Tuesday, September 20, 2022

A Partial Ossicular Replacement Prosthesis With a Concentric Ball Joint in the Headplate

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A Partial Ossicular Replacement Prosthesis With a Concentric Ball Joint in the Headplate

This study focuses on the development of the mCLIP ARC Partial Prosthesis, a new partial middle-ear prosthesis featuring a balanced, centered ball joint. The ball joint allows the headplate to adapt to the individual anatomical features of the reconstructed tympanic membrane and facilitates intraoperative handling.


Objective

In passive middle ear prosthetics, rigid implants have proven successful in reconstructing the ossicular chain. However, these cannot fully replicate the physiology of the ossicular chain. Pressure fluctuations cause high stresses in rigid passive prostheses, which can result in dislocation, protrusion, and pre-tension in the annular ligament resulting in unsatisfactory hearing results.

Methods

In collaboration with MED-EL, we developed a new passive middle ear prosthesis that features a balanced, centered ball joint between the headplate and shaft of the prosthesis. We compared the sound transmission properties of this new prosthesis with those of a standard rigid prosthesis. Using Laser-Doppler-Vibrometry, we measured the sound-induced velocity of the stapes footplate relative to a given acoustic stimulus.

Results

The new prosthesis showed equivalent sound transmission characteristics compared to the rigid prosthesis, whereas retaining the ability to compensate for pressure fluctuations due to its ball joint. This ensures good transmission properties even during displacements of the tympanic membrane.

Conclusion

This development is a further step toward a physiological reconstruction of the ossicular chain.

Level of Evidence

N/A Laryngoscope, 2022

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Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea

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Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea

We assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea. This network meta-analysis demonstrates that intrathecal gadolinium-magnetic resonance cisternography is the most useful diagnostic method to detect CSF rhinorrhea.


Objective

To assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea.

Data Sources

The PubMed, EMBASE, SCOPUS, Web of Science, Cochrane Trials, and Google Scholar databases were searched up to December 2021.

Review Methods

Diagnostic accuracy was compared among seven radiological methods: computed tomography (CT), CT cisternography (CTC), magnetic resonance imaging (MRI), magnetic resonance cisternography (MRC), CT + MRI, radionuclide cisternography, and intrathecal gadolinium (Gd)-MRC. Sensitivity, specificity, and accuracy were used as outcomes of the analysis. Both a traditional pairwise meta-analysis and a network meta-analysis were performed.

Results

Twenty-three trials were included in the analysis. The results of a network meta-analysis performed on a network consisting of seven diagnostic methods showed that all imaging modalities had greater diagnostic accuracy than CT, with the exception of CTC, which had lower sensitivity. Only intrathecal Gd-MRC was significantly superior to other imaging methods with regard to sensitivity and accuracy. Gd-MRC also showed the greatest surface under the cumulative ranking curve values for all of the outcomes (sensitivity: 0.9200; specificity: 0.8364; accuracy: 0.8920).

Conclusion

This network meta-analysis demonstrates that intrathecal Gd-MRC is the most useful diagnostic method to detect CSF rhinorrhea. Laryngoscope, 2022

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Monday, September 19, 2022

Anti‐SARS‐CoV‐2 Activity of Targeted Kinase Inhibitors: Repurposing Clinically Available Drugs for COVID‐19 Therapy

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Abstract

Purpose

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis.

Methods

We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 varian ts.

Results

Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment.

Conclusions

This work supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.

This article is protected by copyright. All r ights reserved.

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14‐day famciclovir treatment significantly reduces the incidence of postherpetic neuralgia in elderly patients with herpes zoster

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14-day famciclovir treatment significantly reduces the incidence of postherpetic neuralgia in elderly patients with herpes zoster

(Left) For elderly patients with herpes zoster, the NRS in the 14-day FCV group was significantly lower than that of the 7-day FCV group on the 14th and 21st days after starting treatment. (Right) The incidence of PHN was 25.4% in the 7-day FCV group and 7.6% in the 14-day FCV group. With moderate or severe initial pain, the incidence of PHN was significantly lower in patients treated with 14-day FCV therapy than in those treated with 7-day FCV therapy.


Abstract

What is known and objective

Pain is the main symptom of herpes zoster (HZ), whilst postherpetic neuralgia (PHN) is a long-term unbearable pain, which seriously affects the quality of life of patients and is also the most intractable problem for clinicians. Early antiviral treatment is considered as a key measure to reduce acute pain and PHN. Nevertheless, most patients still have long-term pain after 7 days of antiviral treatment, and some patients will develop PHN. This study aimed to investigate whether prolonged duration of antiviral therapy could reduce HZ acute pain and the occurrence of PHN.

