Background: Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature. Methods: Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1–9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7–9 (agreement) and fewer than 15% scored 1–3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one’s quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere’s disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, “There are no reliable biomarkers for sensory or emotional factors of tinnitus.”reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire. Conclusion We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus.

Objectives: Limited information is available concerning the epidemiology of stroke and acute myocardial infarction (AMI) in the Republic of Korea. This study aimed to develop a national surveillance system to monitor the incidence of stroke and AMI using national claims data. Methods: We developed and validated identification algorithms for stroke and AMI using claims data. This validation involved a 2-stage stratified sampling method with a review of medical records for sampled cases. The weighted positive predictive value (PPV) and negative predictive value (NPV) were calculated based on the sampling structure and the correspondingsampling rates. Incident cases and the incidence rates of stroke and AMI in the Republic ofKorea were estimated by applying the algorithms and weighted PPV and NPV to the 2018National Health Insurance Service claims data. Results: In total, 2,200 cases (1,086 stroke cases and 1,114 AMI cases) were sampled from the 2018 claims database. The sensitivity and specificity of the algorithms were 94.3% and 88.6% for stroke and 97.9% and 90.1% for AMI, respectively. The estimated number of cases, including recurrent events, was 150,837 for stroke and 40,529 for AMI in 2018. The age- and sex-standardized incidence rate for stroke and AMI was 180.2 and 46.1 cases per 100,000 person-years, respectively, in 2018. Conclusion This study demonstrates the feasibility of developing a national surveillance system based on claims data and identification algorithms for stroke and AMI to monitor their incidence rates.

Purpose: Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and Methods: Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. Results: A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. Conclusion Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Objectives: . The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors affecting the extrusion rate, recurrence rate, and complications of VT insertion. Methods: . A prospective study was conducted between June 2014 and December 2016 (the EVENT study [analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media]), with follow-up data collected until the end of 2017. Patients aged <15 years diagnosed with otitis media with effusion who received VT insertion were recruited at 15 tertiary hospitals. The primary outcomes were time to extrusion of VT, time to effusion recurrence, and complications. Results: . Data from 401 patients were analyzed. After excluding the results of long-lasting tubes (Paparella type II and T-tubes), silicone tubes (Paparella type I) exhibited a significantly longer extended time to extrusion (mean, 400 days) than titanium tubes (collar-button-type 1.0 mm: mean, 312 days; P<0.001). VT material (hazard ratio [HR], 2.117, 95% confidence interval [CI], 1.254–3.572; P=0.005), age (HR, 3.949; 95% CI, 1.239–12.590; P=0.02), and effusion composition (P=0.005) were significantly associated with the time to recurrence of middle ear effusion. Ears with purulent (mean, 567 days) and glue-like (mean, 588 days) effusions exhibited a shorter time to recurrence than ears with serous (mean, 846 days) or mucoid (mean, 925 days) effusions. The revision VT rates during follow-up were 3.5%, 15.5%, 10.4%, and 38.9% in ears with serous, mucoid, glue-like, and purulent effusions, respectively (P<0.001). The revision surgery rates were higher among patients aged <7 years than among those aged ≥7 years. Conclusion . Silicone tubes (Paparella type I) were less prone to early extrusion than titanium 1.0 mm tubes. VT type, patient age, and effusion composition affected the time to recurrence of effusion.

