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Strabismus is prevalent among preterm infants of low gestational age and birth weight in Southeast Asian countries, with intermittent exotropia (IXT) being the most common type in South Korea. In this retrospective, cross-sectional study, we investigated the differences between full-term and premature infants with IXT. IXT patients with available childbirth history were divided into two groups: preterm vs. full-term and low birth weight (LBW) vs. normal birth weight (NBW). Parameters related to exotropia including parental heredity, surgical history, and treatment options were investigated. In univariate regression for gestational age, a result of ≥ 100 s in the Titmus test was 1.352 times more frequent in preterm than in full-term infants. When birth weight was considered instead, a result of ≥ 100 s in the Titmus test was 1.412 times more frequent in the LBW compared to the NBW group. In multivariate regression for birth weight, the frequency of a result of ≥ 100 s in the Titmus test for the LBW group was 2.032 times higher than that for the NBW group. It is particularly important to examine stereopsis in preterm and LBW patients affected by IXT to ensure timely surgical planning and avoid potential recurrence after surgery., (© 2024. The Author(s).)

Background: To investigate whether recovery from or development of metabolic syndrome (MetS) in a population is associated with an altered risk for ocular motor cranial nerve palsy (CNP)., Methods: This cohort study included 4,233,273 adults without a history of ocular motor cranial nerve palsy (ocular motor CNP) who underwent 2 consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2011. They were followed up until December 31, 2018. Participants were categorized into a MetS-free, MetS-developed, MetS-recovered, or MetS-chronic group. A multivariable Cox proportional hazard regression model was used. Model 3 was adjusted for age, sex, smoking status, alcohol consumption, and physical activity., Results: Compared with the MetS-free group, the MetS-chronic group had the highest risk of ocular motor CNP (hazard ratio [HR]: 1.424; 95% confidential interval [CI]: 1.294-1.567, Model 3), followed by the MetS-developed group (HR: 1.198, 95% CI: 1.069-1.343), and the MetS-recovered group (HR: 1.168, 95% CI: 1.026-1.311) after adjusting for potential confounders. The hazard ratio of ocular motor CNP in men with chronic MetS was 1.566 (95% CI, 1.394-1.761) while that of women with chronic MetS was 1.191 (95% CI, 1.005-1.411). Among age groups, those in their 30s and 40s showed the highest association between dynamic MetS status and ocular motor CNP., Conclusions: In our study, recovering from MetS was associated with a reduced risk of ocular motor CNP compared with chronic MetS, suggesting that ocular motor CNP risk could be managed by changing MetS status., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Background and Objectives: While emerging theories suggest that vascular dysfunction may occur concurrently with the amyloid cascade in Alzheimer disease (AD) pathogenesis, the role of vascular components as primary neurodegeneration triggers remains uncertain. The aim of this retrospective, population-based cohort study conducted in Korea was to explore the link between nonarteritic anterior ischemic optic neuropathy (NAION) and dementia risk., Methods: In this nationwide, population-based, retrospective cohort study, we identified newly diagnosed NAION from 2010 to 2017 in the Korean National Health Insurance Service database. The primary outcome was new dementia diagnoses confirmed by new ICD-10 claims coupled with antidementia medication prescriptions. We assessed dementia risk using hazard ratios (HRs) with 95% CIs over an average 2.69-year follow-up after a 1-year lag period., Results: The cohort consisted of 42,943 patients with NAION and 214,715 age-matched and sex-matched controls without NAION (mean age 61.37 years ± 10.75 SD, 55.48% female). The study found a higher risk of all-cause dementia (ACD; HR 1.28, 95% CI 1.20-1.36), AD (HR 1.27, 95% CI 1.18-1.36), vascular dementia (VaD; HR 1.31, 95% CI 1.09-1.58), and other dementia (HR 1.39, 95% CI 1.11-1.73) among patients with NAION, regardless of other potential confounding factors such as age, sex, lifestyle behaviors, economic status, and preexisting health conditions. In subgroup analysis, the associations between NAION and ACD were stronger in the younger age group (HR 1.83 for those younger than 65 years vs 1.23 for those 65 years or older; p for interaction <0.001). Moreover, the association of NAION with both ACD and VaD was particularly strong among current smokers., Discussion: We found a significant association between NAION and increased risk for ACD, AD, VaD, and other dementia even after adjusting for potential confounders such as lifestyle, health conditions, and demographic factors within a nationwide cohort. This study highlights the potential role of vascular pathology in dementia progression and suggests that NAION may serve as a robust predictor for dementia, highlighting the need for comprehensive neurologic assessment in patients with NAION. Further research is needed to clarify the association between NAION and dementia risk.

Background: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension., Methods: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment., Results: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m 2 ; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m 2 . Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients., Conclusion: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients., (© 2024. The Author(s).)

Background: This cohort study aims to examine the relationship between the occurrence of cranial nerve palsy (CNP) affecting the third, fourth, or sixth cranial nerve and the subsequent risk of stroke, with a particular focus on the modulating effect of age on this association., Methods and Results: We established a cohort of individuals diagnosed with third, fourth, or sixth CNP who underwent national health screening within 2 years of diagnosis from 2010 to 2017. A control group was matched by sex and age at a ratio of 1:5. Participants were followed until December 31, 2019. We use multivariable Cox proportional hazards regression analyses to assess the association between ocular motor CNP and subsequent stroke stratified by age. Covariates including lifestyle, health behavior, underlying comorbidities, and Charlson comorbidity index score were also adjusted. Compared with the control group, the ocular motor CNP group had a higher risk of stroke after adjusting for potential confounders (hazard ratio [HR], 1.23 [95% CI,, 1.08-1.39]). The risk of stroke increased by 8.91 times in individuals with ocular motor CNP who were in their 30s (HR, 8.91 [95% CI, 1.63-48.66]). The risk increased by 2.49 times in those who were in their 40s, 1.78 times in those who were in their 50s, and 1.32 times in those who were in their 60s (HRs, 2.49, 1.78, and 1.32 [95% CI, 1.39-4.45, 1.31-2.42, and 1.08-1.62], respectively). However, for those who were in their 20s, 70s, or 80s, the incidence of stroke did not significantly increase., Conclusions: Our study establishes an association between ocular motor CNP and an increased risk of stroke, particularly in young adults.

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age-sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116-2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252-3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP.

