Effect of amniotic membrane/collagen scaffolds on laryngeal cartilage repair.

Objectives: Laryngeal cartilage defects are a major problem that greatly impacts structural integrity and function. Cartilage repair is also a challenging issue. This study evaluated the efficacy of a collagen scaffold enveloped by amniotic membrane (AM/C) on laryngeal cartilage repair. Study Design: Experimental animal study. Methods: Fourteen Dutch rabbits were enrolled in the study. A 5 mm cartilage defect was created in the right and left thyroid lamina. The animals were divided into two groups randomly. Group 1 collagen scaffolds and group 2 AM/C were applied to the right side defects. Left side defects were not repaired, serving as control. Histologic evaluation was done 45 and 90 days following collagen and AM/C application with criteria of tissue and cell morphology, lacuna formation, vascularization, and inflammation. Results: Significant improvement in cartilage repair was observed in the AM/C side compared to the control side in all histologic criteria after 45 days (p<.05). After 90 days, cartilage repair improved in cell morphology, lacuna formation, and inflammation significantly (p<.05). Conclusion: The combination of amniotic membrane and collagen scaffolds provides a promising treatment modality for improving the repair of laryngeal cartilage defects. Level of Evidence: NA.

Functional magnetic resonance imaging in coronavirus disease 2019 induced olfactory dysfunction.

OBJECTIVE: To evaluate the functional magnetic resonance imaging changes in the olfactory structures of coronavirus disease 2019 patients experiencing olfactory dysfunction. METHODS: This study included patients aged 25-65 years who presented with a sudden loss of smell, confirmed coronavirus disease 2019 infection, and persistent olfactory dysfunction for a minimum of 2 months without any treatment. RESULTS: Irrespective of the side of brain activation, the analysis of the cumulative maximum diameter of the activation zones revealed significantly lower activation in the upper frontal lobe (p = 0.037) and basal ganglia (p = 0.023) in olfactory dysfunction patients. Irrespective of the side of activation, the analysis of the number of activation points demonstrated significantly lower activation in the upper frontal lobe (p = 0.036) and basal ganglia (p = 0.009) in olfactory dysfunction patients. CONCLUSION: Patients with coronavirus-triggered olfactory dysfunction exhibited lower activity in their basal ganglia and upper frontal lobe.

Comparison between olfactory training and curcumin therapy in improving olfactory dysfunction in patients with chronic kidney disease.

Objective: Olfactory dysfunction can be seen in chronic kidney disease (CKD) patients. We aimed to investigate the effects of olfactory training and curcumin on olfactory dysfunction in CKD patients and compare their impact with a placebo. Methods: We conducted a double-blind, randomized, placebo-controlled trial in CKD patients, 2021-2022. We enrolled 60 participants in our study into three groups (curcumin, training, and control). Participants were randomized into trials and control groups and assessed using the Iran-smell identification test (Iran-SIT), a questionnaire of olfactory disorders (QOD), and a self-assessment tool. P-value < 0.05 was considered statistically significant. Results: We gathered 58 participants (mean age of 56.1 ± 2.5, 56.9% men). All the tests showed that curcumin improved olfactory function after the trial, though it was significant in QOD (17.5 ± 11.8 vs. 13.1 ± 9.7, p = 0.045) and self-assessment results (8.5 ± 3.1 vs. 9.5 ± 4.0, p = 0.047). Moreover, compared to baseline, training patients experienced an increase in their olfactory function in Iran-SIT (15.3 ± 4.9 vs. 18.8 ± 2.7, p = 0.001), QOD (19.0 ± 10.4 vs. 12.2 ± 9.9, p = 0.003), and self-assessment tools (6.8 ± 1.8 vs. 8.2 ± 3.1, p = 0.027). In contrast, the olfactory function was unchanged in control in all the tests (p > 0.05). Also, the improved change of Iran-SIT and QOD scores during the trial was more significant in training compared to the curcumin group (p < 0.002). Conclusion: The findings of this study indicate that olfactory training, even more than curcumin, can improve olfactory function in CKD patients. This information may help manage olfactory dysfunction in the CKD population.

