Πέμπτη 11 Φεβρουαρίου 2021

Transient Delivery of a KCNQ2/3-Specific Channel Activator 1 Week After Noise Trauma Mitigates Noise-Induced Tinnitus

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Abstract

Exposure to loud noise can cause hearing loss and tinnitus in mice and humans. In mice, one major underlying mechanism of noise-induced tinnitus is hyperactivity of auditory brainstem neurons, due at least in part, to decreased Kv7.2/3 (KCNQ2/3) potassium channel activity. In our previous studies, we used a reflex-based mouse model of tinnitus and showed that administration of a non-specific KCNQ channel activator, immediately after noise trauma, prevented the development of noise-induced tinnitus, assessed 1 week after trauma. Subsequently, we developed RL-81, a very potent and highly specific activator of KCNQ2/3 channels. Here, to test the timing window within which RL-81 prevents tinnitus in mice, we modified and employed an operant animal model of tinnitus, where mice are trained to move in response to sound but not move in silence. Mice with behavioral evidence of tinnitus are expected to move in silence. We validated this mouse model by testing the ef fect of salicylate, which is known to induce tinnitus. We found that transient administration of RL-81 1 week after noise exposure did not affect hearing loss but reduced significantly the percentage of mice with behavioral evidence of tinnitus, assessed 2 weeks after noise exposure. Our results indicate that RL-81 is a promising drug candidate for further development for the treatment of noise-induced tinnitus.

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The Test of Masticating and Swallowing Solids (TOMASS): Reliability, Validity and Normative Data for the Adult Indian Population

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Abstract

The Test of Masticating and Swallowing Solids (TOMASS) is a reliable and well-validated tool to assess the effectiveness of solid bolus ingestion. Previous studies have established normative values for 4 to 80+ years across a range of commercially available crackers and countries. The current study aimed to establish normative data for the TOMASS across age and gender groups for a commercially available biscuit (cracker) for the adult Indian population. A total of 300 typical individuals in the age range of 21 to 80 years grouped by age and sex participated in the study. Participants were instructed to eat a commercially (locally) available biscuit 'as quickly and comfortably as possible,' and the task was video recorded. The recorded video samples were analyzed to obtain measures of the number of bites, number of masticatory cycles, number of swallows, and total time taken to complete the ingestion of biscuit. Cronbach's α values revealed a moderat e to good (0.71 to 0.82) test–retest reliability; ICC values were suggestive of a high level (> 0.76) of interrater reliability for all the measures of TOMASS. The results of the one-way ANOVA revealed a significant main effect of age (F = 3.12, p < 0.01) and gender (F = 4.37, p < 0.01), but not an interaction between the two. Normative data stratified by age and gender were also generated. The TOMASS assessment procedure was feasible, reliable, and valid. In the current study, we observed that males took fewer bites, took less time, chewed less, and swallowed fewer times than females. A definitive age effect was observed for the number of bites, masticatory cycles, and total time. The normative data generated by the current study can serve as clinical benchmarks to assess the ingestion of solid bouls in the adult Indian population.

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Concept and Prelimnary Design of an Economical Bag Valve Mask Compressor as a Prototype for Simple Ventilator During COVID-19

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Abstract

The pandemic of COVID 19 has taken a massive toll of lives since its outbreak. Throughout the world with a large number of people being affected by covid 19, the need for the ventilators has risen. However, there is disproportionate ratio of demand versus supply of ventilators due to the menace caused by Covid 19 which has become unmanageable. This paper describes the design of the low cost portable mechanical bag valve mask compressor which could serve as a preliminary ventilator for the patients needing ventilator support in COVID 19. This prototype ventilator delivers breaths by compressing a conventional bag-valve mask (BVM) with a motor, eliminating the need for a human operator for the BVM. It is driven by a wind shield wiper electric motor powered by a 12 V battery. Additionally it can be used to deliver oxygen through either Laryngeal mask or compact face masks or nasopharyngeal airways where intubation is awaited in early breathlessness. Future additions for our prototype ventilator will include a controllable inspiration to expiration time ratio, a pressure relief valve, PEEP capabilities and an LCD screen. With a prototyping cost of only $150, the concept of BVM compressor is a low-cost, low-power portable ventilator technology that will provide essential ventilator features at a fraction of the cost of existing technology.

