Digits in noise testing in a multilingual sample of Asian adults.

OBJECTIVE: Appropriate speech-in noise assessment is challenging in multilingual populations. This study aimed to assess whether first preferred language affected performance on an English Digits-in-noise (DIN) test in the local Asian multilingual population, controlling for hearing threshold, age, sex, English fluency and educational status. A secondary aim was to determine the association between DIN test scores and hearing thresholds. DESIGN: English digit-triplets in noise testing and pure-tone audiometry were conducted. Multiple regression analysis was performed with DIN scores and hearing thresholds as dependent variables. Correlation analysis was performed between DIN-SRT and hearing thresholds. STUDY SAMPLE: 165 subjects from the Singapore Longitudinal Ageing Study, a population-based longitudinal study of community-dwellers over 55 years of age. RESULTS: Mean DIN speech reception threshold (DIN-SRT) was -5.7 dB SNR (SD 3.6; range 6.7 to -11.2). Better ear pure tone average and English fluency were significantly associated with DIN-SRT. CONCLUSIONS: DIN performance was independent of first preferred language in a multilingual ageing Singaporean population after adjusting for age, gender and education. Those with poorer English fluency had a significantly lower DIN-SRT score. The DIN test has the potential to provide a quick, uniform method of testing speech in noise in this multilingual population.

MicroRNA Landscape in Endometrial Carcinomas in an Asian population: Unraveling Subtype-Specific Signatures.

MicroRNAs (MiRNAs) are small, non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We analyzed the differential expression of miRNAs in 119 endometrial carcinomas, measuring their expression in histological subtypes, molecular subtypes, and tumors with CTNNB1 mutations. Tumors were subdivided into histological and molecular subtypes as defined by The Cancer Genome Atlas. The expression levels of 352 miRNAs were quantified using the PanoramiR panel. Mir-449a, mir-449b-5p, and mir-449c-5p were the top three miRNAs showing increased expression in both endometrioid and de-differentiated carcinomas but were not significantly increased in serous and clear cell carcinomas. The miRNAs with the most increased expression in serous and clear cell carcinomas were miR-9-3p and miR-375, respectively. We also identified 62 differentially expressed miRNAs among different molecular subtypes. Using sequential forward selection, we built subtype classification models for some molecular subtypes of endometrial carcinoma, comprising 5 miRNAs for MMR-deficient tumors, 10 miRNAs for p53-mutated tumors, and 3 miRNAs for CTNNB1-mutated tumors, with areas under curves of 0.75, 0.85, and 0.78, respectively. Our findings confirm the differential expression of miRNAs between various endometrial carcinoma subtypes and may have implications for the development of diagnostic and prognostic tools.

"Vertigo, likely peripheral": the dizzying rise of ChatGPT.

PURPOSE: The use of artificial intelligence (AI) in medical decision-making has once again come to the forefront with the prevalence of Natural Language Processing (NLP). In this exploratory article, we tested one such model, ChatGPT, for its ability to identify vestibular causes of dizziness METHODS: Eight hypothetical scenarios were presented to ChatGPT, which included varying clinical pictures and types of prompts. The responses given by ChatGPT were evaluated for coherence, clarity, consistency, accuracy, appropriateness, and recognition of limitations. ChatGPT provided coherent and logical responses. RESULTS: The model accurately provided differentials for both vestibular and non-vestibular causes of dizziness, with the correct diagnosis presented first in six of the cases, with important limitations CONCLUSION: Being an AI tool, ChatGPT lacks the ability to process certain nuances in clinical decision making, in both identifying atypical dizziness, as well as in recommending further examination steps to elucidate a clearer diagnosis. We believe that AI will continue to forge ahead in the medical field. Merging the immense knowledge base of AI programming with the nuances of clinical assessment and knowledge integration will surely enhance patient care in the years to come.

Radiopathologic predictors of 1- and 2-year frontal sinusotomy outcomes in a southeast Asian chronic rhinosinusitis population.