Coronavirus Disease 2019 and Hypertension: How Anti-hypertensive Drugs Affect COVID-19 Medications and Vice Versa.

BACKGROUND: As a medical problem, hypertension is one of the most common disorders in cardiovascular disease. High blood pressure has been identified as one of the most familiar risk factors for the ongoing COVID-19 pandemic. We planned to explore the possible interactions between anti-hypertensive agents and drugs targeting SARS-CoV-2 with broad investigations of these medications' mechanism of action and adverse effects. METHODS: Two co-authors searched the electronic databases (PubMed, Scopus, and Google Scholar) to collect papers relevant to the subject. The keywords searched were angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II receptor blockers (ARBs), sympatholytic drugs (alpha-1 blockers, beta-blockers), vasodilators (calcium channel blockers, nitrates, and hydralazine), diuretics, chloroquine, hydroxychloroquine, lopinavir/ritonavir, remdesivir, favipiravir, interferons, azithromycin, anti-cytokine agents, glucocorticoids, anticoagulant agents, nitric oxide, and epoprostenol. RESULTS: QT prolongation, arrhythmia, hypokalemia, hypertriglyceridemia are the most dangerous adverse effects in the patients on COVID-19 medications and anti-hypertensive drugs. CONCLUSION: This review emphasized the importance of the potential interaction between drugs used against COVID-19 and anti-hypertensive agents. Therefore, caution must be exercised when these medications are being used simultaneously.

Controversial Role of Folic Acid on Diabetic Auditory Neuropathy.

OBJECTIVE: Diabetic auditory neuropathy (DAN) is a common complication of diabetes that seriously affects the quality of life in patients. In this study, we investigate the role of folic acid in the treatment of DAN in an experimental rat model. METHODS: Thirty-two Sprague-Dawley rats were equally divided into four groups: group 1, normal; group 2, diabetic rats; and groups 3 and 4, diabetic rats treated with folic acid (40 and 80 mg/kg, respectively). We used some tools to investigate the therapeutic effect of folic acid on DAN. We evaluated auditory brain stem response (ABR), estimated the volume and number of spiral ganglion and the volume of stria vascularis and spiral ligament by the stereological method, and measured the blood levels of homocysteine (HCY), malondialdehyde (MDA), and superoxide dismutase (SOD). RESULTS: Our study showed that folic acid treatment was not significantly effective in improving structural and functional disorders in DAN, even though its effectiveness in reducing HCY (P < 0.001) and MDA (P < 0.05) as oxidative biomarkers was significant. CONCLUSION: Folic acid is not effective in relieving morphological and functional disorders in DAN.

Is There any Association Between Total Laryngectomy and Sexual Disorders in Men?

Introduction: According to the prevalence of sexual enjoyment reduction in total or partial laryngectomy patients, the present study aimed to evaluate sexual disorders among men who had undergone total laryngectomy. Materials and Methods: In this cross-sectional case-control study, purposive sampling was carried out to select all the samples that had experienced total laryngectomy. The control group was selected among the male patients who were referred for a routine checkup. In order to compare the groups, the international index of erectile function (IIEF) was performed, and the data were statistically analyzed in SPSS software (version 21). Results: Based on the obtained results, laryngectomy patients had experienced problems with sexual problems, especially in the field of erectile function, sexual desire, and intercourse satisfaction (P<001). Conclusions: According to various studies, sexual dissatisfaction negatively impacts the Quality of life. This problem, commonly observed in total laryngectomy patients, needs to be considered.

Use of Magnetic Resonance Imaging to Assess the Regenerative Effects of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rabbit Cartilaginous Laryngeal Defect Model.