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The Role of Systemic Therapy in Advanced Cutaneous Squamous Cell Carcinoma

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Systemic therapy for patients with head and neck cutaneous squamous cell carcinoma (HNCSCC) generally is used for patients with advanced disease and most often employed for patients in the palliative setting when disease is unresectable and/or widely metastatic. Cytotoxic agents and epidermal growth factor receptor pathway targeted therapy have been utilized most commonly, with few clinical data to support their efficacy. Adjuvant postoperative chemoradiation with platinum has been called into question based on recent data. Programmed cell death protein 1 receptor immune checkpoint inhibitors have demonstrated profound activity in HNCSCC, and cemiplimab and pembrolizumab now are approved for use for unresectable/metastatic disease.
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Posture, Gait, Quality of Life, and Hearing with a Vestibular Implant

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Approximately 1.8 million adults worldwide have severe bilateral vestibular hypofunction that results in chronic disequilibrium, oscillopsia, postural instability, and unsteady gait owing to failure of vestibular reflexes that stabilize the eyes, head, and body. Because affected persons must devote…
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Primary Orbital Melanoma: An Investigation of a Rare Malignancy Using the National Cancer Database

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Objectives

Primary orbital melanoma (POM) is a rare disease with limited data on survival and best treatment practices. Here we utilize the National Cancer Database (NCDB) to determine the overall survival (OS) and covariates that influence mortality.

Study Design: Retrospective cohort study.

Methods

All patients diagnosed with POM from 2004 to 2016 were identified in the NCDB. Patient and oncologic data were analyzed using the Kaplan–Meier method and multivariate models for the primary outcome of OS.

Results

A total of 129 patients were identified. Median OS was 36.9 months (95% confidence interval [CI] 24.1–78.7 months) with mean 5‐year survival of 42.0% (CI 33.2%–53.2%). Treatments received included surgery alone (43.4%), radiation alone (23.3%), and surgery followed by radiation (20.2%). The multivariate model demonstrated an increased risk of death associated with age over 80 years (hazard ratio [HR] 3.41, CI 1.31–8.86, P = .012), a Charlson‐Deyo comorbidity score of 2 or greater (HR 5.30, CI 1.87–15.03, P = .002), and no treatment (HR 2.28, CI 1.03–5.06, P = .042). For every 1 cm increase in tumor size, there was an increased risk of death (HR 1.06, CI 1.00–1.13, P = .039). When compared to surgery alone, no other treatment modality had an effect on OS.

Conclusions

This study leveraged multiyear data from the NCDB to provide prognostic and demographic information on the largest known cohort of POM cases. Increased age, increased comorbidities, not receiving treatment, and larger tumor size were associated with increased mortality. There was no clear survival advantage for specific treatments.

Level of Evidence

IV Laryngoscope, 2021

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Complications of Free Flaps for Oromandibular Reconstruction

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Objectives/Hypothesis

To determine the frequency and management of short‐ and long‐term complications related to oromandibular free flap reconstruction and identify potentially predictive factors of hardware complications.

Study Design

Retrospective chart review.

Methods

A retrospective database from chart review was formed consisting of 266 oromandibular free flap reconstructions performed at a single institution over a 15‐year period. Data were collected on demographics, surgical treatment, complications, and management of complications. Subgroup univariate and multivariate analyses were performed to compare patients with hardware complications and those without.

Results

Eighty‐one of 266 patients (30.5%) that underwent oromandibular reconstruction had an early complication (<4 weeks after surgery), and the most common complications were cervical wound dehiscence (11.3%) and fistulas (9.40%). Eighty of 266 patients (30.1%) had a long‐term complication (>4 weeks after surgery) and the most common complication was plate exposure (26.7%). Univariate and multivariate analyses showed no association between whether there was hardware extrusion and fibula versus scapula, smoking history, virtual surgical planning (VSP), and dental implantation (P > .05). Only early complications (OR, 3.59, 95% CI, 1.83–7.05, P < .01) and patients undergoing oromandibular reconstruction for osteoradionecrosis (OR, 2.26, 95% CI, 1.10–4.64, P = .03) were strongly and independently associated with subsequent hardware extrusion on univariate analysis.

Conclusions

Both short‐ and long‐term complications are common after oromandibular reconstruction. The most important predictive factor for a late complication is an early complication and prior radiation. There was no difference of plate complications among the various free flap types. Dental implantation and use of VSP were not associated with hardware complications.

