Systemic Outcomes in Adults Undergoing Emergent Repair of Orbital Blowout Fractures.

Purpose: To analyze the association between emergent surgery status and systemic adverse outcomes in patients undergoing open orbital floor blowout fracture repair. Methods: This retrospective cohort analysis utilized the 2005-2018 National Surgery Quality Improvement Program (NSQIP) database. Current Procedural Terminology (CPT) codes were used to identify cases with open treatment of orbital floor blowout fractures (21385, 21386, 21387, 21390, 21395). Demographics, comorbidities, and complication incidences were compared between patients undergoing emergent surgery and those undergoing non-emergent orbital blowout fracture repair using chi-square analyses. The independent effect of preoperative emergent status on adverse outcomes was analyzed using binary logistic regression. Results: 1,146 (96.0%) non-emergent and 48 (4.0%) emergent orbital blowout fracture repairs were identified from 2005 to 2018. Chi-square analysis indicated patients undergoing emergent repairs had higher incidences of preoperative wound infection (8.3% vs. 2.3%; p = 0.029) and systemic sepsis (8.3% vs. 0.6%; p = 0.001). The emergent cohort had a higher proportion of patients with Hispanic ethnicity (p = 0.011). Unadjusted chi-square analysis indicated the emergent cohort had a higher incidence of prolonged length of stay (50.1% vs. 10.1%; p < 0.001). After adjusting for confounders, logistic regression analysis indicated emergent status was an independent risk factor for prolonged length of stay (OR 13.05; 95% CI 5.26-32.37; p < 0.001). Conclusion: Emergent surgery status is an important factor associated with increased odds of prolonged length of stay in patients undergoing open orbital blowout fracture repair. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04681-0.

Ocular Adverse Effects of Over-the-Counter Cosmetics and Personal Care Products Reported to the Food and Drug Administration.

PURPOSE: Personal care and cosmetic products can cause periocular and ocular adverse effects (AEs), for example, ocular surface disease, trauma, and hypersensitivity. The publicly available Food and Drug Administration (FDA) Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) database includes AE reports by consumers, healthcare practitioners, and manufacturers. The purpose of this study was to characterize ophthalmic AE associated with cosmetics and personal care products reported by the FDA CAERS database. METHODS: AE related to the eye or ocular adnexa from cosmetics submitted by consumers, healthcare practitioners, and manufacturers from January 2004 to June 2022 were identified after filtering using the Medical Dictionary for Regulatory Activities coding system. Demographic information, case outcome, and categories of product and AE were included. Chi-square analysis, with statistical significance at a = 0.05, was performed to ascertain variation in ocular, periocular, and general outcomes by product category. RESULTS: Reports of ophthalmic AEs related to cosmetics per year increased from 2006 to 2018, reaching a maximum of 161 reports in 2018, then decreased from 2018 to 2021. In total, 959 and 1382 unique periocular and ocular AEs were reported. There were 1711 total incidences of reported periocular AEs and 2485 ocular AEs. The most reported periocular AEs were inflammation (770/1711) and hypersensitivity (331/1711). The most reported ocular effects were discomfort (946/2485) and inflammation (709/2485). Ocular, periocular, and general outcomes significantly varied by product category. CONCLUSIONS: Consumers, healthcare practitioners, and manufacturers should be made aware of potential ophthalmic AE and outcomes associated with cosmetics and personal care products.

Are Alpha-2 Adrenergic Agonists Being Used in Infants?

