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Background/Aims: We aimed to estimate the prevalence of comorbidities and medication use in Korean women with rheumatic diseases (RDs) during their childbearing years.Methods: We included women aged 20 to 44 years with seropositive rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) (n = 41,547) and age-matched women without seropositive RA, SLE, and AS (n = 208,941) from the National Health Insurance Service-National Health Information Database (2009 to 2016). The prevalence of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and cancer and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CSs), and disease-modifying anti-rheumatic drugs (DMARDs) were estimated.Results: Women of childbearing age with RDs were more likely to have at least one of the measured comorbidities than the controls (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.9 to 3.1). The OR (95% CI) was 2.9 (2.8 to 3.0) for HTN, 2.8 (2.7 to 2.9) for HLD, 1.4 (1.4 to 1.5) for DM, and 1.3 (1.3 to 1.4) for cancer. The SLE group had the highest prevalence and odds of all four measured comorbidities. Almost all (97.9%) women of childbearing age with RDs were taking RD-related medications (NSAIDs, 81.6%; CSs, 77.8%; DMARDs, 87.3%). The RD group was 13.8 times more likely to take NSAIDs and 68.2 times more likely to take CSs than the controls. Use of NSAIDs was more prevalent in RA and AS than SLE, whereas use of CSs and DMARDs was more prevalent in RA and SLE than AS.Conclusions: Korean women with RDs have a greater burden of comorbidities and medication use during their childbearing years than women without RDs of the same age.

Purpose Occupational exposure to pesticides is thought to be associated with lung cancer, but studies have yielded conflicting results. We performed a propensity score (PS) based analyses to evaluate the relationship between occupational exposure to pesticides and lung cancer risk in the Korea National Cancer Center community-based cohort study (KNCCCS).Materials and Methods During the follow-up period, 123 incidental lung cancer cases were identified, of the 7,471 subjects in the final statistical analysis. Information about occupational exposure to pesticides and other factors was collected at enrollment (2003-2010). Cox proportional hazards regression analyses were conducted. Four PS-based approaches (i.e., matching, stratification, inverse probability-of-treatment weighting, and the use of the PS as a covariate) were adopted, and the results were compared. PS was obtained from the logistic regression model. Absolute standardized differences according to occupational exposure to pesticides were provided to evaluate the balance in baseline characteristics.Results In the Cox proportional hazards regression model, the hazard ratio (HR) for lung cancer according to occupational exposure to pesticides was 1.82 (95% confidence interval [CI], 1.11 to 2.98). With all the propensity score matching (PSM) methods, the HRs for lung cancer based on exposure to pesticides ranged from 1.65 (95% CI, 1.04 to 2.64) (continuous term with PSM) to 2.84 (95% CI, 1.81 to 4.46) (stratification by 5 strata of the PS). The results varied slightly based on the method used, but the direction and statistical significance remained the same.Conclusion Our results strengthen the evidence for an association between occupational exposure to pesticides and the risk of lung cancer.

Background Characteristics, disabilities, and optimal management of medication overuse headache remain uncertain. This study aimed to elucidate the clinical characteristics of patients with medication overuse headache enrolled in a medication overuse headache registry in Korea. Methods The Registry for Load and Management of MEdicAtion OveruSE Headache (RELEASE), a cross-sectional prospective observational study including seven referral headache centers in Korea, started enrolling adult patients with medication overuse headache in April 2020. Data included information on headache characteristics, burden on daily function, depression, anxiety, history of acute and preventive medications, and treatment strategies. Results A total of 229 patients (85.6% females; mean age, 45.5 ± 13.5 years) were enrolled by June 2021. The average durations of chronic headaches and medication overuse were 6.5 and 4.3 years, respectively. In the past month before enrollment, patients had headaches for 25 days and severe headaches for 12 days, and used acute medications for 20 days. Patients were disabled in 66.8 days in the past 3 months and had moderate/severe depression and anxiety in 56% and 35%, respectively. The proportion of patients on preventive treatments increased from 38% to 93% during the study period. Conclusions RELEASE study reflects the current management status and opportunities to improve the quality of care in patients with medication overuse headache.

Background In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD). Objective We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience. Methods We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations. Results We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate. Conclusion We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD.

Thyroid dysfunction has been implicated as a potential pathophysiological factor in glucose homeostasis and insulin resistance (IR). This study aimed to identify the correlation between thyroid dysfunction and IR. We used data from the sixth Korean National Health and Nutrition Examination Survey to evaluate a total of 5727 participants. The triglyceride glucose (TyG) index and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated to represent IR. Correlation analysis was performed between thyroid dysfunction and IR. The log-transformed TSH (LnTSH) and free T4 were significantly correlated with the TyG index (TSH, beta coefficient 0.025, 95% confidence interval [CI] 0.014–0.036, p p p p p

