Τετάρτη 2 Νοεμβρίου 2022

Xanthomatous erosive arthritis: A new disease entity?

alexandrossfakianakis shared this article with you from Inoreader
View on Web

Rhabdomyosarcoma xenotransplants

alexandrossfakianakis shared this article with you from Inoreader

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

Extent of Surgery for Follicular Thyroid Carcinoma

alexandrossfakianakis shared this article with you from Inoreader
Extent of Surgery for Follicular Thyroid Carcinoma

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

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

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

Monkeypox: Early Estimation of Basic Reproduction Number R0 in Europe

alexandrossfakianakis shared this article with you from Inoreader

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

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

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

Immunological mechanisms and treatable traits of chronic rhinosinusitis

alexandrossfakianakis shared this article with you from Inoreader

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

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

alexandrossfakianakis shared this article with you from Inoreader

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.

View on Web

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

alexandrossfakianakis shared this article with you from Inoreader

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

¿Qué es la Hashitoxicosis?

alexandrossfakianakis shared this article with you from Inoreader

La tiroiditis de Hashimoto es la patología tiroidea más frecuente. Se presenta mucho más frecuentemente en mujeres y puede aparecer a cualquier edad. Es una inflamación crónica autoinmune, generalmente indolora, caracterizada por una infiltración linfocitaria de la glándula tiroidea, parcial o total. La función tiroidea puede no verse alterada o puede producirse una disminución de la misma (hipofunción tiroidea), y se caracteriza por la presencia de anticuerpos antiperoxidasa (anti-TPO) y/o anti-tiroglobulina (anti-Tg). En este tipo de tiroiditis se puede desarrollar un hipotiroidismo de forma lenta y generalmente progresiva.

Excepcionalmente algunos pacientes desarrollan una presentación clínica y bioquímica de hiperfunción tiroidea, desarrollando hipertiroidismo, cuadro conocido como "Hashitoxicosis". Se puede definir como una enfermedad mixta, caracterizada por tirotoxicosis, gran aumento sérico de anticuerpos antitiroideos y presencia de hiperplasia-hipertrofia (aumento de volumen) folicular e infiltración linfocítica.

¿Por qué algunas personas con tiroiditis de Hashimoto tienen Hashitoxicosis?

En pacientes con diagnóstico de tiroiditis de Hashimoto, la incidencia es escasa (5-10%), si bien es cierto que la alteración bioquímica no viene acompañada claramente de una clínica de hiperfunción tiroidea y la clínica puede pasar desapercibida.

La Hashitoxicosis es un cuadro de hipertiroidismo que se presenta generalmente en pacientes con o sin diagnóstico previo de tiroiditis de Hashimoto, que confunde muchas veces el diagnóstico por su similitud con un brote de Enfermedad de Graves – Basedow. De hecho, las características clínicas de hiperfunción tiroidea no varían. El tamaño del bocio suele ser evidente y con más dureza a la palpación, y a nivel bioquímico no difiere en cuanto al nivel de anticuerpos antitiroideos, pero se diferencia de la enfermedad de Graves en que las personas no tendrán niveles elevados de anticuerpos antirreceptor de TSH (TSI).

¿Cuál es la causa del hipertiroidismo derivado de la Hashitoxicosis en la tiroiditis de Hashimoto?

En este caso el hipertiroidismo no es causado por el estímulo de TSH sobre la liberación de hormonas tiroideas como ocurre con la enfermedad de Graves, sino que es producido por la liberación de las hormonas tiroideas contenidas en los folículos que se han destruido. De ahí que el cuadro generalmente sea de corta duración y muchas veces autolimitado.

Muchas veces el diagnóstico de la Hashitoxicosis es tardío y sobre todo debido a una hiperrespuesta al tratamiento con medicamentos antitiroideos en un paciente inicialmente diagnosticado de enfermedad de Graves, por eso es importante hacer una buena valoración clínica inicial que incluya determinación de anticuerpos antirreceptor de TSH (TSI).

¿Hay que tratar la Hashitoxicosis?

El tratamiento con fármacos antitiroideos es pocas veces necesario, porque el cuadro suele ser transitorio y se indica porque la clínica lo aconseja. Debe valorarse al paciente a corto plazo por el riesgo de hipotiroidismo yatrógeno (hipotiroidismo inducido por medicación). Lo más aconsejable es mantener al paciente con un betabloqueante. Durante la fase aguda de la tirotoxicosis, los betabloqueantes pueden ser útiles.

La Hashitoxicosis generalmente precede a un cuadro de hipofunción tiroidea que requerirá tratamiento sustitutivo permanente con hormonas tiroideas.


Si te ha gustado este artículo, quizá te interese leer:

La entrada ¿Qué es la Hashitoxicosis? se publicó primero en Cuida tu tiroides.

View on Web