Purpose: To identify and quantify adverse events (AEs) associated with alpha-2 adrenergic agonists prescribed for the treatment of glaucoma in infants. Methods: We queried the Federal Adverse Event Reporting System (FAERS) from 2004-2023Q1 for AE reports related to brimonidine use in patients aged 12 months or younger. We then conducted a disproportionality analysis using data mining algorithms, including the reporting odds ratio, proportional reporting ratio, empirical bayes geometric mean, and information component to identify significant symptoms. Results: We identified 35 unique AE reports associated with brimonidine. Of these, 27 cases involved hospitalization, 13 cases involved life-threatening complications, 18 cases reported other complications, and 1 case involved a congenital anomaly. The most commonly reported AE was hypotonia, occurring in 20 cases. This was followed by other systemic symptoms, including hypothermia, depressed level of consciousness, lethargy, general toxicity, and pallor, among others. All symptoms were found to be significant in the disproportionality analysis. Notably, most cases were not known to involve an ophthalmic route of exposure. Conclusions: The use of alpha-2 adrenergic agonists in infants aged 1 year or younger has been associated with various systemic AEs, including hypotension, respiratory depression, and central nervous system depression. Ophthalmologists should be aware of these potential risks. Further, more rigorous warnings should be in place to prevent unintentional exposure of infants to brimonidine.

Sex-Stratified Predictors of Prolonged Operative Time and Hospital Admission in Outpatient Parathyroidectomy.

Our retrospective database study investigates sex-stratified predictors of prolonged operative time (POT) and hospital admission following parathyroidectomy for primary hyperparathyroidism (PHPT). The 2016 to 2018 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was queried for patients with PHPT undergoing parathyroidectomy. Cases analyzed were all outpatient status, arrived from home, coded as non-emergent, and elective. POT was defined by the 75th percentile. Hospital admission was defined as LOS ≥ 1 day. Univariate and multivariable binary logistic regressions were utilized. Of 7442 cases satisfying inclusion criteria, the majority were female (78.0%) and White (78.5%). Median OT (IQR) for females and males was 77 (58-108) and 81 (61-109) minutes, respectively (P = 0.003). 1965 (33.9%) females and 529 (32.3%) males required hospital admission. Independent predictors of POT included ASA class III/IV (aOR 1.342, 95% CI 1.007-1.788) and obesity (aOR 1.427, 95% CI 1.095-1.860) for males (P < 0.05). Independent predictors of hospital admission included age (aOR 1.008, 95% CI 1.002-1.014), ASA class III/IV (aOR 1.490, 95% CI 1.301-1.706), obesity (aOR 1.309, 95% CI 1.151-1.489), dyspnea (aOR 1.394, 95% CI 1.041-1.865), chronic steroid use (aOR 1.674, 95% CI 1.193-2.351), and COPD (aOR 1.534, 95% CI 1.048-2.245) for females (P < 0.05); and ASA class III/IV (aOR 1.931, 95% CI 1.483-2.516) and bleeding disorder (aOR 2.752, 95% CI 1.443-5.247) for males (P < 0.005). In conclusion, predictors of POT and hospital admission following parathyroidectomy for PHPT differed by patient sex. Identifying patients at risk for POT and hospital admission may optimize healthcare resource utilization. Level of Evidence: IV. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04444-3.

Blind Spots in Therapy: Unveiling Drug-Induced Angle-Closure Glaucoma Through a National Analysis.

OBJECTIVE: To identify and quantify medications causing angle-closure glaucoma through the FDA Adverse Event Reporting System (FAERS). DESIGN: National retrospective database analysis. SUBJECTS: There were 11 737 133 total adverse event reports from the FDA Federal Adverse Event Reporting System (FAERS) database 2004 to third quarter of 2023 (2023Q3), which included 1629 reports of angle-closure glaucoma. METHODS: Drugs associated with reports of angle-closure glaucoma were identified in FAERS through disproportionality analysis MAIN OUTCOME MEASURES: To ascertain if these reports yielded statistically significant signals, we used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC). We considered a signal to be detected when all 4 disproportionality analysis metrics were positive. RESULTS: We identified a total of 1629 adverse event reports linked to 611 suspected drugs over the course of 20 years (2004-2023Q3). Frequently reported drugs included topiramate (520 reports) and citalopram (69 reports), amongst many others. Eighteen medications yielded a positive signal, including lesser-known medications like olanzapine, phentermine, and ranibizumab. Tropicamide exhibited the most robust statistical significance (n = 18; PRR: 164.263; ROR [95% confidence interval {CI}]: 167.95 [104.994-268.655]; EBGM [EBGM05]: 162.421 [109.5]; IC [IC05]: 7.344 [4.591]), while acetazolamide was the second strongest (n = 51; PRR: 113.088; ROR 95% CI: 114.782 [86.665-152.021]; EBGM [EBGM05]: 109.506 [86.501]; IC [IC05]: 6.775 [5.115]). CONCLUSIONS: Drug-induced glaucoma included both well-known medications such as topiramate as well as lesser-known medications such as olanzapine, phentermine, and ranibizumab. Clinician awareness of these findings is important. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Regional Variation of Infectious Agents Causing Endogenous Endophthalmitis in the United States: A National Database Analysis.