Background: The purpose of this study was to investigate factors associated with AF in patients with hyperthyroidism beyond heart failure (HF), coronary heart disease (CHD), or valvular diseases.Methods: A total of 136 patients (mean age, 52 ± 15 years; 86 [63%] female) who were diagnosed with hyperthyroidism for the first time were enrolled. Patients who had HF, CHD, or significant valvular diseases were excluded. Patients were classified into two groups according to the presence (group 1, n=40) and absence of AF (group 2, n=96). Results: AF occurred in 40 (29%) patients and 23 (58%) of these patients showed paroxysmal AF. Among the symptoms of hyperthyroidism, the most common chief complaint was palpitation (30%). Advanced age, presence of prior cerebrovascular events, and presence of palpitations were associated with AF. Larger left atrial volume index (LAVI), increased left ventricular mass index, and decreased left ventricular ejection fraction (LVEF) and S’ velocity were associated with AF. Among them, presence of palpitations and increased LAVI were independently associated with the occurrence of AF. In addition, strain analysis, decreased LA expansion index (EI), ejection fraction (EF), peak atrial longitudinal strain, contraction strain, and late diastolic strain rate (A sr) and systolic strain rate (S sr) were associated with the occurrence of AF and LAVI.Conclusion: Presence of palpitations and enlarged left atrium were associated with the occurrence of AF in patients with hyperthyroidism irrespective of conventional risk factors. Additional LA analysis revealed that decreased LA function was associated with AF and enlarged left atrium.

Hypoxic‐ischaemic encephalopathy (HIE) is a type of brain injury affecting approximately 1 million newborn babies per year worldwide, the only treatment for which is therapeutic hypothermia. Thrombin‐preconditioned mesenchymal stem cells (MSCs) exert neuroprotective effects by enriching cargo contents and boosting exosome biogenesis, thus showing promise as a new therapeutic strategy for HIE. This study was conducted to evaluate the tissue distribution and potential toxicity of thrombin‐preconditioned human Wharton's jelly‐derived mesenchymal stem cells (th‐hWJMSCs) in animal models before the initiation of clinical trials. We investigated the biodistribution, tumorigenicity and general toxicity of th‐hWJMSCs. MSCs were administered the maximum feasible dose (1 × 105 cells/10 µL/head) once, or at lower doses into the cerebral ventricle. To support the clinical use of th‐hWJMSCs for treating brain injury, preclinical safety studies were conducted in newborn Sprague‐Dawley rats and BALB/c nude mice. In addition, growth parameters were evaluated to assess the impact of th‐hWJMSCs on the growth of newborn babies. Our results suggest that th‐hWJMSCs are non‐toxic and non‐tumorigenic in rodent models, survive for up to 7 days in the brain and hold potential for HIE therapy.

Background The interest in vascular substitutes has recently increased. We evaluated the feasibility of using a homologous parietal peritoneum as a vascular substitute for venous reconstruction during abdominal surgery. Methods The inferior vena cava was replaced with a homologous parietal peritoneum after cross-linking with glutaraldehyde in 36 rabbits. At 7, 14, and 28 days, the patency rate, outer and inner graft diameters, histology, and immunohistochemistry were evaluated. Results Both the 7- and 14-day groups maintained vascular patency. Vascular patency was maintained in 3 rabbits in the 28-day group. The inner diameters of the anastomotic sites were 6.23 ± 0.18, 5.64 ± 0.16, and 2.34 ± 0.21 mm in the 7-day, 14-day, and 28-day groups, respectively. The midpoint inner diameters of the homologous parietal peritoneum grafts were 624 ± 0.46, 5.74 ± 0.26, and 2.14 ± 0.28 mm in each group, respectively. Endothelial cell proliferation on the homologous parietal peritoneum graft surfaces in all groups was based on the histological findings from the first group. Multiple neovascularizations of the homologous parietal peritoneum graft were found in the 14- and 28-day groups, indicating neo-media formation. Acute inflammation appeared to progress to the entire layer of the homologous parietal peritoneum graft without an intraluminal thrombus, but the graft was patent in the 14-day group. In the 28-day group, 6 rabbits showed near-total occlusion and a thrombus formed in the homologous parietal peritoneum graft at the anastomosis site with severe stricture; however, the rabbits were alive and had collateral vessel formation. Conclusion Using homologous parietal peritoneum is feasible for venous reconstruction in abdominal surgery.

Varices are a frequent complication of liver cirrhosis and a major cause of mortality in patients with liver cirrhosis. Patients with decompensated cirrhosis complications have a poor prognosis and require careful management. Portal hypertension is the most common complication of liver cirrhosis, which is the key determinant for varices development. Increased intrahepatic vascular resistance to portal flow leads to the development of portal hypertension. Collateral vessels develop at the communication site between the systemic and portal circulation with the progression of portal hypertension. Varices are the representative collaterals, develop gradually with the progression of portal hypertension and may eventually rupture. Variceal bleeding is a major consequence of portal hypertension and causes the death of cirrhotic patients. The present paper reviews the latest knowledge regarding the diagnosis and management of esophageal and gastric variceal bleeding.