BACKGROUND: The frontal sinus and its drainage pathway are difficult spaces to navigate surgically. The complexity of the frontal recess anatomy as well as inflammatory factors may influence outcomes of endoscopic frontal sinusotomy. It is not clear which factors are more important in determining post-operative frontal ostium patency. OBJECTIVE: The objective is to investigate whether the distribution of fronto-ethmoidal cells, frontal recess dimensions and sinonasal inflammation predict frontal ostium patency at 1- and 2-years after endoscopic frontal sinusotomy. METHODS: A retrospective review of 94 chronic rhinosinusitis patients (185 sides) who had undergone endoscopic frontal sinusotomies between 2015 and 2019 was conducted. Computed tomography was used to evaluate the type of fronto-ethmoidal cells present and determine the dimensions of the frontal recess. The International Classification of the Radiological Complexity of frontal recess and frontal sinus was used to grade the complexity of frontal recess anatomy. Mucosal inflammation was graded according to a structured histopathology report. Frontal ostium patency at 1- and 2-years post-operatively was recorded. RESULTS: The frontal ostium patency rates were 80.9% and 73.4% at 1- and 2-years respectively. Eosinophilic predominance (adjusted OR 3.5, 95% CI 1.6-8.0, p = 0.003) and mucosal ulceration on histology (adjusted OR 4.5, 95% CI 1.1-17.9, p = 0.033) predicted ostial stenosis at 1 year. Smoking (adjusted OR 7.6, 95% CI 2.4-24.7, p = 0.001), aspirin exacerbated respiratory disease (AERD) (adjusted OR 7.6, 95% CI 1.9-30.1, p = 0.004) and histological findings of severe inflammation (adjusted OR 8.9, 95% CI 1.9-41.2, p = 0.005) were independent predictors of ostial stenosis at 2 years. Frontal cell patterns, frontal recess dimensions and frontal recess complexity did not predict frontal ostium stenosis at both 1- and 2-years post-operatively. CONCLUSION: Post-operative control of sinonasal inflammation is important in maintaining frontal ostium patency, regardless of frontal cell patterns or frontal recess dimensions.

Pathophysiology of SARS-CoV-2 Infection of Nasal Respiratory and Olfactory Epithelia and Its Clinical Impact.

PURPOSE OF REVIEW: While the predominant cause for morbidity and mortality with SARS-CoV-2 infection is the lower respiratory tract manifestations of the disease, the effects of SARS-CoV-2 infection on the sinonasal tract have also come to the forefront especially with the increased recognition of olfactory symptom. This review presents a comprehensive summary of the mechanisms of action of the SARS-CoV-2 virus, sinonasal pathophysiology of COVID-19, and the correlation with the clinical and epidemiological impact on olfactory dysfunction. RECENT FINDINGS: ACE2 and TMPRSS2 receptors are key players in the mechanism of infection of SARS-CoV-2. They are present within both the nasal respiratory as well as olfactory epithelia. There are however differences in susceptibility between different groups of individuals, as well as between the different SARS-CoV-2 variants. The sinonasal cavity is an important route for SARS-CoV-2 infection. While the mechanism of infection of SARS-CoV-2 in nasal respiratory and olfactory epithelia is similar, there exist small but significant differences in the susceptibility of these epithelia and consequently clinical manifestations of the disease. Understanding the differences and nuances in sinonasal pathophysiology in COVID-19 would allow the clinician to predict and counsel patients suffering from COVID-19. Future research into molecular pathways and cytokine responses at different stages of infection and different variants of SARS-CoV-2 would evaluate the individual clinical phenotype, prognosis, and possibly response to vaccines and therapeutics.

Epidemiology and aetiology of chronic rhinosinusitis in Asia-A narrative review.

BACKGROUND: Despite having a similar prevalence to Western populations, literature on chronic rhinosinusitis (CRS) in the Asian population is sparse. There is limited data on the epidemiology and aetiology of CRS in Asia. OBJECTIVES: To review the current literature on the epidemiology and aetiology of CRS in Asia. METHODS: This is a narrative review of published data on the epidemiology and aetiology of CRS. Studies on CRS in Asian countries, published in English and indexed on PubMed or Google Scholar were reviewed. Where available, data extracted included epidemiology, endotype and cytokine profiles and genetic profiles. RESULTS AND CONCLUSION: The prevalence of CRS in Asia ranges widely from 2.1% to 28.4%. Type 2 inflammation has been reported in 5%-55% of Asian patients, with lower levels of Type 2 cytokines reported in head to head comparisons of Western versus Asian patients. Notably, there exists marked heterogeneity in criterion of the tissue eosinophilic infiltration for diagnosis of type 2 CRS. Our review suggests that differences in prevalence of CRS and proportion of eosinophilic CRS between Asia and Europe and the Americas requires further study. Large-scale Asian studies utilising standardised definitions are needed to bridge this gap. Head to head genetic and microbiomal analysis may also be useful in understanding differences in CRS between the Asian and Western populations.

Diabetes is a risk factor for hearing loss in older adults: Results of a community screening programme.

