Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Association Between Smoking and Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease of the upper airway. The impact of smoking on CRS has not been clearly established. We aim to clarify the association between first-hand cigarette smoking and the prevalence and prognoses of CRS. REVIEW METHODS: PubMed, Embase, SCOPUS, and Cochrane Library were searched from inception until May 15, 2022. Three blinded reviewers selected relevant studies, extracted data, and evaluated study bias following a PROSPERO-registered protocol (CRD42022345585). We used random-effects meta-analyses to pool the prevalence of smoking in CRS, association between smoking status and CRS, and association of smoking with quality of life (QOL) before and after functional endoscopic sinus surgery (FESS). We also performed descriptive analyses of olfactory function, CT scores, and endoscopy scores before and after FESS. RESULTS: We included 23 cross-sectional studies, 19 cohort studies, two case-control studies, and one prospective clinical trial. The pooled prevalence of ever-smokers was 40% (95% CI = 0.30-0.51) and 33% (95% CI = 0.25-0.43) in patients with and without CRS. Compared to never-smokers, active smokers and past smokers had 1.35 (95% CI = 1.18-1.55) and 1.23 (95% CI = 1.17-1.29) higher odds of having CRS. Among patients with CRS, non-smokers reported higher initial QOL than smokers (standardized mean difference [SMD] = 0.23, 95% CI = 0.11-0.35), although post-FESS QOL was similar (SMD = 0.10, 95% CI = -0.30-0.51). Descriptive analysis found no significant correlations between smoking and post-FESS olfactory function and endoscopy scores. CONCLUSIONS: Cigarette smoking is associated with higher prevalence and odds of CRS. Clinicians should be aware that smoking predisposes to CRS, but does not negatively impact the rhinologic outcomes of FESS. Laryngoscope, 134:2513-2524, 2024.

The association between chronic sinonasal inflammation and nasopharyngeal carcinoma - A systematic review and meta-analysis.

PURPOSE: There has been mounting evidence that inflammation is a key risk factor towards the development of certain cancers. Past studies have shown associations between nasopharyngeal carcinoma (NPC) and sinonasal tract inflammation. We aim to conduct a review and meta-analysis on the association between NPC and chronic sinus inflammation. MATERIALS AND METHODS: We conducted a meta-analysis, searching 4 international databases from 1 January 1973 to 28 March 2022 for studies reporting on sinonasal inflammation and NPC in adult patients (>18 years old). We included cohort, case-control or cross-sectional studies. These studies must examine the association between a prior history of sinonasal inflammation and the risk of developing NPC. The outcome is the incidence of NPC in patients who had prior sinonasal inflammation. RESULTS: 8 studies (8245 NPC; 1,036,087 non-NPC) were included. The overall odds ratio (OR) of patients having NPC after reporting sinonasal inflammation was 1.81 (95 % CI 1.73-1.89). Of note, chronic rhinosinusitis (CRS) (OR of 1.78 (95 %-CI: 1.68-1.90)) was more closely associated with an increased risk of NPC, as compared to allergic rhinitis (AR) (OR of 1.60 (95 %-CI: 1.52-1.68)). CONCLUSION: Chronic sinonasal inflammation is significantly associated with NPC in this systemic review and meta-analysis. The true cause-effect relationship and the potential effects of targeted screening need to be explored thoroughly with large scale prospective studies.

Mepolizumab in chronic rhinosinusitis with nasal polyposis.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a heterogeneous upper airway disease that is prevalent globally. Recent research into the molecular basis of the disease has led to the development of biologics as a new therapeutic option for severe and recalcitrant forms of CRSwNP. Mepolizumab is a monoclonal antibody targeting IL-5, one of the signature cytokines of the type 2 immune response and which plays an important role in the pathogenesis of CRSwNP. Here we present the latest evidence behind mepolizumab, examining disease pathophysiology and pharmacology, as well as data from clinical trials, real-life studies and meta-analyses. As we welcome this promising step forward into precision medicine, we discuss practical issues and future perspectives on mepolizumab and biologics for CRSwNP.

Mepolizumab is a new injectable drug developed to control difficult-to-treat cases of chronic rhinosinusitis with nasal polyposis (CRSwNP), an inflammatory disease of the nose that affects many people worldwide. It works by blocking the action of IL-5, an important protein in the body that regulates inflammation. One of the main effects of this protein is promoting the activity of eosinophils, a type of white blood cell. Eosinophils contribute to tissue damage when activated inappropriately. A recent large-scale study (SYNAPSE) on patients using this drug has been completed, reporting favorable results. In this article, we discuss the science behind the disease, the drug and data from patient studies. We conclude by discussing several future challenges and opportunities in the management of CRSwNP.