Understanding the association between dipstick-detected proteinuria and oculomotor cranial nerve palsy (CNP) could have significant implications for understanding the mechanism of CNP development and for developing preventive strategies against CNP development in patients with proteinuria. This study aimed to determine the relationship between dipstick-determined proteinuria and ocular motor CNP using National Sample Cohort (NSC) database from Korea's National Health Insurance Service (NHIS). A nationwide population-based cohort study was conducted using data from the NSC database of Korea's NHIS. These data were collected from 2009 to 2018. A one-year time lag was established to prevent a situation in which the causal link was inverted. Participants aged 20 years or more who were diagnosed with proteinuria in 2009 were included. Individuals with specific pre-existing CNP, missing data, and those who were newly diagnosed with CNP or who died within one year of being tested were excluded. The study population was classified into six groups according to the degree of proteinuria (negative, trace, or between 1 + and 4 +) based on the urine dipstick test. A Cox proportional hazard regression analysis was performed to determine the linkage between the degree of proteinuria and ocular motor CNP. A total of 5,807 (0.14% of subjects) with ocular motor CNP were assigned to the ocular motor CNP group and 4,047,205 subjects were assigned to the control group. After full adjustment of comorbidities, hazard ratios (HRs) for 1 + , 2 + , 3 + and 4 + proteinuria groups were 1.449 (95% confidence interval [CI] 1.244-1.687), 2.081 (1.707-2.538), 1.96 (1.322-2.904), and 3.011 (1.507-6.014), respectively, for developing ocular motor CNP compared to the proteinuria-negative group. In subgroup analysis, the HR of patients with proteinuria for the development of ocular motor CNP was higher in the younger age group (less than 40 years) (P = 0.0242) and the group with DM (P = 0.04). Our population-based cohort study demonstrated a significant association between proteinuria and the incidence of CNP, suggesting that urine protein level could be a new clinical marker for predicting the development of CNP., (© 2024. The Author(s).)

Background: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers., Research Design and Methods: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness., Results: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response., Conclusions: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

Background: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC., Methods: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan)., Results: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy., Conclusions: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression., Trial Registration: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732)., (© 2024. The Author(s).)

Background: Chronic comorbid conditions are common in patients with sepsis and may affect the outcomes. This study aimed to evaluate the prevalence and outcomes of common comorbidities in patients with sepsis., Methods: We conducted a nationwide retrospective cohort study. Using data from the National Health Insurance Service of Korea. Adult patients (age ≥ 18 years) who were hospitalized in tertiary or general hospitals with a diagnosis of sepsis between 2011 and 2016 were analyzed. After screening of all International Classification of Diseases 10th revision codes for comorbidities, we identified hypertension, diabetes mellitus (DM), liver cirrhosis (LC), chronic kidney disease (CKD), and malignancy as prevalent comorbidities., Results: Overall, 373,539 patients diagnosed with sepsis were hospitalized in Korea between 2011 and 2016. Among them, 46.7% had hypertension, 23.6% had DM, 7.4% had LC, 13.7% had CKD, and 30.7% had malignancy. In-hospital mortality rates for patients with hypertension, DM, LC, CKD, and malignancy were 25.5%, 25.2%, 34.5%, 28.0%, and 33.3%, respectively, showing a decreasing trend over time (P < 0.001). After adjusting for baseline characteristics, male sex, older age, use of mechanical ventilation, and continuous renal replacement therapy, LC, CKD, and malignancy were significantly associated with in-hospital mortality., Conclusions: Hypertension is the most prevalent comorbidity in patients with sepsis, and it is associated with an increased survival rate. Additionally, liver cirrhosis, chronic kidney disease, and malignancy result in higher mortality rates than hypertension and DM, and are significant risk factors for in-hospital mortality in patients with sepsis., (© 2024. The Author(s).)

Objectives: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration., Methods: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments., Results: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD., Conclusion: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Ssajuari-ssuk and sajabal-ssuk have many clinical benefits. It is difficult to discriminate between these two species based on general characteristics aside from the shapes of the leaves. Thus, species identification and quality control between ssajuari-ssuk and sajabal-ssuk are of great concern in plant science and clinical therapy., Objective: The aim of this study is to determine whether fast gas chromatography with uncoated surface acoustic wave sensor (GC-SAW) can be a useful technique for performing species identification and quality control using volatile patterns of ssajuari-ssuk and sajabal-ssuk air-dried for 4 months and 2 years and 4 months., Methodology: Fast GC-SAW sensor provides second unit analysis, simple, on-line measurements that do not require pretreatment of the sample and rapid sensory information. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) was employed to confirm the identification of the volatiles and compared to fast GC-SAW sensor., Results: In air-dried sajabal-ssuk, the concentration of 1,8-cineole was higher than that in air-dried ssajuari-ssuk, while the level of α-thujone was considerably lower than that of air-dried ssajuari-ssuk. Each of ssajuari-ssuk and sajabal-ssuk air-dried for 4 months and 2 years and 4 months has its own characteristic volatile pattern owing to its individual chemotypes or chemical compositions., Conclusion: Consequently, the fast GC-SAW sensor can be a useful technique for species identification and quality control using volatile patterns of ssajuari-ssuk and sajabal-ssuk air-dried for 4 months and 2 years and 4 months. This method can be used for the standardisation of quality control using volatile patterns of herbal medicines., (© 2023 John Wiley & Sons Ltd.)

Purpose: Duodenal fistula in Crohn's disease (CDF) is a rare condition with an unclear optimal surgical management approach. We reviewed a Korean multicenter cohort of CDF surgery cases and assessed their perioperative outcomes to evaluate the effectiveness of the surgical interventions., Methods: The medical records of patients who underwent CD surgery between January 2006 and December 2021 from three tertiary medical centers were retrospectively reviewed. Only CDF cases were included in this study. The demographic and preoperative characteristics, perioperative details, and postoperative outcomes were analyzed., Results: Among the initial population of 2149 patients who underwent surgery for CD, 23 cases (1.1%) had a CDF operation. Fourteen of these patients (60.9%) had a history of previous abdominal surgery, and 7 had duodenal fistula at the previous anastomosis site. All duodenal fistulas were excised and primarily repaired via a resection of the originating adjacent bowel. Additional procedures such as gastrojejunostomy, pyloric exclusion, or T-tube insertion were performed in 8 patients (34.8%). Eleven patients (47.8%) experienced postoperative complications including for anastomosis leakages. Fistula recurrence was noted in 3 patients (13%) of which one patient required a re-operation. Biologics administration was associated with fewer adverse events by multivariable analysis (P = 0.026, odds ratio = 0.081)., Conclusion: Optimal perioperative conditioning of patients receiving a primary repair of a fistula and resection of the original diseased bowel can successfully cure CDF. Along with primary repair of the duodenum, other complementary additional procedures should be considered for better postoperative outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To report the clinical manifestations of non-arteritic anterior ischemic optic neuropathy (NAION) cases after coronavirus disease 2019 (COVID-19) vaccination in Korea., Methods: This multicenter retrospective study included patients diagnosed with NAION within 42 days of COVID-19 vaccination. We collected data on vaccinations, demographic features, presence of vascular risk factors, ocular findings, and visual outcomes of patients with NAION., Results: The study included 16 eyes of 14 patients (6 men, 8 women) with a mean age of 63.5 ± 9.1 (range, 43-77) years. The most common underlying disease was hypertension, accounting for 28.6% of patients with NAION. Seven patients (50.0%) had no vascular risk factors for NAION. The mean time from vaccination to onset was 13.8 ± 14.2 (range, 1-41) days. All 16 eyes had disc swelling at initial presentation, and 3 of them (18.8%) had peripapillary intraretinal and/or subretinal fluid with severe disc swelling. Peripapillary hemorrhage was found in 50% of the patients, and one (6.3%) patient had peripapillary cotton-wool spots. In eight fellow eyes for which we were able to review the fundus photographs, the horizontal cup/disc ratio was less than 0.25 in four eyes (50.0%). The mean visual acuity was logMAR 0.6 ± 0.7 at the initial presentation and logMAR 0.7 ± 0.8 at the final visit., Conclusion: Only 64% of patients with NAION after COVID-19 vaccination have known vascular and ocular risk factors relevant to ischemic optic neuropathy. This suggests that COVID-19 vaccination may increase the risk of NAION. However, overall clinical features and visual outcomes of the NAION patients after COVID-19 vaccination were similar to those of typical NAION., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection., (© 2023. The Author(s).)

