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

alexandrossfakianakis shared this article with you from Inoreader Anti‐SARS‐CoV‐2 Activity of Targeted Kinase Inhibitors: Repurposing Clinically Available Drugs for COVID‐19 Therapy via Journal of Medical Virology 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. View on Web

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

alexandrossfakianakis shared this article with you from Inoreader 14‐day famciclovir treatment significantly reduces the incidence of postherpetic neuralgia in elderly patients with herpes zoster via Journal of Clinical Pharmacy and Therapeutics (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. View on Web

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EGFR, the Lazarus target for precision oncology in glioblastoma

alexandrossfakianakis shared this article with you from Inoreader EGFR, the Lazarus target for precision oncology in glioblastoma via Neuro-Oncology Advance Access 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. View on Web

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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

alexandrossfakianakis shared this article with you from Inoreader Arthrocentesis versus non-surgical intervention as initial treatment for temporomandibular joint arthralgia: a randomized controlled trial with long-term follow-up via International Journal of Oral and Maxillofacial Surgery via MedWorm.com 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) View on Web

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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 Clinical Outcomes and Economic Burden of Seasonal Influenza and Other Respiratory Virus Infections in Hospitalized Adults via Journal of Medical Virology 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. This article is protected by copyright. All rights reserved. View on Web

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The T‐shaped FST pharyngoplasty step‐by‐step closure technique

alexandrossfakianakis shared this article with you from Inoreader The T‐shaped FST pharyngoplasty step‐by‐step closure technique via Head & Neck 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. View on Web

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Immunomodulatory fibrous hyaluronic acid‐Fmoc‐diphenylalanine‐based hydrogel induces bone regeneration

alexandrossfakianakis shared this article with you from Inoreader Immunomodulatory fibrous hyaluronic acid‐Fmoc‐diphenylalanine‐based hydrogel induces bone regeneration via Journal of Clinical Periodontology Abstract Aim To investigate the potential of an ultra-short aromatic peptide hydrogelator integrated with hyaluronic acid (HA) to serve as a scaffold for bone regeneration. Materials and methods Fluorenylmethyloxycarbonyl-diphenylalanine (FmocFF)/HA hydrogel was prepared and characterized using microscopy and rheology. Osteogenic differentiation of MC3T3-E1 preosteoblasts was investigated using Alizarin red, alkaline phosphatase and calcium deposition assays. In vivo, 5-mm diameter calvarial critical-sized defects were prepared in 20 Sprague-Dawley rats and filled with either FmocFF/HA hydrogel, deproteinized bovine bone mineral, FmocFF/Alginate (Alg) hydrogel or left unfilled. 8 weeks following implantation, histology and micro-CT analyses were performed. Immunohistochemistry was performed in 6 rats to assess the hydrogel's immunomodulatory effect. Results A nanofibrous FmocFF/HA hydrogel with a high storage modulus of 46KPa was prepared. It supported osteogenic differentiation of MC3T3-E1 preosteoblasts and facilitated calcium deposition. In vivo, the hydrogel implantation resulted in approximately 93% bone restoration. It induced bone deposition not only around the margins, but also generated bony islets along the defect. Elongated M2 macrophages lining at the periosteum-hydrogel interface were observed 1 week after implantation. After 3 weeks, these macrophages were dispersed through the regenerating tissue surrounding the newly formed bone. Conclusion FmocFF/HA hydrogel can serve as a cell-free, biomimetic, immunomodulatory scaffold for bone regeneration. This article is protected by copyright. All rights reserved. View on Web

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Quantification of Vocal Fold Atrophy in Age‐Related and Parkinson's Disease‐Related Vocal Atrophy

