Recent advances in treatments for congenital adrenal hyperplasia
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Accuracy of semi-quantitative gold nanoparticle-based quick cortisol assay with and without adrenocorticotropic hormone infusion during adrenal vein sampling
Adrenal vein sampling (AVS) is the gold standard for diagnosing unilateral primary aldosteronism. Point-of-care rapid cortisol assays such as the gold nanoparticle based quick cortisol assay (QCA) are used to confirm accurate cannulation of the adrenal veins during the procedure and have improved AVS success rates. In this retrospective cohort study, we reviewed the results of consecutive AVS procedures (n = 37) performed with and without ACTH (synacthen) infusion between October 2020 and December 2022 at our institution. We compared (1) the accuracy of point-of-care QCA at semi-quantitatively assessing successful adrenal vein cannulation before and after ACTH infusion when compared with selectivity index based on laboratory cortisol measurements, (2) accuracy of QCA based on peripheral and adrenal vein cortisol levels and (3) the impact of time of day on the accuracy of QCA. We found the accuracy of QCA compared with formal laboratory cortisol measurements was 71% pre-ACTH and 100% post-ACTH (p-value < 0.001). Pre-ACTH, the accuracy of QCA was higher in the lowest (28–257 nmol/L) and highest (466–25130 nmol/L) adrenal vein cortisol tertiles compared to the mid-tertile. Post-ACTH, the accuracy of QCA remained high regardless of adrenal vein cortisol levels. Time of day did not affect the accuracy of the QCA. We conclude that during basal AVS subjective, visual estimates of adrenal vein cortisol levels using the QCA semi-quantitively should not be solely relied upon to guide catheter placement. These results will help guide clinicians in the appropriate clinical situations in which QCA should be used during AVS.
Speculating suitability of partial adrenalectomy for lateralized primary aldosteronism: With emphasis on partial and complete success as optimistic outcomes
Primary aldosteronism (PA) is the most common secondary hypertension. The best treatment for a lateralized PA is unilateral adrenalectomy. Recent studies explored partial adrenalectomy (pAdx) to reduce the risk of adrenal insufficiency. However, in cases involving multiple aldosterone-producing micronodules/nodules (mAPM/mAPN), pAdx cannot completely remove all origins of excess aldosterone and might not resolve hypertension. CYP11B2 immunohistochemical staining helps HISTALDO (Histopathology of PA) diagnosis, and adrenal specimens were categorized into various groups accordingly. To determine whether pAdx should be considered for lateralized PA, we focused on the success rate of classical (black + grey group) versus non-classical (white group) lateralized PA, and the percentage of co-existing mAPM/mAPN in lateralized PA. The visible tumor in imaging could be either non-functional (incidentaloma; white group), or with concurrent surrounding mAPM/mAPN (grey group) causing hypertension. Among 445 patients who underwent unilateral adrenalectomy, 390 were diagnosed with lateralized PA. There were 63 (30.73%) in the black, 79 (38.54%) in the grey, 63 (30.73%) in the white group. The overall complete clinical success rate was 51.28% in our lateralized PA patients; with 65.08% in the black, 50.63% in the grey, and 26.98% in the white group. The overall partial clinical success rate was 38.54%; with 28.57% in the black, 34.18% in the grey, and 53.97% in the white group. Were pAdx performed, significantly lower success rates would be achieved, especially for lateralized PA patients of the grey and white groups. We speculate that unilateral pAdx is not an appropriate option for the majority of lateralized PA patients.
Esophageal ILC2s mediate abnormal epithelial remodeling in eosinophilic esophagitis via Areg-EGFR signaling
Eosinophilic esophagitis (EoE) is a chronic allergic disorder characterized by eosinophilia and epithelial thickening, resulting in dysphagia. While emerging evidence implicates increased frequencies of group 2 innate lymphoid cells (ILC2s) and increased interleukin (IL)-33 expression in EoE pathogenesis, the precise mechanisms remain unclear. In this study, we investigated the role of ILC2s in EoE pathogenesis. We observed an abundance of KLRG1+ ILC2s in the esophagi of healthy mice, with their numbers significantly increasing in murine EoE models and humans. Using a murine EoE model, we demonstrated the recapitulation of EoE-associated features, including basal-cell hyperproliferation, epithelial thickening, and eosinophilia. Notably, these characteristics are absent in ILC-deficient mice, whereas mice lacking IL-5 or eosinophils display epithelial defects, highlighting the pivotal role of ILC2s in EoE pathogenesis. Further investigations revealed increased amphiregulin (Areg) production by esophageal ILC2s in mice. The administration of Areg induced epithelial defects similar to those observed in EoE. Mechanistic studies using human esophageal cell lines revealed Areg-induced phosphorylation of epidermal growth factor receptor (EGFR). Significatntly, treatment with anti-Areg agents and EGFR inhibitors effectively attenuated EoE development, highlighting the therapeutic potential of targeting the Areg-EGFR axis.
General movement assessments in neonates born with congenital gastrointestinal anomalies: a single site, retrospective study
We aimed to characterize general movements in neonates with congenital gastrointestinal anomalies and to compare them to general movements in extremely low birth weight (ELBW) infants.
Type 2 immunity in allergic diseases
Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.
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