Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin dryness, inflammation, and itch. A major hallmark of AD is an elevation of the immune cytokines IL-4 and IL-13. These cytokines lead to skin barrier disruption and lipid abnormalities in AD, yet the underlying mechanisms are unclear. Sebaceous glands are specialized sebum-producing epithelial cells that promote skin barrier function by releasing lipids and antimicrobial proteins to the skin surface. Here, we show that in AD, IL-4 and IL-13 stimulate the expression of 3β-hydroxysteroid dehydrogenase 1 (HSD3B1), a key rate-limiting enzyme in sex steroid hormone synthesis, predominantly expressed by sebaceous glands in human skin. HSD3B1 enhances androgen production in sebocytes, and IL-4 and IL-13 drive lipid abnormalities in human sebocytes and keratinocytes through HSD3B1. Consistent with our findings in cells, HSD3B1 expression is elevated in the skin of AD patients and can be restored by treatment with the IL-4Rα monoclonal antibody, Dupilumab. Androgens are also elevated in a mouse model of AD, though the mechanism in mice remains unclear. Our findings illuminate a connection between type 2 immunity and sex steroid hormone synthesis in the skin and suggest that abnormalities in sex steroid hormone synthesis may underlie the disrupted skin barrier in AD. Furthermore, targeting sex steroid hormone synthesis pathways may be a therapeutic avenue to restoring normal skin barrier function in AD patients.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.

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Objectives: Patients with vocal cord paralysis can experience feeding, respiratory, and vocal problems leading to disability and decreased quality of life. Current evidence suggests waiting a period of 12 months for spontaneous recovery before permanent interventions. This study aims to determine the time to recover spontaneously and vocal cord movement in a pediatric population and create a model for evidence-based patient counseling. Study Design: Retrospective longitudinal cohort study. Methods: The report is a single institution longitudinal study on vocal cord paralysis recovery. Patients were categorized based on spontaneous recovery with vocal cord movement or no recovery. Recovery rates were determined using the Kaplan-Meier method. Results: Of 158 cases of vocal cord paralysis over a 4-year period, 36 had spontaneous recovery with symptom improvement and motion return. The average recovery was 8.8 months for those who recovered, and 78% recovered within 9 months. Two groups emerged from the data: an early recovery group with spontaneous recovery before 12 months and a late recovery group after 12 months. Children with dysphonia and paralysis due to cardiac surgery were less likely to recover, and children with aspiration were more likely to recover. Children with gastrointestinal comorbidities were less likely to recover; however, those who did recover were more likely to have recovered after 12 months. Based on our model, there is about a 3% chance of recovery between 9 and 12 months. Conclusions: Patients should be counseled about earlier interventions. Waiting the conventional 12 months for only a 3% chance of spontaneous recovery without intervention or laryngeal EMG may not be the preferred option for some patients and their families.

Objective: To characterize the supportive care (SC) needs and receipt of SC services among head and neck cancer (HNC) patients prior to oncologic treatment and to explore the influence of social determinants of health on these outcomes. Materials and Methods: Newly diagnosed HNC patients were surveyed via telephone prior to oncologic treatment between 10/2019 and 1/2021 using a prospective, cross-sectional, bi-institutional, pilot study design. The primary study outcome was unmet SC needs (Supportive Care Needs Survey-Short Form34 [SCNS-SF34]). Hospital type (university- vs county safety-net) was explored as an exposure. Descriptive statistics were performed using STATA16 (College Station, TX). Results: Among 158 potentially eligible patients, 129 were successfully contacted, 78 met the study criteria, and 50 completed the survey. The mean age was 61, 58% exhibited clinical stage III-IV disease, and 68% and 32% were treated at the university and county safety-net hospital, respectively. Patients were surveyed a median of 20 days after their first oncology visit and 17 days prior to initiation of oncology treatment. They had a median of 24 total needs (11 were met and 13 were unmet) and preferred to see a median of 4 SC services but received care from none. County safety-net patients had comparatively more unmet needs than university patients (14.5 vs 11.5, P = .04). Conclusion: Pretreatment HNC patients at a bi-institutional academic medical center report a high number of unmet SC needs with corollary poor receipt of available SC services. Novel interventions to address this significant gap in care are needed.