Τετάρτη 9 Ιουνίου 2021

Choosing the Right Patient for Biologic Therapy in Chronic Rhinosinusitis with Nasal Polyposis

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There are many phenotypes of chronic sinusitis and clinical variables that differ between patients. The ability to accurately diagnose, predict prognosis, and select the appropriate treatment depends on the understanding of disease endotypes. Chronic sinusitis is in the early stages of disease endotyping. The ability to identify endotypes is at the forefront of clinical research. Endotyping of chronic sinusitis uses clinical information, radiographic studies, and pathophysiologic data. Understanding of the full spectrum of chronic sinusitis is in its infancy. A personalized approach to treatment will consider standard medical therapies, sinus surgeries, and targeted use of biologic agents.
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Immunotherapeutic Strategies for Head and Neck Cancer

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Immunotherapy has revolutionized the treatment of cancer, including head and neck squamous cell carcinoma (HNSCC). Most immune therapies consist of biologics, including monoclonal antibodies, vaccines, and cell therapy. This article reviews basic tumor immunology and provides an overview of immunotherapeutic strategies used for HNSCC. The current indications for use of programmed cell death protein 1 immune checkpoint inhibitors in recurrent/metastatic HNSCC are summarized. In addition, new immunotherapeutic biologics and combinations under investigation in early-phase clinical trials are highlighted.
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Advances in Adoptive Cell Therapy for Head and Neck Cancer

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This article reviews the most recent literature describing clinical advances in adoptive cell therapy for patients with head and neck cancer. Clinical trials with tumor-infiltrating lymphocyte and gene-engineered T-cell receptor T-cell therapy are highlighted.
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Knowledge Gaps and Research Needs for Biologic Therapy in Rhinology Practice

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Biologic agents are emerging for chronic rhinosinusitis with nasal polyposis (CRSwNP) patients with recalcitrant disease. Although early work has shown promise, and several trials are ongoing, there is significant work to be done in this field. CRS patients form a heterogeneous group, and identification of appropriate patients for the use of biologic agents is critical. The determination of endotype-specific biomarkers will help define patient selection and predict treatment response. As more biologic agents become approved, head-to-head trials will be needed to compare them with similar products. Ultimately, cost-effectiveness analyses and further quality of life studies will guide treatment recommendations.
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Differences and Reliability of Linear and Nonlinear Acoustic Measures as a Function of Vocal Intensity in Individuals With Voice Disorders

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Linear acoustic indices are significantly influenced by speaking voice intensity. The main aim of this work was to compare acoustic measures based on linear and nonlinear models in different speaking voice intensity levels and to analyze the reliability of those measures in different intensity levels in subjects with voice disorders.
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Detecting epidemiological relevance of adenoid hypertrophy, rhinosinusitis, and allergic rhinitis through an Internet search

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Eur Arch Otorhinolaryngol. 2021 Jun 9. doi: 10.1007/s00405-021-06885-4. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to detect the epidemiological relevance between adenoid hypertrophy (AH) and rhinosinusitis, and AH and allergic rhinitis (AR) through an Internet search.

METHODS: Internet search query data from January 2011 to December 2019 in China were retrieved from the Baidu Index (BI). Spearman's correlation coefficients were used to detect the correlation among the search volumes of AH, rhinosinusitis, and AR. We also collected search data from the first 5 months of 2020, when quarantine was implemented in China due to the coronavirus disease 2019 epidemic. Then, we compared the search data to those obtained during the same period in 2019 to assess the effects of isolation on AH and AR.

RESULTS: Statistically significant relevance was found between the search variations of AH and rhinosinusitis during 201 1-2019 (R = 0.643, P < 0.05). However, the relationship between AH and AR was weak (R = - 0.239, P < 0.05) and that between rhinosinusitis and AR (R = - 0.022, P > 0.05) was not relevant. The average monthly search volume of AH and rhinosinusitis had a strong correlation (R = 0.846, P < 0.01), but AH and AR and rhinosinusitis and AR were not correlated (R = - 0.350, P > 0.05; R = - 0.042, P > 0.05, respectively). AH and rhinosinusitis search volumes decreased consistently during the first 5 months of 2020 (isolation), whereas that for AR increased during January-February.

CONCLUSION: AH had an epidemiological relationship with rhinosinusitis, which was not consistent with AR. The decrease in public gathering effectively reduced the morbidities of AH and rhinosinusitis but not those of AR.

PMID:34104981 | DOI:10.1007/s00405-021-06885-4

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Therapeutic applications of radioactive sources: from image-guided brachytherapy to radio-guided surgical resection

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Q J Nucl Med Mol Imaging. 2021 Jun 9. doi: 10.23736/S1824-4785.21.03370-7. Online ahead of print.