Background: Obstructive sleep apnea (OSA) is closely related to maternal obesity in pregnant women, and the association increases with later pregnancy. Obesity and OSA are risk factors of pregnancy-related complications, including gestational hypertension, gestational diabetes mellitus (GDM), and fetal morbidities. We aimed to determine the prevalence of OSA and to assess the impact of OSA on pregnancy-related disorders in overweight pregnant women., Methods: Eligible participants who were overweight [body mass index (BMI) ≥ 23 kg/m²] in gestational age 30 weeks or more, assessed OSA using a portable polysomnography at home. Clinical data were collected from pregnant women and their babies., Results: The average age of 51 participants was 34.5 years (27-44 years). The number of primipara was 25 (49%) and that of multipara was 26 (51%). Eight cases of GDM (15.7%) and five cases of preeclampsia (9.8%) were reported, and six patients (11.8%) experienced preterm delivery. In results of polysomnography, 14 patients (27.5%) were diagnosed as OSA. Apnea-hypopnea index moderately correlated with BMI ( r = 0.515, P < 0.001). The BMI ( P < 0.005) and preeclampsia rate ( P < 0.017) were higher in the OSA group compared to the control group. Odds ratios (ORs) adjusting age, BMI, parity, and abortion history were calculated. The presence of OSA increased OR of preeclampsia (OR, 13.1; 95% confidence interval, 1.1-171.3). The majority of preeclampsia patients (4/5, 80%) underwent preterm delivery., Conclusion: OSA is an important risk factor for preeclampsia, resulting in preterm delivery. For overweight pregnant women, an OSA evaluation should be mandatory., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal., Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation., Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529)., Conclusion: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Background/aim: The combination of bendamustine and rituximab (BR) is highly effective in both treatment-naïve and relapsed or refractory mantle cell lymphoma (MCL). Due to the rarity of MCL and limited accessibility of BR, clinical outcome from BR in the routine clinical practice in Korean patients are limited., Patients and Methods: To evaluate the real-world outcomes of BR treatment for MCL in Korea, medical records from 37 patients were retrospectively analyzed., Results: Twenty-five patients received BR as first-line treatment, and ten, eight, and seven patients were classified as low-, intermediate-, and high-risk by MIPI-classification, respectively. With the follow-up duration of 24.3 months, the three-year progression-free survival (PFS) rate was 80.5%±11.8%. PFS significantly differed according to MIPI-classification (p=0.002) and TP53 status (p=0.042). The three-year overall survival (OS) rate was 92.0%±5.4%. In 12 patients who received BR as salvage treatment, the median age was 66. The median PFS was 12.8 months, and the three-year OS rate was 66.8%±16.2%., Conclusion: BR is an effective regimen for both newly-diagnosed and relapsed or refractory MCL patients in Korea, with favorable response rates and outcomes., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The aim of this study is to determine the association between mental disorders and strabismus in South Korean children and adolescents., Methods: Using data from the Korean National Health Claims Database from 2011 to 2017, the prevalence rates of mental illnesses and odds ratio were calculated. Children and adolescents (1-19 years) with strabismus and their randomly selected nonstrabismic age- and sex-matched controls (1:1) were enrolled. The odds ratios were adjusted for preterm birth, cerebral palsy, and mental retardation. Subgroup analysis was performed according to sex and the type of strabismus., Results: A total of 327,076 subjects (male, 158,597; female, 168,479) identified as strabismus patients were enrolled. After adjusting for preterm birth, cerebral palsy, and mental retardation, the corrected odds ratio of overall mental illness was 1.10 (95% CI, 1.08-1.12) for the strabismus group compared to the controls: 1.7 (95% CI, 1.62-1.78) for developmental disorder, 1.36 (95% CI, 1.27-1.45) for pervasive developmental disorder (autism), 1.14 (95% CI, 1.10-1.17) for attention-deficit hyperactivity disorder (ADHD), 1.15 (95% CI, 1.05-1.27) for obsessive-compulsive disorder (OCD), 1.08 (95% CI, 1.05-1.11) for pediatric behavioral and emotional disorders, 0.93 (95% CI, 0.88-0.99) for post-traumatic stress disorder (PTSD), and 0.85 (95% CI, 0.82-0.89) for tic disorder., Conclusion: South Korean children and adolescents with strabismus had a higher relative risk for various types of mental disorders such as a developmental disorder, autism, ADHD, and OCD than the controls, whereas they had a relatively lower risk of tic disorder., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To compare obstetric and neonatal outcomes in twin pregnancies with or without gestational diabetes mellitus (GDM) before and after changes in GDM diagnostic criteria., Methods: This was a retrospective cohort study of 1,764 twin pregnancies including 130 women with GDM (GDM group) and 1,634 women without GDM (non-GDM group). Patients with pregestational diabetes, unknown GDM status, and fetal death at < 24 gestational weeks were excluded. Obstetric and neonatal outcomes were compared between the two groups by two periods: period 1 (1995-2005) and period 2 (2005-2018) when National Diabetes Data Group criteria and Carpenter and Coustan criteria were used for diagnosis of GDM, respectively., Results: The incidence of GDM in twin pregnancies increased from 4.0% in period 1 to 9.3% in period 2. Composite obstetric complications rate was significantly higher in the GDM group than that in the non-GDM group during period 1 (72.0% vs. 45.5%, P = 0.009). However, it became comparable during period 2 (60.0% vs. 57.4%, P = 0.601). Interaction between GDM and period indicated a significant differential effect of GDM by period on the rate of composite obstetric complications. The rate of composite neonatal complications was similar between the two groups during both periods. The interaction between GDM and period was not significant., Conclusion: After changes of GDM diagnostic criteria, the incidence of GDM increased more than twice, and the rate of composite obstetric complications decreased, but the rate of composite neonatal complications did not change significantly., (© 2021. The Author(s).)