OBJECTIVE: To describe regional variation in microbes causing infectious endogenous endophthalmitis (EE) in the United States. DESIGN: This is a retrospective, national database analysis utilizing the 2002-2014 National Inpatient Sample database. SUBJECTS: Using the International Classification of Disease 9 codes, we identified cases with EE. Cases were stratified regionally into Northeast, South, West, or Midwest. METHODS: Unadjusted chi-square analysis followed by adjusted multivariate logistic regression was performed to evaluate variation in demographic factors, comorbidities using the Elixhauser Comorbidity Index (ECI), microbial variation, mortality, and use of vitrectomy or enucleation by region. MAIN OUTCOME MEASURES: Proportion of microbes, mortality, and vitrectomy by region in addition to factors with significant odds ratios for mortality and for in-hospital vitrectomy. RESULTS: A total of 10 912 patients with infectious EE were identified, with 2063 cases in the Northeast (18.9%), 2145 cases in the Midwest (19.7%), 4134 cases in the South (37.9%), and 2570 cases in the West (23.6%). Chi-square analysis indicated significant regional variation in patient demographics, microbes causing the infection, ECI, mortality, and surgical intervention. The 4 most common microbes for all regions were methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus, Candida, and methicillin-resistant Staphylococcus aureus. Methicillin-sensitive S. aureus was the most common cause of EE in all regions, although the proportion of MSSA infection did not significantly vary by region (P = 0.03). Further, there was significant regional variation in the proportion of other microbes causing the infection (P < 0.001). Higher rates of vitrectomies were seen in the South and Midwest regions than that in the Northeast and West (P = 0.04). CONCLUSIONS: Regional variation exists in the infectious microbes causing EE. Further studies are needed to elucidate the etiology of these variations. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association Between Modified Frailty Index and Postoperative Outcomes of Tracheostomies.

OBJECTIVE: The 5-item modified frailty index (mFI-5) has been used to stratify patients based on the risk of postoperative complications in several surgical procedures but has not yet been done in tracheostomies. This study investigates the association between the mFI-5 score and tracheostomy complications. STUDY DESIGN: Retrospective database review. SETTING: United States hospitals. METHODS: The National Surgical Quality Improvement Program database was queried for tracheostomy patients between 2005 and 2018. The mFI-5 was calculated for each patient by assigning 1 point for each of the following comorbidities: diabetes mellitus, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and functionally dependent health status. Univariate and multivariable analyses were conducted to determine associations between the mFI-5 score and postoperative complications. RESULTS: A total of 4438 patients undergoing tracheostomies were queried and stratified into the following groups: mFI = 0 (N = 1741 [39.2%], mFI = 1 (N = 1720 [38.8%]), mFI = 2 (N = 726 [16.4%]), and mFI of 3 or higher (N = 251 [5.7%]). Univariate analysis showed that patients with higher mFI-5 scores had a greater proportion of smoking, dyspnea, obesity, steroid use, emergency cases, complications, reoperations, and mortality (P < .001). Multivariable analyses found associations between mFI-5 score and any complication (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.16, P = .035), mortality (OR: 2.32, 95% CI: 1.15-4.68, P = .019), and any medical complication (OR: 2.75, 95% CI: 1.88-4.02, P < .001). CONCLUSION: This study suggests an association between the mFI-5 score and postoperative complications in tracheostomies. mFI-5 score can be used to stratify tracheostomy patients by operative risk.

