Proteomic profiles in the aqueous following anti-vegf therapy in treatment naïve neovascular age-related macular degeneration.

Background/study Objectives: Age-related macular degeneration (AMD), a degenerative disease of the photoreceptor support system of the macula, is a leading cause of vision loss in individuals over 60 years of age. In this exploratory longitudinal study, we studied VEGF-related proteins and other protein concentrations in the aqueous humor of patients with treatment naïve neovascular AMD (defined as patients with a previously untreated and recently diagnosed advanced neovascular form of AMD (NVAMD) who were eligible for an intra-vitreal administration of an anti-VEGF agent to treat choroidal neovascularization). The objectives of this small pilot study were: (1) To determine levels of VEGF-related proteins in the aqueous humor of treatment naïve NVAMD patients compared with control patients, (2) To determine whether levels of VEGF-related proteins change over time with anti-VEGF injections in NVAMD patients, (3) To put these differences into perspective relative to all protein targets and identify other off-target (non-VEGF) proteins that may be related to NVAMD or NVAMD treatment.

Systemic C-reactive protein levels in patients with geographic atrophy stratified by sex.

Aim: To determine the differences in levels of systemic C-reactive protein (CRP) in patients with geographic atrophy (GA) and sex-based differences in CRP levels.

Methods: Blood samples from patients with GA and controls were collected in a prospective age-related macular degeneration (AMD) registry from August 2014 to June 2021. AMD was confirmed using multimodal imaging and the Beckman and Consensus of Atrophy Meeting criteria for GA.

Dynamic Risk of Systemic Complement Activation With Time to Progression to Advanced Age-Related Macular Degeneration.

Importance: Understanding the relationship between longitudinally measured systemic complement factors and intermediate AMD (iAMD) progression may enable the introduction of systemic therapeutics earlier in the disease course, before vision loss occurs.

Objective: To determine the contribution of longitudinal measures of systemic complement factors and ratios to time to progression to advanced AMD (geographic atrophy [GA] or neovascular AMD [NVAMD]).

Design, Setting, And Participants: This cohort study was conducted at Sue Anschutz Rodgers Eye Center, Aurora, Colorado, from 2014 to 2022.

Screening Corneal Tomography for the Diagnosis of Keratoconus in Pediatric Patients With Trisomy 21.

Purpose: The goal of this study is to describe the rates of successful corneal tomography in children with Down Syndrome (DS) and to determine whether high levels of astigmatism or myopia are reliable indicators of keratoconus in children with DS.

Design: Retrospective, cross-sectional study.

Subjects And Controls: Patients aged 4 to 18 years old with and without DS who underwent corneal tomography to evaluate for keratoconus at a tertiary pediatric hospital from July 2018-January 2020.

Urine Metabolites of Suspected Community-Acquired Pneumonia.

Background: Accurate diagnosis of community-acquired pneumonia (CAP) can be challenging. Clinical findings are nonspecific, and interpretations of chest radiographs have poor interrater reliability. Pilot studies demonstrate the potential for metabolomics to identify metabolite concentrations that differentiate children with CAP from those without.

Physiologic Pulmonary Phenotyping of Infants Born Preterm and Post-Discharge Respiratory Morbidity.

Objective: To determine whether airway and parenchymal function identifies subgroups of infants born preterm according to the predominant pulmonary pathophysiology, and whether these subgroups have different risks for respiratory disease during infancy.

Study Design: We prospectively enrolled a cohort of 125 infants born preterm with planned clinical follow-up after neonatal intensive care unit discharge. The study included monthly questionnaires for wheeze and visits to a physician or care provider for any respiratory illness.

Multiplex Polymerase Chain Reaction Versus Standard Bacterial Culture in Critically Ill Children With Suspected Pneumonia.

