This article describes spontaneous globe rupture as a rare but serious complication of retinoblastoma. This warrants acknowledgement and discussion, given the implications for metastatic spread should it not be managed appropriately.

Abstract Objective: At present, human bone marrow mesenchymal stem cells (hBMSCs) used as target vectors for hypopharyngeal cancer is a new therapeutic direction of great potential. However, hBMSCs would be transmitted into cancer-associated fibroblasts(CAFs) under the induction of hypopharyngeal cancer. Here, we aimed to determine whether microRNA-21(miR-21) in exosomes from FaDu cells would play a role in hypopharyngeal cancer induced transition of hBMSCs to CAFs. Methods: qRT-PCR and western blot were employed to investigate expression level of miR-21 in hypopharyngeal cancer patient samples and FaDu cells. The exosomes were collected from FaDu cells then isolated and identified. Cell morphological changes were observed by inverted phase contrast microscope. Expression level of CAF-related proteins, includingα-SMA and FAP, were assessed by qRT-PCR and western blot. Cell cycle of hBMSCs were determined by flow cytometry. Results: MiR-21 expression level was up-regulated in hypopharyngeal cancer tissue and FaDu cells. Exosomes from FaDu cells promoted CAFs-like features of hBMSCs, including up-regulation of α-SMA and FAP and cell morphological changes. Proportions of hMBSCs in G1 phase significantly decreased, while proportions of hMBSCs in G2 phase significantly decreased at the presence of exosomes from FaDu cells. What’s more, miR-21 knock-out in FaDu cells suppressed transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts and reversed the cell cycle change. Conclusions: Our data showed that miR-21 promotes hypopharyngeal cancer induced transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts. Keywords: Hypopharyngeal cancer, Bone marrow mesenchymal stem cells, Cancer-associated fibroblasts, MicroRNA-21, Exosomes

Severe autoimmune lymphoproliferative syndrome phenotype in a pediatric patient with a germline FAS gene variant Authors: Alexandra Dreyzin MD MS1; Jinjun Cheng MD PhD2, David Leitenberg MD PhD3, and Yaser Diab MBBS1Center for Cancer and Blood Disorders, Children’s National Hospital, Washington, DCDivision of Pathology and Laboratory Medicine, Children’s National Hospital, Washington, DCDepartment of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.

TitleA quality improvement project evaluating haemostasis techniques during tonsillectomy

Objective To analyze frequency-specific hearing results surgery for chronic ear diseases, in relation to various surgical factors. Study design Retrospective cohort study. Setting Tertiary referral centre. Participants A total of 173 patients with chronic ear diseases who underwent surgical management at our hospital. Main outcome measures Air conduction threshold (AC), bone conduction threshold (BC), and air-bone gap (ABG) were tested at 250, 500, 1000, 2000, and 4000 Hz, respectively. Frequency-specific results were investigate in relation to various surgical factors. Results The radical mastoidectomy group and tympanoplasty group significantly improved in AC changes at every frequency. In the tympanoplasty group, ABG at all frequencies except 4,000 (P =.069) significantly improved. AC improved at low and mid frequencies when ossicular reconstruction was conducted. Different tympanic membrane repair materials showed significant improvement in AC at all frequencies. In all groups, BC data revealed significant improvements at 500, 1000 and 2000 Hz. Conclusions The hearing improved significantly postoperatively in AC and ABG test, mainly at low and mid frequencies. The BC improved significantly at 500-2000Hz.