Background: Stenosis and scar formation after repair of laryngeal tissue defects are serious problems that can significantly influence a patient's quality of life. Objective: In this study, we evaluated the use of magnetic resonance imaging to assess the efficacy of adipose tissue-derived mesenchymal stem cells (ASCs) on cartilaginous regeneration in an experimental rabbit model. Methods: Ten male white Dutch rabbits each had a 5 mm cartilaginous defect created surgically in the right and left thyroid lamina. On the right side, ASCs labeled with iron oxide particles were infused. As a control, the left side was left untreated. Repair of the defects were then evaluated by direct observation, histological evaluation, and magnetic resonance imaging monitoring done on days 1, 7, 14, and 28. Results: Histological examination revealed that compared with control, transplanted ASCs significantly increased cartilage regeneration (P ˂ 0.001), reduced inflammation (P ˂ 0.001), and fibrosis (P = 0.050). Magnetic resonance imaging tracking showed accurate placement and viability of the infused ASCs, as evidenced by low signal intensity onT2 weighted images at the level of the right thyroid cartilage. Conclusions: Infusion of ASCs improved laryngeal regeneration of surgically induced cartilaginous defects while decreasing fibrous tissue formation in this in vivo rabbit model. Furthermore, magnetic resonance imaging was shown to be a useful, noninvasive method to track correct ASCs placement and viability in cartilage regeneration in this animal model.

Histopathological characteristics of larynx in hypothyroidism in an experimental rabbit model.

Objective: Hypothyroidism has a significant effect on the patients' voices. This study evaluated the histopathological characteristics of larynx following hypothyroidism in an experimental rabbit model. Methods: Eleven male Dutch rabbits were included. Methimazole-induced hypothyroidism was done for nine rabbits. The remaining two rabbits were assigned as controls. Six weeks after starting methimazole, a histological examination was performed with parameters of inflammation, ulceration, hemorrhage, and thickness of epithelium, Reinke's space, vocal ligament, thyroarytenoid muscle, collagen deposition, and periodic acid-Schiff (PAS)-positive materials, as well as confirmation of hypothyroidism by T4 measurement. Results: Histologic examination showed a significant thickening of epithelium, Reinke's space, vocal ligament, and collagen PAS-positive materials deposition in hypothyroid rabbits (p < .05). There was significant reduction in thyroarytenid muscle thickness (p < .05). Inflammation, ulceration, and bleeding were not significantly different between hypothyroid and control rabbits' laryngeal specimens. Conclusion: Hypothyroidism causes significant changes in the laryngeal tissues. Thickening of epithelium, Reinke's space, vocal ligament, collagen, PAS-positive materials, and reduced thickness of thyroarytenoid muscle are the major findings of this study.

Magnesium sulfate administration in difficult laryngoscopy: An effective and safe method.

PURPOSE: Difficult laryngeal exposure during laryngeal microsurgery and laser surgery is a major concern for otolaryngologists. This study evaluated the efficacy and safety of magnesium sulfate administration in difficult laryngeal exposure patients. STUDY DESIGN: Quasi-experimental design. MATERIALS AND METHODS: Forty adult patients scheduled for laryngeal microsurgery with difficult laryngeal exposure according to Cormack-Lehane (CL) classification were included. Magnesium sulfate 50% (20-30 mg/kg) was administered as a bolus injection. Laryngeal exposure and hemodynamic stability were evaluated before and after the intervention. RESULTS: CL grading was shown a statistically significant improvement after magnesium sulfate administration. There are no clinically significant changes in the mean arterial pressure, heart rate, and oxygen saturation levels in the patients who received magnesium sulfate for better laryngeal exposure. CONCLUSION: Magnesium sulfate is an effective and safe drug for better viewing in difficult laryngeal exposure patients.

Factors associated with anosmia recovery rate in COVID-19 patients.

