Solitary Isolated Oropharyngeal Neurofibroma Presenting With Dysphagia in the Setting of Von Recklinghausen's Disease.

A 24-year-old man with von Recklinghausen's disease presented with complaints of difficulty in swallowing for 6 months and change of voice for 3 months. He also had recent-onset difficulty in breathing. Telelaryngoscopy and subsequent contrast-enhanced computed tomography scan revealed a well-defined, smooth submucosal mass in the oropharynx (attached to the posterior pharyngeal wall, superior to the level of left aryepiglottic fold), obscuring the ipsilateral pyriform fossa, and nearly blocking the pharyngeal lumen. The mass was removed with endoscopic coblation-assisted laryngeal surgery, and subsequent histopathology revealed it to be neurofibroma. Neurofibromas are rare neoplasms to be encountered in the oropharynx. However, in the setting of von Recklinghausen's disease (neurofibromatosis type 1), one or more well-demarcated, submucosal nodular lesions in the upper aerodigestive tract may be considered as neurofibromas, and workup and treatment should be directed accordingly based on this clinical presumption. Endoscopic coblation during laryngeal surgery can effectively be used as a surgical tool to excise such lesions. It provides a relatively bloodless field compared to the conventional cold steel excision, and reduces the risk of complications at surgery and during the follow-up period. This clinical record illustrates the presentation and management of a solitary, isolated oropharyngeal neurofibroma in a man suffering from von Recklinghausen's disease. It further emphasizes the role of endoscopic coblation-assisted laryngeal surgery in this setup, and the need to maintain a low threshold of suspicion in having a provisional clinical diagnosis of such lesions.

Craniocervical Tetanus: A Practical Consideration During Work-up of Acute-Onset Trismus.

This clinical record revisits the classical and pathognomonic features of craniocervical tetanus in a 65-year-old farmer who presented with acute-onset trismus, multiple cranial nerve pareses (III, IX, and X), risus sardonicus, and spasm of the head-neck musculature. This paper explores the relevant literature and presents a brief pictorial analysis of the global epidemiologic data. With most countries successfully adopting the maternal and neonatal tetanus elimination (MNTE) program, the incidence and mortality of tetanus across age groups have sharply reduced in high-income and most middle-income nations. In adults, tetanus is now encountered in specialized situations like waning immunity and incomplete vaccination, in the resource-poor and low-income nations, in countries achieving MNTE recently, and as cluster cases in the aftermath of natural disasters involving human settlements. Therefore, present-day practicing otolaryngologists and residents who have limited exposure to the tell-tale clinical features of craniocervical tetanus should consider it during work-up of acute-onset trismus in adults in susceptible situations and with a conducive background. The clinical spectrum of craniocervical tetanus as depicted in this report, including the demonstration of the pathognomonic positive spatula test, provides valuable learning points for otolaryngologists in this regard.

Identification of antiviral phytochemicals from cranberry as potential inhibitors of SARS-CoV-2 main protease (Mpro).

Cranberry phytochemicals are known to possess antiviral activities. In the current study, we explored the therapeutic potential of cranberry against SARS-CoV-2 by targeting its main protease (Mpro) enzyme. Firstly, phytochemicals of cranberry origin were identified from three independent databases. Subsequently, virtual screening, using molecular docking and molecular dynamics simulation approaches, led to the identification of three lead phytochemicals namely, cyanidin 3-O-galactoside, ß-carotene and epicatechin. Furthermore, in vitro enzymatic assays revealed that cyanidin 3-O-galactoside had the highest inhibitory potential with IC50 of 9.98 µM compared to the other two phytochemicals. Cyanidin 3-O-galactoside belongs to the class of anthocyanins. Anthocyanins extracted from frozen cranberry also exhibited the highest inhibitory potential with IC50 of 23.58 µg/ml compared to the extracts of carotenoids and flavanols, the class for ß-carotene and epicatechin, respectively. Finally, we confirm the presence of the phytochemicals in the cranberry extracts using targeted LC-MS/MS analysis. Our results, therefore, indicate that the identified cranberry-derived bioactive compounds as well as cranberry could be used for therapeutic interventions against SARS-CoV-2.