Methods

The outpatient data of HZ patients over 50 years old who visited the Dermatology Department from January 2016 to May 2018 were retrospectively analysed. According to the different courses of treatment of famciclovir (FCV), the patients were divided into 7-day FCV group and 14-day FCV group. The numerical rating scale (NRS) score at the first visit and on the 7th, 14th and 21st days after the start of treatment, the adverse drug reactions and the incidence of PHN were compared between the two groups.

Results

A total of 219 patients were involved in the analysis. For acute pain control, the 14-day FCV group was better than the 7-day FCV group. For patients with mild initial pain, there was no significant difference in NRS between the two treatments. For patients with moderate-to-severe initial pain, the NRS in the 14-day FCV group was significantly lower than that of the 7-day FCV group on the 14th and 21st days after starting treatment. PHN occurred in patients with moderate-to-severe initial pain, and the incidence was significantly lower in the 14-day FCV group than in the 7-day FCV group. There was no significant difference in the number of adverse reactions between the two groups.

What is new and conclusion

Compared with the traditional 7-day antiviral therapy, the 14-day course of FCV can reduce the acute pain and the incidence of PHN in elderly patients with HZ, especially in patients with moderate to severe initial pain. Prolonging the course of medication did not increase the side effects.

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EGFR, the Lazarus target for precision oncology in glioblastoma

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Abstract
The Lazarus effect is a rare condition that happens when someone seemingly dead shows signs of life. The epidermal growth factor receptor (EGFR) represents a target in the fatal neoplasm glioblastoma (GBM) that through a series of negative clinical trials has prompted a vocal subset of the neuro-oncology community to declare this target dead. However, an argument can be made that the core tenets of precision oncology were overlooked in the initial clinical enthusiasm over EGFR as a therapeutic target in GBM. Namely, the wrong drugs were tested on the wrong patients at the wrong time. Furthermore, new insights into the biology of EGFR in GBM vis-à-vis other EGFR-driven neoplasms, such as non-small cell lung cancer, and development of novel GBM-specific EGFR therapeutics resurrects this target for future studies. Here, we will examine the distinct EGFR biology in GBM, how it exacerbates the challenge of treating a CNS neoplasm, how these unique ch allenges have influenced past and present EGFR-targeted therapeutic design and clinical trials, and what adjustments are needed to therapeutically exploit EGFR in this devastating disease.
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Sunday, September 18, 2022

Prevention of the Occupational Silicosis Epidemic

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Abstract
An Australian National Dust Disease Taskforce was established to address the re-emergence of occupational lung disease, in particular silicosis. Exposure to respirable crystalline silica (RCS) occurs in various industries in Australia. We asked occupational hygienists about their practical experiences and perspectives on RCS exposure and regulatory action. A total of 105 members of the Australian Institute of Occupational Hygienists completed an anonymous questionnaire, which addressed individual characteristics, experience, perceived level of employer awareness, effectiveness of current regulation, and recommendations for improvement, across three main industrial sectors. Based on professional experience, 71% were concerned about the potential for RCS over-exposure. Barriers to adequate exposure control included lack of management commitment and financial resources. The employment of specialist occupational hygiene inspectors was considered to b e the most effective regulatory strategy. Given the large number of exposed workers in the construction industry, with only a moderate awareness, there is the potential for significant cost shifting of the burden of occupational lung disease from employers on to individuals and the public health system. A nationally consistent approach to RCS exposure control across all industrial sectors is now recommended, with an increased focus on measuring and controlling exposure.
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Arthrocentesis versus non-surgical intervention as initial treatment for temporomandibular joint arthralgia: a randomized controlled trial with long-term follow-up

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Arthrocentesis for arthralgia of the temporomandibular joint (TMJ) is often only indicated when conservative, non-surgical interventions have failed. However, performing arthrocentesis as initial therapy may facilitate earlier and better recuperation of the joint. The aim of this study was to assess the efficacy of this therapy with a long-term follow-up. Eighty-four patients were randomly allocated to receive either arthrocentesis as initial treatment (n  = 41) or non-surgical intervention (n = 43). (Source: International Journal of Oral and Maxillofacial Surgery)
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The T‐shaped FST pharyngoplasty step‐by‐step closure technique

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Abstract

Pharyngocutaneous fistula is one of the most common and serious complications associated with total laryngectomy. Numerous studies tried to evaluate causative and predisposing factors associated with this complication, but data are considerably variable and there is still no international consensus. Incidence rate varies considerably between studies, with reported rates from 3% to 65%. This 4K video presents our T-shaped four-step technique (FST) for closing the pharyngeal mucosa after total laryngectomy in a step-by-step manner. All sutures were performed by braided absorbable 3/0 26 mm 1/2c (Vicryl plus 3.0; Ethicon, Somerville, NJ, USA). Recordings were performed using a Karl Storz 4K 3D VITOM® exoscope (Karl Storz SE & Co. KG, Tuttlingen, Germany). We have been described this technique through a high-definition video, showing each step, and tips from the authors. Our T-shaped pharyngoplasty closure technique can be divided into four steps: 1. "Key Stitches"; 2. "A rea Refinement Stitches"; 3. "Modified Connell Suture"; 4. "Modified Purse String Suture." Our T-shaped FST closure technique proved to be an effective and reproducible method, which we feel could be the preferred choice for primary pharyngoplasty closure.

