Fasudil prevents neomycin-induced hair cell damage by inhibiting autophagy through the miR-489/NDP52 signaling pathway in HEI-OC1 cells

xlomafota13 shared this article with you from Inoreader Fasudil prevents neomycin-induced hair cell damage by inhibiting autophagy through the miR-489/NDP52 signaling pathway in HEI-OC1 cells Via Experimental and therapeutic medicine Exp Ther Med. 2022 Jan;23(1):43. doi: 10.3892/etm.2021.10965. Epub 2021 Nov 12. ABSTRACT Hearing loss is a common sensory disorder that is mainly caused by the loss of hair cells (HCs). Drug-induced deafness, for which there is currently no effective treatment, is mainly caused by the inappropriate use of aminoglycoside antibiotics. Fasudil (Fas), a novel isoquinoline sulfonamide derivative, has exhibited antioxidant abilities in a number of previous studies. The aim of the present study was to investigate the potential effects of Fas against neomycin (Neo)-induced hair cell damage and elucidate the underlying mechanism. Flow cytometry and western blot analysis were used to detect the effects of Fas on cell apoptosis and to determine the expression levels of autophagy-related proteins, LC3B and Beclin 1, induced by Neo. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were detected using fluorescent probes. The effect of Fas on Neo-induced hair cell injury marker, GFP-LC3B, was also examined using the immunofluorescence technique. Fas was found to inhibit Neo-induced mitochondrial autophagy and mitochondrial membrane potential decline, in addition to reducing ROS levels and cell apoptosis caused by Neo treatment. However, Fas failed to inhibit the Neo-induced these above changes in cells with NDP52 overexpression. The putative binding sites of microRNA (miR)-489 on the 3'-untranslated region of nuclear dot protein 52 (NDP52) were predicted using the TargetScan 7.0 online tool, and this association was further verified using a dual-luciferase reporter assay. Moreover, the expression of miR-489 negatively regulated the expression of NDP52. Fas and miR-489 mimic inhibited the Neo-induced mitochondrial autophagy and mitochondrial membrane potential decline, in addition to reducing ROS levels and cell apoptosis. Knockdown of miR-489 expression using a miR-489 inhibitor blocked the inhibitory e ffects of Fas on the mitochondrial membrane potential, cell apoptosis and ROS production. Therefore, Fas may upregulate the expression of miR-489 to negatively regulate the expression of NDP52 at the post-transcriptional level, which in turn inhibits the activation of mitophagy and cell injury induced by Neo. Thus, Fas may act as a novel therapeutic option in the clinical treatment of hearing loss in the future. PMID:34849158 | PMC:PMC8613531 | DOI:10.3892/etm.2021.10965 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The omission of intentional primary site radiation following transoral robotic surgery in 59 patients: No local‐regional failures

xlomafota13 shared this article with you from Inoreader The omission of intentional primary site radiation following transoral robotic surgery in 59 patients: No local‐regional failures Via Head & Neck Abstract Background We assessed locoregional control with omission of intentional primary site radiation after transoral robotic surgery (TORS) and quantified nontargeted primary site dose. Methods Following Institutional Review Board (IRB) approval, patients treated with primary TORS resection for squamous cell carcinomas of the oropharynx were reviewed. Patients with cT1-2 tumors, >2 mm margins, in whom the surgeon resected the primary without revising specimen-driven margins, qualified for omission of primary site radiation. Results From 2014 to 2019, 112 patients met criteria. Fifty-nine (52%) patients did not receive radiation targeting the primary site; of whom, 22 received no radiation. In this group, there were no local failures; mean age was 58 years and median follow-up was 25 months. Thirty-seven patients received adjuvant radiation targeting the neck, mean bystander dose to the primary site was 28.8 Gy (range, 13.3–50.6 Gy). Conclusion In a 59 patient population, omission of radiation to the primary site after TORS resulted in no locoregional failures. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clarifying optimal outcome measures in intermittent and continuous laryngeal neuromonitoring