Introduction: The easiest way to prevent noise-induced hearing loss (NIHL) is to wear earplugs. The Republic of Korea (ROK) Ministry of National Defense (MND) is supplying earplugs to prevent NIHL, but many patients still suffer from this. We speculated that earplugs would have a high NIHL rate, depending on the rate of use of earplugs, regardless of the rate of supply. Therefore, we conducted this study to investigate the relationship between the use of earplugs and hearing loss by ROK military personnel., Methods: The study used data from the Military Health Survey conducted in 2014-2015, which included 13 470 questionnaires completed by ROK military personnel. Hearing loss and earplug use were self-reported. Logistic regression analysis was used to assess associations between earplug use and hearing loss., Results: The study sample included 13 470 ROK military personnel (response rate of 71.2%) (Army, 8330 (61.8%); Navy/Marines, 2236 (16.6%); and Air Force, 2904 (21.6%)). Overall, 18.8% of Korean military personnel reported that they always wore earplugs, and 2.8% reported hearing loss. In logistic regression analysis, there were significant differences in the rates of hearing loss associated with wearing earplugs sometimes (OR=1.48, 95% CI 1.07 to 2.05) and never wearing earplugs (OR=1.53, 95% CI 1.12 to 2.10). In subgroup analysis, in Air Force, non-combat branch, forward area and long-term military service personnel increased hearing loss was associated with not wearing earplugs., Conclusion: Our study confirmed that within the ROK military, there is an association between hearing loss and lack of earplug use. In the ROK MND, Army, Navy/Marines and Air Force headquarters must provide guidelines for the use of earplugs during field training to protect military personnel's hearings and, if necessary, need to be regulated or institutionalised., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To assess the association between metabolic syndrome (MetS) and the development of third, fourth, and sixth cranial nerve palsy (CNP). Health checkup data of 4,067,842 individuals aged between 20 and 90 years provided by the National Health Insurance Service (NHIS) of South Korea between January 1, 2009, and December 31, 2009, were analyzed. Participants were followed up to December 31, 2017. Hazard ratio (HR) and 95% confidence interval (CI) of CNP were estimated using Cox proportional hazards regression analysis after adjusting for potential confounders. Model 1 included only incident CNP as a time-varying covariate. Model 2 included model 1 and individual's age and sex. Model 3 included model 2, smoking status, alcohol consumption, and physical activity of individuals. We identified 5,835 incident CNP cases during the follow-up period (8.22 ± 0.94 years). Individuals with MetS (n = 851,004) showed an increased risk of CNP compared to individuals without MetS (n = 3,216,838) after adjustment (model 3: HR = 1.35, 95% CI 1.273-1.434). CNP incidence was positively correlated with the number of MetS components (log-rank p < 0.0001). The HR of CNP for males with MetS compared to males without MetS was higher than that of females with MetS compared to females without MetS (HR: 1.407, 95% CI 1.31-1.51 in men and HR: 1.259, 95% CI 1.13-1.40 in women, p for interaction = 0.0017). Our population-based large-scale cohort study suggests that MetS and its components might be risk factors for CNP development., (© 2021. The Author(s).)

Background: People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m² and 30.0 kg/m², respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m²: overweight, ≥ 25 kg/m²: obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women., Methods: We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to follow-up were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5-22.9, 23.0-24.9, 25.0-29.9, and ≥ 30.0 kg/m², respectively., Results: Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission., Conclusion: Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m² after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Objective: To investigate the association between maternal pre-pregnancy body mass index (BMI) and the risk for gestational diabetes mellitus (GDM) in women with twin pregnancy in South Korea., Materials and Methods: We performed a single-center, retrospective cohort study involving 1028 women with twin pregnancy from January 2006 to December 2018 in South Korea. Pregnancies with monoamnionic twins, twin-twin transfusion syndrome, fetal death in utero before 24 weeks, pre-gestational diabetes mellitus, and unknown BMI or GDM status were excluded. Subjects were grouped into four groups based on pre-pregnancy BMI: underweight (<18.5 kg/m 2 ), normal (18.5-22.9 kg/m 2 ), overweight (23.0-24.9 kg/m 2 ), and obese (≥25.0 kg/m 2 )., Results: Among 1028 women who were included in the analysis, 169 (16.4%), 655 (63.7%), 111 (10.8%), and 93 (9.0%) women were underweight, normal, overweight, and obese, respectively, before pregnancy. The incidence of GDM was 8.9% in the total study population: 4.7%, 8.2%, 11.7%, and 17.2% in the underweight, normal, overweight, and obese group, respectively (p = 0.005). The incidence of GDM significantly increased according to the increase in pre-pregnancy BMI (p < 0.001). Women in the obese group were more likely to be affected by GDM compared to the normal group (adjusted odds ratio = 2.20, 95% confidence interval = 1.19-4.08) after controlling for maternal age, parity, type of conception, and chorionicity., Conclusion: In twin pregnancies in South Korea, the risk of GDM increased as maternal pre-pregnancy BMI increased and obese women before pregnancy were more likely to be affected by GDM., Competing Interests: Declaration of competing interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Korean mugwort has been used as a traditional medicine. Specifically, air-dried Artemisia princeps Pamp. cv. ssajuari (ssajuari-ssuk; Korean mugwort) has been used as moxa in moxibustion therapy. Thus, the evaluation of high quality ssajuari-ssuk containing herbal volatiles is of great interest in clinical therapy and the food industry., Objective: The aim of this study is to determine whether fast gas chromatography with uncoated surface acoustic wave (fast GC/SAW) sensor can be a useful technique for performing quality control using herbal volatiles of ssajuari-ssuk air-dried for different times., Methodology: Fast GC/SAW sensor, called "Electronic zNose", is also a headspace sampling method and is an effective simple analytical method with a second unit analysis providing on-line measurements without the need for pretreatment of the sample. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) was employed to confirm the identification of the volatiles and compared to fast GC/SAW sensor., Results: Artemisia princeps Pamp. cv. ssajuari air-dried for 2 years and 4 months (the third year), containing the highest total amount of herbal volatiles, was superior to the others (the first year, the second year, the fourth year) in quality. Moreover, fast GC/SAW sensor shows a high repeatability (relative standard deviation 0.77% ∼ 6.23%), excellent sensitivity (limit of detection value of 0.47 pg/mL), and good linearity (correlation coefficient r 2 = 0.997) over the range of nanogram for α-thujone., Conclusion: Therefore, the fast GC/SAW sensor can be a useful analytical method for the discrimination and quality control of volatiles of herbal and medicinal plants according to air-drying time, as it provides a simple and second unit analysis., (© 2020 John Wiley & Sons Ltd.)