Short-Term Reported Urologic Adverse Events Following COVID-19 Immunization: A Vaccine Adverse Event Reporting System Analysis.

INTRODUCTION: Medical misinformation regarding COVID-19 immunization remains rampant and a public concern, and as such, there is a need for national studies evaluating the immunization's safety profile. We sought to quantify and analyze urologic adverse events and symptoms after COVID-19 immunization, compare these events reported between COVID-19 vaccine types, and compare these events reported following COVID-19 immunization relative to those reported following other immunizations. METHODS: We conducted a retrospective case-control disproportionality analysis by querying the Food and Drug Administration Vaccine Adverse Event Reporting System for all reported symptoms following COVID-19 immunization through December 23, 2022, as well as for all non-COVID immunizations. RESULTS: Using a total of 704,231 event reports containing 2,982,187 symptoms related to COVID vaccination and a total of 770,975 event reports containing 2,198,993 symptoms related to all vaccinations other than COVID-19 for disproportionality analysis, no urologic symptom produced a positive signal when grouping all vaccinations. When stratifying by manufacturer, some symptoms related to Janssen vaccination were positive, but this may be in part due to overreporting secondary to media attention rather than a strong association between Janssen vaccination and urologic adverse events. CONCLUSIONS: Although there have been anecdotal reports of adverse events associated with the COVID-19 vaccine, our review of the Vaccine Adverse Event Reporting System database did not produce positive signals across all 4 measures for any potential adverse event. Our findings do not suggest increased scrutiny is required regarding these adverse events potentially related to the COVID-19 immunization. Further evaluation and analysis of the COVID-19 immunization is ongoing.

Ophthalmology residency programs on social media.

PURPOSE: With the transition from away rotations and in-person interviews during the COVID-19 pandemic came a search for alternative methods to represent and promote residency programs. We investigated utilization of social media by ophthalmology residency programs in response to the pandemic. METHODS: Social media accounts of accredited ophthalmology residency programs were found through a manual search on Facebook, Instagram, and Twitter. Each program's geographical region (Northeast, Midwest, South, or West) was identified, and year of account creation (2009-2021) was noted. An exponential regression model was used to model total number of social media accounts over time. Comparisons of total number of social media accounts before/after the pandemic and by region, stratified by social media platform, were evaluated through chi-square analysis. RESULTS: Of 125 ophthalmology residency programs, 63% (n = 79) had at least one account on a social platform. 142 acc. Instagram held the most accounts (45%, n = 64), followed by Facebook (29%, n = 41) and Twitter (26%, n = 37). From 2009 to 2021, there has been an exponential increase in social media accounts (R2 = 0.962). 45% (n = 65) of all accounts were created after March 2020. Instagram increased the most, with 45 ophthalmology residency accounts created after the pandemic as compared to 19 created prior (p < 0.001). The number of social media accounts did not vary by region. CONCLUSIONS: Based on current trends, the presence of ophthalmology residency programs on social media will likely continue expanding, with major social platforms becoming a vaster source of information for ophthalmology residency applicants.

A review on anti-nutritional factors: unraveling the natural gateways to human health.

Humans are constantly facing multiple health challenges from both communicable and non-communicable diseases that significantly affect their health. Additionally, drug resistance or failure has made the situation even worse and poses serious challenges for researchers to develop new drugs. Hence, to address these problems, there is an urgent need to discover and develop timely and long-term-based therapeutic treatments from different sources. One such approach is harnessing the potential of plant secondary metabolites. Plants have been utilized for therapeutic purposes in addition to being used for nutritional benefits. In the last two decades, plant-based drug developments have been one of the effective means of treating human diseases owing to their multiple functions. More recently, anti-nutritional factors (ANFs) have emerged as one of the important targets for novel plant-based drug development due to their multifaceted and potential pharmacological properties. However, their anti-nutritional properties have been the major setback for their limited success in the pharmacological sector. In this review, we provide an overview of ANFs and their beneficial roles in preventing human diseases with multiple case studies. We also highlight the recent developments and applications of ANFs in the food industry, agriculture, and pharmaceutics with future perspectives. Furthermore, we evaluate meta-analyses on ANFs from the last 30 years in relation to their function in human health benefits. This review is an endeavor to reevaluate the merit of these natural compounds and explore their potential for both human and animal health.