Comprehensive In silico analysis of chaperones identifies CRYAB and P4HA2 as potential therapeutic targets and their small-molecule inhibitors for the treatment of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a subtype of liver cancer with increasing incidence, poor prognosis, and limited treatment modalities. It is, therefore, imperative to identify novel therapeutic targets for better management of the disease. Chaperones are known to be significant regulators of carcinogenesis, however, their role in CCA remains unclear. This study aims to screen chaperones involved in CCA pathogenesis and identify drugs targeting key chaperones to improve the therapeutic response to the disease. To achieve this, first we mined the literature to create an atlas of human chaperone proteins. Next, their expression in CCA was determined by publicly available datasets of patients at mRNA and protein levels. In addition, our analysis involving protein-protein interaction and pathway analysis of eight key dysregulated chaperones revealed that they control crucial cancer-related pathways. Furthermore, topology analysis of the CCA network identified crystallin alpha-B protein (CRYAB) and prolyl-4-hydroxylase subunit 2 (P4HA2) as novel therapeutic targets for the disease. Finally, drug repurposing of 286 clinically approved anti-cancer drugs against these two chaperones performed by molecular docking and molecular dynamics simulations showed that tucatinib and regorafenib had a modulatory effect on them and could be potential inhibitors of CRYAB and P4HA2, respectively. Overall, our study, for the first time, provides insights into the pan-chaperone expression in CCA and explains the pathways that might drive CCA pathogenesis. Further, our identification of potential therapeutic targets and their inhibitors could provide new and complementary approaches to CCA treatment.

Like Versus Unlike: Closure of a Moderate-sized Circular Tissue Defect Following Wide Local Excision of Primary Cutaneous Squamous Cell Carcinoma of Face by Rhombic Transposition Flap with Modification.

Closure of a circular tissue defect in the head-neck-face region is challenging because most transposition flaps are rhombic or triangular. For a tension-less closure, both rhombic transposition flap and the circular tissue defect need to be engineered maintaining strict geometric calculations. The present illustration demonstrates a modified rhombic transposition flap with greater freedom in rotation and mobility for closing a moderate-sized circular defect resulting from wide local excision of cutaneous squamous cell carcinoma in the mid-face. The circular shape of the primary tissue defect did not need to be altered. The authors revisited an earlier published technique in the process, adding their own modification to the rhombic transposition flap.

The socio-demographic determinants of the outcome of type 1 cartilage tympanoplasty in children: Results from a tertiary-care teaching institute in India.

OBJECTIVE: To explore whether and how the established socio-demographic parameters pertaining to a lower-middle income nation influence the outcome of cartilage tympanoplasty in children with chronic otitis media (COM), inactive mucosal variety. METHODS: In this prospective cohort study, children aged 5-12 years with COM (dry, large/subtotal perforation) were considered for type 1 cartilage tympanoplasty following definite selection criteria. Relevant socio-demographic parameters were noted for each child. These included parents' education (literate/illiterate), living area (slum/village/others), mothers' occupation (laborer/business/housewife or home-maker), family type (nuclear/joint), and monthly family income. Outcome at 6 months follow-up was interpreted as "success" (favorable; anatomically intact and well-epithelialized neograft and dry ear) and "failure" (unfavorable; residual or recurrent perforation and/or discharging ear). The role of individual socio-demographic factor in determining the outcomes was analyzed with relevant statistical methods. RESULTS: The average age of the 74 children included in the study was 9.30 ± 2.13 years. At six months, 86.5% had a successful outcome, with a statistically significant hearing gain (closure of the air-bone gap) of 17.02 ± 8.96 dB (p = .003). Mothers' education had a significant influence on the success rate (Chi: 4.13; significant at p < .05); children of ∼97% of the literate mothers had a successful outcome. Living area was significantly associated with success (Chi: 13.94; significant at p < .01); ∼90% of children living in the slum areas had success, compared to 50% of those residing in villages. The family type also significantly influenced the surgical outcome (Chi: 3.81; significant at p < .05); ∼97% of the children belonging to the joint families encountered success, compared to ∼81% of those brought up in the nuclear families. The success also depended on the mothers' occupation (Chi: 6.47; significant at p < .05); ∼97% of the housewife mothers had children who were successful, against ∼77% of mothers engaged as laborers. Another factor significantly associated with success was the monthly household income. Nearly 97% of the children belonging to families with a monthly household income of >₹3000 (cut-off limit set by the median value) experienced success, in contrast to 79% of those having a monthly family income of <₹3000 (Chi: 4.83; significant at p < .05). CONCLUSION: Socio-demographic parameters are valuable determinants of the outcome of surgical management of COM in children. For type 1 cartilage tympanoplasty, mothers' education and occupation, family type, living area, and monthly family income significantly influenced the surgical outcome.