Background: The purpose of this study was to assess the correlation between sedatives and mortality in critically ill patients who required mechanical ventilation (MV) for ≥ 48 hours from 2008 to 2016., Methods: We conducted a nationwide retrospective cohort study using population-based healthcare reimbursement claims database. Data from adult patients (aged ≥ 18) who underwent MV for ≥ 48 hours between 2008 and 2016 were identified and extracted from the National Health Insurance Service database. The benzodiazepine group consisted of patients who were administered benzodiazepines for sedation during MV. All other patients were assigned to the non-benzodiazepine group., Results: A total of 158,712 patients requiring MV for ≥ 48 hours were admitted in 55 centers in Korea from 2008 to 2016. The benzodiazepine group had significantly higher in-hospital and one-year mortality compared to the non-benzodiazepine group (37.0% vs. 34.3%, 55.0% vs. 54.4%, respectively). Benzodiazepine use decreased from 2008 to 2016, after adjusting for age, sex, and mean Elixhauser comorbidity index in the Poisson regression analysis (incidence rate ratio, 0.968; 95% confident interval, 0.954-0.983; P < 0.001). Benzodiazepine use, older age, lower case volume (≤ 500 cases/year), chronic kidney disease, and higher Elixhauser comorbidity index were common significant risk factors for in-hospital and one-year mortality., Conclusion: In critically ill patients undergoing MV for ≥ 48 hour, the use of benzodiazepines for sedation, older age, and chronic kidney disease were associated with higher in-hospital mortality and one-year mortality. Further studies are needed to evaluate the impact of benzodiazepines on the mortality in elderly patients with chronic kidney disease requiring MV for ≥ 48 hours., Competing Interests: Ho Geol Ryu has received an honorarium and research funds from Pfizer. Other authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Introduction: According to data released by the Korea National Statistical Office, the number of accidents has been decreasing since 2012. However, a considerable number of deaths related to safety accidents (23-46 deaths) are still reported annually. This study aimed to observe the correlation between accident prevention activities in the Republic of Korea (ROK) military and the incidence of safety accidents., Methods: The study used data from the 2014-2015 Military Health Survey and included 13 618 responses (Army: 8414 (61.8%); Navy/Marine: 2262 (16.6%); Air Force: 2942 (21.6%)) from the ROK military personnel. Accident experiences and thoughts on accident prevention activities were self-reported. Multiple logistic regression analysis was used to examine the validity of accident prevention activity and accident experience., Results: Of the 13 618 military personnel who responded, 12.0% reported experiencing safety accidents in the military and 1020 (7.5%) felt that accident prevention activities in the military were insufficient. On logistic regression analysis, we found a significant difference (insufficiency OR=1.56, CI 1.31 to 1.86). In particular, military personnel who belong to the Army and Navy were more likely to think that accident prevention activities were insufficient. In addition, military personnel who experienced falls/slips, crash, and laceration/puncture wound/amputation/penetrating wound accidents were more likely to think accident prevention activities were insufficient., Conclusions: Our study found that accident prevention activities in the military and accident experiences were related. It is necessary for the ROK Ministry of Defense, Army, Navy and Air Force headquarters to re-evaluate their accident prevention systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.

The mucosa-associated lymphoid tissue (MALT) International Prognostic Index (IPI) was recently proposed as a prognostic index for patients with MALT lymphoma. We aimed to investigate the prognostic value of the serum β2-microglobulin level in the context of MALT-IPI, and we proposed a new prognostic index. Survival outcomes were analysed with regard to β2-microglobulin level, MALT-IPI, and the new prognostic index in MALT lymphoma patients (n = 571). The validity of the new prognostic index was assessed using an independent cohort (n = 216). Patients with high β2-microglobulin levels had significantly worse progression-free survival (PFS) and overall survival (OS) outcomes. A high β2-microglobulin level was independently associated with poor PFS and OS. β2-microglobulin levels further stratified patients in the MALT-IPI intermediate-risk group in terms of PFS and OS. A new prognostic index based on the MALT-IPI and the β2-microglobulin level, MALT-IPI-B, was proposed. The MALT-IPI-B was able to stratify patients into subgroups having distinct PFS and OS outcomes in both the training and validation cohorts. MALT-IPI-B enabled the identification of patients with poor survival outcomes who were classified into the intermediate-risk group by the MALT-IPI. In conclusion, this new β2-microglobulin-based prognostic index may have the specific advantage of identifying high-risk patients who may require systemic treatment., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

This study sought to adapt the existing value framework (VF) to produce a reliable and valid Korean oncology VF. Two VFs developed by The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) were selected for examination in the present study. Forward and backward translations were conducted for six high-priced drugs indicated for non-small-cell lung cancer and multiple myeloma. Inter-rater reliability was measured based on the intraclass correlation coefficient (ICC) and variation was described using the coefficient of variation. The relative weights of factors critically considered by Korean oncologists were derived following the analytic hierarchy process (AHP), and focus group interviews (FGIs) were used to obtain qualitative data regarding the applications of these two VFs in the Korean setting. The ICCs of the Korean VFs were 0.895 (0.654-0.983) for ASCO and 0.726 (0-0.982) for ESMO translations, suggesting excellent reliability for ASCO and good reliability for ESMO. AHP demonstrated that clinical benefit has the highest priority, which is consistent with the ASCO VF. The FGIs suggested that the result for AHP is acceptable and that both ESMO and ASCO VFs should be used complementarily. Although further evaluation with a larger sample size is needed, the Korean versions of ESMO/ASCO VFs are valid and reliable tools and are acceptable to Korean stakeholders, yet they should be applied with caution.

Beta-2 adrenergic receptor (B2AR) agonists, used as asthma treatments and tocolytics during pregnancy, have recently been reported to be associated with autism in their offspring. However, the particular link between autism and ritodrine, a common type of B2AR agonist used solely as tocolytics, has never been substantiated with any nationwide database. Thus, we aimed to examine the association between in utero exposure of ritodrine and the risk of autism in their offspring using a national database. This population-based cohort study was conducted by merging the Korea National Health Insurance claims database and National Health Screening Program for Infants and Children database. These databases included all women who had delivered singleton between January 2007 and December 2008 in Korea. Out of the total 770,016 mothers, 30,959 (4.02%) were exposed to ritodrine during pregnancy, and 5583 (0.73%) of their children were identified as having autism, defined until 8 years of age. According to our analysis, the overall cumulative incidence of autism up to 8 years was 1.37% in ritodrine exposure group and 0.70% in ritodrine non-exposure group (p < 0.05, log-rank test). By Cox proportional hazard analysis, use of ritodrine in preterm birth was associated with significantly higher hazard of autism [adjusted hazard ratio: 1.23, 95% CI 1.04-1.47], after adjusting for confounding variables including maternal age, parity, cesarean section, preterm labor, steroid use, birth weight, gender, and preeclampsia. Thus, in utero exposure to ritodrine was associated with an increased risk of autism in their offspring.