Objectives: The present study aimed to assess the 4- and 8-week recovery rate of anosmia and determine the factors associated with recovery in COVID-19 patients. Method: This retrospective study was conducted from December 2020 to March 2021. RT-PCR-proven COVID-19 adult patients (over 18 years of age) with a positive history of anosmia were included in this study. Anosmia was assessed based on the COVID-19 Anosmia Reporting Tool. The recovery rate of anosmia after 4 and 8 weeks were evaluated, and the relationship between the patients' recovery and their clinical and demographic data was assessed. Results: A total of 235 patients were included. Their mean age (±SD) was 43.95 ± 15.27 years. Anosmia recovery was reported in 207(88.51%) and 219 (93.19%) participants till 4 and 8 weeks. The mean recovery time was 19.42 ± 8.81 days. The result of logistic regression showed that smoking (P = .031; OR = 10.813), ageusia (P = .002; OR = 5.340), headache (P = .006; OR = 0.243), and nasal discharge (P < .001; OR = 0.080) were significantly associated with 4 weeks anosmia recovery. The only risk factor which was associated with a lower rate of 8 weeks anosmia recovery was presence of nasal discharge (OR = 0.106, P = .002). Conclusion: The only risk factor which was associated with a lower rate of 8 weeks anosmia recovery was presence of nasal discharge. Our result demonstrated that although smoking was associated with higher recovery rate till 4 weeks, it could not be considered as a protective factor after 8 weeks. More studies are recommended to investigate the relationship between anosmia and the associated factors by consideration of both short- and long-term recovery rates and assess the possible mechanisms that could justify this association. Levels of Evidence: 3b.

Detection of human papillomavirus (HPV) DNA in benign laryngeal lesions and role of cigarette smoking as an inducing factor.

The association of human papillomavirus (HPV) in laryngeal malignancies is largely known. This study evaluated the association between HPV and benign laryngeal lesions and also the role of smoking and alcohol consumption in increasing the prevalence of HPV in such benign lesions. Seventy-eight specimens of benign laryngeal lesions including 26 polyps, 26 dysplasia, and 26 other lesions such as nodules and cysts were enrolled in this study. Polymerase chain reaction (PCR) technique was used to detect HPV DNA in the tissues. The role of smoking and alcohol consumption in the prevalence of HPV was also evaluated through appropriate statistical tests. This study showed that the prevalence of HPV in benign laryngeal lesions was not statistically significant. The Cohen's effect size for comparing polyps vs. other lesions was nearly 0.7, indicating that HPV prevalence in laryngeal polyps may be clinically meaningful. Another finding in our study is the role of smoking in increasing the HPV prevalence in laryngeal polyps (P = 0.034). In benign laryngeal polyps, HPV prevalence may be clinically important. Smoking acts as a co-factor to induce HPV infection in laryngeal polyps in our study.

Effect of Rutin on Diabetic Auditory Neuropathy in an Experimental Rat Model.

OBJECTIVES: Diabetic auditory neuropathy is a common complication of diabetes mellitus that has a major impact on patients' quality of life. In this study, we assessed the efficacy of rutin in treating diabetic auditory neuropathy in an experimental rat model. METHODS: Forty Sprague-Dawley rats were randomly assigned to the following groups: group 1, control; group 2, diabetic rats; and groups 3-5, rats treated with rutin (at doses of 50, 100, and 150 mg/kg, respectively). We used auditory brain stem response, stereology of the spiral ganglion, and measurements of superoxide dismutase (SOD) and malondialdehyde (MDA) to evaluate the effects of treatment. RESULTS: Significant improvements in auditory neuropathy were observed in the rutin-treated groups in comparison with the diabetic group (P<0.05). Auditory threshold, wave latency, wave morphology, the volume and number of neurons in the spiral ganglion, and SOD and MDA activity showed improvements following treatment. CONCLUSION: Rutin shows promise as a treatment modality for diabetic auditory neuropathy, but more trials are warranted for its clinical application.

The Healing Effect of Amniotic Membrane in Laryngeal Defects in Rabbit Model.

OBJECTIVE: Fibrosis and scar formation following laryngeal repairing is a major concern. This study evaluated the efficacy of applying amniotic membrane (AM) as a biologic dressing to reduce fibrosis and inflammation and promote cartilage repair. STUDY DESIGN: Experimental animal study. METHODS: Nine male white Dutch rabbits were selected. A standard defect (5 mm) was created in right and left thyroid lamina. In the right side, two layers of AM were applied while the left side was kept intact for future comparison. Histologic examination with criteria of inflammation, fibrosis, and cartilage regeneration was performed 2, 4, and 6 weeks following AM application. All procedures were done according to animal ethics rules. RESULTS: Histologic and gross examination showed that AM application was able to reduce inflammation and fibrosis and improve cartilage regeneration significantly. CONCLUSION: As a useful intervention, AM application can reduce inflammation and fibrosis and enhance cartilage regeneration, following laryngeal defect repair. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E527-E533, 2021.