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves.

OBJECTIVE: To clarify in patients with covid-19 the recovery rate of smell and taste, proportion with persistent dysfunction of smell and taste, and prognostic factors associated with recovery of smell and taste. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library, and medRxiv from inception to 3 October 2021. REVIEW METHODS: Two blinded reviewers selected observational studies of adults (≥18 years) with covid-19 related dysfunction of smell or taste. Descriptive prognosis studies with time-to-event curves and prognostic association studies of any prognostic factor were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data, evaluated study bias using QUIPS, and appraised evidence quality using GRADE, following PRISMA and MOOSE reporting guidelines. Using iterative numerical algorithms, time-to-event individual patient data (IPD) were reconstructed and pooled to retrieve distribution-free summary survival curves, with recovery rates reported at 30 day intervals for participants who remained alive. To estimate the proportion with persistent smell and taste dysfunction, cure fractions from Weibull non-mixture cure models of plateaued survival curves were logit transformed and pooled in a two stage meta-analysis. Conventional aggregate data meta-analysis was performed to explore unadjusted associations of prognostic factors with recovery. MAIN OUTCOME MEASURES: The primary outcomes were the proportions of patients remaining with smell or taste dysfunction. Secondary outcomes were the odds ratios of prognostic variables associated with recovery of smell and taste. RESULTS: 18 studies (3699 patients) from 4180 records were included in reconstructed IPD meta-analyses. Risk of bias was low to moderate; conclusions remained unaltered after exclusion of four high risk studies. Evidence quality was moderate to high. Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6% (95% confidence interval 2.7% to 11.0%, I2=70%, τ2=0.756, 95% prediction interval 0.7% to 33.5%) and 4.4% (1.2% to 14.6%, I2=67%, τ2=0.684, 95% prediction interval 0.0% to 49.0%) of patients, respectively. Sensitivity analyses suggest these could be underestimates. At 30, 60, 90, and 180 days, respectively, 74.1% (95% confidence interval 64.0% to 81.3%), 85.8% (77.6% to 90.9%), 90.0% (83.3% to 94.0%), and 95.7% (89.5% to 98.3%) of patients recovered their sense of smell (I2=0.0-77.2%, τ2=0.006-0.050) and 78.8% (70.5% to 84.7%), 87.7% (82.0% to 91.6%), 90.3% (83.5% to 94.3%), and 98.0% (92.2% to 95.5%) recovered their sense of taste (range of I2=0.0-72.1%, τ2=0.000-0.015). Women were less likely to recover their sense of smell (odds ratio 0.52, 95% confidence interval 0.37 to 0.72, seven studies, I2=20%, τ2=0.0224) and taste (0.31, 0.13 to 0.72, seven studies, I2=78%, τ2=0.5121) than men, and patients with greater initial severity of dysfunction (0.48, 0.31 to 0.73, five studies, I2=10%, τ2<0.001) or nasal congestion (0.42, 0.18 to 0.97, three studies, I2=0%, τ2<0.001) were less likely to recover their sense of smell. CONCLUSIONS: A substantial proportion of patients with covid-19 might develop long lasting change in their sense of smell or taste. This could contribute to the growing burden of long covid. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021283922.

Association of Olfactory Impairment With All-Cause Mortality: A Systematic Review and Meta-analysis.

Importance: Olfactory impairment is highly prevalent and associated with multiple comorbidities, including neurodegenerative, cardiovascular, nutritional, and immune disorders. However, epidemiologic associations between olfactory impairment and mortality are discordant. Objective: To systematically clarify the epidemiologic associations between olfactory impairment and mortality. Data Sources: The PubMed, Embase, and Cochrane Library databases were searched from inception to August 13, 2021. Study Selection: Two blinded reviewers selected observational studies published as full-length, English-language articles in peer-reviewed journals that reported the presence or severity of chronic olfactory impairment, whether objectively measured or self-reported, in association with any mortality estimate, among adults aged 18 years or older. Data Extraction and Synthesis: Two reviewers independently extracted data, evaluated study bias using the Newcastle-Ottawa Scale, and appraised the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework, following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, heterogeneity was measured using I2 statistics, sources of heterogeneity were investigated using meta-regression and subgroup meta-analyses, and publication bias was qualitatively and quantitatively assessed. Main Outcomes and Measures: Hazard ratios for all-cause mortality. Results: One retrospective cohort study and 10 prospective cohort studies (with a total of 21 601 participants) from 1088 nonduplicated records were included. Ten studies had a low risk of bias, whereas 1 study had a moderate risk; exclusion of the latter did not alter conclusions. Nine studies were included in the meta-analysis. Olfactory loss was associated with a significantly higher pooled hazard of all-cause mortality (hazard ratio, 1.52; 95% CI, 1.28-1.80; I2 = 82%). Meta-regression sufficiently explained heterogeneity, with longer mean follow-up duration weakening the pooled association, accounting for 91.3% of heterogeneity. Self-reported and objective effect sizes were similar. Associations were robust to trim-and-fill adjustment and the Egger test for publication bias. The overall quality of evidence was moderate. Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that olfactory impairment is associated with all-cause mortality and may be a marker of general health and biological aging. Further research is required to establish the underlying mechanisms and the scope for interventions.