Level of Evidence

4 Laryngoscope, 2021

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Trends in Operative Complex Middle and Upper Maxillofacial Trauma: A 17‐Year Study

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Objectives/Hypothesis

Over 3 million incidents of facial trauma occur each year in the United States. This study aims to determine trends in operative middle and upper maxillofacial trauma in one of the largest US cities.

Study Design

Retrospective case‐control study.

Methods

Retrospective chart review of all operative middle and upper maxillofacial trauma from July 1993 to July 2010 presenting to Los Angeles County Hospital, a Level I Trauma Center. Data included demographics, mechanism of injury, and fracture characteristics.

Results

Analysis was performed for a total of 4,299 patients and 5,549 facial fractures. Mean patient age was 34.6, and most patients were male (88%). Between the two time periods (1993–2001 and 2002–2010), there was a 42% reduction in operative maxillofacial trauma (3,510 to 2,039). Orbital floor and zygomaticomaxillary complex fractures were the most prevalent types of fractures. Panfacial fractures demonstrated the largest reduction in number of fractures (325 to 5, P<0.01). Assault and motor vehicle accidents (MVA) were the two most common mechanisms of injury. Operative fractures due to MVAs decreased (390 to 214, P = .74), whereas fractures due to assault increased (749 to 800, P<0.01). Compared to adults, pediatric facial trauma (age < 18) were caused by a higher percentage of MVAs (27% vs. 13%), auto versus pedestrian (9% vs. 5%), and gunshot wounds (8% vs. 4%) (P<0.01).

Conclusions

Operative middle and upper maxillofacial trauma decreased over a 17‐year period. Assault was the most significant mechanism of trauma overall. These trends suggest that focusing future prevention strategies on curtailing interpersonal violence may more effectively address the burden of facial trauma.

Level of Evidence

3 Laryngoscope, 2021

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Extracranial/Intracranial Vascular Bypass in the Treatment of Head and Neck Cancer ‐ Related Carotid Blowout Syndrome

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Objective/Hypothesis

To investigate the endovascular intervention or extracranial/intracranial (EC/IC) vascular bypass in the management of patients with head and neck cancer‐related carotid blowout syndrome (CBS).

Study Design

Retrospective case series.

Methods

Retrospective analysis of clinical data of patients with head and neck cancer‐related CBS treated by endovascular intervention and/or EC/IC vascular bypass, analysis of its bleeding control, neurological complications, and survival results.

Results

Thrity‐seven patients were included. Twenty‐five were associated with external carotid artery (ECA); twelve were associated with internal or common carotid artery (ICA/CCA). All patients with ECA hemorrhage were treated with endovascular embolization. Of the 12 patients with ICA/CCA hemorrhage, 9 underwent EC/IC bypass, 1 underwent endovascular embolization, and 3 underwent endovascular stenting. For patients with ECA‐related CBS, the median survival was 6 months, and the 90‐day, 1‐year, and 2‐year survival rates were 67.1%, 44.7%, and 33.6%, respectively; the estimated rebleeding risk at 1‐month, 6‐month, and 2‐year was 7.1%, 20.0%, and 31.6%, respectively. For patients with ICA/CCA‐related CBS, the median survival was 22.5 months, and the 90‐day, 1‐year, and 2‐year survival rates were 92.3%, 71.8%, and 41.0%, respectively; the estimated rebleeding risk at 1 month, 6 months, and 2 years is 7.7%,15.4%, and 15.4%, respectively. ICA/CCA‐related CBS patients have significantly longer survival time and lower risk of rebleeding, which may be related to the more use of EC/IC vascular bypass as a definite treatment.

Conclusions

For patients with ICA/CCA‐related CBS, if there is more stable hemodynamics, longer expected survival, EC/IC vascular bypass is preferred.

Level of Evidence

4 Laryngoscope, 2021

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Sirolimus Therapy for Intractable Lymphatic Malformations

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Objective/Hypothesis

To evaluate the efficacy of initial sirolimus therapy in the treatment of intractable head and neck lymphatic malformations (LMs) in children.

Study Design

Prospective open‐label study.

Methods

In this study, Twenty‐seven children diagnosed with LMs were given oral sirolimus as primary treatment over a minimum 6‐month trial. The major parameter to evaluate therapeutic outcome was percentage of lesion volume change compared with baseline. Average serum sirolimus concentrations, and adverse side effects, were monitored throughout the study period.

