Concurrence of a kinase‐dead BRAF and an oncogenic KRAS gain‐of‐function mutation in juvenile xanthogranuloma

alexandrossfakianakis shared this article with you from Inoreader Concurrence of a kinase‐dead BRAF and an oncogenic KRAS gain‐of‐function mutation in juvenile xanthogranuloma via Pediatric Blood & Cancer View on Web

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Rhabdomyosarcoma xenotransplants

alexandrossfakianakis shared this article with you from Inoreader Rhabdomyosarcoma xenotransplants in zebrafish embryos via Pediatric Blood & Cancer Abstract Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High-risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost-efficient estimates of antitumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish-based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water-soluble chemicals. Under optimized temperature conditions, embryonal RMS xenografts were established in zebrafish embryos at 3 h postfertilization (hpf). In proof-of-principle experiments, chemotherapy drugs with established clinical anti-RMS efficacy (vincristine, dactinomycin) and the mitogen-activated protein kinase kinase inhibitor trametinib were shown to significantly reduce the cross-sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost-effective solution for preclinical candidate drug testing. View on Web

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Identification Accuracy of Safety‐Relevant Environmental Sounds in Adult Cochlear Implant Users

alexandrossfakianakis shared this article with you from Inoreader Identification Accuracy of Safety‐Relevant Environmental Sounds in Adult Cochlear Implant Users via The Laryngoscope Twenty-one experienced cochlear implant users completed an Environmental Sound Identification (ESI) test consisting of 42 common environmental sounds, 28 of which were relevant to personal safety. Overall ESI accuracy was 57% correct for the safety-relevant sounds and 55% correct for control sounds, suggesting mediocre ESI accuracy in postlingual adult CI users. Deficits in identification of these sounds may put CI listeners at increased risk of accidents or injuries and may require a specific rehabilitation program to improve CI outcomes. Objective Examine cochlear implant (CI) users' ability to identify safety-relevant environmental sounds, imperative for safety, independence, and personal well-being. Methods Twenty-one experienced adult CI users completed an Environmental Sound Identification (ESI) test consisting of 42 common environmental sounds, 28 of which were relevant to personal safety, along with 14 control sounds. Prior to sound identification, participants were shown sound names and asked to rate the familiarity and, separately, relevance to safety of each corresponding sound on a 1–5 scale. Results Overall ESI accuracy was 57% correct for the safety-relevant sounds and 55% correct for control sounds. Participants rated safety-relevant sounds as more important to safety and more familiar than the non-safety sounds. ESI accuracy significantly correlated with familiarity ratings. Conclusion The present findings suggest mediocre ESI accuracy in postlingual adult CI users for safety-relevant and other environmental sounds. Deficits in the identification of these sounds may put CI listeners at increased risk of accidents or injuries and may require a specific rehabilitation program to improve CI outcomes. Level of Evidence 4 Laryngoscope, 2022 View on Web

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Extent of Surgery for Follicular Thyroid Carcinoma

alexandrossfakianakis shared this article with you from Inoreader Extent of Surgery for Follicular Thyroid Carcinoma via The Laryngoscope Our study informs physicians and patients on the survival outcomes of undergoing operation for follicular thyroid cancer particularly when using clinical T staging as a stratification method. Similar survival between thyroidectomy versus lobectomy emphasizes that decisions on extent of surgery should take into careful consideration future quality of life as total thyroidectomy requires lifelong pharmacotherapy and higher risk of injury to adjacent structures whereas lobectomy poses higher risk of recurrence. Our findings suggest that demographic factors may ultimately play a bigger role in deciding extent of thyroid resection surgery given similar rates of survival. Objectives To examine the association between the extent of surgery and overall survival in follicular thyroid cancer (FTC) patients. Study Design Retrospective analysis of the National Cancer Database (NCDB). Methods Patients who underwent surgical intervention for FTC from 2004 to 2015 were selected. Patients were >18 years old, with tumor size 1–4 cm, no other malignancies, and >0 follow up time. Patients were divided into two cohorts based on extent of surgery: lobectomy (≥1 lobe resected) and thyroidectomy (total or near total resection). Pearson's chi-squared analysis was used to compare cohorts. Kaplan–Meier survival and Cox hazards models were utilized to determine overall survival between two cohorts with p < 0.05 used for significance. Results A total of 6871 patients were identified with FTC, of which 1507 patients underwent lobectomy and 5364 patients underwent total thyroidectomy. There were no significant differences in patient demographics, comorbidity index, local spread, or tumor grade. Patients undergoing lobectomy had mean survival of 12.94 versus 12.71 years for those undergoing thyroidectomy. Extent of surgery was not associated with a significant difference in survival (5 years OS = 96% in lobectomy and 95.5% in total thyroidectomy, p = 0.08). Stratification by tumor grade resulted in no significant difference in survival between lobectomy and thyroidectomy. Conclusion Survival time was not significantly different in patients with more extensive resection of FTC. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Acute In Vitro and In Vivo Effects of Dexamethasone in the Vocal Folds: a Pilot Study

