Clinical characteristics and outcomes of patients with mpox during the 2022 mpox outbreak compared with those before the outbreak: A systematic review and meta-analysis.

On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre-outbreak (2003-2021) and the current mpox outbreak. In this systematic review and meta-analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword "monkeypox" and "mpox" up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52-17.08), fever (0.68, 0.49-0.94), pruritus (0.25, 0.19-0.32), myalgia (0.50, 0.31-0.81), headache (0.56, 0.35-0.88), skin ulcer (0.32, 0.17-0.59), abdominal symptom (0.29, 0.20-0.42), pharyngitis (0.32, 0.18-0.58), nausea or vomiting (0.15, 0.02-0.93), conjunctivitis (0.11, 0.03-0.38), concomitant infection with HIV (1.70, 0.95-3 0.04), and death (0.02, 0.001-0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox-related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat.

Global burden of vaccine-associated multiple sclerosis, 1967-2022: A comprehensive analysis of the international pharmacovigilance database.

Vaccine-associated multiple sclerosis (MS) is rare, with insufficient evidence from case reports. Given the scarcity of large-scale data investigating the association between vaccine administration and adverse events, we investigated the global burden of vaccine-associated MS and potential related vaccines from 1967 to 2022. Reports on vaccine-associated MS between 1967 and 2022 were obtained from the World Health Organization International Pharmacovigilance Database (total number of reports = 120 715 116). We evaluated global reports, reporting odds ratio (ROR), and information components (IC) to investigate associations between 19 vaccines and vaccine-associated MS across 156 countries and territories. We identified 8288 reports of vaccine-associated MS among 132 980 cases of all-cause MS. The cumulative number of reports on vaccine-associated MS gradually increased over time, with a substantial increase after 2020, owing to COVID-19 mRNA vaccine-associated MS. Vaccine-associated MS develops more frequently in males and adolescents. Nine vaccines were significantly associated with higher MS reporting, and the highest disproportional associations were observed for hepatitis B vaccines (ROR 19.82; IC025 4.18), followed by encephalitis (ROR 7.42; IC025 2.59), hepatitis A (ROR 4.46; IC025 1.95), and papillomavirus vaccines (ROR 4.45; IC025 2.01). Additionally, MS showed a significantly disproportionate signal for COVID-19 mRNA vaccines (ROR 1.55; IC025 0.52). Fatal clinical outcomes were reported in only 0.3% (21/8288) of all cases of vaccine-associated MS. Although various vaccines are potentially associated with increased risk of MS, we should be cautious about the increased risk of MS following vaccination, particularly hepatitis B and COVID-19 mRNA vaccines, and should consider the risk factors associated with vaccine-associated MS.

Global and regional burden of vaccine-associated facial paralysis, 1967-2023: Findings from the WHO international pharmacovigilance database.

The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.

Global burden of vaccine-associated anaphylaxis and their related vaccines, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

BACKGROUND: Vaccine-associated anaphylaxis is a rare but life-threatening reaction that occurs within minutes to hours of exposure to allergens. As studies utilizing large-scale data to investigate this topic are limited, further research is needed to assess its burden, long-term trends, and associated risk factors so as to gain a comprehensive understanding of vaccine-associated anaphylaxis globally. Therefore, this study aimed to investigate the global burden of vaccine-associated anaphylaxis and related vaccines. METHOD: This study utilized the World Health Organization International Pharmacovigilance Database, in which reports of vaccine-associated anaphylaxis between 1967 and 2023 were obtained (total reports = 131,255,418). We estimated the global reporting counts, reported odds ratio (ROR), and information component (IC) to identify the relationship between 19 vaccines and associated anaphylaxis in 156 countries and territories. RESULTS: We identified 31,676 reports of vaccine-associated anaphylaxis among 363,290 reports of all-cause anaphylaxis. The cumulative number of reports on vaccine-associated anaphylaxis has gradually increased over time, with a dramatic increase after 2020, owing to reports of COVID-19 mRNA vaccine-associated anaphylaxis. The typhoid vaccines were associated with the most anaphylactic reports (ROR: 4.35; IC0.25 : 1.86), followed by encephalitis (3.27; 1.45), hepatitis B (2.69; 1.30), cholera (2.65; 0.54), hepatitis A (2.44; 1.12), influenza (2.36; 1.16), inactivated whole-virus COVID-19 (2.21; 1.02), and COVID-19 mRNA vaccines (1.89; 0.79). In terms of age- and sex-specific risks, vaccine-associated anaphylaxis reports develop more frequently in females and at young ages. The Ad5-vectored COVID-19 vaccine anaphylaxis reports were associated with the highest fatality rate (15.0%). CONCLUSIONS: Although multiple vaccines are associated with various spectra and risks of anaphylaxis, clinicians should recognize the possibility of anaphylaxis occurring with all vaccines, particularly the COVID-19 mRNA and inactivated whole-virus COVID-19 vaccines, and consider the risk factors associated with vaccine anaphylaxis reports. Further studies are warranted to identify better ways of preventing vaccine-associated anaphylaxis.

