Sociodemographic Factors Associated with Emergent Eye-Related Emergency Department Visits: A Multicenter Analysis.

OBJECTIVE: To compare sociodemographic factors in patients presenting to the emergency department (ED) with emergent and non-emergent eye-related concerns. DESIGN: Cross-sectional multicenter study. SUBJECTS: 60,677 patients with eye-related concerns who visited EDs at Bascom Palmer Eye Institute, Wills Eye Hospital, Massachusetts Eye and Ear, and Johns Hopkins Hospital/Wilmer Eye Institute from January 1st, 2019 until December 31st, 2019. METHODS: Descriptive statistics were performed using STATA 17. MAIN OUTCOME MEASURES: 1) Sociodemographic factors associated with emergent diagnoses, 2) Visit patterns across ED settings (i.e. standard ED vs eye ED), and 3) the most common emergent and non-emergent diagnoses. RESULTS: A total of 60,677 eye-related ED encounters were included in the study, including 22,434 at Bascom Palmer Eye Institute, 16,124 at Wills Eye Hospital, 15,487 at Massachusetts Eye and Ear, and 6,632 at Johns Hopkins Hospital/Wilmer Eye Institute. Most patients had non-emergent diagnoses (56.7%). Males (OR 1.85, 95% CI 1.79-1.92) were more likely to have an emergent diagnosis than females. Patients with private/employer-based insurance (OR 0.88, 95% CI 0.81-0.96), Medicare (OR 0.80, 95% CI 0.72-0.87), and Medicaid (OR 0.81, 95% CI 0.74-0.89) were all less likely to have an emergent diagnosis than uninsured patients. Those with veteran/military insurance (OR 1.08, 95% CI 0.87-1.34) were equally likely to have an emergent diagnosis compared to uninsured patients. Non-White Hispanic patients (OR 1.26, 95% CI 1.12-1.42) were more likely to present with an emergent condition than White patients. Patient seen in the standard ED setting were more likely to have emergent diagnoses than those who visited standalone eye EDs (P < 0.001). The most common emergent diagnoses were corneal abrasion (12.97%), extraocular foreign body (7.61%), and corneal ulcer (7.06%). The most common non-emergent diagnoses were dry eye (7.90%), posterior vitreous detachment (7.76%), and chalazion (6.57%). CONCLUSIONS: ED setting was associated with the acuity of patient diagnoses. Lack of insurance coverage and non-White Hispanic race/ethnicity were associated with emergent eye-related ED visits. Improving access to ophthalmic care in these populations may reduce the incidence of preventable eye emergencies related to untreated chronic conditions. This combined with measures to redirect non-emergent issues to outpatient clinics may alleviate ED overload.

Psoriasis in the Era of Targeted Cancer Therapeutics: A Systematic Review on De Novo and Pre-existing Psoriasis in Oncologic Patients Treated with Emerging Anti-neoplastic Agents.

New advancements in medicine have paved the way for targeted therapies and immune checkpoint inhibitors (ICIs), which have become mainstays of cancer therapy. Targeted therapies work by pinpointing specific molecules in cancer pathways and inhibiting their function, while ICIs target irregularities in the immune system and DNA repair, participating in the induction of cell death. Although these agents have demonstrated great efficacy in treating a diverse set of cancers, they can frequently provoke serious dermatologic adverse effects. The side effects caused by an ICI are classified as immune-related adverse events since ICIs are immunomodulating, while the cutaneous side effects of targeted therapies are known as dermatologic adverse effects. Multiple studies have reported psoriasis and psoriasiform eruptions among the side effects observed in neoplastic patients receiving targeted therapies or ICIs. Psoriasis is an immune-mediated disease characterized by overactive T-cells and keratinocytes. To conduct this review, we retrieved 1363 studies from the PubMed database published between 2008 and 2023 using the terms "psoriasis" AND "cancer treatment." Many of these studies aimed to understand how patients with cancer receiving treatment may develop or even achieve psoriasis remission. Given that cancer and psoriasis involve a delicate balance between immune activation and suppression, ICIs and targeted therapies might produce varying effects. The aim of this review was to explore the relationship between psoriasis and cancer therapeutics while also highlighting the need to prioritize proper management of cutaneous side effects in neoplastic patients.