alexandrossfakianakis shared this article with you from Inoreader Acute In Vitro and In Vivo Effects of Dexamethasone in the Vocal Folds: a Pilot Study via The Laryngoscope Atrophy has been reported following dexamethasone injection into the vocal folds. Dexamethasone increased MuRF-1 gene expression in TA myoblasts. A single injection of dexamethasone, however, did not alter atrogene expression, TA morphology, or epithelial thickness in vivo. Objectives/Hypothesis Glucocorticoids (GC)s are commonly employed to treat vocal fold (VF) pathologies. However, VF atrophy has been associated with intracordal GC injections. Dexamethasone-induced skeletal muscle atrophy is well-documented in other tissues and believed to be mediated by increased muscle proteolysis via upregulation of Muscle Ring Finger (MuRF)-1 and Atrogin-1. Mechanisms of dexamethasone-mediated VF atrophy have not been described. This pilot study employed in vitro and in vivo models to investigate the effects of dexamethasone on VF epithelium, thyroarytenoid (TA) muscle, and TA-derived myoblasts. We hypothesized that dexamethasone will increase atrophy-associated gene expression in TA muscle and myoblasts and decrease TA muscle fiber size and epithelial thickness. Study Design In vitro, pre-clinical. Methods TA myoblasts were isolated from a female Sprague–Dawley rat and treated with 1 μM dexamethasone for 24-h. In vivo, 15 New Zealand white rabbits were randomly assigned to three treatment groups: (1) bilateral intracordal injection of 40 μL dexamethasone (10 mg/ml; n = 5), (2) volume-matched saline (n = 5), and (3) untreated controls (n = 5). Larynges were harvested 7-days post-injection. Across in vivo and in vitro experimentation, MuRF-1 and Atrogin-1 mRNA expression were measured via RT-qPCR. TA muscle fiber cross-sectional area (CSA) and epithelial thickness were also quantified in vivo. Results Dexamethasone increased MuRF-1 gene expression in TA myoblasts. Dexamethasone injection, however, did not alter atrophy-associated gene expression, TA CSA, or epithelial thickness in vivo. Conclusion Dexamethasone increased atrogene expression in TA myoblasts, providing foundational insight into GC induced atrophic gene transcription. Repeated dexamethasone injections may be required to elicit atrophy in vivo. Level of Evidence N/A Laryngoscope, 2022 View on Web

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Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism

alexandrossfakianakis shared this article with you from Inoreader Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism via Journal of Medical Virology ABSTRACT Cancer patients who receive radiotherapy have a high risk of SARS-CoV-2 infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-β-cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19. This article is protected by copyright. All rights reserved. View on Web