Repurposing drugs targeting metabolic diseases for cancer therapeutics.

Hurdles in the identification of new drugs for cancer treatment have made drug repurposing an increasingly appealing alternative. The approach involves the use of old drugs for new therapeutic purposes. It is cost-effective and facilitates rapid clinical translation. Given that cancer is also considered a metabolic disease, drugs for metabolic disorders are being actively repurposed for cancer therapeutics. In this review, we discuss the repurposing of such drugs approved for two major metabolic diseases, diabetes and cardiovascular disease (CVD), which have shown potential as anti-cancer treatment. We also highlight the current understanding of the cancer signaling pathways that these drugs target.

Molecular insights into the role of electronic cigarettes in oral carcinogenesis.

Electronic cigarette (EC) usage or vaping has seen a significant rise in recent years across various parts of the world. They have been publicized as a safe alternative to smoking; however, this is not supported strongly by robust research evidence. Toxicological analysis of EC liquid and aerosol has revealed presence of several toxicants with known carcinogenicity. Oral cavity is the primary site of exposure of both cigarette smoke and EC aerosol. Role of EC in oral cancer is not as well-researched as that of traditional smoking. However, several recent studies have shown that it can lead to a wide range of potentially carcinogenic molecular events in oral cells. This review delineates the oral carcinogenesis potential of ECs at the molecular level, providing a summary of the effects of EC usage on cancer therapy resistance, cancer stem cells (CSCs), immune evasion, and microbiome dysbiosis, all of which may lead to increased tumor malignancy and poorer patient prognosis. This review of literature indicates that ECs may not be as safe as they are perceived to be, however further research is needed to definitively determine their oncogenic potential.

Nasopharyngeal Fibroangioma: Revisiting the "Other End" of the Spectrum.

Significance StatementNasopharyngeal angiofibroma rarely presents in post-adolescent and elderly men, either as the natural evolution of a pre-existing lesion or as a de novo skull-base tumor. As the lesion ages, its composition changes from vessel-predominant to stroma-predominant-the angiofibroma-fibroangioma spectrum. As a fibroangioma, it has restrained clinical features (asymptomatic or occasional epistaxis), minimal avidity for contrast agents, and limited spread potential evident on imaging. These atypical features lead to a diagnostic dilemma when an innocuous choanal/nasopharyngeal fibrovascular mass is encountered in hitherto asymptomatic adult men presenting with epistaxis.

How Does Preoperative Pure Tone Audiometry Relate to the Findings at Surgery to Explain the Hearing Status in Chronic Otitis Media?

Objective: Pure tone audiometry (PTA) guides surgical decision-making in chronic otitis media (COM), and PTA values depend upon the type and extent of COM. Methods: Our cross-sectional study included patients with COM with/without cholesteatoma who were scheduled for surgery. Findings on examination of the middle ear under the microscope and at surgery which could explain the hearing loss were corroborated with preoperative PTA through appropriate statistical methods. Results: The study included 114 patients (mean age: 31.07 years; range: 7-57). Following preoperative PTA, 50% of patients had moderate hearing loss and ~73% had air-bone gap (ABG) <35 dB. Conductive hearing loss affected 109 patients (97.61%); five had mixed hearing loss. At surgery, 27 patients (23.68%) had ossicular discontinuity, with the incus being the most affected. Twenty-one patients in this group had ABG ≥35 dB. Perforations involving the anterior and posterior halves of the pars tensa, and subtotal perforations, demonstrated the maximum mean hearing loss [45.39±8.29 dB HL (p=0.075), 51.08±12.51 dB HL (p=0.26), respectively]. The mean pure tone average in the intact ossicles group was 43.62±8.07 dB HL and that in the absent/eroded ossicles group was 58.15±11.05 dB HL (p<0.0001); the mean ABG was 27.89±4.77 dB and 38.88±6.47 dB, respectively (p<0.0001). Conclusions: Hearing loss was significantly associated with the size but not the site of the central perforation. With ossicular discontinuity, hearing loss and ABG deteriorated significantly. The findings re-establish the relationship between preoperative PTA and the middle ear status which should help surgeons plan surgery and counsel patients regarding hearing outcomes.