Results

Fifteen girls and twelve boys, average age 27 months (16 days–171 months), constitute the study group. Treatment was deemed effective for twenty‐three participants, judged as fair in seven, good in nine, and excellent in seven. Two patients had minimal improvement, and two had increased volume to some degree. Effectiveness differed among LMs subtypes with responsiveness of macrocystic LMs exceeding that of microcystic LMs (P < .05). Adverse drug reactions totaled 27 events in ten patients, the majority being mild with upper respiratory infections being most common.

Conclusions

Sirolimus as initial therapy is effective in decreasing lesion volume in intractable LMs in head and neck region, especially in macrocystic subtypes. Although most cases cannot be completely cured, side effects are few and tolerable.

Level of Evidence

IV Laryngoscope, 2021

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Simultane Implantation von Epithesenankern und Bonebridge zur Versorgung großer Ohrmissbildungen

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Laryngorhinootologie
DOI: 10.1055/a-1369-9530

Hintergrund Die chirurgische Versorgung mit einem Hörimplantat und Epithesen bei Ohrmissbildungen bietet eine gute Kombination aus Hörrehabilitation und kosmetischer Rekonstruktion. Oft wird die Versorgung in 2-zeitigen Operationsschritten durchgeführt. Ziel der Arbeit war es, Erfahrungswerte mit einem Vorgehen zu gewinnen, bei dem das Hörimplantat und die Epithesenanker simultan eingesetzt werden. Material und Methoden Vier Ohren von 3 Patienten (nw = 1, nm = 2) mit großen Ohrmissbildungen (Typ III nach Weerda) erhielten jeweils in einer Operation eine MedEL Bonebridge und einen Epithesenanker mit 3 Basispfosten. Zuvor war die Indikation mithilfe des Active Middle Ear Implant (aMEI) -Scores nach Frenzel (2013) gestellt worden. Ergebnisse Alle Patienten erzielten jeweils 4 Punkte im aMEI-Score, was auf eine ungünstige Prognose für eine erfolgreiche Implantation eines aktiven Mittelohrimplantats hinwies. Die Versorgung mit der Bonebridge und einem Epithesenanker konnte daraufhin komplikationslos durchgeführt werden. Postoperativ erfolgten nach 4 Wochen die audiologische Erstanpassung und die Bestückung mit Magneten. In der Audiometrie bestand ein funktioneller Gewinn von bis zu 30 dB sowie ein verbessertes Sprachverständnis. Die Epithese wurde dem gesunden Ohr nachgebildet. Nach der Versorgung waren die Patienten mit dem audiologischen und kosmetischen Ergebnis zufrieden. Schlussfolgerungen Das simultane chirurgische Vorgehen mit einem Hörimplantat und Epithesenankern stellt eine gute Option in der Versorgung von Ohrmissbildungen dar. Der aMEI-Score war ein hilfreiches Instrument zur Indikationsstellung. Durch das Vorgehen konnten das Operationsrisiko und der Aufwand der Versorgung reduziert werden.
[...]

Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract & nbsp;|  Full text

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Extracranial & Intracranial Complications in Chronic Suppurative Otitis Media

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Abstract

Prior to antibiotic era, complications rate of CSOM was 2.3 to 4% cases. With advent of newer antibiotics, radiological surgical techniques the complication greatly reduced to 0.15–0.04% and mortality decreases from 25 to 8% 5, still early diagnoses and management is still the cornerstone of prevention of CSOM complications. To study the prevalence of extracranial and intracranial complications in CSOM. It is a prospective cross sectional study done in one year from January 2018 to January 2019, at Department of ENT, G R Medical College, Gwalior, M P, India. In our study 50 patients presented with complications of CSOM during January 2018 to January 2019, ECC was found more common than ICC ECC—52%, ICC—46%, mastoid abscess was found most commonly in ECC 50%, brain abscess was the most common found intracranial complication of CSOM. Continuous negligence of CSOM leads to various extracranial complications lethal intracranial complications like brain abscess, meningitis, etc. hence it is recommended that health education program should be provided as prevalence is still higher in younger age group and low socioeconomic class especially in rural and tribal regions. In spite of newer antibiotics, radiological modalities and surgical advancement.

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