Objectives: . This study was conducted to evaluate the user satisfaction, efficacy, and safety of round window (RW) vibroplasty using the Vibrant Soundbridge (VSB) in patients with persistent mixed hearing loss after mastoidectomy. Methods: . The study included 27 patients (mean age, 58.7 years; age range, 28–76 years; 11 men and 16 women) with mixed hearing loss after mastoidectomy from 15 tertiary referral centers in Korea. The VSB was implanted at the RW. The Korean translation of the Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire and the Korean version of the International Outcome Inventory for Hearing Aids (K-IOI-HA) questionnaire were used to evaluate user satisfaction as the primary outcome. The secondary outcome measures were audiological test results and complication rates. Results: . The mean scores for ease of communication (61.3% to 29.7% to 30.2%), reverberation (62.1% to 43.1% to 37.4%), and background noise (63.3% to 37.7% to 34.3%) subscales of the APHAB questionnaire significantly decreased after VSB surgery. The mean K-IOI-HA scores at 3 and 6 months after surgery were significantly higher than the mean preoperative score (18.6 to 27.2 to 28.1). The postoperative VSB-aided thresholds were significantly lower than the preoperative unaided and hearing aid (HA)-aided thresholds. There was no significant difference between preoperative unaided, preoperative HA-aided, and postoperative VSB-aided maximum phonetically balanced word-recognition scores. None of the 27 patients experienced a change in postoperative bone conduction pure tone average. One patient developed temporary facial palsy and two developed surgical wound infections. Conclusion . RW vibroplasty resulted in improved satisfaction and audiological test results in patients with mixed hearing loss after mastoidectomy, and the complication rate was tolerable.

BACKGROUND: In Vitro follicular maturation (IVFM) of ovarian follicles is an emerging option for fertility preservation. Many paracrine factors and two-dimensional or three-dimensional (3D) environments have been used for optimization. However, since most studies were conducted using the murine model, the physiological differences between mice and humans limit the interpretation and adaptation of the results. Marmoset monkey is a non-human primate (NHPs) with more similar reproductive physiology to humans. In this study, we attempted to establish a 3D matrix (Matrtigel)-based IVFM condition for marmoset ovarian follicles in combination with anti-apoptotic factor, X-linked inhibitor of apoptosis protein (XIAP). METHODS: Marmoset follicles were isolated as individual follicles and cultured in a single drop with the addition of 0, 10, and 100 lg/mL of XIAP molecules. Matured oocytes and granulosa cells from mature follicles were collected and analyzed. The average number of isolated follicles was less than 100, and primordial and antral follicles were abundant in the ovaries. RESULTS: IVFM of marmoset follicles in 3D matrix conditions with XIAP increased the rates of survival and In Vitro follicle development. Furthermore, oocytes from the 3D cultures were successfully fertilized and developed In Vitro. The addition of XIAP increased the secretion of estradiol and aromatase. Furthermore, expression of granulosa-specific genes, such as bone morphogenetic protein 15, Oct4, and follicle-stimulating hormone receptor were upregulated in the In Vitro-matured follicles than in normal, well-grown, and atretic follicles. Apoptosis-related B-cell lymphoma-2 was highly expressed in the atretic follicles than in the XIAP-treated follicles, and higher caspase-3 was localized in the XIAP-treated follicles. CONCLUSION In this study, we attempted to establish a 3D-matrix-based marmoset IVFM condition and demonstrated the synergistic effects of XIAP. The use of a 3D matrix may be applied as an optimal culture condition for marmoset ovarian follicles.

Background: Few studies have been conducted in Korea on concordance regarding chronic diseases and lifestyle factors among couples. We, therefore, evaluated spousal concordance regarding lifestyle factors and chronic diseases among Korean couples. Methods: A total 1,040 participants (520 couples) who visited family physicians were recruited from 22 hospitals. All participants were aged ≥40 years. Participants completed questionnaires on smoking, drinking, physical activity, and irregular eating habits, including skipping breakfast. We estimated the spousal concordance regarding lifestyle factors and chronic diseases using McNemar tests and logistic regression analysis. Results: The concordance rate was high among couples who shared unhealthy behaviors, such as low physical activity, irregular diet, and skipping breakfast (P<0.05). When cardiovascular risk factors such as overweight (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.14–2.63), hypertension (OR, 1.88; 95% CI, 1.23–2.86), or hyperlipidemia (OR, 2.41; 95% CI, 1.60–3.64) were prevalent among husbands, the odds that their wives also had the same risk factors at the same time was significantly high. The odds of being depressed when the spouse was depressed were also significantly high in both men (OR, 5.54; 95% CI, 2.19–13.96) and women (OR, 4.52; 95% CI, 1.77–11.53). Conclusion There was a high level of concordance regarding lifestyle factors among couples, which could lead to an increase in the prevalence of chronic diseases among couples. In addition, if a spouse has depression, the odds of their partner also having depression was high.

Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes.

BACKGROUND: This study assessed the association between shift work and high-sensitivity C-reactive protein (hs-CRP) level, a risk factor for cardiovascular disease (CVD), in female workers in electronics manufacturing services (EMS). METHODS: Female EMS workers who received special medical examinations for workers in Gyeongnam, Korea between January 2017 and December 2017 were enrolled in this study. Their age, marital status, education level, alcohol consumption, smoking habit, regular exercise, quality of sleep, work stress, and depression were investigated, and blood tests were conducted. The t- and χ2 tests were conducted to compare the general and biochemical characteristics between daytime and shift worker groups. Age-adjusted partial correlation analysis was performed to examine the linear relationship between hs-CRP level and other risk factors for CVDs. In addition, the difference in hs-CRP levels according to work schedule was analyzed by ANCOVA after adjusting for variables that could affect the hs-CRP level. RESULTS: Although the average hs-CRP levels did not differ significantly between daytime and shift workers (0.92 ± 1.87 and 1.07 ± 2.20 mg/dL, respectively), shift workers tended to show a higher hs-CRP level (p = 0.067). After adjusting for variables that can affect the hs-CRP level, the estimated average hs-CRP level was significantly higher in shift workers (1.325 ± 0.156 mg/dL) than that in daytime workers (0.652 ± 0.350 mg/dL) (p = 0.003). CONCLUSIONS: The results of this study identified a relationship between shift work and hs-CRP level increase in women. Because multiple studies have reported associations between increased hs-CRP and CVD, follow-up of hs-CRP may help early detection of CVD in shift workers.
Alcohol Drinking ; Appointments and Schedules ; C-Reactive Protein ; Cardiovascular Diseases ; Depression ; Education ; Female ; Follow-Up Studies ; Hematologic Tests ; Humans ; Inflammation ; Korea ; Marital Status ; Risk Factors ; Smoke ; Smoking

BACKGROUND: Despite recent advance in conventional cancer therapies including surgery, radiotherapy, chemotherapy, and immunotherapy to reduce tumor size, unfortunately cancer mortality and metastatic cancer incidence remain high. Along with a deeper understanding of stem cell biology, cancer stem cell (CSC) is important in targeted cancer therapy. Herein, we review representative patents using not only normal stem cells as therapeutics themselves or delivery vehicles, but also CSCs as targets for anti-cancer strategy. METHODS: Relevant patent literatures published between 2005 and 2017 are discussed to present developmental status and experimental results on using normal stem cells and CSCs for cancer therapy and explore potential future directions in this field. RESULTS: Stem cells have been considered as important element of regenerative therapy by promoting tissue regeneration. Particularly, there is a growing trend to use stem cells as a target drug-delivery system to reduce undesirable side effects in non-target tissues. Noteworthy, studies on CSC-specific markers for distinguishing CSCs from normal stem cells and mature cancer cells have been conducted as a selective anti-cancer therapy with few side effects. Many researchers have also reported the development of various substances with anticancer effects by targeting CSCs from cancer tissues. CONCLUSION: There has been a continuing increase in the number of studies on therapeutic stem cells and CSC-specific markers for selective diagnosis and therapy of cancer. This review focuses on the current status in the use of normal stem cells and CSCs for targeted cancer therapy. Future direction is also proposed.
Biology ; Diagnosis ; Drug Therapy ; Immunotherapy ; Incidence ; Mortality ; Neoplastic Stem Cells* ; Radiotherapy ; Regeneration ; Stem Cells*