Background: Bacterial lower respiratory tract infection, particularly ventilator-associated pneumonia (VAP), is a significant cause of morbidity and mortality in children who require mechanical ventilation (MV). Microbiologic diagnosis has relied on bacterial culture, but reverse transcriptase polymerase chain reaction (RT-PCR) with bacterial targets is now available for clinical use. We compared the diagnostic performance of tracheal aspirate (TA) multiplex RT-PCR to culture in children requiring MV with suspected lower respiratory tract infection.

The relationship between discordant birth weight in twin pairs and the development of retinopathy of prematurity.

The association of low birth weight and development of retinopathy of prematurity (ROP) is well established for singletons; however, the association of birth weight and ROP in twins of discordant weight is understudied. Using an ROP registry, we investigated whether smaller twins were at greater risk for developing any stage ROP (stage 1 or greater in either eye) compared with their larger siblings, after adjusting for birth weight and gestational age. Discordance was defined as a birth weight difference of >25%.

Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy.

Introduction: Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD.

Metabolomics analysis of bronchoalveolar lavage fluid predicts unique features of the lower airway in pediatric cystic fibrosis.

Background: Progressive, obstructive lung disease resulting from chronic infection and inflammation is the leading cause of morbidity and mortality in persons with cystic fibrosis (PWCF). Metabolomics and next -generation sequencing (NGS) of airway secretions can allow for better understanding of cystic fibrosis (CF) pathophysiology. In this study, global metabolomic profiling on bronchoalveolar lavage fluid (BALF) obtained from pediatric PWCF and disease controls (DCs) was performed and compared to lower airway microbiota, inflammation, and lung function.

Did COVID-19 ICU patient mortality risk increase as Colorado hospitals filled? A retrospective cohort study.

Objectives: To assess whether increasing levels of hospital stress-measured by intensive care unit (ICU) bed occupancy (primary), ventilators in use and emergency department (ED) overflow-were associated with decreasing COVID-19 ICU patient survival in Colorado ICUs during the pre-Delta, Delta and Omicron variant eras.

Design: A retrospective cohort study using discrete-time survival models, fit with generalised estimating equations.

Setting: 34 hospital systems in Colorado, USA, with the highest patient volume ICUs during the COVID-19 pandemic.

The relationship between severe hypertensive diseases of pregnancy and moderate-severe bronchopulmonary dysplasia.

Objective: Determine the association between severe hypertensive disease of pregnancy (HDP) with moderate-severe bronchopulmonary dysplasia (BPD) in preterm infants (< 31 weeks' gestation).

Study Design: Preterm birth cohort study of 693 mother-infant dyads. Severe HDP was defined as severe preeclampsia, HELLP syndrome or eclampsia.

Integrating airway microbiome and blood proteomics data to identify multi-omic networks associated with response to pulmonary infection.

Host response to airway infections can vary widely. Cystic fibrosis (CF) pulmonary exacerbations provide an opportunity to better understand the interplay between respiratory microbes and the host. This study aimed to investigate the observed heterogeneity in airway infection recovery by analyzing microbiome and host response (i.

The antibiotic resistance reservoir of the lung microbiome expands with age in a population of critically ill patients.

Antimicrobial resistant lower respiratory tract infections are an increasing public health threat and an important cause of global mortality. The lung microbiome can influence susceptibility of respiratory tract infections and represents an important reservoir for exchange of antimicrobial resistance genes. Studies of the gut microbiome have found an association between age and increasing antimicrobial resistance gene burden, however, corollary studies in the lung microbiome remain absent.

An Evaluation of the Repeatability of Visual Function Following Surgical Repair of Macula-Off Rhegmatogenous Retinal Detachment.

Purpose: To evaluate the reliability and reproducibility of visual function assessments for patients with macula-off rhegmatogenous retinal detachment (RRD).

Methods: This prospective study included patients with unilateral macula-off RRD of <10-day duration successfully treated with a single, uncomplicated surgery at least 1 year following repair. Visual function assessments were performed at time of enrollment and 1 month later.

Cataract Phacoemulsification in People with Dementia: Characterization and Outcomes.