ABSTRACT

It is well known nowadays that radioactivity can destroy the living cells it interacts with. It is therefore unsurprising that radioactive sources, such as iodine-125, were historically developed for treatment purposes within radiation oncology with the goal of damaging malignant cells. However, since then, new techniques have been invented that make creative use of the same r adioactivity properties of these sources for medical applications. Here, we review two distinct kinds of therapeutic uses of radioactive sources with applications to prostate, cervical, and breast cancer: brachytherapy and radioactive seed localization. In brachytherapy (BT), the radioactive sources are used for internal radiation treatment. Current approaches make use of real-time image guidance, for instance by means of magnetic resonance imaging, ultrasound, computed tomography, and sometimes positron emission tomography, depending on clinical availability and cancer type. Such image-guided BT for prostate and cervical cancer presents a promising alternative and/or addition to external beam radiation treatments or surgical resections. Radioactive sources can also be used for radio-guided tumor localization during surgery, for which the example of iodine-125 seed use in breast cancer is given. Radioactive seed localization (RSL) is increasingly popular as an alternative tumor loca lization technique during breast cancer surgery. Advantages of applying RSL include added flexibility in the clinical scheduling logistics, an increase in tumor localization accuracy, and higher patient satisfaction; safety measures do however have to be employed. We exemplify the implementation of RSL in a clinic through experiences at the Netherlands Cancer Institute.

PMID:34105339 | DOI:10.23736/S1824-4785.21.03370-7

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The aryl hydrocarbon receptor at the forefront of host‐microbe interactions in the skin: a perspective on current knowledge gaps and directions for future research and therapeutic applications

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Abstract

The skin is home to a community of skin microbiota including bacteria, viruses and fungi, which are widely accepted to be of importance for skin homeostasis but also associated to skin diseases. Detailed knowledge on the skin microbiota composition and its changes in a number of skin diseases is available. Yet, specific interactions between microbes and the host skin cells or how they communicate with each other are less well understood. To identify, understand and eventually therapeutically exploit causal relationships of microbial dysbiosis with disease, studies are required that address the receptors and mediators involved in host-microbe interactions. In this perspective article, we provide an outlook on one of such receptors, namely the aryl hydrocarbon receptor (AHR). The AHR is well known for being a ligand-activated transcription factor regulating the proliferation, differentiation and function of many cell types present in the skin. Its targeting by anti-inflammatory ther apeutics such as coal tar and Tapinarof is effective in atopic dermatitis and psoriasis. AHR signaling is activated upon binding of wide variety of small chemicals, or ligands, including microbiota-derived metabolites. New evidence has emerged pointing towards a key role for epidermal AHR signaling through skin microbiota derived metabolites. In response, AHR-driven expression of antimicrobial peptides and stratum corneum formation may alter the skin microbiota composition. This a self-perpetuating feedback loop calls for novel therapeutic intervention strategies for which we herein discuss the requirements in future mechanistic studies.

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Perceptual Evaluation of Vocal Fold Vibratory Asymmetry

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Objectives

Laryngeal vibratory asymmetry occurring with paresis may result in a perceptually normal or abnormal voice. The present study aims to determine the relationships between the degree of vibratory asymmetry, acoustic measures, and perception of sound stimuli.

Study Design

Animal Model of Voice Production, Perceptual Analysis of Voice.

Methods

In an in vivo canine model of phonation, symmetric and asymmetric laryngeal vibration were obtained via graded unilateral recurrent laryngeal nerve (RLN) stimulation simulating near paralysis to full activation. Phonation was performed at various contralateral RLN and bilateral superior laryngeal nerve stimulation levels. Naïve listeners rated the perceptual quality of 182 unique phonatory samples using a visual sort-and-rate task. Cepstral peak prominence (CPP) was calculated for each phonatory condition. The relationships among vibratory symmetry, CPP, and perceptual ratings were evaluated.

Results

A significant relationship emerged between RLN stimulation and perceptual rating, such that sound samples from low RLN levels were preferred to those from high RLN levels. When symmetric vibration was achieved at mid-RLN stimulation, listeners preferred samples from symmetric vibration over those from asymmetric vibration. However, when symmetry was achieved at high RLN levels, a strained voice quality resulted that listeners dispreferred over asymmetric conditions at lower RLN levels. CPP did not have a linear relationship with perceptual ratings.

Conclusions

Laryngeal vibratory asymmetry produces variable perceptual differences in phonatory sound quality. Though CPP has been correlated with dysphonia in previous research, its complex relationship with quality limits its usefulness as clinical marker of voice quality perception.