Objective: This study aims to explore the prevalence of anosmia and dysgeusia and their impact on COVID-19 patients. Design: This is a cross-sectional study. Patients diagnosed with COVID-19 between 1st October 2020 and 30th June 2021 were randomly selected from a national COVID-19 registry. The Anosmia Reporting Tool and a brief version of the questionnaire on olfactory disorders were used to measure the outcomes via telephone interviews. Data were analyzed using SPSS 27 statistics software. Results: A total of 405 COVID-19 adults were included in this study, 220 (54.3%) were males and 185 (45.8%) were females. The mean±SD age of participants was 38.2 ± 11.3 years. Alterations in the sense of smell and taste were reported by 206 (50.9%), and 195 (48.1%) of the patients respectively. Sex and nationality of participants were significantly associated with anosmia and dysgeusia (p<0.001) and (p-value=0.001) respectively. Among patients who experienced anosmia and dysgeusia, alterations in eating habits (64.2%), impact on mental wellbeing (38.9%), concerns that the alterations were permanent (35.4%), and physical implications and difficulty performing activities of daily living (34% ) were reported. Conclusion: Anosmia and dysgeusia are prevalent symptoms of COVID-19 disease, especially among females. Neuropsychological implications of COVID-19 in the acute infection phase and prognosis of anosmia and dysgeusia in COVID-19 are areas for further exploration.

Introduction: There is an increased demand for well-validated PROMs in otology. This study will systematically assess the methodological quality of all published patient-reported outcome measures (PROMS) for patients with multiple ear complaints and to identify the best suitable PROM for use by clinicians treating patients with multiple ear complaints. Methods: An extensive systematic mapping review on all otology questionnaires was performed to identify questionnaires measuring multiple ear complaints. The ‘Consensus‐based standards for the selection of health measurement Instruments’ (COSMIN) checklists were used to evaluate the quality of the questionnaire by two researchers. The worst item score per aspect of the methodological assessment counted. Results: Twelve multiple complaint questionnaires were included in the study for quality assessment. Ten questionnaires were disease specific (COMQ-12, CES, ZCMEI-21, MD-POSI, PAN-QOL, ETDQ-7, MDOQ, GYSSCDQ, COMOT-15 and DEU-MDDS). Two questionnaires were ear domain specific (OQUA and COQOL). The majority of multiple complaint questionnaires lacked good design with concept elicitation and patient involvement. Conclusion: For the majority of questionnaires, the quality assessment was inadequate as only a few authors consulted with patients affected by the complaints in the development. Modifications of earlier versions of PROMS or combinations of multiple questionnaires lead to ongoing (cross-cultural) validation of these questionnaires albeit the mediocre design and validation. The two domain specific questionnaires are the COQOL and OQUA, both with adequate quality but different focus. COOQL to quantify the quality of life and OQUA to measure and evaluate severity and impact of ear complaints.

Background: There is an increasing importance to increasing the day-case rate for children undergoing adenotonsillectomy. The primary aim of this study was to evaluate the immediate post-operative complication (IPOC) rate of children undergoing adenotonsillectomy for the treatment of paediatric obstructive sleep apnoea (OSA), with a view to increasing the day-case rate. IPOC was defined as any adverse clinical events experienced if admitted, or as a re-presentation to the emergency department/ward if done as a day-case, within 24 hours of the surgery. The secondary aim was to evaluate the risk factors predictive of IPOC. Methods: A retrospective analysis of children undergoing adenotonsillectomy for OSA between 01/11/2019–31/03/2022. Results: 464 children were included. Children done as a day-case experienced 0% IPOC (n=260; 220 were planned day-case). Children done as an inpatient experienced 16.7% IPOC (n=34/204). Every child who experienced IPOC had one or more of the following four clinical features: age <3 years, <15 kg, >98th weight centile, significant medical comorbidities. 269 children had none of these four clinical features, and experienced 0.371% IPOC (n=1/269; primary post-tonsillectomy bleed). Children with pre-operative oximetry scores of McGill 3-4 experienced 0% IPOC if they had none of the four clinical features (n=20). The overall readmission rate was 2.80% (n=13/464). Conclusion: Our experience suggests children with none of the four clinical risk factors identified can have adenotonsillectomy performed as a day-case procedure, irrespective of the pre-operative oximetry results. Pre-operative oximetry does not appear to add any additional value in predicting adverse post-operative events.