Global and regional burden of vaccine-induced thrombotic thrombocytopenia, 1969-2023: Comprehensive findings with critical analysis of the international pharmacovigilance database.

OBJECTIVE: The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination. METHODS: This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries. RESULTS: We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC0.25], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%). CONCLUSION: A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis.

Limitations of the Cough Sound-Based COVID-19 Diagnosis Artificial Intelligence Model and its Future Direction: Longitudinal Observation Study.

BACKGROUND: The outbreak of SARS-CoV-2 in 2019 has necessitated the rapid and accurate detection of COVID-19 to manage patients effectively and implement public health measures. Artificial intelligence (AI) models analyzing cough sounds have emerged as promising tools for large-scale screening and early identification of potential cases. OBJECTIVE: This study aimed to investigate the efficacy of using cough sounds as a diagnostic tool for COVID-19, considering the unique acoustic features that differentiate positive and negative cases. We investigated whether an AI model trained on cough sound recordings from specific periods, especially the early stages of the COVID-19 pandemic, were applicable to the ongoing situation with persistent variants. METHODS: We used cough sound recordings from 3 data sets (Cambridge, Coswara, and Virufy) representing different stages of the pandemic and variants. Our AI model was trained using the Cambridge data set with subsequent evaluation against all data sets. The performance was analyzed based on the area under the receiver operating curve (AUC) across different data measurement periods and COVID-19 variants. RESULTS: The AI model demonstrated a high AUC when tested with the Cambridge data set, indicative of its initial effectiveness. However, the performance varied significantly with other data sets, particularly in detecting later variants such as Delta and Omicron, with a marked decline in AUC observed for the latter. These results highlight the challenges in maintaining the efficacy of AI models against the backdrop of an evolving virus. CONCLUSIONS: While AI models analyzing cough sounds offer a promising noninvasive and rapid screening method for COVID-19, their effectiveness is challenged by the emergence of new virus variants. Ongoing research and adaptations in AI methodologies are crucial to address these limitations. The adaptability of AI models to evolve with the virus underscores their potential as a foundational technology for not only the current pandemic but also future outbreaks, contributing to a more agile and resilient global health infrastructure.

The Impact of the COVID-19 Pandemic on Bell's Palsy and Ramsay-Hunt Syndrome: A Multicenter Retrospective Study.

BACKGROUND: This article presents a comprehensive review of data on the impact of facial palsy during the coronavirus disease 2019 (COVID-19) pandemic. The possible causes and pathophysiological mechanisms of changes in the epidemiology of facial palsy during the COVID-19 pandemic are also discussed. METHODS: This multicenter retrospective cohort study included 943 patients diagnosed with Bell's palsy or Ramsay Hunt syndrome. This study compared patient demographics, comorbidities, symptoms, and treatments before the COVID-19 pandemic (from 2017 to 2019) and during the COVID-19 pandemic, from 2020 to 2022). RESULTS: Following the COVID-19 outbreak, there has been a significant increase in the number of cases of Bell's palsy, particularly among elderly individuals with diabetes. Bell's palsy increased after the COVID-19 outbreak, rising from 75.3% in the pre-COVID-19 era to 83.6% after the COVID-19 outbreak. The complete recovery rate decreased from 88.2% to 73.9%, and the rate of recurrence increased from 2.9% to 7.5% in patients with Bell's palsy. Ramsay Hunt syndrome showed fewer changes in clinical outcomes. CONCLUSION: This study highlights the impact of the COVID-19 pandemic on the presentation and management of facial palsy, and suggests potential associations with COVID-19. Notably, the observed increase in Bell's palsy cases among elderly individuals with diabetes emphasizes the impact of the pandemic. Identifying the epidemiological changes in facial palsy during the COVID-19 pandemic has important implications for assessing its etiology and pathological mechanisms of facial palsy disease.