Purpose: The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients., Methods: The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors., Results: The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033-0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432-3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778-19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042-0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups., Conclusion: In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death., (© 2021 S. Karger AG, Basel.)

This study assessed epidemiologic data and clinical outcomes, including venous thromboembolism (VTE) recurrence and bleeding events, in patients with cancer-associated VTE, and assessed factors associated with clinical outcomes. Data were extracted from retrospective medical-chart review of adult patients diagnosed with cancer-associated deep vein thrombosis or pulmonary embolism who received anticoagulation treatment for ≥3 months. Patients were classified by: low-molecular-weight heparin (LMWH), direct oral anticoagulants (DOACs), and other anticoagulants. First VTE recurrence and bleeding events, and factors associated with their occurrence, were assessed during the initial 6 months of treatment. Overall, 623 patients (age: 63.7 ± 11.3 years, 49.3% male) were included (119, 132, and 372 patients in LMWH, DOACs and other anticoagulants groups, respectively). The cumulative 6-month incidence of VTE recurrence was 16.6% (total), 8.3% (LMWH), 16.7% (DOACs), and 20.7% (other); respective bleeding events were 22.5%, 11.0%, 12.3%, and 30.7%). VTE recurrence and bleeding rates differed only between LMWH and other anticoagulants (HR 2.4, 95% CI: 1.2-5.0 and 3.6, 1.9-6.8, respectively). These results highlight the importance of initial VTE treatment choice for preventing VTE recurrence and bleeding events. LMWH or DOACs for ≥3 months can be considered for effective VTE management in cancer patients.

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, high-risk, 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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

This study investigated toxic metal distribution in roadside soil and dust in the metropolitan city of Ulsan, South Korea, and the factors affecting distribution, using Korean waste-leaching tests, determination of total concentrations, sequential extraction, and statistical analysis. Composite grab samples were collected from high-traffic roads (7 sites), low-traffic roads (2 sites), and an uncontaminated control area (2 sites) in Ulsan. The pH of roadside soil and dust was slightly alkaline. The concentrations of copper, lead, and zinc in soil as determined by Korean waste-leaching tests decreased as soil depth increased, while those of arsenic, nickel, and chromium increased. Leaching concentrations in dust were lower than in soil, with the exception of copper. Total concentrations decreased as soil depth increased, and total concentrations of metals in dust were higher than in soil. The sampling sites that exceeded the regulation levels of soil contamination in South Korea were 7 points in topsoil, 3 points in middle soil, and 9 points in dust. TCLP tests showed that the concentrations of arsenic, cadmium, and lead in topsoil and dust at Duwang and Myeongchon intersections were higher than regulatory levels. The maximum correlation coefficient among two metals in soil and dust was 0.987 (p < 0.01), for cadmium and lead. Concentrations of cadmium, copper, arsenic, lead, nickel, and mercury, mostly from tire and brake-pad abrasion, were highly correlated. The strong positive correlation between traffic volume and metals in dust suggests that vehicle emissions may be responsible for metal contamination of soil and dust. Pollution indices of topsoil at 4 sites and all dust at 7 high-traffic sites were higher than 1.0, which is consistent with an effect of vehicle traffic on metal contamination in soil and dust.

Background & Aims: Elderly patients are being increasingly admitted to the intensive care unit (ICU) for mechanical ventilation (MV) and prevalence of decreased skeletal muscle mass which develop with aging is subsequently increasing. The objective of this study was to identify the association between decreased skeletal muscle mass and extubation failure in patients undergoing long-term MV., Methods: Adults (≥18 years of age) with long-term MV for > 7 days between January 2014 and February 2019 were included retrospectively. Patients who died or were transferred with MV, underwent tracheostomy with failure of weaning from MV, and had not undergone abdominal computed tomography within 3 days before or after intubation were excluded. Failed extubation was defined as reintubation within 48 h after extubation following long-term MV for >7 days. We divided the patients into extubation success and failure groups., Results: Parameters including patients' demographics, cause of intubation, initial setting of MV, maximum inspiratory pressure (MIP) and rapid shallow breath index (RSBI) at extubation, and skeletal muscle mass were compared between the two groups. Decreased skeletal muscle mass was set a standard as a L3 muscle index of less than 49 cm 2 /m 2 for men and of less than 31 cm 2 /m 2 for women using Korean-specific cut-offs for sarcopenia as evaluated on previous epidemiologic study. Among 104 patients who were screened, 45 were included, and 11 (24.4%) failed to be extubated. Mean MIP (23.5 ± 11.8 vs. 32.4 ± 9.3, p = 0.134) and RSBI (57.2 ± 26.5 vs. 55.3 ± 20.4, p = 0.803) were not different between the two groups. The proportions of patients whose MIP or RSBI satisfied the cutoff for extubation were not different between the groups. There were no significant differences in age, sex, body mass index, comorbidities, nutritional status, and cause of intubation between the two groups. The extubation failure group showed a higher proportion of decreased skeletal muscle mass (90.9% vs. 58.8%, p = 0.05) and longer duration of MV (10.7 ± 4.1 vs. 9.6 ± 3.4, p < 0.001) than the extubation success group. Multivariate analysis showed that the duration of intubation (OR = 1.439, 95% CI = 1.12-1.85), and decreased skeletal muscle mass (OR = 24.382, 95% CI = 1.00-594.86) were associated with extubation failure., Conclusions: Decreased skeletal muscle mass was associated with extubation failure after long-term MV for > 7 days. It is important to diagnose decreased skeletal muscle mass in critically ill patients to reduce extubation failure rates., Competing Interests: Conflict of Interest All authors declare that they have no conflict of interests., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: To improve the health outcomes of survivors of stroke, it is critical that they are highly motivated to engage in rehabilitation activities. Despite the increasing prevalence of strokes among middle-aged adults, there is limited knowledge regarding factors that may affect survivors' motivation to engage in rehabilitation., Objective: The aim of this study was to examine the relationship among factors that predict the rehabilitation motivation of middle-aged survivors after a stroke through structural equation modeling., Methods: A total of 200 middle-aged (40-64 years) survivors of stroke from 9 rehabilitation hospitals in Korea completed questionnaires on depressive symptoms, self-efficacy, social support, and rehabilitation motivation. Information on clinical characteristics, including physical function (activities performed during daily life), was collected through the review of medical records. Structural equation modeling was used to construct a prediction model of rehabilitation motivation., Results: The average subject's age was 56.2 ± 6.6 years, and the mean time since the event of their stroke was 15.02 ± 8.95 months. Subjects' self-efficacy (being able to live everyday life) after their stroke (β = .500, P < .001) and the social support provided by family and medical personnel (β = .284, P < .010) directly affected their rehabilitation motivation. The bootstrapping method showed that depressive symptoms indirectly affected rehabilitation motivation through self-efficacy, as did physical function., Conclusions: In middle-aged survivors of stroke, self-efficacy and social support play a critical role in maintaining intrinsic motivation to engage in rehabilitation activities. Self-efficacy should be evaluated periodically and improved by encouraging individuals to achieve goals, emphasizing their self-regulation, especially among those who reported depressive symptoms and low physical function.

