatively associated with zone 2 (OR 0.35; P = 0.005). HIV positivity increased RC odds (OR, 4.45; P = 0.047). CONCLUSION: Higher RPR correlated with SOR and zone 1, whereas HIV positivity correlated with RC. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Using Large Language Models to Generate Educational Materials on Childhood Glaucoma.

PURPOSE: To evaluate the quality, readability, and accuracy of large language model (LLM)-generated patient education materials (PEMs) on childhood glaucoma, and their ability to improve existing the readability of online information. DESIGN: Cross-sectional comparative study. METHODS: We evaluated responses of ChatGPT-3.5, ChatGPT-4, and Bard to 3 separate prompts requesting that they write PEMs on "childhood glaucoma." Prompt A required PEMs be "easily understandable by the average American." Prompt B required that PEMs be written "at a 6th-grade level using Simple Measure of Gobbledygook (SMOG) readability formula." We then compared responses' quality (DISCERN questionnaire, Patient Education Materials Assessment Tool [PEMAT]), readability (SMOG, Flesch-Kincaid Grade Level [FKGL]), and accuracy (Likert Misinformation scale). To assess the improvement of readability for existing online information, Prompt C requested that LLM rewrite 20 resources from a Google search of keyword "childhood glaucoma" to the American Medical Association-recommended "6th-grade level." Rewrites were compared on key metrics such as readability, complex words (≥3 syllables), and sentence count. RESULTS: All 3 LLMs generated PEMs that were of high quality, understandability, and accuracy (DISCERN ≥4, ≥70% PEMAT understandability, Misinformation score = 1). Prompt B responses were more readable than Prompt A responses for all 3 LLM (P ≤ .001). ChatGPT-4 generated the most readable PEMs compared to ChatGPT-3.5 and Bard (P ≤ .001). Although Prompt C responses showed consistent reduction of mean SMOG and FKGL scores, only ChatGPT-4 achieved the specified 6th-grade reading level (4.8 ± 0.8 and 3.7 ± 1.9, respectively). CONCLUSIONS: LLMs can serve as strong supplemental tools in generating high-quality, accurate, and novel PEMs, and improving the readability of existing PEMs on childhood glaucoma.

Targeting CD73 with flavonoids inhibits cancer stem cells and increases lymphocyte infiltration in a triple-negative breast cancer mouse model.

Introduction: Chemotherapy remains the mainstay treatment for triple-negative breast cancer (TNBC) due to the lack of specific targets. Given a modest response of immune checkpoint inhibitors in TNBC patients, improving immunotherapy is an urgent and crucial task in this field. CD73 has emerged as a novel immunotherapeutic target, given its elevated expression on tumor, stromal, and specific immune cells, and its established role in inhibiting anti-cancer immunity. CD73-generated adenosine suppresses immunity by attenuating tumor-infiltrating T- and NK-cell activation, while amplifying regulatory T cell activation. Chemotherapy often leads to increased CD73 expression and activity, further suppressing anti-tumor immunity. While debulking the tumor mass, chemotherapy also enriches heterogenous cancer stem cells (CSC), potentially leading to tumor relapse. Therefore, drugs targeting both CD73, and CSCs hold promise for enhancing chemotherapy efficacy, overcoming treatment resistance, and improving clinical outcomes. However, safe and effective inhibitors of CD73 have not been developed as of now. Methods: We used in silico docking to screen compounds that may be repurposed for inhibiting CD73. The efficacy of these compounds was investigated through flow cytometry, RT-qPCR, CD73 activity, cell viability, tumorsphere formation, and other in vitro functional assays. For assessment of clinical translatability, TNBC patient-derived xenograft organotypic cultures were utilized. We also employed the ovalbumin-expressing AT3 TNBC mouse model to evaluate tumor-specific lymphocyte responses. Results: We identified quercetin and luteolin, currently used as over-the-counter supplements, to have high in silico complementarity with CD73. When quercetin and luteolin were combined with the chemotherapeutic paclitaxel in a triple-drug regimen, we found an effective downregulation in paclitaxel-enhanced CD73 and CSC-promoting pathways YAP and Wnt. We found that CD73 expression was required for the maintenance of CD44highCD24low CSCs, and co-targeting CD73, YAP, and Wnt effectively suppressed the growth of human TNBC cell lines and patient-derived xenograft organotypic cultures. Furthermore, triple-drug combination inhibited paclitaxel-enriched CSCs and simultaneously improved lymphocyte infiltration in syngeneic TNBC mouse tumors. Discussion: Conclusively, our findings elucidate the significance of CSCs in impairing anti-tumor immunity. The high efficacy of our triple-drug regimen in clinically relevant platforms not only underscores the importance for further mechanistic investigations but also paves the way for potential development of new, safe, and cost-effective therapeutic strategies for TNBC.