National trends in physical activity among adolescents in South Korea before and during the COVID-19 pandemic, 2009-2021.

With the ongoing COVID-19 pandemic, several previous studies from different countries showed that physical activity (PA) decreased during the COVID-19 outbreak. However, few studies have examined the recent tendency of PA in the adolescent population. Thus, we aimed to investigate the long-term trend of PA in Korean youth and the prevalence changes between before and during the COVID-19 pandemic. Data from Korea Youth Risk Behavior Web-Based Survey (KYRBS) was collected for consecutive years between 2009 and 2021. The period was separated into prepandemic (2009-2019), early-pandemic (2020), and mid-pandemic (2021). Self-reported amount of PA was categorized into four groups (insufficient, aerobic, muscle strengthening, and both physical activities) according to World Health Organization (WHO) PA guidelines. A total of 840 488 adolescents aged 12-18 who fully responded to the survey were selected (response rate: 95.2%). The 13-year trends in the proportion of adolescents who reported aerobic and muscle-strengthening activities met or exceeded 2020 WHO exercise guidelines for adolescents plateaued (11.9% from 2009 to 2011, 14.2% from 2018 to 2019, 14.4% from 2020, and 14.0% from 2021); however, the slope decreased during the pandemic (ßdiff , -0.076; 95% confidence interval [CI], -0.123 to -0.029). Proportion of sufficient aerobic exercise among adolescents sharply decreased midst the pandemic (28.0% from 2009 to 2011, 29.4% from 2018 to 2019, and 23.8% from 2020; ßdiff , -0.266; 95% CI, -0.306 to -0.226) but increased again in 2021 (26.0% from mid-COVID 19; 95% CI, 25.4-26.7). Similar patterns were observed in Metabolic Equivalent Task (MET) score (MET-min/week; 804.1 from 2018 to 2019, 720.9 from 2020, and 779.6 from 2021). The mean difference in MET score between pre-COVID and post-COVID was -55.4 MET-min/week (95% CI, -70.5 to -40.3). Through a nationwide representative study, there was no significant difference with regard to the number of Korean adolescents who achieved the PA guidelines (pre and postpandemic); however, the prevalence of recommended levels of PA needs to increase more based on the trend before the COVID-19 outbreak. The findings of this study suggest reinforcement of the importance of public health policies for Korean youths to be more physically active, especially during and after the pandemic.

Artificial Intelligence-Driven Respiratory Distress Syndrome Prediction for Very Low Birth Weight Infants: Korean Multicenter Prospective Cohort Study.

BACKGROUND: Respiratory distress syndrome (RDS) is a disease that commonly affects premature infants whose lungs are not fully developed. RDS results from a lack of surfactant in the lungs. The more premature the infant is, the greater is the likelihood of having RDS. However, even though not all premature infants have RDS, preemptive treatment with artificial pulmonary surfactant is administered in most cases. OBJECTIVE: We aimed to develop an artificial intelligence model to predict RDS in premature infants to avoid unnecessary treatment. METHODS: In this study, 13,087 very low birth weight infants who were newborns weighing less than 1500 grams were assessed in 76 hospitals of the Korean Neonatal Network. To predict RDS in very low birth weight infants, we used basic infant information, maternity history, pregnancy/birth process, family history, resuscitation procedure, and test results at birth such as blood gas analysis and Apgar score. The prediction performances of 7 different machine learning models were compared, and a 5-layer deep neural network was proposed in order to enhance the prediction performance from the selected features. An ensemble approach combining multiple models from the 5-fold cross-validation was subsequently developed. RESULTS: Our proposed ensemble 5-layer deep neural network consisting of the top 20 features provided high sensitivity (83.03%), specificity (87.50%), accuracy (84.07%), balanced accuracy (85.26%), and area under the curve (0.9187). Based on the model that we developed, a public web application that enables easy access for the prediction of RDS in premature infants was deployed. CONCLUSIONS: Our artificial intelligence model may be useful for preparations for neonatal resuscitation, particularly in cases involving the delivery of very low birth weight infants, as it can aid in predicting the likelihood of RDS and inform decisions regarding the administration of surfactant.

Expression and Role of Toll-like Receptors in Facial Nerve Regeneration after Facial Nerve Injury.

Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1-13. Among these, TLR2-5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1-5, TLR8, and TLR10-13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration.

