Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n = 259) or multisystem inflammatory syndrome in children (MIS-C; n = 4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.

High-Resolution Profiling of Human Vocal Fold Cellular Landscapes With Single-Nuclei RNA Sequencing.

INTRODUCTION: The function of the vocal folds (VFs) is determined by the phenotype, abundance, and distribution of differentiated cells within specific microenvironments. Identifying this histologic framework is crucial in understanding laryngeal disease. A paucity of studies investigating VF cellular heterogeneity has been undertaken. Here, we examined the cellular landscape of human VFs by utilizing single-nuclei RNA-sequencing. METHODS: Normal true VF tissue was excised from five patients undergoing pitch elevation surgery. Tissue was snap frozen in liquid nitrogen and subjected to cellular digestion and nuclear extraction. Nuclei were processed for single-nucleus sequencing using the 10X Genomics Chromium platform. Sequencing reads were assembled using cellranger and analyzed with the scanpy package in python. RESULTS: RNA sequencing revealed 18 global cell clusters. While many were of epithelial origin, expected cell types, such as fibroblasts, immune cells, muscle cells, and endothelial cells were present. Subcluster analysis defined unique epithelial, immune, and fibroblast subpopulations. CONCLUSION: This study evaluated the cellular heterogeneity of normal human VFs by utilizing single-nuclei RNA-sequencing. With further confirmation through additional spatial sequencing and microscopic imaging, a novel cellular map of the VFs may provide insight into new cellular targets for VF disease. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3193-3200, 2024.

Meibum sphingolipid composition is altered in individuals with meibomian gland dysfunction-a side by side comparison of Meibum and Tear Sphingolipids.

PURPOSE: Sphingolipids (SPL) play a role in cell signaling, inflammation, and apoptosis. The purpose of this study was to examine meibum and tear SPL composition in individuals with poor versus good meibum quality. METHODS: Individuals were grouped by meibum quality (n = 25 with poor quality, case group and n = 25 with good quality, control group). Meibum and tears were analyzed with liquid chromatography-mass spectrometry (LC-MS) to quantify SPL classes. Semiquantitative and relative composition (mole percent) of SPL and major classes, Ceramide (Cer), Hexosyl-Ceramide (Hex-Cer), Sphingomyelin (SM), Sphingosine (Sph), and sphingosine 1-phosphate (S1P) were compared between groups. RESULTS: Demographic characteristics were similar between the two groups. Overall, individuals with poor meibum quality had more SPL pmole in meibum and tears than controls. Relative composition analysis revealed that individuals with poor meibum quality had SPL composed of less Cer, Hex-Cer, and Sph and more SM compared to individuals with good quality meibum. This pattern was not reproduced in tears as individuals with poor meibum quality had SPL composed of a similar amount of Cer, but more Hex-Cer, Sph and SM compared to controls. In meibum, SPL pmole and relative composition most strongly correlated with MG metrics while in tears, SPL pmole and relative composition most strongly correlated with tear production. SPL in both compartments, specifically Cer pmole in meibum and S1P% in tears, correlated with DE symptoms. CONCLUSION: SPL composition differs in meibum and tears in patients with poor vs good meibum quality. These findings may be translated into therapeutic targets for disease.