Socio-demographic and Audiological Profile of the Board-Reviewed Applicants for Hearing Handicap Certification in a Tertiary Care Teaching Institute in Eastern India.

To analyze the socio-demographic and audiological profile of the applicants for hearing handicap certification in the Medical Board (henceforth, "Board") of a tertiary care teaching institute. This is a retrospective record review (March 2019-February 2020) from the archival computer database of the institutional Board. The procedure for audiological assessment prior to Board review and thereafter, the evaluation at the Board (computation of hearing impairment) for eligibility for certification was discussed. The socio-demographic profile of the applicants (age, gender, faith) and the types of hearing impairment [HI%; organic (sensorineural, mixed), non-organic (malingering)] were analyzed with relevant statistical parameters. A HI% scale was introduced to classify the severity of the hearing deficit. Of the 163 applicants, 148 had organic hearing loss (average age: 35.4 years; 1.9 times male preponderance) and 15 were malingerers (average age: 35.7 years; 14 times male preponderance). The left ear contributed more to the hearing handicap. Most applicants having sensorineural hearing loss (SNHL; n = 124) were within 10-19 years and 40-49 years (19.35% each), with 12% being ≧ 60 years (age-associated hearing loss). Of the 13 applicants of age ≦ 12 years, eight were diagnosed with brainstem evoked response audiometry, and 10 had HI score of ≥ 70%. Muslim population with SNHL tended to avail certification 1.34 times more than the Hindus. Most of the applicants with mixed hearing loss (MHL; n = 24) were in their fifth and sixth decades (29.2% each), with three times male preponderance. Among the malingerers, the average malingering impairment was 66% (median: 61%; range 44-100%). Among the SNHL population, ~ 30% had HI at 90-100% in contrast to the MHL population of whom 8% had HI at > 90% and 29% had HI at 40- < 55%. Ten applicants among the organic hearing loss group (6.76%) (two with SNHL; eight with MHL) had HI scores of < 40% and were considered ineligible for certification. The outcomes of the review provided a comprehensive account of the socio-demographic profile of the applicants for handicap certification and the type of hearing loss prevailing in a given population. These data, and the severity stratification of the hearing disability through the HI% scale would provide the policymakers and stakeholders with proper directions to work upon.

Should Silicone Lacrimal Stenting be a Better Choice for Primary Endoscopic Powered Dacryocystorhinostomy?

Objective: To compare endoscopic dacryocystorhinostomy (EnDCR) with and without silicone lacrimal stenting through subjective (patients') and objective (surgeons') outcome parameters. Methodology: Following defined selection criteria, EnDCR was performed on patients with primary chronic dacryocystitis with post-saccal stenosis. Every alternate patient had silicone lacrimal stenting (group A: no stenting; group B: with stenting); stents were removed at three months. At six months (minimum follow-up period), patients' responses on symptom relief (through a five-point score) and naso-endoscopic evaluation (visualization of rhinostome; presence of granulations and synechiae; lacrimal drainage patency by estimating methylene blue flow pattern) were compared between the groups. Results: Each group had 20 patients. There was no statistically significant difference in group-wise follow-up periods. Five-point score at six months revealed 85% and 95% of patients in groups A and B, respectively, experienced "success"; among them, 60% and 75% were "symptom-free". The majority (75%) in group B experienced no discomfort from stenting. Naso-endoscopy revealed 80% patients in group A and 65% in group B had well-delineated rhinostome, albeit with granulations in 25% and 50%, respectively. Spontaneous dye flow was achieved, respectively, in 75% and 90%. The difference in none of the subjective and endoscopic parameters achieved statistical significance. None had synechia; fibrosis was seen in the four patients with no dye flow even with pressure/massaging. Conclusion: There was no statistically significant difference in EnDCR with and without silicone lacrimal stenting in the overall outcome of symptomatic improvement and endoscopic assessment of the surgical site.