Neuroradiological Basis of COVID-19 Olfactory Dysfunction: A Systematic Review and Meta-Analysis.

OBJECTIVE: Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention. METHODS: PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD. RESULTS: We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes. CONCLUSION: Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.

Next-Generation Allergic Rhinitis Care in Singapore: 2019 ARIA Care Pathways.

Allergic rhinitis (AR) is prevalent in Singapore, with a significant disease burden. Afflicting up to 13% of the population, AR impairs quality of life, leads to reduced work productivity and is an independent risk factor for asthma. In the last 2 decades, local studies have identified patient and physician behaviours leading to suboptimal control of the disease. Yet, there is an overall lack of attention to address this important health issue. Allergic Rhinitis and its Impact on Asthma (ARIA) is a European organisation aimed at implementing evidence-based management for AR worldwide. Recent focus in Europe has been directed towards empowering patients for self-management, exploring the complementary role of mobile health, and establishing healthcare system-based integrated care pathways. Consolidation of these ongoing efforts has led to the release of the 2019 ARIA care pathways. This review summarises the ARIA update with particular emphasis on the current status of adult AR in Singapore. In addition, we identify unmet needs and future opportunities for research and clinical care of AR in the local context.

Prognostic significance of cystic lymph nodal metastasis in nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to determine the prevalence of cystic lymph nodal metastasis (CLNM) and its prognostic value in patients with nasopharyngeal carcinoma (NPC). METHODS: A retrospective review was conducted on 257 patients with NPC, analyzing the presence of CLNM on MRI or CT scans. Oncologic outcomes were performed using the Kaplan-Meier analysis. RESULTS: One hundred eleven patients (43.2%) had CLNM at diagnosis. Overall, patients with CLNM had a poorer disease-specific survival (DSS; P < .001) and overall survival (OS; P < .001) compared with patients without CLNM. When analyzed according to nodal status, CLNM was associated with a higher rate of distant metastasis recurrence (P = .007), a poorer DSS (P < .001), and a poorer OS (P < .001) among patients with N2 disease. CONCLUSION: The prevalence of CLNM was 43.2%. In patients with N2 disease, the presence of CLNM was significantly associated with a poorer DSS, OS, and increased risk of distant metastasis recurrence.

Teary eyes due to 21 pence?

A woman in her late 70s with chronic bilateral epiphora under ophthalmology review was referred to our department for dacryocystorhinostomy after punctoplasty and detection of nasolacrimal duct obstruction. A CT scan of the paranasal sinuses for preoperative planning revealed complete opacification of the right maxillary, anterior ethmoid, frontal and sphenoid sinuses, left septal deviation and an incidental finding of foreign bodies in the right anterior nasal airspace. She proceeded with functional endoscopic sinus surgery (FESS) and removal of foreign bodies. To our surprise, a partially eroded 20 pence and 1 penny coin were found and removed from her right nasal airway. There was no history given about foreign bodies in her nose. Her symptoms improved postoperatively.

A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue.

Fluorescence lifetime imaging (FLIM) has previously been shown to provide contrast between normal and diseased tissue. Here we present progress towards clinical and preclinical FLIM endoscopy of tissue autofluorescence, demonstrating a flexible wide-field endoscope that utilised a low average power blue picosecond laser diode excitation source and was able to acquire ∼mm-scale spatial maps of autofluorescence lifetimes from fresh ex vivo diseased human larynx biopsies in ∼8 seconds using an average excitation power of ∼0.5 mW at the specimen. To illustrate its potential for FLIM at higher acquisition rates, a higher power mode-locked frequency doubled Ti:Sapphire laser was used to demonstrate FLIM of ex vivo mouse bowel at up to 2.5 Hz using 10 mW of average excitation power at the specimen.