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Clinical Outcomes and Economic Burden of Seasonal Influenza and Other Respiratory Virus Infections in Hospitalized Adults

alexandrossfakianakis shared this article with you from Inoreader

ABSTRACT

Background

The cost of influenza and other respiratory virus infections should be determined to analyze the real burden of these diseases. We aimed to investigate the clinical outcomes and cost of illness due to respiratory virus infections in hospitalized adult patients.

Methods

Hospitalized patients who had nasal swab sampling for a suspected viral infection between 1 August 2018 to 31 March 2019 were included. Outcome variables were oxygen requirement, mechanical ventilation need, intensive care unit admission and cost.

Results

At least one viral pathogen was detected in 125 (47.7%) of 262 patients who were included in the study. Fifty-five (20.9%) of the patients were infected with influenza. Influenza-positive patients had higher rates for respiratory support, intensive care unit admission and mortality compared to all other patients. The average cost of hospitalization per person was 2,879.76 USD in the influenza-negative group, while the same cost was 3,274.03 USD in the influenza-positive group. Although all of the vaccinated influenza-positive patients needed oxygen support, neither of them required invasive mechanical ventilation or intensive care unit admission. The average hospitalization cost per person was 779.70 USD in the vaccinated group compared to 3,762.01 USD in the unvaccinated group. Disease-related direct cost of influenza in the community was estimated as 22,776,075.61 USD in the 18-65 years of age group and 15,756,120.02 USD in the 65 years of age and over group per year.

Conclusion

Influenza, compared to other respiratory virus infections, can lead to untoward clinical outcomes and mortality as well as higher direct medical costs in adults.

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Functional Outcomes of Swallowing Following Surgery for Obstructive Sleep Apnea

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Functional Outcomes of Swallowing Following Surgery for Obstructive Sleep Apnea

Identification, evaluation, and management of pre-and postoperative swallowing dysfunction in patients undergoing upper airway surgery for obstructive sleep apnea (OSA) is limited. This study evaluated subjective swallowing function pre and postoperatively in patients undergoing multi-level reconstructive pharyngeal sleep surgery.


Objective

Identification and evaluation of swallowing dysfunction in patients undergoing upper airway surgery for obstructive sleep apnea (OSA) is limited. This study evaluated subjective swallowing function pre and postoperatively in patients undergoing multi-level reconstructive pharyngeal sleep surgery.

Methods

A retrospective analysis of prospectively-administered Eating Assessment Tool (EAT-10) scores was conducted among adult patients undergoing surgery for OSA at a tertiary sleep surgery center. Preoperative and 1, 3, and 6-month postoperative time points were assessed. Patients were subdivided into two groups based on the degree of upper airway reconstruction performed. All patients underwent uvulopalatopharyngoplasty +/−tonsillectomy and tongue-base reduction. Patients undergoing Phase 1 reconstructive surgery additionally underwent tongue-base advancement procedures.

Results

A total 100 patients underwent airway reconstructive surgery. Forty-one patients underwent Phase 1 surgery; 59 patients underwent Mini-Phase 1 surgery. Neither group demonstrated preoperative dysphagia. Both groups experienced significant subjective dysphagia at 1-month postoperatively, which was greater among Phase 1 patients (mean EAT-10 14.8; SD 10.4) versus Mini-Phase 1 patients (mean EAT-10 6.7; SD 7.5) (p < 0.001). Swallowing function among both groups normalized by 3 and 6 months postoperatively. Phase 1 patients with pre-operative dysphagia (mean EAT-10 9.6; SD 5) demonstrated initial worsening of their swallowing postoperatively; however, reported improved swallowing versus pre-operative levels by 6 months postoperatively (mean EAT-10 3.6; SD 4.3) (p = 0.03).

Conclusion

Pharyngeal surgery resulted in no significant, persistent adverse change in swallowing function. Among both groups, significant subjective dysphagia was reported at 1 month postoperatively, yet returned to preoperative levels by 6 months postoperatively. OSA patients with pre-existing dysphagia undergoing Phase 1 surgery trended towards improved swallowing function postoperatively.

Level of Evidence

2 Laryngoscope, 2022

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