We aimed to report the case of a Pakistani female who presented with MMD and hyperthyroidism, and the worldwide literature review of the case reports on MMD associated with hyperthyroidism. Methods: The study was carried out using PRISMA’s recommendations. An electronic search on PubMed, Cochrane Library, and Google Scholar was carried out. Articles explaining the association between Moyamoya disease and thyroid-related diseases were included. Results: A total of 31 studies were included in the review, with the preponderance of Japanese females. The review has systematically compiled in detail all the aspects of moyamoya syndrome and thyroid disorders- from detailed histories of the included patients to the treatment interventions used and their outcomes. Conclusion: The authors are with the suggestion that more cases of MMD and its association with other major factors should be presented in Pakistan as well as in all parts of the world.

Objective: This study aimed to investigate the effect of the disease on the middle ear resonance frequencies with wide-band tympanometry in the people with temporomandibular disorder (TMD). Methods: A total of 40 individuals (24 patients, 16 control groups), 18 years of age and older, 25 females and 15 males, were included in the study. For the patients who came to the Oral Diagnosis Department of XXXX University with the complaint of TMD, the patient’s history and detailed examination were taken by the specialist dentist. Pure tone audiometry (125-8000 Hz air-way, 250-4000 Hz bone conduction thresholds) and speech audiometry, acoustic immitance and middle ear resonance measurements, outer ear resonance test were applied. Results: TMD ipsilateral and contralateral middle ear resonance values for each individual of the study group and control group and statistical data were determined. No difference was observed in the mean values of the 3 groups for middle ear resonance. However, there was a significant difference between the middle ear resonance values of the TMD ipsilateral and control groups. Conclusion: In a patient population with TMD the increase in middle ear RF values in the ipsilateral ears of the lesion may provide evidence of an increase in the stiffness of the middle ear system, offering a new perspective on the pathophysiology of the disease. KEY POINTS 1) Middle ear canal resonance frequency can be determined with wideband tympanometry (WBT). 2) There was no difference in the mean values of the three groups for the ipsilateral of the temporamandibular disorder, the contralateral of the temporamandibular disorder and the middle ear resonance values of the control group. 3) It was observed that there was a significant difference between the ipsilateral resonance values of the TMD patient group and the middle ear resonance values of the control group. 4) This study aims to present additional findings and methods for differential diagnosis by showing the differences between clinical tests applied to individuals with TMD and middle ear findings of normal individuals. 5) This study will also provide the first findings of minor middle ear pathology in patients with TMJ disorders by WBT.

Abstract Objective: To evaluate the results of the excision and chemotherapy treatment methods for ALHs located on the arytenoids. Study design: retrospective study. Methods: Twenty-six ALH patients in 29 different cases were enrolled in the study. Some patients were treated more than once. Twenty-nine cases of ALHs treated with either chemotherapy or excision were studied to assess the efficacy of both treatments. Results: All the patients in the ALH excision group were cured, and the ALHs did not recur. The mean lumen constriction score for the chemotherapy group was 2.95. The score for the ALH excision group was higher than that for the chemotherapy group. Conclusion: Both chemotherapy and excision are safe and effective treatments for ALHs located on the arytenoids. On the condition that the ALH is well exposed and can be completely removed, ALH excision surgery is a better method to treat ALHs located on the arytenoids.

Key points:  Diagnosis of AIFRS should be alert in the immunocompromised patient presenting with new-onset, rapidly progressive sinusitis with facial-cranio-orbital spread.  Extended debridement should be considered on a case-by-case basis.  Antifungal agent contributed greatly to the outcome of AIFRS.  Prognosis mostly up to the balance of underlying disease and fungal invasion, more emphasizes should be focused on comprehensive treatment.  AIFRS with facial-cranio-orbital involved often had a disastrous end.