Dysregulation of the Skin-Liver Axis in Prurigo Nodularis: An Integrated Genomic, Transcriptomic, and Population-Based Analysis.

Pruritus has long been linked to hepatic dysfunction; however, there are limited data characterizing the association between liver disease and prurigo nodularis (PN), a chronic inflammatory skin disease featuring severe pruritis. We thus conducted a cross-sectional analysis of hepatic comorbidities in PN patients using TriNetX, a large global health research network. This analysis revealed that PN patients had a higher risk (p < 0.001) of developing liver cirrhosis, acute and subacute hepatic failure, inflammatory liver disease, chronic hepatitis, nonalcoholic steatohepatitis, portal hypertension, fatty liver, chronic passive congestion of the liver, and hepatocellular carcinoma compared with healthy controls. The cumulative incidence of liver disease was about three times higher in PN patients compared with healthy controls. These findings provided the basis for translational studies to investigate a genetic mechanism for this association. Cutaneous transcriptomic analysis performed on PN patients revealed the dysregulation of genes related to hepatic failure in lesional PN compared with both nonlesional PN and control skin. Similarly, gene set variation analysis (GSVA) revealed a significantly increased (p < 0.05) activation of liver metabolism, chronic hepatic failure, acute hepatic failure, cholestatic liver disease, polycystic liver disease, and hepatocellular carcinoma pathways in lesional PN compared with control skin. A subsequent genome-wide association study (GWAS) identified shared single-nucleotide polymorphisms (SNPs) in the genes AR, EDIL3, MACROD2, PCSK5, RUNX1T1, TENM4, and ZEB2 between PN and liver disease from the FinnGen cohort. Significant dysregulation of the skin-liver axis in PN patients may explain the increased incidence and severity of hepatic comorbidities and help identify future therapeutic targets for PN.

Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade.

Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson's r=0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson's r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.

Pembrolizumab-Induced Lichen Planus Pemphigoides in a Patient with Metastatic Adrenocortical Cancer: A Case Report and Literature Review.

While the advent of immune-checkpoint inhibitors has revolutionized cancer therapy, immune-related adverse effects (irAEs) have also been on the rise. Cutaneous toxicities are among the most common irAEs, especially in the context of programmed cell death protein-1 (PD-1) inhibitors like pembrolizumab. Herein, we report a case of anti-PD-1-induced lichen planus pemphigoides (LPP)-a rare autoimmune blistering disorder with characteristics of both lichen planus and bullous pemphigoid. To our knowledge, this is the first reported case of LPP following anti-PD-1 therapy for metastatic adrenocortical cancer. Recognizing that LPP is within the spectrum of irAEs is important, especially as the indications for immunotherapy grow to include rarer malignancies like adrenocortical cancer. In addition to our case presentation, we also provide a comprehensive review of the literature surrounding immunotherapy-induced LPP-highlighting key characteristics towards the early recognition and clinical management of this cutaneous irAE.

Most Common Ophthalmic Diagnoses in Eye Emergency Departments: A Multicenter Study.