OBJECTIVES: To investigate the association between diabetes mellitus (DM) and the prevalence and severity of hearing loss in a population of community-dwelling older adults in Singapore. MATERIALS AND METHODS: This is a retrospective, cross-sectional study of 1787 adults aged 60-100 who had undergone a comprehensive audiological assessment in a community-based audiology clinic. Data extracted included their age, hearing profile, medical history, and comorbidities collected through verbal interview at the point of audiologic assessment. Multivariate linear regression and multivariate logistic regression were performed to investigate the relationship between DM and hearing loss. RESULTS: The prevalence of DM in our studied population is 17.9%. After controlling for age, gender, race, hypertension, and hyperlipidaemia status, DM was found to be independently associated with at least moderate hearing loss (adjusted OR 1.3 [95% CI 1.06-1.59], p = .012). This was especially so in the younger (<70) age group (adjusted OR 1.7 [95% CI 1.18-2.44], p = .004). CONCLUSION: DM is an independent risk factor for the presence of at least moderate hearing in community-dwelling seniors. Individuals aged <70 with DM should be screened for hearing loss to enable early intervention.

Clinical-Pathological Correlation of the Pathophysiology and Mechanism of Action of COVID-19 - a Primer for Clinicians.

PURPOSE OF REVIEW: Increasing knowledge of the pathogenesis of the SARS-CoV-2 infection and the complex interaction between host and viral factors have allowed clinicians to stratify the severity of COVID-19 infection. Epidemiological data has also helped to model viral carriage and infectivity. This review presents a comprehensive summary of the pathophysiology of COVID-19, the mechanisms of action of the SARS-CoV-2 virus, and the correlation with the clinical and biochemical characteristics of the disease. RECENT FINDINGS: ACE2 and TMPRSS2 receptors have emerged as a key player in the mechanism of infection of SARS-CoV-2. Their distribution throughout the body has been shown to impact the organ-specific manifestations of COVID-19. The immune-evasive and subsequently immunoregulative properties of SARS-CoV-2 are also shown to be implicated in disease proliferation and progression. Information gleaned from the virological properties of SARS-CoV-2 is consistent with and reflects the clinical behavior of the COVID-19 infection. Further study of specific clinical phenotypes and severity classes of COVID-19 may assist in the development of targeted therapeutics to halt progression of disease from mild to moderate-severe. As the understanding of the pathophysiology and mechanism of action of SARS-CoV-2 continues to grow, it is our hope that better and more effective treatment options continue to emerge.

Design and Multicenter Clinical Validation of a 3-Dimensionally Printed Nasopharyngeal Swab for SARS-CoV-2 Testing.

Importance: Three-dimensionally printed nasopharyngeal swabs (3DP swabs) have been used to mitigate swab shortages during the coronavirus disease 2019 (COVID-19) pandemic. Clinical validation for diagnostic accuracy and consistency, as well as patient acceptability, is crucial to evaluate the swab's performance. Objective: To determine the accuracy and acceptability of the 3DP swab for identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design, Setting, and Participants: A diagnostic study was conducted from May to July 2020 at 2 tertiary care centers in Singapore with different reference swabs (FLOQSwab [COPAN Diagnostics] or Dacron swab [Deltalab]) and swab processing techniques (wet or dry) to evaluate the performance of the 3DP swab compared with traditional, standard-of-care nasopharyngeal swabs used in health care institutions. The participants were patients with COVID-19 in the first 2 weeks of illness and controls with acute respiratory illness with negative test results for SARS-CoV-2. Paired nasopharyngeal swabs were obtained from the same nostril and tested for SARS-CoV-2 by reverse-transcriptase polymerase chain reaction. The sequence of swabs was randomized based on odd and even participant numbers. Main Outcomes and Measures: Primary outcome measures were overall agreement (OA), positive percentage agreement (PPA), and negative percentage agreement of the 3DP swab compared with reference swabs. Secondary outcome measures were the correlation of cycle threshold (Ct) values of both swabs. Results: The mean (SD) age of participants was 45.4 (13.1) years, and most participants were men (87 of 89 [97.8%]), in keeping with the epidemiology of the COVID-19 pandemic in Singapore. A total of 79 patients with COVID-19 and 10 controls were recruited. Among the patients with COVID-19, the overall agreement and PPA of the 3DP swab was 91.1% and 93.5%, respectively, compared with reference swabs. The PPA was 100% for patients with COVID-19 who were tested within the first week of illness. All controls tested negative. The reverse-transcriptase polymerase chain reaction Ct values for the ORF1ab and E-gene targets showed a strong correlation (intraclass correlations coefficient, 0.869-0.920) between the 3DP and reference swab on independent testing at each institution despite differences in sample processing. Discordant results for both gene targets were observed only at high Ct values. Conclusions and Relevance: In this diagnostic study of 79 patients with COVID-19 and 10 controls, the 3DP swab performed accurately and consistently across health care institutions and could help mitigate strained resources in the escalating COVID-19 pandemic.