Introduction: Vaccine hesitancy has historically played a large role in the low rate of the human papillomavirus (HPV) vaccine coverage in the United States and has further surfaced to the forefront of public discourse since the start of the COVID-19 pandemic. This study aims to determine how HPV vaccination attitudes and trends among primary care physicians and patients have changed since the COVID-19 pandemic. Design: Physicians and patients (aged 9-45) participated in a voluntary survey regarding HPV vaccination. In patients under 18 years of age, the survey was completed by the patient’s parent or guardian. Results: Of the 27 healthcare providers surveyed, 22.2% agreed that there has been an increase in misinformation about the HPV vaccine since the COVID-19 pandemic and 7.4% of providers believed that patients were less willing to discuss or receive the HPV vaccine. A majority of patients surveyed (87.7%) were aware of the HPV vaccine but only about a third of those patients had received all three doses of the vaccine (28.1%). Conclusion: Recent trends in receiving the HPV vaccine may be associated with the polarizing climate during the COVID-19 pandemic. Understanding how trends in vaccine hesitancy have changed since the pandemic will allow further and more targeted efforts to increase HPV vaccine uptake.

A document by Mohammad Haghani Dogahe. Click on the document to view its contents.

Objectives: to determine the Epidermal growth factor receptor (EGFR) over-expression in laryngeal carcinoma primary tumor and in first echelon node in N0 neck. Design: A Cross sectional retrospective study. Setting: Otolaryngology and Pathology Departments, Suez Canal University Hospital (Ismailia, Egypt). Participants: Twenty five patients. Main outcome measures: EGFR expression is linked to early neoplastic transformation, cellular proliferation, and the metastatic process in laryngeal cancer. Twenty paraffin preserved primary laryngeal squamous cell carcinoma (LSCC) and their cervical lymph nodes stained with hematoxylin & eosin and EGFR using immunohistochemical technique with scoring system. Results: EGFR expression in occult metastasis was associated with higher T stage (p=<0.001) and higher tumor grade (p=0.001). EGFR expression in occult metastasis was correlated with primary LSCC cartilage invasion (p=0.05), lymphovascular invasion (p=0.028) & muscle invasion (p=0.05). Laryngeal expression of EGFR and cervical lymph node metastasis as evidenced by EGFR immunohistochemical staining (p=0.001). Conclusion: EGFR immunohistopathological analysis of the lymph nodes and the primary tumour is a highly valuable tool for the detection of the cervical metastatic status and the N stage. Key words: Epidermal Growth Factor Receptor (EGFR), Larynx, N0, Squamous cell Carcinoma, Metastasis

Abstract Objective: To analyse the role of surgery along with antimicrobials to improve clinical outcomes in treating refractory cases of skull base osteomyelitis (SBO). Study design and setting: A prospective comparative study in a tertiary care centre with 70 SBO patients meeting eligibility criteria. Participants: The study population comprised 35 patients refractory to systemic antimicrobials of at least four weeks duration who later underwent surgery in addition to medication (surgical group). They were compared with a medical group that responded to medications alone. Main outcome measures: The outcome variables studied were the resolution of clinical features (pain, discharge, radiology, and inflammatory markers), culture yield, and total duration of treatment. Results: According to our study, relief of pain was faster in the surgical group(1.66 against 4.57 months) with statistical significance (p< 0. 001). Relief of symptoms (p< 0.001), radiological improvement (p= 0.001), and normalizing of inflammatory markers (p<0.001) were better in the surgical group than in the medical group. The duration of treatment was an average of 9. 2 months in the surgical group compared to 11.3 months in the medical group (p= 0.019). Microbial culture from deep tissue sampling was positive in 24 surgical patients (68.57%). Conclusion: The treatment response to surgery and antimicrobials in treating refractory cases of SBO was better than the group who responded to antimicrobials alone. Surgery provided higher microbial yield resulting in culture-specific antimicrobials. The surgical group observed faster relief of symptoms, reduced hospital stay, and total treatment duration.

Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by defective DNA repair, leading to hypersensitivity to ultraviolet (UV) sunlight and predisposes to various cutaneous and non-cutaneous malignancies. Platinum compounds are used against cutaneous cancers as concurrent chemoradiotherapy. But the XP gene polymorphism has a potential role in metabolism of these agents and their susceptibility. Here, we report a case of cutaneous squamous cell carcinoma in a patient with XP who had severe toxicity to chemotherapy. We also discuss other similar cases reported in literature of this entity, to highlight this potentially lethal pharmacogenomic association.

Surgical Management of Broad-basedSessileVocal Cord Polyps: Transnasal Vocal Fold Polypectomy Versus Microlaryngoscopic Surgery- Our Experience in 159 CasesRunning title: Surgical Management of Broad-based Sessile Vocal Cord Polyps

Objectives: Airway reconstruction for laryngotracheal stenosis (LTS) improves dyspnoea. There is little evidence relating to impact upon voice and swallowing. We explored voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. Design: With ethical approval, twenty consecutive LTS patients undergoing airway reconstruction at a tertiary referral center were prospectively recruited. Outcome measures were collected pre-reconstructive surgery, two-weeks post-surgery and up to 4-6 months post-surgery. These included physiological values (maximum phonation time (MPT) and fundamental frequency; penetration-aspiration score, residue score), clinician-reported (GRBAS, functional oral intake score, 100ml Water Swallow Test) and patient-reported outcomes (Voice Handicap Index-10, Reflux Symptoms Index, Eating Assessment Tool, Dysphagia Handicap Index). Results: The observational study identified patient-reported and clinician-reported voice and swallow difficulties pre- and post-surgery; median and interquartile range are reported at each timepoint: Voice Handicap Index-10 23 (8-31); 20.5 (9-33.5), 24.5 (12.5-29); Dysphagia Handicap Index 9 (0-37); 13 (7-44); 15 (4-34); GRBAS grade 1(1-2); 2 (1-2.5); 2(1-2); 100ml Water Swallow Test volume score 16.7 (11.1-20); 14.3 (12.5-16.7); 16.7 (14.3-20.0); 100ml Water Swallow Test capacity score 16.3 ± 9.0; 11.0 ± 4.1; 12.5 ± 2.6. Conclusion: We present the first prospective data on voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. The variability of the outcomes was higher than expected but importantly, for many the voice and swallow outcomes were not within normal limits before surgery. The clinical value of the study demonstrates the need for individual assessment and management of LTS patients’ voice and swallowing.

Objectives: We aimed to evaluate the trend of HPV infection status in oropharyngeal squamous cell carcinoma (OPSCC) according to various epidemiologic factors in the United States. Design: Retrospective cohort study. Setting: Surveillance, Epidemiology, and End Results (SEER) 2010-2016 database. Participants: A total of 13081 patients with OPSCC were enrolled. Patients were diagnosed with OPSCC primarily in the base of tongue, posterior pharyngeal wall, soft palate, and tonsil between 2010 and 2016 and were tested for HPV infection status. Main outcome measures: We analyzed how the number of OPSCC patients changed according to various demographic factors from 2010 to 2016. Additionally, we forecasted and confirmed the number of HPV (+) and (-) patients with OPSCC using the autoregressive integrated moving average (ARIMA) model. Results: The number of HPV (+) patients with OPSCC has increased over the past 7 years, but the degree of increase varied greatly according to the age, sex, and subsites. The number of HPV (-) patients increased until 2015 in all age groups for each site but did not change or decrease since then. Appropriate ARIMA models were applied to forecast HPV (+) and (-) patients, and the predicted data matched the actual data well. Conclusions: This large population-based study suggests that HPV (+) patients with OPSCC has increased and will continue to increase. However, the trends in HPV infection status in patients differed greatly according to various demographic factors. These results present a direction for establishing appropriate preventive measures to deal with HPV-related OPSCC in more detail.