Induction of Autophagy and Its Role in Peripheral Nerve Regeneration after Peripheral Nerve Injury.

No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.

Bacteriology and trends of antimicrobial resistance of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in otitis media: A retrospective data analysis.

OBJECTIVES: Otitis media (OM) has a high prevalence worldwide and the treatment is crucial because hearing loss in children can lead to growth disorders such as language development disorders. The aim of this study is to analyse the changes in bacterial strains and the trends of antibiotic susceptibility in otitis media with effusion (OME), chronic otitis media (COM) and cholesteatomatous otitis media (Chole OM). DESIGN: This retrospective study involved 2926 patients diagnosed with OME, COM, or Chole OM between January 2000 and December 2020. The clinical data were collected and analysed through chart review from May 2021 to July 2021. SETTING: Two tertiary medical centres. PARTICIPANTS: The 2926 OM patients. MAIN OUTCOMES AND MEASURES: An otorrhea sample was collected on the first day of their hospital visit. Middle ear fluid samples for bacterial culture and antibiotics susceptibility test were collected from patients during middle ear surgery, including ventilation tube insertion. In each type of OM, the distribution of bacterial strains in the 2000s and the 2010s was compared. In addition, changes in the detection rate of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) and trends in their antibiotic susceptibility over the last 10 years were analysed. RESULTS: The most frequently detected bacterial strains in OME, COM and Chole OM over the study period were coagulase-negative Staphylococcus (CNS) (29.6%), MRSA (24.1%), and PA (20.1%). Compared to the 2000s, the proportion of non-typable Haemophilus influenzae in OME and MRSA in COM increased in the 2010s (27.4%-31.6% and 1.5%-29.5%, respectively). In total three types of OM, although there was no significant trend of change in detection rates of MRSA, PA, and multidrug resistant-P. aeruginosa (MDR-PA) during the last 10 years, resistance to the Quinolone class of MRSA and PA tended to increase (P < .05). CONCLUSIONS: The composition of bacterial strains in each types of OM has changed over the past 20 years. Additionally, the antibiotic resistance of MRSA and PA has increased in the last decade. Therefore, when using empirical antibiotics in necessary situations, it is necessary to change to an appropriate antibiotic through a bacterial culture test and antimicrobial susceptibility test.

Usefulness of Short-Term Imaging and Squamous Cell Carcinoma Antigen to Early Predict Response to Concurrent Chemoradiotherapy in Patients With Cervical Cancer.

OBJECTIVE: The objective is to investigate the factors that can predict early treatment response in patients receiving concurrent chemoradiotherapy (CCRT) for cervical cancer. METHODS: We assessed clinical factors and treatment response in patients who underwent CCRT for cervical cancer at four time points: initial, 2.5 weeks, 6 weeks after starting CCRT, and 3 months after completing CCRT. The final treatment response was determined by positron emission tomography-computed tomography (PET-CT) 3 months after completion of CCRT. Patients were divided into two groups according to the final treatment response: complete response (CR) group or non-CR group. And the early CCRT response prediction model was developed using stepwise multivariate logistic regression analysis. RESULTS: Of the 62 patients who underwent CCRT for cervical cancer, 57 patients who completed all 4 time points examinations were included in the analyses and classified as CR (n = 32) and non-CR (n = 25) group. Tumor volume and serum squamous cell carcinoma antigen (SCC Ag) of the initial, 2.5 weeks, and 6 weeks after CCRT were significantly associated with the final treatment response. For the early treatment response prediction model, we selected patient age, tumor volume, and SCC Ag measured at initial and 2.5 weeks of CCRT as variables, and the equation of the final model was yielded. Using a cutoff of 0.433, this model had a sensitivity of 72.0%, a specificity of 84.4%, and a probability of 0.8225 (P < .0001). CONCLUSION: Short-term (at 2.5 weeks after starting CCRT) measurements of tumor volume and serum SCC Ag were significant predictors of response to CCRT in patients with cervical cancer.

Investigation of Bacterial Community Using 16s rRNA Amplicon Sequencing for Children with Otitis Media Effusion in Korea.

