Objectives: . The recent expansion of eligibility for cochlear implantation (CI) by the U.S. Food and Drug Administration (FDA) to include infants as young as 9 months has reignited debates concerning the clinically appropriate cut-off age for pediatric CI. Our study compared the early postoperative trajectories of receptive and expressive language development in children who received CI before 9 months of age with those who received it between 9 and 12 months. This study involved a unique pediatric cohort with documented etiology, where the timing of CI was based on objective criteria and efforts were made to minimize the influence of parental socioeconomic status. Methods: . A retrospective review of 98 pediatric implantees recruited at a tertiary referral center was conducted. The timing of CI was based on auditory and language criteria focused on the extent of delay corresponding to the bottom 1st percentile of language development among age-matched controls, with patients categorized into very early (CI at <9 months), early (CI at 9–12 months) and delayed (CI at 12–18 months) CI groups. Postoperative receptive/expressive language development was assessed using the Sequenced Language Scale for Infants receptive and expressive standardized scores and percentiles. Results: . Only the very early CI group showed significant improvements in receptive language starting at 3 months post-CI, aligning with normal-hearing peers by 9 months and maintaining this level until age 2 years. During this period (<2 years), all improvements were more pronounced in receptive language than in expressive language. Conclusion . CI before 9 months of age significantly improved receptive language development compared to later CI, with improvements sustained at least up to the age of 2. This study supports the consideration of earlier CI, beyond pediatric Food and Drug Administration labeling criteria (>9 months), in children with profound deafness who have a clear deafness etiology and language development delays (<1st percentile).

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Background: Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. Methods: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. Results: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. Conclusion DA-2802 is considered an effective and safe treatment for patients with CHB.

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background: Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. Methods: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. Results: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. Conclusion This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

OBJECTIVES: Uterine sarcoma is a rare malignant tumor, which is usually diagnosed in postmenopausal women. These sarcomas are occasionally misdiagnosed as uterine fibroids, thereby leading to delayed diagnosis in the advanced stages. We analyzed the sonographic and clinical characteristics of unexpected uterine sarcomas detected after surgery in women in the late reproductive age.METHODS: The medical records of 61 patients preoperatively diagnosed with uterine leiomyomas through sonography but confirmed as uterine sarcomas after surgery from January 2005 to December 2018 at Asan Medical Center were retrospectively analyzed. We evaluated the clinical symptoms, sonographic findings, and Doppler indexes, and investigated whether there were any significant characteristics that could clearly differentiate uterine sarcoma from fibroids.RESULTS: The most common clinical finding was increased mass size (15 patients, 24.6%), while 9 patients (14.8%) showed no symptoms. Ultrasonography showed that the maximum diameter of most fibroids was > 5 cm (49 patients, 80.3%), and the average diameter was 75.6 ± 36.3 mm. All the patients showed heterogeneous echogenicity in sonographic imaging. Secondary degeneration of the myomas was reported in 36 patients (59%), and approximately 90% (32/36, 88.9%) showed cystic changes. Of the 40 patients who underwent the evaluation of vascularity, 35 showed increased vascularity of the mass.CONCLUSIONS: In this study, sarcomas misdiagnosed as leiomyomas were usually > 5 cm, and ultrasonography showed heterogeneous echogenicity and irregular cystic degeneration. No definite clinical symptoms were helpful; a thorough evaluation is necessary to rule out uterine sarcomas in women having uterine mass with these characteristics.
Chungcheongnam-do ; Delayed Diagnosis ; Diagnostic Errors ; Female ; Humans ; Leiomyoma ; Medical Records ; Myoma ; Retrospective Studies ; Sarcoma ; Ultrasonography

BACKGROUND: A small subset of adolescents atopic dermatitis (AD) tends to persist. This also leads to get more antibiotics exposure with advancing years. Antibiotic resistance has been regarded as a serious problem during Staphylococcus aureus treatment, especially methicillin-resistant S. aureus (MRSA). OBJECTIVE: It was investigated the S. aureus colonization frequency in the skin lesions and anterior nares of adolescent AD patients and evaluated the changes in S. aureus antimicrobial susceptibility for years. METHODS: Patients who visited our clinic from September 2003 to August 2005 were classified into group A, and patients who visited from August 2010 to March 2012 were classified into group B. To investigate the differences with regard to patients' age and disease duration, the patients were subdivided into groups according to age. Lesional and nasal specimens were examined. RESULTS: Among the 295 AD patients, the total S. aureus colonization rate in skin lesions was 66.9% (95/142) for group A and 78.4% (120/153) for group B. No significant changes in the systemic antimicrobial susceptibilities of S. aureus strains isolated from adolescent AD patients were observed during about 10-year period. The increased trend of MRSA isolation in recent adolescent AD outpatients suggest that the community including school could be the source of S. aureus antibiotic resistance and higher fusidic acid resistance rates provides evidence of imprudent topical use. CONCLUSION: Relatively high MRSA isolation and fusidic acid resistance rates in recent AD patients suggest that the community harbors antibiotic-resistant S. aureus.
Adolescent ; Anti-Bacterial Agents ; Colon ; Dermatitis, Atopic* ; Drug Resistance, Microbial ; Fusidic Acid ; Humans ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Outpatients ; Skin ; Staphylococcus aureus* ; Staphylococcus*

BACKGROUND: Arsenic is a carcinogenic heavy metal that has a species-dependent health effects and abandoned metal mines are a source of significant arsenic exposure. Therefore, the aims of this study were to analyze urinary arsenic species and their concentration in residents living near abandoned metal mines and to monitor the environmental health effects of abandoned metal mines in Korea. METHODS: This study was performed in 2014 to assess urinary arsenic excretion patterns of residents living near abandoned metal mines in South Korea. Demographic data such as gender, age, mine working history, period of residency, dietary patterns, smoking and alcohol use, and type of potable water consumed were obtaining using a questionnaire. Informed consent was also obtained from all study subjects (n = 119). Urinary arsenic species were quantified using high performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP/MS). RESULTS: The geometric mean of urinary arsenic (sum of dimethylarsinic acid, monomethylarsonic acid, As3+, and As5+) concentration was determined to be 131.98 μg/L (geometric mean; 95% CI, 116.72–149.23) while urinary inorganic arsenic (As3+ and As5+) concentration was 0.81 μg/L (95% CI, 0.53–1.23). 66.3% (n = 79) and 21.8% (n = 26) of these samples exceeded ATSDR reference values for urinary arsenic (>100 μg/L) and inorganic arsenic (>10 μg/L), respectively. Mean urinary arsenic concentrations (geometric mean, GM) were higher in women then in men, and increased with age. Of the five regions evaluated, while four regions had inorganic arsenic concentrations less than 0.40 μg/L, one region showed a significantly higher concentration (GM 15.48 μg/L; 95% CI, 7.51–31.91) which investigates further studies to identify etiological factors. CONCLUSION: We propose that the observed elevation in urinary arsenic concentration in residents living near abandoned metal mines may be due to environmental contamination from the abandoned metal mine. TRIAL REGISTRATION: Not Applicable (We do not have health care intervention on human participants).
Arsenic* ; Cacodylic Acid ; Chromatography, Liquid ; Delivery of Health Care ; Drinking Water ; Environmental Health ; Female ; Humans ; Informed Consent ; Internship and Residency ; Korea* ; Male ; Mass Spectrometry ; Plasma ; Reference Values ; Smoke ; Smoking