Antibody-Drug Conjugates and Ocular Toxicity.

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents for the purpose of treating cancers that often have relapsed or failed first- and second-line treatments. ADCs are composed of extremely potent cytotoxins with a variety of side effects, one of the most significant being ocular toxicity. The available literature describes these toxicities as varying in severity and in incidence, although with disparate methods of evaluation and management. Some of the most common toxicities include microcyst-like epithelial keratopathy and dry eye. We discuss proposed mechanisms of ocular toxicity and describe the reports that mention these toxicities. We focus on ADCs with the most published literature and the most significant effects on ocular tissue. We propose areas for further investigation and possible ideas of future management. We provide a comprehensive look at the reports of ADCs in current literature to better inform clinicians on an expanding drug class.

The Impact of Diabetes on Morbidity and Mortality Following Thyroidectomy.

OBJECTIVES: To explore the association between diabetes and outcomes in thyroidectomy patients. METHODS: This retrospective cohort analysis used the 2015-2017 American College of Surgeons National Surgery Quality Improvement Program database. Current Procedural Terminology (CPT) codes were used to identify thyroidectomy cases (60210, 60212, 60220, 60225, 60240, 60252, 60254, 60260, 60270, and 60271). Demographics, comorbidities, and complication incidences were compared between diabetic and nondiabetic patients using Pearson's chi-square test/Fisher's exact test as appropriate. The independent effect of diabetes on outcomes was analyzed using binary logistic regression. RESULTS: A total of 47,776 (95.4%) nondiabetic and 2307 (4.6%) diabetic patients undergoing thyroidectomy were identified from 2015 to 2017. Chi-square analysis demonstrated that diabetic patients had higher incidences of obesity (55.2% vs. 33.2%; p < 0.001), dyspnea (12.7% vs. 4.8%; p < 0.001), poor functional status (1.9% vs. 0.4%; p < 0.001), ventilator dependence (0.6% vs. 0.1%; p < 0.001), chronic obstructive pulmonary disease (COPD; 6.8% vs. 2.2%; p < 0.001), congestive heart failure (1.1% vs. 0.3%; p < 0.001), acute renal failure (0.3% vs. 0.0%; p < 0.001), hypertension (79.2% vs. 32.4%; p < 0.001), dialysis (2.0% vs. 0.4%; p < 0.001), open wound (1.1% vs. 0.1%; p < 0.001), steroid use (5.3% vs. 2.3%; p < 0.001), bleeding disorders (3.6% vs. 0.9%; p < 0.001), preoperative blood transfusions (0.2% vs. 0.0%; p = 0.001), and systemic sepsis (1.0% vs. 0.3%; p < 0.001). Demographic characteristics were significantly different between the cohorts including gender (p < 0.001), age (p < 0.001), race (p < 0.001), and Hispanic ethnicity (p = 0.033). After adjusting for these factors, logistic regression analyses showed that diabetes was associated with acute renal failure (OR: 5.836; 95% CI: 1.060-32.134; p = 0.043), wound disruption (OR: 6.194; 95% CI: 1.752-21.900; p = 0.005), prolonged length of stay (OR: 1.430; 95% CI: 1.261-1.622; p < 0.001), unplanned readmission (OR: 1.380; 95% CI: 1.096-1.737; p = 0.006), superficial incisional surgical site infections (OR: 0.240; 95% CI: 0.058-0.995; p = 0.049), urinary tract infection occurrences (OR: 2.173; 95% CI: 1.186-3.980; p = 0.012), organ space surgical site infection occurrences (OR: 3.322; 95% CI: 1.016-10.864; p = 0.047), pneumonia occurrences (OR: 2.091; 95% CI: 1.125-3.884; p = 0.020), any medical complication (OR: 1.697; 95% CI: 1.246-2.313; p = 0.001), and any complication (OR: 1.495; 95% CI: 1.136-1.968; p = 0.004). CONCLUSION: Diabetes mellitus is a significant factor associated with increased odds of complications following thyroidectomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3628-3632, 2023.