Level of Evidence

NA, basic science Laryngoscope, 2021

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Underrepresented Women Leaders: Lasting Impact of Gender Homophily in Surgical Faculty Networks

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Objective

Despite the increase of women in surgical fields and resources toward advancing women, there is no corresponding increased representation of women in higher academic ranks and leadership. The following hypotheses are explored: 1) men and women build/maintain different relationship networks and 2) women are not similarly included within the organization and do not receive the same sponsorship as male counterparts.

Study Design

Prospective observational study.

Methods

Three months of prospective, passive organizational network data of full-time faculty at an academic medical center were collected by analysis of deidentified internal email communication logs. Data were analyzed and strength of network relationships was assessed using algorithms measuring the tie, or connection, score. Data analysis was performed with standard statistical methods and multivariable regression models, comparing network relationships based on gender and academic rank.

Results

Among 345 full-time faculties from surgical departments, 45.2% were female Assistant Professors, but only 9.8% were female full Professors. Men had 55% more network relationships with other men than women had with men. Gender homophily was particularly pronounced at the higher academic ranks. Men compared to women in higher ranks had 157% more network relationships to other men in lower ranks. Multivariable regression models suggested direct association of these gender differences in relationships with more women in lower academic ranks.

Conclusion

Higher academic rank can be predicted by male gender, tenure, and number of meaningful relationships. Women are underrepresented at the leadership level in surgical departments. Gender homophily is present in collaboration networks among academic surgeons and is associated with impeded female career advancement.

Level of Evidence

2 Laryngoscope, 2021

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The Nasoseptal Flap for Reconstruction of Lateral Oropharyngectomy Defects: A Clinical Series

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Objectives/Hypothesis

To study use of the nasoseptal flap (NSF) to reconstruct lateral transoral robotic surgery (TORS) oropharyngectomy defects.

Study Design

Retrospective case series.

Methods

A clinical series of six patients undergoing NSF reconstruction of lateral TORS oropharyngectomy defects was retrospectively studied. All patients underwent TORS for the treatment of intermediate-risk human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma of the lateral pharyngeal wall between January and June 2017. All patients underwent NSF reconstruction of lateral TORS defects with retrospective analysis of outcomes and complications.

Results

Six patients underwent NSF reconstruction of lateral TORS defects. Operative times decreased from 180 minutes to 90 minutes over the study period. There were two cases of partial flap dehiscence and partial necrosis. There were no major donor site complications. All patients had temporary nasal obstruction and crusting. Two experienced temporary aural fullness. In all patients, the lateral wall was mucosalized in 1–3 weeks. Cephalometric analysis of preoperative imaging revealed that patients with high-arched palates (>3 cm) and defect lengths that are longer than NSF flap lengths are poor candidates for this technique.

Conclusions

This NSF is a vascularized, locoregional rotational flap that can reconstruct lateral TORS defects in salvages cases or those where the parapharyngeal carotid or mandibular bone are exposed. Postoperative morbidity is limited to temporary nasal dyspnea, aural fullness, and crusting. Preoperative imaging can determine which patient will have successful defect coverage.

Level of Evidence

4 Laryngoscope, 2021

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Topographic anatomical localization of the motor nerve entry points (MEPs) of the masseter muscle

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Surg Radiol Anat. 2021 Jun 9. doi: 10.1007/s00276-021-02780-z. Online ahead of print.

ABSTRACT

PURPOSE: The masseteric nerve, which is a branch of the mandibular nerve, passes lateral to the mandibular notch and then spreads in the muscle to achieve motor innervation. The muscle entry points of these motor branches are the target points of minimally invasive interventions preferred in the treatment of masseter hypertrophy. The aim of this study was to reveal the areas where the motor entry points are concentrated in the muscle by dividing the muscle into topographic regions using reliable anatomic landmarks.

METHODS: Bilateral 20 masseter muscles (40 in total) belonging to 20 formalin-fixed cadavers (10 female and 10 male) were examined. The distribution of the nerve in the muscle and its motor entry points were demonstrated and marked on the muscle surface. The masseter muscle was divided into six areas by lines passing through reliable anatomical landmarks (Areas 1-6).

RESULTS: The total number of MEPs was 231.The mean distance of the MEPs from the Line-1 was 27.4 ± 11 mm, and the same distance from the Line-6 was 30.32 ± 7.2 mm. Most of the MEPs (123/231) were located in Area-4. Area-6 was the second (82/231) and Area-5 (19/231) was the third.

CONCLUSION: We suggest that interventions in Area-4 (especially in the middle part) may have less complications as a result of less relationship with surrounding anatomical structures and m ore effective with high MEP number.

PMID:34106326 | DOI:10.1007/s00276-021-02780-z

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