BACKGROUND: Recently, microbiome of otitis media with effusion (OME) was investigated using high throughput sequencing (HTS) in children to discover unbiased causal bacteria and natural otitis media microbiomes. However, there are very few studies in the Asian population, and there are no studies in Koreans yet. METHODS: We investigated bacterial community of OME from 27 Korean children. Routine bacterial culture, PCR targeting six frequent bacteria, and 16S rRNA amplicon sequencing were performed on effusion samples. Medical records of patients were reviewed. RESULTS: The most common bacteria found in culture and PCR were coagulase negative Staphylococci and Hemophilus influenza, respectively. The most abundant taxon in 16S rRNA amplicon sequencing was Hemophilus. The bacteria that showed positive PCR were found to be the most abundant taxon in 16S rRNA amplicon sequencing. Alloiococcus was not found in all three methods. CONCLUSIONS: Our findings will contribute to a better understanding of causative agents of otitis media in children. The technical advancement of HTS in the clinical field will help further understanding.

The Roles of NOD-like Receptors in Innate Immunity in Otitis Media.

Acute otitis media (AOM) can persist or lead to various complications in individuals in which the innate immune system is impaired. In this context, impaired expression of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), an intracellular pathogen-recognition receptor (PRR), is involved in the etiology of OM in humans and animals, affecting its development, severity, chronicity, recurrence, and associated complications. To assess this relationship, we reviewed literature reports relating NLR expression patterns with the pathophysiology and clinical features of OM in the larger context of impaired innate immunity. We summarized the results of published studies on the expression of NLRs in animals and humans in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. NLRs were expressed mainly in association with bacterial infection in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. In addition, expression of NLRs was affected by the presence or absence of bacteria, fluid characteristics, disease recurrence, tissue type, and repeated surgery. Various factors of the innate immune system are involved in the pathogenesis of OM in the middle ear. NLRs are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. Impaired NLR expression induced the development, chronicity and recurrence of OM and exacerbated associated complications, indicating that NLRs have important roles in the pathogenesis of OM.

Role of Biomarkers as Prognostic Factors in Acute Peripheral Facial Palsy.

Acute peripheral facial palsy (APFP), including Bell's palsy and Ramsay Hunt syndrome, is a disease that affects daily life through facial motor dysfunction, causing psychological problems. Various tests to evaluate prognosis have been studied; however, there are no validated predictive biomarkers to guide clinical decision making. Therefore, specific biomarkers that respond to treatment are required to understand prognostic outcomes. In this review, we discuss existing literature regarding the role of APFP biomarkers in prognosis and recovery. We searched the PubMed, EMBASE, and Cochrane Library databases for relevant papers. Our screening identified relevant studies and biomarkers correlating with the identification of predictive biomarkers. Only studies published between January 2000 and October 2021 were included. Our search identified 5835 abstracts, of which 35 were selected. All biomarker samples were obtained from blood and were used in the evaluation of disease severity and prognosis associated with recovery. These biomarkers have been effective prognostic or predictive factors under various conditions. Finally, we classified them into five categories. There is no consensus in the literature on the correlation between outcomes and prognostic factors for APFP. Furthermore, the correlation between hematologic laboratory values and APFP prognosis remains unclear. However, it is important to identify new methods for improving the accuracy of facial paralysis prognosis prediction. Therefore, we systematically evaluated prognostic and potentially predictive APFP biomarkers. Unfortunately, a predictive biomarker validating APFP prognosis remains unknown. More prospective studies are required to reveal and identify promising biomarkers providing accurate prognosis.

Objective and Measurable Biomarkers in Chronic Subjective Tinnitus.

Tinnitus is associated with increased social costs and reduced quality of life through sleep disorders or psychological distress. The pathophysiology of chronic subjective tinnitus, which accounts for most tinnitus, has not been clearly elucidated. This is because chronic subjective tinnitus is difficult to evaluate objectively, and there are no objective markers that represent the diagnosis or therapeutic effect of tinnitus. Based on the results of studies on patients with chronic subjective tinnitus, objective and measurable biomarkers that help to identify the pathophysiology of tinnitus have been summarized. A total of 271 studies in PubMed, 303 in EMBASE, and 45 in Cochrane Library were found on biomarkers related to chronic subjective tinnitus published until April 2021. Duplicate articles, articles not written in English, review articles, case reports, and articles that did not match our topic were excluded. A total of 49 studies were included. Three specimens, including blood, saliva, and urine, and a total of 58 biomarkers were used as indicators for diagnosis, evaluation, prognosis, and therapeutic effectiveness of tinnitus. Biomarkers were classified into eight categories comprising metabolic, hemostatic, inflammatory, endocrine, immunological, neurologic, and oxidative parameters. Biomarkers can help in the diagnosis, measure the severity, predict prognosis, and treatment outcome of tinnitus.