alexandrossfakianakis shared this article with you from Inoreader Quantification of Vocal Fold Atrophy in Age‐Related and Parkinson's Disease‐Related Vocal Atrophy via The Laryngoscope In this study, features of vocal fold atrophy were quantified and compared across dysphonia severity and between age-related and Parkinson's disease-related vocal atrophy. The results support an association between vocal fold bowing and dysphonia severity based on CAPE-V scores, and demonstrate that patients with Parkinson's-related atrophy have more significant bowing compared to those with age-related vocal atrophy. Objective Vocal fold atrophy (VFA) is associated with aging and Parkinson's disease (PD). Clinical diagnosis of VFA depends on several visual-perceptual laryngostroboscopy findings that are inherently subjective. The purpose of this study was to use quantitative measurements to; (1) examine the relationships between VFA and dysphonia severity and (2) evaluate differences in VFA in patients with age-related VFA versus PD. Methods Thirty-six patients >60 years of age with VFA were included in this retrospective cohort study. Demographic information, medical history, Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V), Voice Handicap Index-10 (VHI-10), and still images from the stroboscopic exam were obtained. Image J™ was used to measure VFA, including bowing index (BI), normalized glottal gap area, and normalized mucosal wave amplitude. Pearson's correlation was used to evaluate the relationship between VFA, CAPE-V, and VHI-10. t-Tests and multivariate linear regression were used to compare VFA measures by dysphonia severity (CAPE-V <30 vs. >30) and diagnosis (age-related vocal atrophy [ARVA] and PD). Results BI was positively correlated with CAPE-V. Patients with CAPE-V >30 had a significantly larger BI compared to those with CAPE-V <30. Patients with PD had significantly larger BI than those with ARVA. Diagnosis of PD also predicted a larger BI after controlling for age and CAPE-V. Conclusion Quantitative measures supported an association between bowing severity and dysphonia severity in patients with PD and ARVA. A PD diagnosis significantly predicted more severe BI. These findings demonstrate the potential utility of BI. Quantitative VFA measures might also provide insight into the mechanisms of ARVA and dysphonia. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Vertebral fractures assessed by dual-energy X-ray absorptiometry and all-cause mortality. The Tromsø Study 2007-2020

alexandrossfakianakis shared this article with you from Inoreader Vertebral fractures assessed by dual-energy X-ray absorptiometry and all-cause mortality. The Tromsø Study 2007-2020 via American Journal of Epidemiology - Advance Access Abstract Vertebral fractures have been associated with increased mortality, but findings are inconclusive, and many vertebral fractures avoid clinical attention. We investigated this association in a general population of 2476 older adults aged ≥55 years from Tromsø, Norway, who were followed over 2007-2020, using dual-energy X-ray absorptiometry (DXA) at baseline to evaluate vertebral fractures (mild, moderate, severe). We used multiple Cox regression models to estimate hazard ratios (HRs) for all-cause mortality, adjusted for age, sex, body mass index, education, smoking, alcohol intake, cardiovascular disease and respiratory disease. Mean follow-up in the cohort was 11.2±2.7 years. 341 participants (13.8%) had one or more vertebral fractures at baseline, and 636 participants (25.7%) died between baseline and follow-up. Fully adjusted models showed a non-significant association between vertebral fracture status (yes/no) and mortality. Participants with ≥three vertebral fractures (HR 2.43, 95% CI 1.57-3.78), or at least one severe vertebral fracture (HR 1.65, 95% CI 1.26-2.15) had increased mortality compared to those with no vertebral fractures. DXA-based screening could be a potent and feasible tool in detecting vertebral fractures that are often clinically silent yet independently associated with premature death. Our data indicate that detailed vertebral assessment could be warranted for a more accurate survival estimation. View on Web

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Development of the remote 100 ml water swallow test versus clinical assessment in patients with head and neck cancer: Do they agree?

alexandrossfakianakis shared this article with you from Inoreader Development of the remote 100 ml water swallow test versus clinical assessment in patients with head and neck cancer: Do they agree? via Head & Neck Abstract Background The 100 ml water swallow test (WST) is a validated swallow assessment used in head and neck cancer (HNC). We aimed to determine the level of agreement when completing the 100 ml WST via clinician-graded video-testing or patient self-testing compared to standard face-to-face assessment (FTF). Methods Convenience sampling from four UK centers. Inclusion criteria: patients with HNC treated with any modality prior to, or within 5 years of treatment. Participants were recruited to complete the 100 ml WST by video-testing or self-testing and compared with FTF. Results Sixty-three patients were recruited; 1 was unable to perform the task; 30 in video-testing; and 32 in self-testing. There was no difference in swallow capacity (p = 0.424) and volume (p = 0.363) for the video-testing or the self-testing swallow capacity (p = 0.777) and volume (p = 0.445). Conclusions This study demonstrates that video-testing and self-testing are reliable methods of completing the 100 ml WST for this sample of patients with HNC. View on Web

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