xlomafota13 shared this article with you from Inoreader Clarifying optimal outcome measures in intermittent and continuous laryngeal neuromonitoring Via Head & Neck Abstract Background Intraoperative neuromonitoring (IONM) techniques have evolved over the past decade into intermittent IONM (I-IONM) and continuous IONM (C-IONM) modes of application. Despite many prior publications on both types of IONM, there remains uncertainty about what outcomes should be measured for each form of IONM. The primary objective of this paper is to define categories of benefit for I-IONM/C-IONM and to clarify and standardize their reporting outcomes. Methods Expert review consensus statement utilizing modified Delphi methodology. Results I-IONM provides diagnosis, classification, and prevention of nerve injury through accurate and early nerve identification. C-IONM provides real-time information on nerve functional integrity and thus may prevent some types of nerve injury but cannot assist in nerve localization. Sudden mechanisms of nerve injury cannot be predicted or prevented by either technique. Conclusions I-IONM and C-IONM are complementary techniques. Future studies evaluating the utility of IONM should focus on outcomes that are appropriate to the type of IONM being utilized. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Emergence of Invasive Fungal Rhinosinusitis in Recently Recovered COVID-19 Patients

xlomafota13 shared this article with you from Inoreader Emergence of Invasive Fungal Rhinosinusitis in Recently Recovered COVID-19 Patients Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Dec 1:34894211060923. doi: 10.1177/00034894211060923. Online ahead of print. ABSTRACT OBJECTIVE: The risk of invasive fungal rhinosinusitis is increased in Coronavirus disease 2019 (COVID-19) because of its direct impact in altering innate immunity and is further exacerbated by widespread use of steroids/antibiotics/monoclonal antibodies. The study aims to describe this recently increased clinical entity in association with COVID-19. METHO D: A prospective, longitudinal study including patients diagnosed with acute invasive fungal rhinosinusitis (AIFRS) who recently recovered from COVID-19 infection or after an asymptomatic carrier state. A single-center, descriptive study investigating demographic details, clinical presentation, radio-pathological aspects, and advocated management. RESULT: A total of 21 patients were included with a mean age of 49.62 years (SD: 14.24). Diabetes mellitus (DM) was the most common underlying disorder (90.48%), and 63.16% of all patients with DM had a recent onset DM, either diagnosed during or after COVID-19 infection. Nineteen patients (90.48%) had recently recovered from active COVID-19 infection, and all had a history of prior steroid treatment (oral/parenteral). Remaining 2 patients were asymptomatic COVID-19 carriers. Surprisingly, 2 patients had no underlying disorder, and 5 (23.81%) recently received the Covishield vaccine. Fungal analysis exhibited Mucor (95.24%) and Asper gillus species (14.29%). Most common sign/symptom was headache and facial/periorbital pain (85.71%), followed by facial/periorbital swelling (61.90%). Disease involvement: sinonasal (100%), orbital (47.62%), pterygopalatine fossa (28.58%), infratemporal fossa (14.29%), intracranial (23.81%), and skin (9.52%). Exclusive endoscopic debridement and combined approach were utilized in 61.90% and 38.10%, respectively. Both liposomal amphotericin B and posaconazole were given in all patients except one. CONCLUSION: A high suspicion of AIFRS should be kept in patients with recent COVID-19 infection who received steroids and presenting with headache, facial pain, and/or facial swelling. Asymptomatic COVID-19 carriers and COVID-19 vaccinated candidates are also observed to develop AIFRS, although the exact immuno-pathogenesis is still unknown. Prompt diagnosis and early management are vital for a favorable outcome. PMID:34852669 | DOI:10.1177/00034894211060923 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Measurement of Lingual Artery Using Ultrasound Versus Computed Tomography Angiography for Midline Glossectomy in Patients With Obstructive Sleep Apnea