Effect of Oral Prednisone on the Prevention and Management of Proliferative Vitreoretinopathy After Open-Globe Injury.

Purpose: To determine the impact of oral prednisone on the final visual acuity (VA) and prevention of proliferative vitreoretinopathy (PVR) in patients having pars plana vitrectomy (PPV) for globe injuries. Methods: A retrospective chart review was performed of all globe injuries with an initial repair and subsequent PPV between 2009 and 2018. Data included the initial VA, zones of injury, initial closure date, time to secondary intervention (PPV), oral prednisone (1 mg/kg/day) use, the final VA, and enucleation rate. Multivariable regression models were used to assess the impact of oral prednisone use on anatomic and functional outcomes. Results: The mean (±SD) patient age was 46.25 ±18.56 years (range, 13-92); 131 (83.9%) were men. Oral prednisone intake was recorded in 81 patients (52.3%). The prednisone group had significantly more zone 3 involvement (P = .001), worse initial VA (2.28 vs 1.92 logMAR; P = .003), and a greater mean number of surgeries (P = .020) than the no-steroids (control) group but an equivalent final logMAR VA (1.57 vs 1.52; P = .881). The prednisone group had significant VA improvement (P = .025); however, oral prednisone use did not predict the development of PVR (29.23% vs 12.90%; odds ratio [OR], 2.81; 95% CI, 0.89-8.85) or retinal detachment (27.27% vs 29.58%; OR, 0.59; 95% CI, 0.23-1.56). Conclusions: Despite a worse initial clinical presentation, patients who received oral prednisone had significant visual improvement compared with the control group. However, oral prednisone (1 mg/kg/day) use at the time of injury did not decrease the PVR rate.

Trends in Medicare Submitted Charges to Allowed Payment Ratios for Ophthalmology Services.

Purpose: Many physicians charge more than the Medicare insurance program pays. Current charge-to-payment ratios in ophthalmology and trends over the years are unknown. In this work, we examined physician charge-to-payment ratios in ophthalmology across procedures and consultations. Methods: We utilized data from 100% final-action physician/supplier Part B Medicare fee-for-service (FFS) population from 2015 to 2020. We retrieved data on ophthalmic procedures and consultations, both facility-based and non-facility-based, conducted by ≥ 50 ophthalmologists. We analyzed median charge-to-payment ratios, which were calculated as submitted charges divided by the Medicare-allowed payments, between ophthalmic procedures and consultations to assess for trends over the study period. Results: We find that the median charge-to-payment ratio for all current procedural terminology (CPT) codes in 2020 was 2.23 (Interquartile range (IQR): 1.54-3.27) as compared to 2.00 (IQR: 1.39-2.92) in 2015, an overall 2.76% average annual growth rate from 2015-2020. For ophthalmic procedures, the median charge-to-payment ratio in 2020 was 3.03 (IQR: 2.13-4.41) compared to 2.79 (IQR: 1.96-3.97) in 2015, corresponding to a 2.01% AAGR from 2015-2020. For consultations, those rates were 2.06 (IQR: 1.48-2.96), 1.85 (IQR: 1.33-2.59), and 2.71%, respectively. Conclusion: We found that the submitted charge-to-Medicare payment ratios among ophthalmic procedures and consultations have steadily increased since 2015. However, there was a relatively low rate of excess charges for ophthalmology services compared to other surgical-based specialties with minimal variation among providers.

The impact of the COVID-19 pandemic on ocular trauma in American infants and toddlers.