Purpose: To characterize cataract surgery in people with dementia (PWD) using a cataract surgery outcomes database.

Methods: Demographics, medical and ocular history, surgical characteristics, and postoperative measures were analyzed for differences between PWD and non-PWD cohorts. Patient-level data were analyzed with Fisher's Exact Test, and eye-level data were analyzed with logistic regression using generalized estimating equations to account for correlation of eyes from the same individual.

Limited effects of azithromycin on the oropharyngeal microbiome in children with CF and early pseudomonas infection.

Background: Tobramycin inhalation solution (TIS) and chronic azithromycin (AZ) have known clinical benefits for children with CF, likely due to antimicrobial and anti-inflammatory activity. The effects of chronic AZ in combination with TIS on the airway microbiome have not been extensively investigated. Oropharyngeal swab samples were collected in the OPTIMIZE multicenter, randomized, placebo-controlled trial examining the addition of AZ to TIS in 198 children with CF and early P.

Autonomous artificial intelligence increases real-world specialist clinic productivity in a cluster-randomized trial.

Autonomous artificial intelligence (AI) promises to increase healthcare productivity, but real-world evidence is lacking. We developed a clinic productivity model to generate testable hypotheses and study design for a preregistered cluster-randomized clinical trial, in which we tested the hypothesis that a previously validated US FDA-authorized AI for diabetic eye exams increases clinic productivity (number of completed care encounters per hour per specialist physician) among patients with diabetes. Here we report that 105 clinic days are cluster randomized to either intervention (using AI diagnosis; 51 days; 494 patients) or control (not using AI diagnosis; 54 days; 499 patients).

The antibiotic resistance reservoir of the lung microbiome expands with age.

Antimicrobial resistant lower respiratory tract infections (LRTI) are an increasing public health threat, and an important cause of global mortality. The lung microbiome influences LRTI susceptibility and represents an important reservoir for exchange of antimicrobial resistance genes (ARGs). Studies of the gut microbiome have found an association between age and increasing antimicrobial resistance gene (ARG) burden, however corollary studies in the lung microbiome remain absent, despite the respiratory tract representing one of the most clinically significant sites for drug resistant infections.

Viral Detection by Reverse Transcriptase Polymerase Chain Reaction in Upper Respiratory Tract and Metagenomic RNA Sequencing in Lower Respiratory Tract in Critically Ill Children With Suspected Lower Respiratory Tract Infection.

Objectives: Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs).

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy.

Purpose: Chronic local inflammation underlies the pathogenesis of age-related macular degeneration (AMD) causing damage to the neurosensory retina. However, there is minimal research on systemic cell-mediated inflammation in AMD. Interleukin-4 (IL-4) is an immunoregulatory cytokine with an important role in modulating inflammation in chronic immune mediated disease.

Cardiopulmonary Phenotypes and Protein Signatures in Children With Down Syndrome.

Pulmonary disease, lower respiratory tract infection, and pneumonia are the largest causes of morbidity and mortality in individuals with Down syndrome (DS), but whether pulmonary diagnoses in children with DS are common and occur independently of cardiac disease and pulmonary hypertension (PH) is unknown. Cardiopulmonary phenotypes were examined in a cohort of 1248 children with DS. Aptamer-based proteomic analysis of blood was performed in a subset (n = 120) of these children.

A Randomized Prospective Trial Comparing Repository Corticotropin Injection and Intravenous Methylprednisolone for Neuroprotection in Acute Optic Neuritis.

Background: Repository corticotrophin injection (RCI, Acthar Gel) and intravenous methylprednisolone (IVMP) improve the rate but not the extent of visual recovery following acute optic neuritis. RCI has adrenal-stimulating and melanocortin receptor-stimulating properties that may endow it with unique anti-inflammatory properties relative to IVMP.

Methods: Individuals with acute optic neuritis of less than 2 weeks duration were prospectively enrolled and randomized 1:1 to receive either RCI or IVMP.