xlomafota13 shared this article with you from Inoreader Measurement of Lingual Artery Using Ultrasound Versus Computed Tomography Angiography for Midline Glossectomy in Patients With Obstructive Sleep Apnea Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Dec 1:34894211062697. doi: 10.1177/00034894211062697. Online ahead of print. ABSTRACT OBJECTIVE: To clarify the differences in assessing the course of the lingual artery between lingual artery computed tomography angiography (CTA) and ultrasound (US). METHODS: Twenty-six OSA patients were included in this study and accomplished lingual artery CTA and US, respectively. The differences in the depths of the lingual arteries and the distances between the bilateral lingual arteries on 3 measurement levels based on lingual artery CTA and US were compared. RESULTS: The depths of the lingual arteries on 3 measurement levels by CTA were deeper than those by US (P < .01). There was no significant difference in the distances between bilateral lingual arteries on 3 measurement levels between CTA and US (P > .05). CONCLUSIONS: The parameters of lingual artery measured by lingual artery US were similar to or smaller than those measured by lingual artery CTA. Like lingual artery CTA, lingual artery US could be used as an effective method to ensure the safety of the operation. PMID:34852648 | DOI:10.1177/00034894211062697 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tracheostomy Outcomes in COVID-19 Patients in a Low Resource Setting

xlomafota13 shared this article with you from Inoreader Tracheostomy Outcomes in COVID-19 Patients in a Low Resource Setting Via otol rhinol Ann Otol Rhinol Laryngol. 2021 Dec 1:34894211062542. doi: 10.1177/00034894211062542. Online ahead of print. ABSTRACT OBJECTIVES: COVID-19 predominately affects safety net hospitals. Tracheostomies improve outcomes and decrease length of stay for COVID-19 patients. Our objectives are to determine if (1) COVID-19 tracheostomies have similar complication and mortality rates as non-COVID-19 tracheostomies and (2) to determine the effectiveness of our tracheostomy protocol at a s afety net hospital. METHODS: Patients who underwent tracheostomy at Los Angeles County Hospital between August 2009 and August 2020 were included. Demographics, SARS-CoV-2 status, body mass index (BMI), Charlson Co-morbidity Index (CCI), length of intubation, complication rates, decannulation rates, and 30-day all-cause mortality versus tracheostomy related mortality rates were all collected. RESULTS: Thirty-eight patients with COVID-19 and 130 non-COVID-19 patients underwent tracheostomies. Both groups were predominately male with similar BMI and CCI, though the COVID-19 patients were more likely to be Hispanic and intubated for a longer time (P = .034 and P < .0001, respectively). Both groups also had similar, low intraoperative complications at 2% to 3% and comparable long-term post-operative complications. However, COVID-19 patients had more perioperative complications within 7 days of surgery (P < .01). Specifically, they were more likely to have perioperative bleeding at their tracheostomy sites (P = .03) and long-term post-operative mucus plugging (P < .01). However, both groups had similar 30-day mortality rates. There were no incidences of COVID-19 transmission to healthcare workers. CONCLUSIONS: COVID-19 tracheostomies are safe for patients and healthcare workers. Careful attention should be paid to suctioning to prevent mucus plugging. LEVEL OF EVIDENCE: 3. PMID:34852660 | DOI:10.1177/00034894211062542 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis

xlomafota13 shared this article with you from Inoreader Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis Via The Laryngoscope Objectives/Hypothesis Clinical trials of biologics to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) have evaluated objective outcomes (e.g., University of Pennsylvania Smell Identification Test [UPSIT], nasal polyps score [NPS], and computed tomography Lund-Mackay score [CT-LMK]) and patient-reported symptoms (e.g., nasal congestion/obstruction [NC], loss of smell [LoS], and total symptom score [TSS]). We estimated anchor-based thresholds for clinically meaningful change in objective and patient-reported outcomes in patients with CRSwNP using data from LIBERTY NP SINUS-24 and SINUS-52 trials (NCT02912468; NCT02898454). Methods Target patient-reported outcomes were NC, LoS, and TSS; target objective outcomes were UPSIT, NPS, and CT-LMK. Anchor measures were the 22-item sinonasal outcome test (SNOT-22) rhinologic symptoms domain and total score and rhinosinusitis visual analog scale (VAS). The appropriateness of each anchor measure was evaluated by reviewing correlations between change in anchor measures and target outcomes and descriptive scores on target outcomes by levels of change in the anchor measure. Established thresholds for anchor measures (3.8 points for SNOT-22 rhinologic symptoms, 8.9 points for SNOT-22 total, 1-category improvement for rhinosinusitis VAS) were used to estimate clinically meaningful score changes for each target outcome. Results Based on correlations between change in anchor measures and target outcomes, SNOT-22 rhinologic symptoms domain was deemed the most appropriate anchor measure. Using this anchor measure, thresholds for clinically meaningful within-patient change were NC: 1 point; LoS: 1 point; TSS: 3 points; UPSIT: 8 points; NPS: 1 point; and CT-LMK: 5 points. Conclusion These thresholds support interpretation of efficacy results for target outcomes in CRSwNP trials. Level of Evidence 2 Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hearing Preservation Microsurgery in Vestibular Schwannomas: Worth Attempting in “Larger” Tumors?

xlomafota13 shared this article with you from Inoreader Hearing Preservation Microsurgery in Vestibular Schwannomas: Worth Attempting in "Larger" Tumors? Via The Laryngoscope Objectives/Hypothesis To review hearing preservation after microsurgical resection of sporadic vestibular schwannomas according to tumor size. Study Design Retrospective cohort. Methods Baseline, intraoperative, and postoperative patient and tumor characteristics were retrospectively collected for a cohort who underwent hearing preservation microsurgery. Serviceable hearing was defined by a pure tone average ≤50 dB and word recognition score ≥50%. Results A total of 243 patients had serviceable hearing preoperatively. Fifty (21%) tumors were confined to the internal auditory canal, and the median tumor size was 16.2 mm (interquartile range [IQR] 11.3–23.2) for tumors with cerebellopontine angle extension. Serviceable hearing was maintained in 64% of patients with tumors confined to the internal auditory canal, 28% with cerebellopontine angle extension <15 mm, and 9% with cerebellopontine angle extension ≥15 mm. On multivariable analysis, the odds ratios of acquiring nonserviceable hearing postoperatively for tumors extending <15 mm and ≥15 mm into the cerebellopontine angle were 5.75 (95% confidence interval [CI] 2.13–15.53; P < .001) and 22.11 (95% CI 7.04–69.42; P < .001), respectively, compared with intracanalicular tumors. Conclusions The strongest predictor of hearing preservation with microsurgery after multivariable adjustment is tumor size. Approximately 10% of patients with tumors ≥15 mm of cerebellopontine angle extension will retain serviceable hearing after microsurgery. Furthermore, hearing preservation techniques offer cochlear nerve preservation and cochlear patency allowing for possible future cochlear implantation. An attempt at hearing preservation, including avoiding surgical approaches that necessarily sacrifice hearing, is worthwhile even in larger tumors if serviceable hearing is present preoperatively. Level of Evidence IV Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Discrepancies of SARS-CoV-2 testing results among patients with total laryngectomy