Role of Bilateral Inferior Turbinoplasty as an Adjunct to Septoplasty in Improving Nasal Obstruction and Subjective Performance in Patients With Deviated Nasal Septum Associated With Allergic Rhinitis: An Interventional, Prospective Study.

BACKGROUND: Patients with nasal obstruction due to deviated nasal septum (DNS) often have allergic rhinitis (AR) as contributing factor. When optimal medical therapy for AR fails, septoplasty alone may not adequately treat nasal obstruction. Therefore, with bilateral inferior turbinate hypertrophy representing long-standing AR, adding bilateral inferior turbinoplasty (BIT) to septoplasty might be beneficial. OBJECTIVE: To assess whether septoplasty with/without BIT alleviates nasal obstruction in the above patient cohort and whether adding BIT to septoplasty brings significant benefit. METHODOLOGY: In this interventional, prospective study, patients with nasal obstruction due to DNS and persistent, moderate-severe AR refractory to optimal medication were randomly allocated into group A (septoplasty alone) and group B (septoplasty with BIT). Nasal Obstruction and Symptom Evaluation (NOSE) score, along with Subjective Performance parameters (days-off/month; number of outdoor visits/month; overall satisfaction score [OSS]) were used to assess the symptom and quality of life, respectively, at follow-up. RESULTS: Each group had 40 age/sex-matched patients. Friedman test, and subsequent pair-wise comparison within groups without Bonferroni correction, revealed that septoplasty with/without BIT elicited significant reduction in NOSE scores and in the Subjective Performance parameters (days-off/month; number of outdoor visits/month) at 3 and 6 months. Wilcoxon Signed Rank test revealed that the OSS within groups also improved significantly with time. Further, comparison between groups revealed significant improvement in NOSE scores at all levels of follow-up when BIT was included. However, there were no significant differences between groups in the Subjective Performance parameters at any level of follow-up. Improvement in OSS between groups was significant only at 3 months but not subsequently. CONCLUSION: Septoplasty with/without BIT is helpful in treating patients with DNS and refractory AR. However, although adding BIT brings significant benefit in decreasing nasal obstruction, it does not significantly improve the Subjective Performance parameters during follow-up, except for OSS at the third month.

Sequestered, Iatrogenic Epidermoid Implantation Cysts Associated With Retroauricular (Wilde's) Incision.

OBJECTIVE: To report two patients with iatrogenic, epidermoid implantation cysts associated with the standard retroauricular (Wilde's) incision, to establish their etiology, to explore means to prevent them, and to ensure that this experience adds to the learning curve of the surgical training of the residents. METHODS: Case series with the review of literature. RESULTS: One of the two patients, who had an unremarkable follow-up period after cortical mastoidectomy and cartilage tympanoplasty performed three years back, presented with a retroauricular cystic swelling visible since two months. It was hyperintense on T2-weighted magnetic resonance imaging. A sequestered cystic mass was encountered at surgery in the subcutaneous plane in association with the retroauricular scar tissue from previous surgery. In the other patient, two similar cysts (one of them sequestered) were incidental findings at revision tympanomastoid surgery. Histopathology in both instances was consistent with epidermoid cyst. Given their subcuticular location and intimate association with a pre-existing surgical scar, they were considered to be of implantation in origin. This was a potential outcome of persistent inversion of one or both skin edges following simple interrupted suturing. The reason could be a faulty surgical technique, due to improper placement of the needle with respect to skin, inadequate or uneven tissue bite, a tight knot, or failure to manually evert the apposing edges at the point(s) of suspicion. CONCLUSIONS: Sequestered epidermoid implantation cysts due to persistent inversion of sutured skin edges are unusual complications. The illustrations in this case series emphasize the need to adhere to the basic principles of surgical practice. They provide a caveat to the resident surgeons and the faculties who supervise them, that inadvertent and apparently innocuous misses, even at the elementary steps of surgery (like suturing), could lead to complications that are unwanted and potentially avoidable.

The Anatomic Variations of the Nose and Paranasal Sinuses and Their Effect on Chronic Rhinosinusitis in Adult Patients.