Optic Neuritis After COVID-19 Vaccination: An Analysis of the Vaccine Adverse Event Reporting System.

BACKGROUND: To investigate the association of optic neuritis (ON) after the COVID-19 vaccines. METHODS: Cases of ON from Vaccine Adverse Event Reporting System (VAERS) were collected and divided into the prepandemic, COVID-19 pandemic, and COVID-19 vaccine periods. Reporting rates were calculated based on estimates of vaccines administered. Proportion tests and Pearson χ 2 test were used to determine significant differences in reporting rates of ON after vaccines within the 3 periods. Kruskal-Wallis testing with Bonferroni-corrected post hoc analysis and multivariable binary logistic regression was used to determine significant case factors such as age, sex, concurrent multiple sclerosis (MS) and vaccine manufacturer in predicting a worse outcome defined as permanent disability, emergency room (ER) or doctor visits, and hospitalizations. RESULTS: A significant increase in the reporting rate of ON after COVID-19 vaccination compared with influenza vaccination and all other vaccinations (18.6 vs 0.2 vs 0.4 per 10 million, P < 0.0001) was observed. However, the reporting rate was within the incidence range of ON in the general population. Using self-controlled and case-centered analyses, there was a significant difference in the reporting rate of ON after COVID-19 vaccination between the risk period and control period ( P < 0.0001). Multivariable binary regression with adjustment for confounding variables demonstrated that only male sex was significantly associated with permanent disability. CONCLUSIONS: Some cases of ON may be temporally associated with the COVID-19 vaccines; however, there is no significant increase in the reporting rate compared with the incidence. Limitations of this study include those inherent to any passive surveillance system. Controlled studies are needed to establish a clear causal relationship.

Effect of Hypoalbuminemia in Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism.

OBJECTIVES: Treatment for primary hyperparathyroidism is parathyroidectomy. This study identifies the association between hypoalbuminemia (HA) and outcomes in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS: This retrospective cohort analysis utilized the 2006-2015 National Surgical Quality Improvement Program database. Current Procedure Terminology codes were used to identify patients undergoing parathyroidectomy for primary hyperparathyroidism. Prolonged length of stay (LOS) was defined as a duration of 2 days or greater. Demographics and comorbidities were compared between HA (serum albumin <3.5 g/dL) and non-HA cohorts using chi-square analysis. The independent effect of HA on adverse outcomes was analyzed using binary logistic regression. RESULTS: A total of 7183 cases with primary hyperparathyroidism were classified into HA (n = 381) and non-HA (n = 6802) cohorts. HA patients had increased complications, including renal insufficiency (0.8% vs. 0.0%, p = 0.001), sepsis (1.0% vs. 0.1%, p = 0.003), pneumonia (0.8% vs. 0.1%, p = 0.018), acute renal failure (1.0% vs. 0.0%, p < 0.001), and unplanned intubation (1.3% vs. 0.2%, p = 0.004). HA patients had increased risk of death (1.6% vs. 0.1%, p < 0.001), prolonged LOS (40.9% vs. 6.3%, p < 0.001), and any complication (5.5% vs. 1.2%, p < 0.001). Adjusted binary logistic regression indicated HA patients experienced increased odds of progressive renal insufficiency (OR 18.396, 95% CI 1.844-183.571, p = 0.013), prolonged LOS (OR 4.892; 95% CI 3.571-6.703; p < 0.001), unplanned reoperation (OR 2.472; 95% CI 1.012-6.035; p = 0.047), and unplanned readmission (OR 3.541; 95% CI 1.858-6.748; p < 0.001). CONCLUSIONS: HA may be associated with adverse complications in patients undergoing parathyroidectomy for primary hyperparathyroidism. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2035-2039, 2023.