Background: Intra and post-operative blood loss is a major risk in head and neck (H&N) surgery. Recently the use of tranexamic acid (TXA) has been investigated by multiple studies for reducing intra and post-operative bleeding, however reported results are variable. Objectives: To determine the safety and efficacy of tranexamic acid use in Head and Neck surgery. Methods: Systematic review of MEDLINE, EMBASE, CINAHL, Cochrane Library, PubMed, ClinicalKey and Clinicaltrials.gov according to the PRISMA guidelines. Studies were included if they reported on intraoperative bleeding, volume or duration of post-operative drain or return to theatre rate for post-operative haemorrhage in adult populations following use of TXA. Risk of bias assessment with Cochrane Risk of Bias (RoB2) tool for RCTs and NOS tool for non-randomised studies. Results: 16 studies were identified (114, 407 patients). 8 studies evaluated TXA in major H&N surgery and 8 studies in tonsillectomy. Primary outcomes were reduction in intraoperative or post-operative bleeding. Secondary outcomes included the duration of post-operative drain placement and return to theatre rate. No adverse events were reported in any patients. TXA is effective in reducing intra-operative blood loss in tonsillectomy. However, the effect on post-tonsillectomy haemorrhage was unclear. Insufficient evidence exists of benefit of TXA on intra-operative bleeding in major H&N procedures. Post-operative bleeding rates were substantially reduced in most major H&N studies. The duration of drain placement and risk of blood transfusion was unchanged in most cases. Conclusion: TXA use is safe in H&N patients. Whilst sufficient evidence exists to support the use of TXA in tonsillectomy, insufficient evidence exists to recommend use in major H&N surgery. Key words: Tranexamic acid, Head and Neck surgery, thyroidectomy, tonsillectomy

Objectives: To analyze the value of neutrophil‐to‐lymphocyte ratio (NLR) and anemia on results in patients with laryngeal squamous cell carcinomas (LSCC). Design and setting: The patients were categorized into 2 groups as low and high. The relationship between NLR and anemia overall survival (OS), disease-free survival (DFS), and local regional recurrence-free survival (LRRFS) was investigated. Participants: LSCC patients included. Results: OS and DFS were better in patients in low NLR group. In the multivariate analysis, high NLR was significant indicator of worse OS and DFS. Conclusions: NLR is  a biomarker in LSCC.

Objective: To investigate post-intubation laryngeal complications in severe COVID-19 patients. Methods: From September 2020 to April 2021, consecutive patients presenting with laryngological symptoms following severe COVID-19 infection and related intubation were included. Demographic, age, gender, comorbidities, symptoms, intubation duration, tracheostomy features, and laryngeal findings were collected. Videolaryngostroboscopy findings were analyzed by two senior laryngologists in a blind manner. Results: Forty-three patients completed the evaluations. The intubation duration was <14 days in 22 patients (group 1) and >14 days in 21 patients (group 2). The following abnormalities were found on an average post-intubation time of 51.6 days: posterior glottic stenosis (N=14), posterior commissure hypertrophy (N=19) or laryngeal diffuse edema (N=10), granuloma (N=8), laryngeal necrosis (N=2), vocal fold atrophy (N=2), subglottic stenosis (N=1) and glottic flange (N=1). Sixteen patients required surgical treatment (N=17 procedures). The number of intubation days was significantly higher in patients with posterior glottic stenosis (26.1 ± 9.4) compared with those presenting posterior commissure hypertrophy (11.5 ± 2.9) or granuloma (15.1 ± 5.8; p<0.001). Fourteen patients required surgical management. Conclusion: Prolonged intubation used in severe COVID-19 patients is associated with significant laryngeal disorders. Patients with a history of >2-week intubation have a higher risk of posterior glottic stenosis.

To perform surgery with a minimally invasive procedure is preferred during daily practices. With the endoscope development in otology, a direct view of ossicles or lesions in the tympanic cavity without disturbing the mastoid becomes possible. Accompanied by a growing number of endoscopic surgeries, the complications were more commonly seen due to certain drawbacks, like single-hand practices and loss of three-dimensional images[1]. Rarely, to our knowledge, dislocated stapes protrudes into the vestibule cavity during endoscopic surgery, which results in profound hearing loss and vertigo.