PURPOSE: To characterize the most common ophthalmic conditions seen in the emergency department (ED) DESIGN: Cross-sectional study METHODS: This is a multicenter study of 64,988 patients who visited the Bascom Palmer Eye Institute, Massachusetts Eye and Ear, Wills Eye Hospital, and Johns Hopkins Hospital/Wilmer Eye Institute from January 1, 2019, until December 31, 2019. Demographic and primary diagnosis data were extracted including gender, age, race, ethnicity, insurance type, and ophthalmology consult status. Descriptive statistics were performed on all data using STATA IC 14 (64-bit). RESULTS: A total of 64,988 patients with primary ocular diagnoses were seen across all 4 EDs. The majority of patients were White (63.1%), non-Hispanic/Latino (64.8%), and female (52.3%). The most frequently seen age group was 50-64 years (28.6%). The most common diagnoses across all institutions were conjunctivitis (7.91%), corneal abrasions (5.61%), dry eye (4.49%), posterior vitreous detachments (4.15%), chalazions (3.71%), corneal ulcers (3.01%), subconjunctival hemorrhages (2.96%), corneal foreign bodies (2.94%), retinal detachments (2.51%), and glaucoma (2.12%). Specifically, viral conjunctivitis (2283 of 5139, 44.4%) and primary open-angle glaucoma (382 of 1379, 27.7%) were the most frequently seen subtypes of conjunctivitis and glaucoma. CONCLUSIONS: The most regularly treated ophthalmic conditions in high-volume EDs tend to be lower acuity diagnoses. To combat ED overcrowding and rising health care costs in the United States, we suggest diverting eye-related ED visits to a specialized eye ED service or same-day eye clinic appointment in addition to expanding education for patients and primary care clinicians.

Is Sentinel Lymph Node Biopsy Necessary in Patients who Undergo Prophylactic Mastectomy?

BACKGROUND: Over the last decade, rates of risk-reducing prophylactic mastectomy (PM) have risen dramatically. A topic of debate regarding the procedure is whether to use sentinel lymph node biopsy (SLNB) at the time of PM and what factors might predict for such need. In order to assess the rate of identifying presence of occult invasive breast cancer in the PM specimen, we performed a retrospective review of the pathology findings from a single-surgeon case-series of PM. METHODS: Patients undergoing PM between January 2013 and June 2019 at Orlando Health Cancer Institute were identified for a retrospective chart review. Demographic, clinical, and histopathological data from the surgical procedure were collected and analyzed for the incidence of occult invasive breast cancer in the PM specimen. RESULTS: A total of 146 consecutive patients with PM were identified; 120 (82.2%) underwent contralateral PM (CPM) and 26 (17.8%) underwent bilateral PM (BPM). Final pathology of the 172 PM specimens identified 4 (3.3%) with lobular carcinoma in situ, 3 (2.5%) with atypical ductal hyperplasia, and 2 (1.7%) with atypical lobular hyperplasia and 2 (1.7%) with intraductal papilloma. No invasive malignancy was detected in any of the 172 PM specimens. CONCLUSIONS: The absence of occult invasive carcinoma in 172 consecutive PM specimens suggests a limited clinical utility in routinely performing SLNB in this setting. This study also suggests that use of preoperative breast MRI imaging could offer a potential non-invasive tool to detect occult malignancy and select patients who can safely undergo omission of SLNB at the time of PM.

Generation and characterization of genetically and antigenically diverse infectious clones of dengue virus serotypes 1-4.

Dengue is caused by four genetically distinct viral serotypes, dengue virus (DENV) 1-4. Following transmission by Aedes mosquitoes, DENV can cause a broad spectrum of clinically apparent disease ranging from febrile illness to dengue hemorrhagic fever and dengue shock syndrome. Progress in the understanding of different dengue serotypes and their impacts on specific host-virus interactions has been hampered by the scarcity of tools that adequately reflect their antigenic and genetic diversity. To bridge this gap, we created and characterized infectious clones of DENV1-4 originating from South America, Africa, and Southeast Asia. Analysis of whole viral genome sequences of five DENV isolates from each of the four serotypes confirmed their broad genetic and antigenic diversity. Using a modified circular polymerase extension reaction (CPER), we generated de novo viruses from these isolates. The resultant clones replicated robustly in human and insect cells at levels similar to those of the parental strains. To investigate in vivo properties of these genetically diverse isolates, representative viruses from each DENV serotype were administered to NOD Rag1-/-, IL2rgnull Flk2-/- (NRGF) mice, engrafted with components of a human immune system. All DENV strains tested resulted in viremia in humanized mice and induced cellular and IgM immune responses. Collectively, we describe here a workflow for rapidly generating de novo infectious clones of DENV - and conceivably other RNA viruses. The infectious clones described here are a valuable resource for reverse genetic studies and for characterizing host responses to DENV in vitro and in vivo.