Contribution of Hepatic Steatosis-Intensified Extracellular Vesicle Release to Aggravated Inflammatory Endothelial Injury in Liver-Specific Asah1 Gene Knockout Mice.

To study the mechanism by which nonalcoholic fatty liver disease (NAFLD) contributes to vascular endothelial Nod-like receptor pyrin domain 3 (NLRP3) inflammasome activation and neointima hyperplasia, NAFLD was established in high-fat diet (HFD)-treated Asah1fl/fl/Albcre (liver-specific deletion of the acid ceramidase gene Asah1) mice. Compared with Asah1 flox [Asah1fl/fl/wild type (WT)] and wild-type (WT/WT) mice, Asah1fl/fl/Albcre mice exhibited significantly enhanced ceramide levels and lipid deposition on HFD in the liver. Moreover, Asah1fl/fl/Albcre mice showed enhanced expression of extracellular vesicle (EV) markers, CD63 and annexin II, but attenuated lysosome-multivesicular body fusion. All these changes were accompanied by significantly increased EV counts in the plasma. In a mouse model of neointima hyperplasia, liver-specific deletion of the Asah1 gene enhanced HFD-induced neointima proliferation, which was associated with increased endothelial NLRP3 inflammasome formation and activation and more severe endothelial damage. The EVs isolated from plasma of Asah1fl/fl/Albcre mice on HFD were found to markedly enhance NLRP3 inflammasome formation and activation in primary cultures of WT/WT endothelial cells compared with those isolated from WT/WT mice or normal diet-treated Asah1fl/fl/Albcre mice. These results suggest that the acid ceramidase/ceramide signaling pathway controls EV release from the liver, and its deficiency aggravates NAFLD and intensifies hepatic EV release into circulation, which promotes endothelial NLRP3 inflammasome activation and consequent neointima hyperplasia in the mouse carotid arteries.

Educational quality and content of YouTube videos on diabetic macular edema.

PURPOSE: Diabetic macular edema (DME) is a vision-threatening complication of diabetes mellitus due to increased vascular permeability. Patients are increasingly using YouTube videos to educate themselves about DME. This study analyzes the content and quality of YouTube videos about DME. METHODS: Videos were searched in December 2021 for "diabetic macular edema." The first 100 videos sorted by both relevance and view count were reviewed (n = 200). Quantitative metrics and content were collected. Two reviewers assessed videos using the JAMA (0-4), modified DISCERN (1-5), and Global Quality Scale (GQS, 1-5). Videos were sorted into author groups: 1 (academic institutions/organizations), 2 (private practices/organizations), and 3 (independent users; ophthalmologist users noted). Statistical analyses were deemed significant at a = 0.05. RESULTS: One hundred four videos were included after applying exclusion criteria. Overall mean + standard deviations were 2.25 ± 0.83 (JAMA), 3.47 ± 0.55 (DISCERN), and 3.95 ± 0.95 (GQS). 51.9% of videos stated a definition, 32.7% mentioned screening, and 50% mentioned any DME risk factor. Healthcare professional-targeted videos had higher JAMA and DISCERN scores than patient-targeted videos (p < 0.05). Videos using ophthalmologists had higher JAMA and DISCERN scores than those lacking their presence (p < 0.05). JAMA scores significantly varied between author groups; within group 3, ophthalmologist-authored videos had higher DISCERN scores (p < 0.05). CONCLUSION: Videos without ophthalmologists or targeted toward patients had poor quality and content coverage. The rising prevalence of diabetes, coupled with increased internet use for acquiring medical information, creates a strong need for high-quality information about DME.