PURPOSE: To assess the impact of the COVID-19 pandemic on infant and toddler ocular trauma in the United States. METHODS: This retrospective analysis of ocular injury data for children ≤3 years of age focused on epidemiologic trends in pediatric ocular injuries in the United States caused by consumer products from 2017 to 2021 and compared differences between pre-pandemic (2017-2019) and pandemic (2020-2021) time periods. Data were collected from the US Consumer Product Safety Commission National Electronic Injury Surveillance System, which includes emergency department visits caused by consumer product-related injuries from a nationally representative sample of hospitals. RESULTS: The national-level estimate of ocular injuries in infants and toddlers was 51,250 (95% CI, 30471-72030). Most injuries occurred at home. We found a significant decline in the proportion of projectile ocular injuries from 0.89% (95% CI, 0.35-2.25) to 0.12% (95% CI, 0.03-0.45) (P = 0.037). The proportion of patients diagnosed with chemical-burn-related injuries increased significantly, from 23.34% (95% CI, 19.73-27.38) in the pre-pandemic period to 31.63% (95% CI, 26.98-36.69) in the pandemic period (P = 0.048), with 71.75% (95% CI, 65.25-77.46) due to cleaning products. After adjusting for confounding variables, the odds of sustaining a chemical-burn-related injury in the post-pandemic period were 1.51 times higher than in the pre-pandemic period (95% CI, 1.10-2.08). CONCLUSIONS: The proportion of children diagnosed with chemical-burn-related injuries increased significantly in the post-pandemic period, with a large portion due to cleaning products.

Risk of abducens nerve palsy following COVID-19 vaccination.

PURPOSE: To investigate the prevalence and risk of new-onset abducens nerve palsy and acute-onset diplopia following mRNA COVID-19 vaccination. METHODS: In this retrospective, population-based study, patient data from the COVID-19 Research Network of TriNetX was searched via the TriNetX Analytics platform for patients who received specific vaccinations based on Common Procedural Technology codes. We recorded instances of newly diagnosed abducens nerve palsy and diplopia within 21 days following each vaccination event. RESULTS: Of the 3,545,224 patients (mean age at vaccination, 46.2 ± 21.3 years) who received the mRNA COVID-19 vaccine, 12 (<0.0001%) patients had a new diagnosis of abducens nerve palsy and 453 (0.013%) had acute-onset diplopia within 21 days of first dose of COVID-19 vaccination. After propensity score matching, the relative risk for new abducens nerve palsy diagnosis after the first dose of COVID-19 vaccination was not significantly different from that after influenza (RR, 0.77), Tdap (RR, 1.0), or the second dose of the COVID-19 vaccinations (RR, 1.00). Furthermore, there was a lower risk of abducens nerve palsy diagnosis after the first dose of the COVID-19 vaccination compared with the risk after COVID-19 infection (RR, 0.15). CONCLUSIONS: The risk of a new abducens nerve palsy diagnosis following the first dose of the COVID-19 vaccine is lower than the risk associated with COVID-19 infection itself. There is no evidence to suggest a causal relationship between COVID-19 vaccination and the development of abducens nerve palsy.

Recent advances in the role of MXene based hybrid architectures as electrocatalysts for water splitting.

The development of non-noble metal based and cost-effective electrocatalysts for water splitting has attracted significant attention due to their potential in production of clean and green hydrogen fuel. Discovered in 2011, a family of two-dimensional transition metal carbides, nitrides, and carbonitrides, have demonstrated promising performance as electro catalysts in the water splitting process due to their high electrical conductivity, very large surface area and abundant catalytic active sites. However, their-long term stability and recyclability are limited due to restacking and agglomeration of MXene flakes. This problem can be solved by combining MXene with other materials to create their hybrid architectures which have demonstrated higher electrocatalytic performance than pristine MXenes. Electrolysis of water encompasses two half-cell reactions, hydrogen evolution reaction (HER) at the cathode and oxygen evolution reaction (OER) at the anode. Firstly, this concise review explains the mechanism of water splitting. Then it provides an overview of the recent advances about applications of MXenes and their hybrid architectures as HER, OER and bifunctional electrocatalysts for overall water splitting. Finally, the recent challenges and potential outlook in the field have been presented. This concise review may provide further understanding about the role of MXene-based hybrid architectures to develop efficient electrocatalysts for water splitting.