To find out the anatomic variations of nose/paranasal sinuses and how they affect the sinuses in chronic rhinosinusitis (CRS). This observational cross-sectional study included adults with CRS, refractory to optimum medical management, planned for functional endoscopic sinus surgery (FESS). Pre-operative naso-endoscopy and computed tomography (CT) were utilized to estimate the extent of CRS, and to note the anatomic variations of the sinuses. The findings were corroborated within the practical scope of FESS. The anatomic variations were evaluated to establish how they affected the related sinus(es). Most of the 53 patients were young adults presenting with nasal obstruction (77%), discharge (76%) and headache (68%). On diagnostic naso-endoscopy, prominent agger bulge (83% of the nasal sides), prominent uncinate (18%), inferior turbinate hypertrophy (34%), concha bullosa (38%), mucopus and polyp in the middle meatus (51%, 19%; respectively), and gross septal deviation (55%) were noted. The spheno-ethmoid and frontal recesses were predominantly unremarkable. CT revealed inferior turbinate hypertrophy (38% of the nasal sides), agger (100%), and lateralized/collapsed uncinate (8%). Ethmoids and maxillary sinuses were diseased in 50% and 65% respectively, with blocked ostiomeatal complex in 32% and prominent bulla in 48%. Frontal and sphenoid sinuses were least involved (10%, 2%; respectively). Enlarged agger caused maxillary sinusitis (87%), whereas anterior ethmoiditis resulted from enlarged agger (100%), bulla (89%) and frontal cells (51%). Identification of the anatomic variations of the nose/paranasal sinuses through CT and naso-endoscopy (diagnostic, per-operative) is crucial to understand the pattern, extent and severity of the involvement of sinuses in CRS.

Endonasal endoscopic removal of intra-orbital (extralacrimal, extraconjunctival) oculosporidiosis: Anatomical and surgical considerations.

This report illustrates the successful removal of a proper intra-orbital oculosporidiosis (extralacrimal, extraconjunctival) exclusively by the endonasal endoscopic approach. It also introduces the naso-orbital pseudofontanelle as an important surgical landmark and describes a hitherto undefined intra-orbital extramucosal three-dimensional potential wedge that harbored the Rhinosporidium seeberi infestation as a nodular conglomerate. The patient, a 50-year-old woman, was operated on three years ago for rhinosporidiosis of the nasal cavity and the distal lacrimal drainage system (lacrimal sac and nasolacrimal duct). The resulting alterations in regional anatomy were evident on imaging. They could explain the present recurrence and formation of the pseudofontanelle that allowed the conglomerate to bulge through the lateral nasal wall on digital pressure, making endoscopic intervention feasible. The primary principle for adopting this approach was to protect the facial skin from possible seeding. With an angled endoscope, the pseudofontanelle was breached and the intra-orbital extramucosal wedge between the bony orbital wall and the peri-orbita entered. The nodules that formed the conglomerate were densely adherent with the peri-orbita and skin. They were carefully and meticulously removed to avoid inadvertent injury to vital intra-orbital structures. Endonasal endoscopic intervention for a true intra-orbital oculosporidiosis has never been documented before. The surgical approach, the newly defined anatomical domain for the intra-orbital extramucosal oculosporidiosis, and the concept of pseudofontanelle characterize this report as a novel clinical experience worth presenting.

Perspectives and early experience on endoscopic stapedotomy from a group of "traditional school" otologists.

Background: This paper evaluates endoscopic stapedotomy from the perspectives of a group of 3 surgeons, each of whose experience in endoscopic and microscopic stapedotomy is 3 years and more than 12 years, respectively.Methods: Thirty-four patients clinically diagnosed with stapedial otosclerosis were alternately assigned for unilateral, microscope- and endoscope-assisted stapedotomy following the selection criteria given. Results were evaluated with predetermined epidemiologic, preoperative, perioperative, and postoperative outcome parameters.Results: The microscope group had 12 ears with otosclerosis and the endoscope-assisted group 14. Ears found to have conditions other than otosclerosis at surgery, and patients lost to follow-up were excluded. Apart from the operative time, the difference in the results of none of the parameters was statistically significant in the two groups. The average operative times for microscope- and endoscope-assisted stapedotomy were 63 minutes and 86.5 minutes, respectively, the difference being statistically significant (P < .001).Conclusions: From the perspectives of otologists in differential positions in the learning curve for microscope- and endoscope-assisted stapedotomy, there were no statistically significant differences between the two procedures in the execution of the steps to achieve "adequate surgical exposure" and in postoperative outcomes, except for operative time.