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Monkeypox: Early Estimation of Basic Reproduction Number R0 in Europe

alexandrossfakianakis shared this article with you from Inoreader Monkeypox: Early Estimation of Basic Reproduction Number R0 in Europe via Journal of Medical Virology Abstract This world outbreak of Monkeypox-MPX infections outside Africa emerged on May 2022 in Europe and spread worldwide with unique characteristics: inter-human contagion and infection in men without specific previous immunization, prevalently men-having-sex-with-men MSM. Phylogenetic analysis confirmed a unique clade, the West African clade, subclade IIb. On August 30, WHO stated 48,895 laboratory confirmed cases from 101 different countries, of which 28,050 were in Europe. It has therefore become important to define new epidemiological indices. Starting from our new surveillance system EpiMPX open data, we defined an early R0 measure, using European ECDC confirmed cases from the epidemic start to the end of August 2022; our early R0 pooled median is 2.44, with high variability between countries. We observed the higher R0 in Portugal and Germany, followed by Italy, Spain and France. Anyway, these high estimates refer to the MSM gr oup rather than to the general population. Early estimation of R0 can be used to support the epidemiological understanding of transmission dynamics and contain MPX from spreading in naive populations and core groups with risk factors. MPX is in an evolving situation with much to learn and to do to combat the current epidemic outbreak. This article is protected by copyright. All rights reserved. View on Web

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Spatial‐temporal dynamics and time series prediction of HFRS in mainland China: a long‐term retrospective study

alexandrossfakianakis shared this article with you from Inoreader Spatial‐temporal dynamics and time series prediction of HFRS in mainland China: a long‐term retrospective study via Journal of Medical Virology Abstract Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China. The current study aims to characterize the spatial-temporal dynamics of HFRS in mainland China during a long-term period (1950-2018). A total of 1,665,431 cases of HFRS were reported with an average annual incidence of 54.22 cases/100,000 individuals during 1950-2018. The joint regression model was used to define the global trend of the HFRS cases with an increasing-decreasing-slightly increasing-decreasing-slightly increasing trend during the 68 years. Then spatial correlation analysis and wavelet cluster analysis were used to identify four types of clusters of HFRS cases located in central and northeastern China. Lastly, the Prophet model predicts that 14,223 cases of HFRS will occur in mainland China during 2019-2038. Our findings will help reduce the knowledge gap on the transmission dynamics and distribution patterns of the HFRS in mainland China and facilitate to take rel evant preventive and control measures for the high-risk epidemic area. This article is protected by copyright. All rights reserved. View on Web

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Immunological mechanisms and treatable traits of chronic rhinosinusitis

alexandrossfakianakis shared this article with you from Inoreader Immunological mechanisms and treatable traits of chronic rhinosinusitis in Asia– a Narrative Review via Clinical Otolaryngology Abstract Objectives To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia. Design This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype, and treatment. Results and Conclusion CRS is a heterogeneous disease characterized by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non-eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonization than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment, and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the managemen t of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics. This article is protected by copyright. All rights reserved. View on Web

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Comparison of clinical features and surgical outcomes between hypopnea‐ and apnea‐predominant obstructive sleep apnea

alexandrossfakianakis shared this article with you from Inoreader Comparison of clinical features and surgical outcomes between hypopnea‐ and apnea‐predominant obstructive sleep apnea via Clinical Otolaryngology Abstract Objectives This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA). Design Cohort study Setting Single tertiary care center Participants This study included 190 patients with OSA who underwent multilevel upper airway surgery between September 2012 and September 2021. The patients were divided into two groups according to the proportion of each respiratory event: hypopnea-predominant (n = 102) and apnea-predominant (n = 88). Main outcome measures The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery. Results The apnea-predominant group included more male patients and had higher AHI, respiratory disturbance index (RDI), and oxygen desaturation index (ODI) than the hypopnea-predominant group. Both groups showed significant improvements in AHI, apnea index, RDI, supine AHI, REM AHI, non-REM AHI, ODI, lowest O2 saturation, and Epworth Sleepiness Scale scores following the surgery. Notably, hypopnea index increased after surgery in the apnea-predominant OSA group. Although the improvement in the absolute value of AHI by surgery was significantly greater in the apnea-predominant group than in the hypopnea-predominant group, the two groups showed no significant difference in the percentage improvement in AHI from baseline AHI. Conclusion Patients with apnea-predominant OSA had more severe disease than those with hypopnea-predominant OSA; however, surgical outcomes, as evaluated by percentage AHI improvement, were comparable between the two groups. In addition, multilevel upper airway surgery may induce the transition from apnea to hypopnea in patients with apnea-predominant OSA. View on Web

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