Τετάρτη 2 Νοεμβρίου 2022

Desmoid tumor occurrence in a patient with severe congenital neutropenia type 4: Case history and follow‐up

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

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

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

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

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Monkeypox: Early Estimation of Basic Reproduction Number R0 in Europe

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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.

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

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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.

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Immunological mechanisms and treatable traits of chronic rhinosinusitis

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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.

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Wound healing in endoscopic sinus surgery ‐ Phase 1 clinical trial evaluating the role of Chitogel with adjuvants

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Abstract

Background & Objectives

Ostial stenosis and persistent inflammation are the main reasons for revision endoscopic sinus surgery (ESS). Post-operative (PO) dressings can improve PO wound healing and patient outcomes after ESS. This study aimed to determine the safety and efficacy of Chitogel, with and without Deferiprone (Def) and Gallium Protoporphyrin (GaPP), as a promoter of wound healing to improve surgical outcomes.

Design, Setting & Outcome

A double-blinded, randomized control human clinical trial was conducted in patients undergoing ESS as treatment for CRS. Participants underwent functional endoscopic sinus surgery (1) or FESS with drill out (DO) as required and were randomised to receive test product Chitogel, Chitogel in combination with Def or Def-GaPP versus no packing (control). Patients were followed up at 2, 6 and 12 weeks PO, outcome scores such as SNOT-22, VAS and LKS, pre and post-surgery (12 weeks) were compared.

Results

79 patients completed the study, there was a significant reduction in SNOT-22 score and improvement of VAS at 12-week in patients treated with Chitogel compared to control (p<0.05). In those patients, the mean ostium area for the Chitogel and the Chitogel + Def + GaPP groups were higher across all 3 sinuses compared to the no-treatment control group, without statistical significance. Sphenoid sinus ostium was significantly more patent in patients treated with Chitogel compared to control at the 12-week time point (p < 0.05).

Conclusion

Chitogel as a post-operative dressing after ESS results in the best patient reported symptom scores and objective measurements. The combination of Def and GaPP to Chitogel though proving safe, had no effect on the ostium patency or mucosal healing.

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