xlomafota13 shared this article with you from Inoreader Discrepancies of SARS-CoV-2 testing results among patients with total laryngectomy Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 Dec 2. doi: 10.1007/s00405-021-07203-8. Online ahead of print. ABSTRACT PURPOSE: Prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is obtained with nasopharyngeal swabs. By the way, there is no consensus regarding sampling in totally laryngectomized subjects (who thus breathe directly by the tracheostomy and, theoretically, may be infected in the trachea). The aim of this study is to evaluate possible differences between swab results in the trachea and in the nasopharynx of this category of patients. METHODS: A retrospective chart review was performed in April 2021 among patients who previously had been operated on for total laryngectomy and who underwent swabs for SARS-CoV-2 research in 3 health-care centers in Northern-Eastern Italy. Data regarding the site of swabbing (trachea or nasopharynx) were analyzed. A comprehensive review of the literature regarding the same topic was then performed. RESULTS: A total of 25 totally laryngectomized subjects underwent swabs. Among them, 5 tested positive in the trachea (1) and in the nasopharynx (4). According to the literature review, 4 more subjects tested positive in the trachea (1) and in the nasopharynx (3). Data were overall divergent and no statistically significant correlations emerged between results of the tests performed in the two sites. CONCLUSION: Due to these discrepancies, both tracheal and nasopharyngeal swabs are recommended in these kinds of patients, to obtain a reliable test and to avoid false negatives. PMID:34853865 | DOI:10.1007/s00405-021-07203-8 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Land use as an effective factor on the occurrence of chromosomal diseases in Brazil

xlomafota13 shared this article with you from Inoreader Land use as an effective factor on the occurrence of chromosomal diseases in Brazil Via International Journal of Molecular Epidemiology and Genetics Int J Mol Epidemiol Genet. 2021 Oct 15;12(5):102-111. eCollection 2021. ABSTRACT BACKGROUND: The occurrence of chromosomal diseases is a worldwide health problem. The use of agrochemicals, urbanization processes, and solar radiation can be predictive factors of the elevated risk of congenital malformations. In this sense, predicting the geographical potential of the distribution of chromosomal diseases has high relevance for public health. OBJECTIVES: This study aimed to describe chromosomal prevalence in Brazil regions, from 2005 to 2015, to model a potential distribution of chromosomal disease occurrence probability associated with land use. METHODS: We used chromosomal prevalence to model a potential distribution of chromosomal diseases using machine learning algorithms. As the predictors of the models, we used the variables global forest canopy height, distance from the built-up area, and solar radiation. We characterized the predictive areas as potential occurrence of chromosomal diseases by land use and occupation. RESULTS: Georeferenced data of 43,672 karyotypes detected 7,237 cases of chromosomal diseases and used 5,362 to build the models. The models generated were accurate (TSS>0.5). DISCUSSION: The areas with greater occurrence of chromosomal diseases present a significant association with pasture areas, crops and agroforestry systems, and urbanized areas. This research is the first Brazilian study with this approach that seems promising in predicting the potential distribution of chromosomal diseases. Therefore, it can be an excellent management tool in public health. PMID:34853634 | PMC:PMC8611229 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Melanoma susceptibility: an update on genetic and epigenetic findings

xlomafota13 shared this article with you from Inoreader Melanoma susceptibility: an update on genetic and epigenetic findings Via International Journal of Molecular Epidemiology and Genetics Int J Mol Epidemiol Genet. 2021 Oct 15;12(5):71-89. eCollection 2021. ABSTRACT Malignant melanoma is one of the most highly ranked cancers in terms of years of life lost. Hereditary melanoma with its increased familial susceptibility is thought to affect up to 12% of all melanoma patients. In the past, only a few high-penetrance genes associated with familial melanoma, such as CDKN2A and CDK4, have been clinically tested. However, findings now indicate that melanoma is a cancer most likely to develop not only due to high-penetrance variants but also due to polygenic inheritance patterns, leaving no clear division between the hereditary and sporadic development of malignant melanoma. Various pathogenic low-penetrance variants were recently discovered through genome-wide association studies, and are now translated into polygenic risk scores. These can show superior sensitivity rates for the prediction of melanoma susceptibi lity and related mixed cancer syndromes than risk scores based on phenotypic traits of the patients, with odds ratios of up to 5.7 for patients in risk groups. In addition to describing genetic findings, we also review the first results of epigenetic research showing constitutional methylation changes that alter the susceptibility to cutaneous melanoma and its risk factors. PMID:34853632 | PMC:PMC8611230 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.