Bell's palsy in Singapore: a view from the patient's perspective.

INTRODUCTION: Bell's palsy is a well-recognised disease with robust research on its possible aetiologies and epidemiology, but scant information on patients' concerns and concepts regarding the condition is available. We aimed to evaluate the ideas, concerns and expectations of patients with Bell's palsy in Singapore. METHODS: A cross-sectional study was conducted at a single tertiary-care hospital in Singapore. Participants were all patients with newly diagnosed Bell's palsy referred to the otolaryngology department either from the emergency department or by general practitioners. Participants were given a self-administered questionnaire and their facial nerve palsies were graded by the consultant doctor. RESULTS: A total of 52 patients were recruited, of which 41 were available for analysis. 78.0% of patients were concerned that they were having a stroke upon presentation of the symptoms. Other beliefs about the cause of the disease included overwork or stress (36.6%), something that the patient had eaten (9.8%) and supernatural forces (2.4%). About 50% of patients had tried some form of complementary or alternative therapy other than the steroids/medicines prescribed by their general practitioner or emergency physician. While 39.0% of patients agreed that the Internet had helped them understand more about their condition in addition to the information provided by the physician, 9.8% of them specifically disagreed with this statement. CONCLUSION: We have found that patients with Bell's palsy in Singapore are not very knowledgeable about the disease. Although the Internet is a useful resource, a physician's explanation of the disease and its natural progression remains of utmost importance.

Voice problems amongst primary school teachers in Singapore.

HYPOTHESIS/OBJECTIVES: Teachers are often cited to be at high risk of vocal disturbances. Many studies were performed in the West, but none locoregionally. The aim of this study is to determine the prevalence of voice problems amongst primary school teachers in six schools in Singapore and explore the associated risk factors. METHODS: A cross-sectional study was conducted across six primary schools and 214 full-time teachers were surveyed. Teachers were asked to report if they have voice problems at the day of the interview, during the past 1 year and throughout their careers. Teachers who reported having current voice problems were invited for videolaryngostroboscopy. Multivariate analyses were performed to analyze risk factors associated with voice problems. RESULTS: The point prevalence was 13.1% (95% confidence intervals [CI]: 9.3-18.3%). The past year prevalence and career prevalence were 25.4% (95% CI: 20-31.6%) and 32.1% (95% CI: 26.2-38.6%), respectively. Results showed that reflux symptoms (adjusted odds ratio [adj OR]=6.1, CI: 2.5-14.6) and microphone usage (adj OR=5.6, CI: 1.8-17.6) are risk factors for current voice disorders. Allergic rhinitis symptoms (adj OR=2.1, CI: 1.1-4.3), hypothyroid-like symptoms (adj OR=2.6, CI: 1.3-5.1), and microphone use (adj OR=3.4, CI: 1.1-10.0); allergic rhinitis symptoms (adj OR=2.6, CI: 1.4-5.1), reflux symptoms (adj OR=3.1, CI: 1.5-6.5), and the teaching of arts and theater studies (adj OR=2.8, CI: 1.4-5.9) are risk factors for voice problems in past 1 year and throughout the career, respectively. CONCLUSION: The findings confirm that teaching is a high-risk profession for acquiring voice problems. The risk factors uncovered are statistically and clinically significant and biologically plausible. There is a need for educational authorities and healthcare providers to develop effective and comprehensive prevention programs to arrest vocal attrition and its detrimental effects on the quality of teaching.

Outcomes of oral tongue cancer: does age matter?

INTRODUCTION: This is a retrospective study aimed to analyse the outcomes of oral tongue cancer with emphasis on young people. MATERIALS AND METHODS: Patients treated radically between 1998 and 2006 were included and categorised according to treatment modalities (Group A: Surgery, Group B: Surgery and adjuvant therapy, Group C: Definitive radiotherapy) and age groups (≤ 40 and > 40 years). Overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRS) and metastasis-free survival (MFS) were estimated using Kaplan-Meier method. RESULTS: There were 123 patients with 32%, 53% and 15% in Group A, B and C, respectively. Of these, 17 patients (14%) were ≤40 years with 6 (15%), 8 (12%) and 3 (16%) young oral tongues in Group A, B and C, respectively. Five-year OS and DFS were 69%/72%, 41%/47% and 16%/9.5% for Group A, B and C, respectively. Young patients had similar survival as the older population with 5-year OS of 83%, 75% and 33% in Group A, B and C, as compared to the older patients (66%, 36% and 13%, respectively). CONCLUSION: Young oral tongue patients did not have worse outcomes.