Clinical Diagnostic Study of a Novel Injection Molded Swab for SARS-Cov-2 Testing.

INTRODUCTION: The gold standard for COVID-19 diagnosis is currently a real-time reverse transcriptase polymerase chain reaction (RT-PCR) to detect SARS-CoV-2. This is most commonly performed on respiratory secretions obtained via a nasopharyngeal swab. Due to supply chain limitations and high demand worldwide because of the COVID-19 pandemic, access to commercial nasopharyngeal swabs has not been assured. 3D printing methods have been used to meet the shortfall. For longer-term considerations, 3D printing may not compare well with injection molding as a production method due to the challenging scalability and greater production costs of 3D printing. METHODS: To secure sufficient nasopharyngeal swab availability for our national healthcare system, we designed a novel injection molded nasopharyngeal swab (the IM2 swab). We performed a clinical diagnostic study comparing the IM2 swab to the Copan FLOQSwab. Forty patients with a known diagnosis of COVID-19 and 10 healthy controls were recruited. Paired nasopharyngeal swabs were obtained from the same nostril of each participant and tested for SARS-CoV-2 by RT-PCR. RESULTS: When compared to the Copan FLOQswab, results from the IM2 swab displayed excellent overall agreement and positive percent agreement of 96.0% and 94.9%, respectively. There was no significant difference in mean RT-PCR cycle threshold values for the ORF1ab (28.05 vs. 28.03, p = 0.97) and E-gene (29.72 vs. 29.37, p = 0.64) targets, respectively. We did not observe any significant adverse events and there was no significant difference in patient-reported pain. CONCLUSION: In summary, the IM2 nasopharyngeal swab is a clinically safe, highly accurate option to commercial nasopharyngeal swabs.

Using 3D-printed nose models in nasopharyngeal swab training.

BACKGROUND: The COVID-19 pandemic has swept across the globe with massive effects on health care systems as well as global economies. Enhanced testing has been put forward as a means to reduce transmission while awaiting the development of targeted therapy or effective vaccination. However, achieving accurate testing necessitates proper nasopharyngeal swab techniques. METHODS AND RESULTS: We aimed to design and investigate the utility of an anatomically accurate three-dimensional (3D) printed model of the nose in the training for nasopharyngeal swabs. These models were implemented during training sessions for healthcare workers. All participants surveyed felt that the 3D printed models were useful and beneficial in the training of nasopharyngeal swab techniques. CONCLUSIONS: 3D printed nose models are a useful tool in nasopharyngeal swab training. Their usage may help to facilitate the training of potential swabbing manpower in the upscaling of testing capabilities and volumes in this COVID-19 era.

Frequency and Clinical Utility of Olfactory Dysfunction in COVID-19: a Systematic Review and Meta-analysis.

BACKGROUND: Olfactory dysfunction (OD) has been gaining recognition as a symptom of COVID-19, but its clinical utility has not been well defined. OBJECTIVES: To quantify the clinical utility of identifying OD in the diagnosis of COVID-19 and determine an estimate of the frequency of OD amongst these patients. METHODS: PubMed was searched up to 1 August 2020. Meta-analysis A included studies if they compared the frequency of OD in COVID-19 positive patients (proven by reverse transcription polymerase chain reaction) to COVID-19 negative controls. Meta-analysis B included studies if they described the frequency of OD in COVID-19 positive patients and if OD symptoms were explicitly asked in questionnaires or interviews or if smell tests were performed. RESULTS: The pooled frequency of OD in COVID-19 positive patients (17,401 patients, 60 studies) was 0.56 (0.47-0.64) but differs between detection via smell testing (0.76 [0.51-0.91]) and survey/questionnaire report (0.53 [0.45-0.62]), although not reaching statistical significance (p = 0.089). Patients with reported OD were more likely to test positive for COVID-19 (diagnostic odds ratio 11.5 [8.01-16.5], sensitivity 0.48 (0.40 to 0.56), specificity 0.93 (0.90 to 0.96), positive likelihood ratio 6.10 (4.47-8.32) and negative likelihood ratio 0.58 (0.52-0.64)). There was significant heterogeneity amongst studies with possible publication bias. CONCLUSION: Frequency of OD in COVID-19 differs greatly across studies. Nevertheless, patients with reported OD were significantly more likely to test positive for COVID-19. Patient-reported OD is a highly specific symptom of COVID-19 which should be included as part of the pre-test screening of suspect patients.