This study aimed to identify factors influencing self-management in patients with Parkinson's disease (PD) based on social cognitive theory. A cross-sectional design was used; data were collected at three tertiary medical centers in Korea from a convenience sample of 356 PD patients. Higher self-management scores were associated with higher education level, having a religion, and higher family income. Self-management score was positively correlated with activities of daily living, self-efficacy, and social support, and negatively correlated with non-motor symptoms. Hierarchical regression analysis revealed that demographic factors and non-motor symptoms explained 26.2% of the variance in self-management in PD. The explanatory power increased by 7.5% when self-efficacy was added, and by 6.7% when social support was added. Assessment of self-management in patients with PD should consider self-efficacy and social support, along with demographic factors and non-motor symptoms. Self-management programs that reflect these factors may be useful for improving self-management in PD patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To determine the age- and sex-specific prevalence and incidence of demyelinating optic neuritis and the risk of multiple sclerosis (MS) in pediatric and adult populations in South Korea., Design: A nationwide, population-based, retrospective study using data from the Korean National Health Claims database from 2010 to 2016., Participants: The entire South Korean population aged 65 years of age or younger (n = 44 700 564). All patients with optic neuritis from the entire Korean population were included., Methods: Patients aged 14 years of age or younger were classified as pediatric patients, and those aged 15 to 65 years were classified as adults. Each group was analyzed separately. Patients with optic neuritis had a subsequent diagnosis, including idiopathic, MS, neuromyelitis optica (NMO), and acute disseminated encephalomyelitis. Prevalence and incidence, conversion rate to MS, and treatment modalities (steroids, plasmapheresis, interferon-β, and immunosuppressants) were estimated., Main Outcome Measures: Prevalence and incidence of optic neuritis, and conversion rate to MS., Results: Among 44 700 564 individuals, 531 pediatric patients (50.7% female) and 7183 adults (53.3% female) were identified as having optic neuritis. Annual incidence was 1.04 (95% confidence interval [CI], 1.01-1.07) per 100 000 pediatric individuals and 3.29 (95% CI, 3.28-3.30) per 100 000 adults. Peak incidence was observed at 10 to 14 years in the pediatric population and at 30 to 34 years and 50 to 54 years in the adult population. Conversion rate to MS was 13.8% in the pediatric population and 11.4% in the adult population. Fourteen percent of all patients were treated with chronic immunosuppressants, 38% of patients with NMO underwent plasmapheresis, and 50% of patients with MS were treated with interferon-β., Conclusions: This is a nationwide epidemiologic study of optic neuritis in individuals of all ages in South Korea. The incidence of optic neuritis and subsequent risk of MS in the pediatric population are comparable to those reported in western countries but are lower in the adult population than in western countries. The incidence rate in adults was 3.2-fold higher than in the pediatric population, and the overall MS conversion rate in the entire Korean population was estimated to be 10.6%., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/aims: The multidisciplinary team (MDT) approach is a cornerstone of clinical oncology. This study investigated the current state of MDT care, including patient satisfaction, in Korea., Methods: We obtained the annual number of cancer patients who have received MDT care since 2014 from the registry of the Health Insurance Review and Assessment Service (HIRA). In addition, patients who received MDT care from August 2014 to May 2017 at four university hospitals were further characterized, and patient satisfaction was measured prospectively using a patient-reported questionnaire., Results: The total number of patients who received MDT care increased from 2014 to 2016 (2,113 to 9,998 patients, respectively) in the HIRA Cohort. The type of cancer that most often required MDT was breast cancer (23.8%), followed by colorectal cancer (19.1%). In the Representative Cohort (n = 1,032), MDT was requested by the surgeon more than half the time (55.7%). The main focus of MDT was decision making for further treatment planning (99.0%). The number of doctors participating in the MDT was usually five (70.0%). After initiating an MDT approach, the treatment plan changed for 17.4% of patients. Among these patients, 359 completed a prospective satisfaction survey regarding their MDT care. The overall satisfaction with the MDT approach was very high, with an average score of 9.6 out of 10 points., Conclusion: The application of MDT care is a rapidly growing trend in clinical oncology, and shows high patient satisfaction. Further research is needed to determine which types of cancer patients could benefit most from MDT, and to enable MDT care to operate more efficiently so that it may expand successfully throughout Korea.

Background : Preterm birth is strongly associated with increasing mortality, incidence of disability, intensity of neonatal care required, and consequent costs. We examined the clinical utility of the potential preterm birth risk factors from admitted pregnant women with symptomatic preterm labor and developed prediction models to obtain information for prolonging pregnancies. Methods: This retrospective study included pregnant women registered with the KOrean Preterm collaboratE Network (KOPEN) who had symptomatic preterm labor, between 16 and 34 gestational weeks, in a tertiary care center from March to November 2016. Demographics, obstetric and medical histories, and basic laboratory test results obtained at admission were evaluated. The preterm birth probability was assessed using a nomogram and decision tree according to birth gestational age: early preterm, before 32 weeks; late preterm, between 32 and 37 weeks; and term, after 37 weeks. Results: Of 879 registered pregnant women, 727 who gave birth at a designated institute were analyzed. The rates of early preterm, late preterm, and term births were 18.16%, 44.02%, and 37.83%, respectively. With the developed nomogram, the concordance index for early and late preterm births was 0.824 (95% CI: 0.785-0.864) and 0.717 (95% CI: 0.675-0.759) respectively. Preterm birth was significantly more likely among women with multiple pregnancy and had water leakage due to premature rupture of membrane. The prediction rate for preterm birth based on decision tree analysis was 86.9% for early preterm and 73.9% for late preterm; the most important nodes are watery leakage for early preterm birth and multiple pregnancy for late preterm birth. Conclusion: This study aims to develop an individual overall probability of preterm birth based on specific risk factors at critical gestational times of preterm birth using a range of clinical variables recorded at the initial hospital admission. Therefore, these models may be useful for clinicians and patients in clinical decision-making and for hospitalization or lifestyle coaching in an outpatient setting., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Pathogenic water molds have a significant impact on many species, especially amphibians. The genus Saprolegnia is a pathogenic oomycete restricted to aquatic and moist habitats, and its presence is strongly linked to the abundance of amphibians and fishes. We investigated the influence of Saprolegnia presence on egg mortality and egg occurrence under varying environmental conditions in the Asiatic toad Bufo gargarizans at 27 breeding sites in the Republic of Korea. We then assessed the impact of Saprolegnia on the presence of B. gargarizans at the 27 sites surveyed weekly during the B. gargarizans breeding season for 3 consecutive years. We used molecular tools to identify the water molds as belonging to an undescribed S. ferax strain. We demonstrated that the presence of S. ferax was positively associated with higher water conductivity and ponds. In addition, while S. ferax prevalence was associated with a reduction in B. gargarizans breeding activity and breeding success, we could not determine its impact on the subsequent breeding seasons. Our study highlights the potential negative effects of Saprolegnia on amphibian reproduction, although additional research is necessary to determine the relationship between Saprolegnia, its hosts and the impacts of habitat loss on amphibians.