Endothelial Acid Sphingomyelinase Promotes NLRP3 Inflammasome and Neointima Formation During Hypercholesterolemia.

The NOD-like receptor pyrin domain 3 (NLRP3) inflammasome is activated during atherogenesis, but how this occurs is unclear. Here, we explored the mechanisms activating and regulating NLRP3 inflammasomes via the acid sphingomyelinase (ASM)-ceramide signaling pathway. As a neointima formation model, partial left carotid ligations were performed on endothelial cell (EC)-specific ASM transgene mice (Smpd1trg/ECcre) and their control littermates (Smpd1trg/WT and WT/WT) fed on the Western diet (WD). We found neointima formation remarkably increased in Smpd1trg/ECcre mice over their control littermates. Next, we observed enhanced colocalization of NLRP3 versus adaptor protein ASC (the adaptor molecule apoptosis-associated speck-like protein containing a CARD) or caspase-1 in the carotid ECs of WD-treated Smpd1trg/ECcre mice but not in their control littermates. In addition, we used membrane raft (MR) marker flotillin-1 and found more aggregation of ASM and ceramide in the intima of Smpd1trg/ECcre mice than their control littermates. Moreover, we demonstrated by in situ dihydroethidium staining, carotid intimal superoxide levels were much higher in WD-treated Smpd1trg/ECcre mice than in their control littermates. Using ECs from Smpd1trg/ECcre and WT/WT mice, we showed ASM overexpression markedly enhanced 7-ketocholesterol (7-Ket)-induced increases in NLRP3 inflammasome formation, accompanied by enhanced caspase-1 activity and elevated interleukin-1ß levels. These 7-Ket-induced increases were significantly attenuated by ASM inhibitor amitriptyline. Furthermore, we determined that increased MR clustering with NADPH oxidase subunits to produce superoxide contributes to 7-Ket-induced NLRP3 inflammasome activation via a thioredoxin-interacting protein-mediated controlling mechanism. We conclude that ceramide from ASM plays a critical role in NLRP3 inflammasome activation during hypercholesterolemia via MR redox signaling platforms to produce superoxide, which leads to TXNIP dissociation.

Impairment of Ceramide-Mediated Endothelial Instant Membrane Resealing During Diabetes Mellitus.

Recent studies have indicated that instant cell membrane resealing (ICMR) controls the activation of NOD-like receptor pyrin domain containing 3 (Nlrp3) inflammasomes in endothelial cells, thereby initiating and promoting vascular inflammation. It remains unknown whether this impaired ICMR occurs under diabetic condition or hyperglycemia contributing to endothelial dysfunction leading to vascular inflammation, a hallmark of diabetic vascular injury. The present study aims to examine whether ICMR occurs during in control and diabetic mice and to explore related molecular mechanisms associated with acid sphingomyelinase (ASM)-mediated ceramide production. Using confocal microscopy, we demonstrated that mouse aortic endothelial cells (MAECs) exposed to high glucose levels exhibited much more retarded ICMR after laser-induced membrane injury, compared to that in control cells. The high glucose-induced impairment of membrane resealing in MAECs was prevented when these cells were pretreated with sphingomyelin or C24-ceramide. Mechanistically, high glucose treatment decreased association of membrane ceramide with annexin A5, an essential element of membrane repair machinery. Consistently, the association of ceramide with annexin A5 was significantly reduced in the coronary arterial endothelium of mice with streptozotocin-induced diabetes mellitus compared to that in non-diabetic control mice. Moreover, a marked reduction of the association of ceramide with annexin A5 was observed in coronary arterial endothelium of ASM knockout mice regardless of their diabetic status. Lastly, high glucose treatment or ASM gene deletion substantially impaired ICMR in coronary arterial endothelium of mice receiving membrane puncturing agents. Collectively, our data suggest that ceramide-mediated ICMR in vascular endothelial cells is impaired during diabetes mellitus due to dissociation of ceramide with annexin A5 and ASM play a critical role in this ICMR.