Cross-cultural Adaptation and Validation of the Persian Version of Voice Disability Coping Questionnaire (P-VDCQ): Introducing a New Instrument.

OBJECTIVES: Coping is one of the important concepts in psychology, which is pertinent to how persons with illness manage the stress of that condition. Voice Disability Coping Questionnaire (VDCQ) is an assessment tool for quantifying coping strategies in those with voice disability. The purpose of the present study was to investigate reliability and validity of the Persian version of VDCQ (P-VDCQ). METHOD: Translation procedure was performed according to the World Health Organization guidelines, and then 138 persons (88 persons with voice disorders and 50 controls) completed the questionnaire. Psychometric properties of the P-VDCQ were investigated. RESULTS: There was a significant difference between the mean value of patients with dysphonia and that of the control group. The results of test-result reliability indicated that there is a high correlation between repeated administration of the questionnaire (intraclass correlation coefficient = 89.7). Also, a high Cronbach's alpha coefficient (α = 0.94) revealed a good internal consistency. Participants' scores in this instrument had a moderate correlation with their scores on Voice Activity Participation Profile-Persian version (r = 0.41, P < 0.001). CONCLUSION: The P-VDCQ is a reliable and a valid instrument that can be used to investigate coping strategies of patients with dysphonia in clinical settings and for research purposes.

Assessing whether EORTC QLQ-30 and FACT-G measure the same constructs of quality of life in patients with total laryngectomy.

BACKGROUND: The European Organization for Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) and the Assessment of Cancer Therapy-General (FACT-G) are the two most widely used measures of cancer-specific health-related quality of life (HRQOL). This study aims to assess whether the two instruments measure the same constructs of HRQOL in patients with total laryngectomy. METHODS: The EORTC QLQ-30 and the FACT-G was completed by 132 patients with total laryngectomy. Convergent, discriminant, and construct validity of the EORTC QLQ-C30 and the FACT-G were assessed by Spearman's correlation and explanatory factor analysis. RESULTS: The results of factor analysis showed that the EORTC QLQ-C30 and the FACT-G measure different aspects of HRQOL. Moreover, both instruments showed excellent convergent and discriminant validity, except for nausea and vomiting symptom subscale in the EORTC QLQ-C30 questionnaire. The internal consistency was close or greater than 0.7 for all domains of both instruments except for functional wellbeing in FACT-G. CONCLUSIONS: This study revealed that neither of the two instruments can be replaced by the other in the assessment of HRQOL in Iranian patients with total laryngectomy. Accordingly, clinicians should exactly define their research questions related to patient-reported outcomes before choosing which instrument to use.

Numerical analysis and comparison of flow fields in normal larynx and larynx with unilateral vocal fold paralysis.

In this study, laryngeal flow fields are investigated and compared in normal larynx and models of larynx with unilateral vocal fold paralysis (UVFP). In paralytic models, three fixed initial glottal gaps are considered to understand the positive or probable negative impacts of surgical operation on unilaterally paralytic larynx, by which the paralyzed vocal fold is brought closer to the mid-plane. Various features of the flow fields have been discussed in detail including glottal gap width, glottal flow rate, glottal exit pressure pattern and glottal jet evolution. The numerical solution of fluid-structure interaction is carried out using ANSYS, and the results confirm some of the favorable effects of surgery on the patient's larynx. It is also shown that by tightening the glottal gap, some of the problems caused by the presence of a motionless vocal fold, such as leakage through glottal gap in the closure phase resulting in breathy voice can be moderated, although some of the symptoms of this disorder remain relatively unchanged.

The Healing Effect of Conditioned Media and Bone Marrow-Derived Stem Cells in Laryngotracheal Stenosis: A Comparison in Experimental Dog Model.