Aims: This study aimed to describe the etiologies of acquired onset of diplopia due to isolated third, fourth, and sixth cranial nerve palsies in young adults in Korea., Methods: This retrospective study included 127 patients aged 20 to 50 years with acquired onset isolated third, fourth, and sixth cranial nerve palsies who received care at the Strabismus and Neuro-ophthalmology Department of Samsung Medical Center from 2013 to 2017. The etiologies of the palsies determined by clinical assessment, high-resolution magnetic resonance imaging (MRI) with three-dimensional constructive interference in steady state, and laboratory testing were analyzed., Results: Fifty-nine patients manifested sixth cranial nerve palsy. Forty-six patients had fourth cranial nerve palsy and 22 patients had third cranial nerve palsy. The most common etiologies of the ocular motor nerve palsies were presumed inflammatory lesions (21.3%), followed by presumed microvascular causes (17.3%), and neoplasms involving the central nervous system (15.7%). Neoplasms were the most common cause of sixth cranial nerve palsy (25.4%). The most common cause of fourth cranial nerve palsy was presumed microvascular ischemia (28.3%), and presumed inflammatory lesions was the most common cause of third cranial nerve palsy (36.4%). Other non-traumatic causes included vascular lesions, ischemic brainstem stroke, intracranial hemorrhage, non-aneurysmal neuro-vascular contact, multiple sclerosis, and infection., Conclusion: A substantial proportion of young adult patients with ocular motor nerve palsies manifested pathologies other than presumed microvascular ischemia or idiopathic causes. Neuroimaging and laboratory tests have important roles in the evaluation of patients aged 20-50 years with acquired ocular motor nerve palsies., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: This study aimed to estimate the incidence and clinical outcomes of sepsis in Korea from 2007 to 2016., Design: Retrospective observational study., Setting: Nationwide study with population-based healthcare reimbursement claims database., Patients: Using data from the National Health Insurance Service of Korea, patients who were hospitalized with a diagnosis of sepsis from 2007 to 2016 were analyzed. The incidence of sepsis was calculated using mid-year census population and analyzed according to year, age, and sex. The Elixhauser Comorbidity Index score was calculated to adjust for the impact of comorbidities on clinical outcome. In-hospital mortality, hospital length of stay, ICU admission rates, and risk factors for in-hospital mortality were also analyzed., Interventions: None., Measurements and Main Results: The incidence of sepsis increased from 173.8 per 100,000 population in 2007 to 233.6 per 100,000 population in 2016. In-hospital mortality decreased from 30.9% in 2007 to 22.6% in 2016 (p < 0.0001). From 2007 to 2016, hospital length of stay and ICU admission rates associated with sepsis decreased from 26.0 ± 33.5 days to 21.3 ± 24.4 days (p < 0.0001) and from 16.2% to 12.7% (p < 0.0001), respectively. Male sex, age greater than 50 years, Elixhauser Comorbidity Index greater than 10, and mechanical ventilation were identified as risk factors for in-hospital mortality after adjusting for baseline characteristics., Conclusions: The incidence of sepsis in Korea increased from 2007 to 2016, while the associated in-hospital mortality, hospital length of stay, and ICU admission rates decreased.

Background: The environmental risks of multiple sclerosis (MS), including adolescent obesity and vitamin D deficiency, are increasing in Korea. We aimed to determine whether the patterns and/or severity of MS in Korea can change according to the year of birth or disease onset., Methods: Two hundred and sixty-six patients with adult-onset MS, including 164 with an available baseline magnetic resonance imaging (MRI), were retrospectively included from 17 nationwide referral hospitals in Korea. The demographics, MRI T2 lesion burden at disease onset, cerebrospinal fluid markers, and prognosis were assessed., Results: The birth year, time from disease onset to first MRI, and female sex were associated with a higher number of baseline MRI T2 lesions. The birth year was also associated with the presence of oligoclonal band in the cerebrospinal fluid and high immunoglobin G index. An increased female/male ratio was observed among those with a more recent year of birth and/or disease onset., Conclusions: In Korea, the disease pattern of adult-onset MS may be changing toward a more baseline T2 MRI lesions, intrathecal humoral immune responses, and also higher female ratio., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Primary effusion lymphoma (PEL) is a type of body cavity-based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden., Materials and Methods: We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea., Results: Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival., Conclusion: PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.

Sleep is exceedingly important for our physical, physiological, psychological, and social health. Currently, few Koreans get the recommended daily amount of sleep. Stress can also have a major impact on our physiological, neurological, and mental health. In this study, we explored the correlation between sleep duration and perceived stress. The study used data from the Community Health Survey (CHS), 2017, which included 133,444 responses from Koreans. Sleeping time and stress were measured by self-diagnosis. The relationship between sleeping time and stress was analyzed using the chi-square test and multivariable regression. Both men and women felt the most stress when they slept for an average of 6 h a day. The results of the subgroup analysis showed that even when they sleep for the same time, younger people felt more stressed than older people. In the group that slept for an average of 6 h a day, women were the most stressed. We observed a correlation between sleeping time and stress in Korean adults. We found that about 16.7% of Koreans were sleeping for less than 5 h. This is less than the 7-9 h of sleep recommended by the National Sleep Foundation (NSF). In addition, stress was found to increase when sleep was insufficient. In particular, it was also observed that young people who slept for less than 8 h felt stressed more easily.

Background: The purpose of this study was to evaluate whether institutional case volume affects clinical outcomes in patients receiving mechanical ventilation for 48 hours or more., Methods: We conducted a nationwide retrospective cohort study using the database of Korean National Healthcare Insurance Service. Between January 2007 and December 2016, 158,712 adult patients were included at 55 centers in Korea. Centers were categorized according to the average annual number of patients: > 500, 500 to 300, and < 300., Results: In-hospital mortality rates in the high-, medium-, and low-volume centers were 32.6%, 35.1%, and 39.2%, respectively. After adjustment, in-hospital mortality was significantly higher in low-volume centers (adjusted odds ratio [OR], 1.332; 95% confidence interval [CI], 1.296-1.368; P < 0.001) and medium-volume centers (adjusted OR, 1.125; 95% CI, 1.098-1.153; P < 0.001) compared to high-volume centers. Long-term survival for up to 8 years was better in high-volume centers., Conclusion: Centers with higher case volume (> 500 patients/year) showed lower in-hospital mortality and long-term mortality, compared to centers with lower case volume (< 300 patients/year) in patients who required mechanical ventilation for 48 hours or more., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)