Potential Therapeutic Strategies and Substances for Facial Nerve Regeneration Based on Preclinical Studies.

Despite advances in microsurgical technology and an improved understanding of nerve regeneration, obtaining satisfactory results after facial nerve injury remains a difficult clinical problem. Among existing peripheral nerve regeneration studies, relatively few have focused on the facial nerve, particularly how experimental studies of the facial nerve using animal models play an essential role in understanding functional outcomes and how such studies can lead to improved axon regeneration after nerve injury. The purpose of this article is to review current perspectives on strategies for applying potential therapeutic methods for facial nerve regeneration. To this end, we searched Embase, PubMed, and the Cochrane library using keywords, and after applying exclusion criteria, obtained a total of 31 qualifying experimental studies. We then summarize the fundamental experimental studies on facial nerve regeneration, highlighting recent bioengineering studies employing various strategies for supporting facial nerve regeneration, including nerve conduits with stem cells, neurotrophic factors, and/or other therapeutics. Our summary of the methods and results of these previous reports reveal a common feature among studies, showing that various neurotrophic factors arising from injured nerves contribute to a microenvironment that plays an important role in functional recovery. In most cases, histological examinations showed that this microenvironmental influence increased axonal diameter as well as myelination thickness. Such an analysis of available research on facial nerve injury and regeneration represents the first step toward future therapeutic strategies.

Immunoglobulins and Transcription Factors in Otitis Media.

The causes of otitis media (OM) involve bacterial and viral infection, anatomo-physiological abnormalities of the Eustachian canal and nasopharynx, allergic rhinitis, group childcare centers, second-hand smoking, obesity, immaturity and defects of the immune system, formula feeding, sex, race, and age. OM is accompanied by complex and diverse interactions among bacteria, viruses, inflammatory cells, immune cells, and epithelial cells. The present study summarizes the antibodies that contribute to immune reactions in all types of otitis media, including acute otitis media, otitis media with effusion, and chronic otitis media with or without cholesteatoma, as well as the transcription factors that induce the production of these antibodies. The types and distribution of B cells; the functions of B cells, especially in otorhinolaryngology; antibody formation in patients with otitis media; and antibodies and related transcription factors are described. B cells have important functions in host defenses, including antigen recognition, antigen presentation, antibody production, and immunomodulation. The phenotypes of B cells in the ear, nose, and throat, especially in patients with otitis media, were shown to be CD5low, CD23high, CD43low, B220high, sIgMlow, sIgDhigh, Mac-1low, CD80(B7.1)low, CD86(B7.2)low, and Syndecam-1low. Of the five major classes of immunoglobulins produced by B cells, three (IgG, IgA, and IgM) are mainly involved in otitis media. Serum concentrations of IgG, IgA, and IgM are lower in patients with OM with effusion (OME) than in subjects without otitis media. Moreover, IgG, IgA, and IgM concentrations in the middle ear cavity are increased during immune responses in patients with otitis media. B cell leukemia/lymphoma-6 (Bcl-6) and paired box gene 5 (Pax-5) suppress antibody production, whereas B lymphocyte inducer of maturation program 1 (Blimp-1) and X-box binding protein 1 (XBP-1) promote antibody production during immune responses in patients with otitis media.

Toll-Like Receptors: Expression and Roles in Otitis Media.

Otitis media is mainly caused by upper respiratory tract infection and eustachian tube dysfunction. If external upper respiratory tract infection is not detected early in the middle ear, or an appropriate immune response does not occur, otitis media can become a chronic state or complications may occur. Therefore, given the important role of Toll-like receptors (TLRs) in the early response to external antigens, we surveyed the role of TLRs in otitis media. To summarize the role of TLR in otitis media, we reviewed articles on the expression of TLRs in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. Many studies showed that TLRs 1-10 are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. TLR expression in the normal middle ear mucosa is absent or weak, but is increased in inflammatory fluid of AOM, effusion of OME, and granulation tissue and cholesteatoma of COM. In addition, TLRs show increased or decreased expression depending on the presence or absence of bacteria, recurrence of disease, tissue type, and repeated surgery. In conclusion, expression of TLRs is associated with otitis media. Inappropriate TLR expression, or delayed or absent induction, are associated with the occurrence, recurrence, chronicization, and complications of otitis media. Therefore, TLRs are very important in otitis media and closely related to its etiology.