Defining a cohort of oligometastatic nasopharyngeal carcinoma patients with improved clinical outcomes.

OBJECTIVES: To compare the clinical outcomes of oligometastatic versus widely metastatic NPC patients. MATERIALS AND METHODS: Retrospective review of 157 patients with metastatic NPC at a tertiary hospital was performed. Multivariate analysis was carried out to compare the overall and progression-free survival (OS and PFS) of these two cohorts of NPC patients. The number of organ involvement and discrete metastatic lesions associated with improved OS and PFS were ascertained. RESULTS: Patients with oligometastatic NPC (single organ, less than six discrete metastatic lesions) had a better median OS than patients with widespread metastasis (24.8 versus 12.8 months, P < .001). Similarly, the median PFS of oligometastatic NPC was better than that of polymetastatic NPC (11.7 versus 7.3 months, P < .001). CONCLUSION: Single organ disease with less than six discrete lesions is a good indicator of limited metastatic load in NPC, and is associated with improved survival.

Prognostic stratification of patients with metastatic nasopharyngeal carcinoma using a clinical and biochemical scoring system.

PURPOSE: Metastatic nasopharyngeal cancer (NPC) is known to have poor survival outcomes. Clinical and biochemical parameters may impact survival outcomes among patients with metastatic NPC and may be used for prognostication. METHODS: One-hundred and fifty-eight patients with metastatic NPC treated at a single tertiary institution were analyzed retrospectively. Multivariate analysis was carried out on patients who were given disease control treatment (n = 135). A numerical score derived from the regression coefficients of each identified independent variable was used to create prognostic groups (PG). A p value of less than 0.05 was considered significant. RESULTS: Independent negative prognostic factors included ECOG status >1, LDH level >580 U/L, hemoglobin level <12.0 g/dL and having more than one metastatic organ involvement. Three PGs were obtained: low risk (total score = 0), intermediate risk (1-2) and high risk (3-4). Median survivals of the 3 groups (low, intermediate and high risk) were 57.1, 18.1 and 8.0 months for the three different risk groups, respectively (p < 0.001). CONCLUSION: Risk stratification of patients with metastatic nasopharyngeal cancer is possible using a prognostic scoring system based on clinical and biochemical parameters. Patients with low-risk score may achieve good metastatic survival and may benefit from additional therapy for disease control.

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.

Topical versus oral antibiotics, with or without corticosteroids, in the treatment of tympanostomy tube otorrhea.

OBJECTIVE: Antibiotic treatment is the standard of care for tympanostomy tube otorrhea. This meta-analysis aims to evaluate the efficacy of topical antibiotics with or without corticosteroids versus oral antibiotics in the treatment of tube otorrhea in children. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and ProQuest. REVIEW METHODS: The above databases were searched using a search strategy for randomized controlled trials for optimal treatment of tube otorrhea in the pediatric population. PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines were followed. Primary outcome was cure (i.e. clearance of otorrhea) at 2-3 weeks. Secondary outcomes were microbiological eradication and complications such as dermatitis and diarrhea. The incidence of these events was defined as dichotomous variables and expressed as a risk ratio (RR) and number needed to benefit (NNTB) in a random-effects model. RESULTS: We identified 1491 articles and selected 4 randomized controlled trials which met our inclusion criteria. Topical treatment had better cure (NNTB = 4.7, pooled RR = 1.35, p < 0.001) and microbiological eradication (NNTB = 3.5, pooled RR = 1.47, p < 0.001 among 3 of the studies) than oral antibiotics. Oral antibiotics had higher risk of diarrhea (pooled RR = 21.5, 95% CI 8.00-58.0, p < 0.001, Number needed to harm (NNTH) = 5.4) and dermatitis (pooled RR = 3.14, 95% CI 1.20-8.20, p = 0.019, NNTH = 32). The use of topical steroids in addition to topical antibiotics was associated with a higher cure rate (pooled RR = 1.59, p < 0.001 vs pooled RR = 1.57, p = 0.293). CONCLUSION: Topical antibiotics should be the recommended treatment for management of tympanostomy tube otorrhea in view of its significantly improved clinical and microbiological efficacy with lower risk of systemic toxicity as compared to oral antibiotics. Further research is necessary to confirm the benefits of topical corticosteroids as an adjunct to topical antibiotics.