BACKGROUND: Differences in causes, severities, areas of stenosis, and the association with swallowing and phonation of larynx and trachea can result into Laryngotracheal stenosis (LTS).This study evaluated the healing effect of bone marrow stem cells (BMSCs) in experimentally induced LTS dog model. METHODS: Seven dogs were enrolled. BMSCs were isolated from proximal humerus and shoulder of a dog and cultured in media containing alpha minimal essential medium, fetal bovine serum, penicillin and streptomycin, and L-glutamine. BMSCs were characterized morphologically, by RT-PCR, and osteogenic induction. Karyotyping was undertaken for chromosomal stability. Mechanical trauma to laryngeal mucosa was identically conducted by Tru-cut punch forceps in right and left vocal folds. Two milliliter of conditioned media or BMSCs (2×106) were injected in the right site of the tissue and the left side was considered as control after LTS induction. The larynx was visualized 2, 4 and 6 weeks after treatment. Six weeks post-treatment, the larynges were evaluated histologically. RESULTS: BMSCs were adhered to culture flasks, spindle shape and positive for mesenchymal marker and negative for hematopoietic markers. Osteogenic induction was verified by Alizarin red staining. Karyotype was normal. A complete epithelialization and minimal chronic inflammatory cell infiltration were noted in submucosa of both left (control) and right (cases) vocal folds. The healing effect of conditioned media and BMSCs in comparison to the control group was more prominent. CONCLUSION: As thickness of fibrosis in cases were less than control group, conditioned media and BMSCs were shown to be good choices in healing of LTS.

Effects of Steroids and Curcumin on Prevention of Laryngeal Stenosis Secondary to Trauma.

INTRODUCTION: The aim of this study was to compare the preventive effects of corticosteroids and curcumin on subglottic stenosis in an animal model. MATERIALS AND METHODS: Twenty-one male German Shepherd dogs were used for this study. After standardized trauma to the subglottic area, the dogs were divided into three groups. Group A received curcumin (450 mg/ day) for 15 days; Group B received beclomethasone (2 puffs/day, 50 µg/dose) for 15 days; Group C received saline spray only. At 6 weeks after the injury, the larynx specimens were examined histopathologically to assess epithelialization, inflammation, and fibrosis. RESULTS: Complete epithelial covering of the steroid-treated group was significantly less than that of the control group. Despite inflammation and fibrosis, there was no significant difference between the steroid and control groups. In the curcumin-treated group, there was no significant difference between the groups. CONCLUSION: Topically applied steroid decreases epithelialization after induced subglottic injury. It is recommended that further studies be conducted in order to investigate the effects of the two drugs on airway stenosis prevention.

The validity and reliability of script concordance test in otolaryngology residency training.

INTRODUCTION: The script concordance test (SCT) is one the best tools used to evaluate clinical reasoning in ill-defined clinical situations. The aim of this study was to demonstrate SCT application in otolaryngology residency training. METHODS: A 20 item otolaryngology SCT containing 60 questions was administered to 26 otolaryngology residents. The test was prepared by two otolaryngologists familiar to medical education. These questions have been validated by otolaryngology experts. The panel consisted of 9 academic staff in the field of otolaryngology. Pearson correlation test was used to assess the reliability of the test. RESULTS: The obtained mean scores were 68.4±5.8 (out of 100) for residents and 78.2±6.4(out of 100) for experts. There was a significant difference between the two scores (p<0.005). Cronbach's alpha value was 0.80. CONCLUSION: The SCT is a reliable tool to evaluate clinical reasoning in otolaryngology residents. It should be included in otolaryngology residency training.

Primary tuberculosis of the vallecula and pyriform sinus: a case report and review of literature.

INTRODUCTION: Tuberculosis (TB) is a relatively prevalent infectious disease caused by a bacterium called mycobacterium tuberculosis. It primarily involves the lungs, but it can also affect other organs causing a variety of symptoms. CASE REPORT: In this report, a rare case with primary involvement of pyriform sinus and vallecula due to tuberculosis in a 74-year-old woman who complained of odynophagia for 6 months, is reported. There were no clinical or radiological pulmonary findings. CONCLUSION: The authors point out the epidemiological importance of tuberculosis and the need for more suspicion when dealing with uncommon lesions to make an early diagnosis.