Background and aims Bile acid (BA) dysregulation is related to not only metabolic diseases but also nonalcoholic fatty liver disease (NAFLD). We investigated whether circulating BA levels are altered according to the histological severity of NAFLD independent of metabolic derangements. Methods Global metabolic profiling and targeted BA analysis using sera collected from biopsy-proven no-NAFLD (n = 67), nonalcoholic fatty liver (NAFL) (n = 99), and nonalcoholic steatohepatitis (NASH, n = 75) subjects were performed sequentially. Circulating metabolome analysis integrated with the hepatic transcriptome was performed to elucidate the mechanistic basis of altered circulating BA profiles after stratification by obesity (body mass index ≤ 25 kg/m2 ). Circulating BA alterations were also validated in an independent validation cohort (29 no-NAFLD, 70 NAFL and 37 NASH). Results Global profiling analysis showed that BA was the metabolite significantly altered in NASH compared to NAFL. Targeted BA analysis demonstrated that glyco-/tauro-conjugated primary BAs were commonly increased in nonobese and obese NASH, while unconjugated primary BAs increased only in nonobese NASH. These characteristic primary BA level changes were maintained even after stratification according to diabetes status and were replicated in the independent validation cohort. Compared to nonobese NAFL patients, nonobese NASH patients exhibited upregulated hepatic expression of CYP8B1. Conclusions BA metabolism is dysregulated as the histological severity of NAFLD worsens, independent of obesity and diabetes status; dysregulation is more prominent in nonobese NAFLD patients. Metabolome-driven omics approach provides new insight into our understanding of altered BA metabolism associated with individual phenotypes of NAFLD.

Background: Data on the association between coronavirus disease 2019 (COVID-19) and thyroid have been reported, including overt thyrotoxicosis and suppression of thyroid function. We aimed to evaluate the thyroid hormone profile and its association with the prognosis of COVID-19 in Korean patients.Methods: The clinical data of 119 patients with COVID-19, admitted in the Myongji Hospital, Goyang, South Korea, were retrospectively evaluated. The thyroid hormone profiles were analyzed and compared based on disease severity (non-severe disease vs. severe to critical disease). Clinical outcomes were analyzed according to the tertiles of thyroid hormones.Results: Of the 119 patients, 76 (63.9%) were euthyroid, and none presented with overt thyroid dysfunction. Non-thyroidal illness syndrome was the most common manifestation (18.5%), followed by subclinical thyrotoxicosis (14.3%) among patients with thyroid dysfunction. Thyroid stimulating hormone (TSH) and triiodothyronine (T3) levels were significantly lower in patients with severe to critical disease than in those with non-severe disease (P1.00 ng/mL) T3 tertiles (P

Objective The distinction between idiopathic normal pressure hydrocephalus (iNPH) and hydrocephalus ex vacuo caused by encephalic volume loss remains to be established. This study aims to investigate radiological parameters as clinically useful tools to discriminate iNPH from hydrocephalus ex vacuo caused by Alzheimer’s disease (AD).Methods A total of 54 patients with ventriculomegaly (iNPH, 25; hydrocephalus ex vacuo, 29) were recruited in this study. Consequently, nine radiological parameters were compared between iNPH and hydrocephalus ex vacuo using magnetic resonance imaging (MRI).Results A small callosal angle (CA), the Sylvian fissure dilatation, and absence of narrowing of superior parietal sulci discriminated the iNPH group from the hydrocephalus ex vacuo group (p

Canine mammary carcinoma (CMC) is the most common type of neoplasm in intact female dogs. While a previous study in Western countries validated the 2011 classification as an independent prognostic indicator in CMC, its role in CMC prognostication in Asian countries such as Korea remains unclear. In the present study, we estimate the survival rates in CMC types defined by the 2011 classification, elucidate the prognostic significance of the histological subtype and grade and that of the lymphatic invasion status in CMC, and validate the 2011 classification as an independent prognostic indicator in a large cohort of CMCs (excluding cases of multicentric CMCs). A total of 155 CMC cases retrieved from archived formalin-fixed, paraffin-embedded tissues, along with 2-year follow-up data, were retrospectively analysed. A significant association was found between the histological subtype of the 2011 classification and the tumour-specific survival. Carcinosarcoma, adenosquamous carcinoma and anaplastic carcinoma subtypes were associated with the poorest prognosis. Dogs with comedocarcinoma and solid carcinoma followed a disease course that was more aggressive than that observed in dogs with a carcinoma arising in a benign mixed tumour. Moreover, age, histological grade and lymphatic invasion status significantly correlated with tumour-specific survival in univariate analysis. In multivariate analysis, histological subtype, age and lymphatic invasion status remained independent prognostic factors for CMC.

The presence of parapapillary choroidal microvasculature dropout (CMvD) may affect optic nerve head (ONH) perfusion in glaucoma patients, since parapapillary choroidal vessels provide vascular supply to the neighboring ONH. However, it remains to be determined whether the presence of parapapillary CMvD is associated with diminished perfusion in the nearby ONH. The present study investigated the spatial relationship between CMvD and ONH vessel density (ONH-VD) loss in open-angle glaucoma (OAG) eyes using optical coherence tomography angiography (OCT-A). This study included 48 OAG eyes with a single localized CMvD confined to the inferotemporal parapapillary sector and 48 OAG eyes without CMvD, matched for demographic and ocular characteristics. Global and regional ONH-VD values were compared between eyes with and without CMvD. The relationships between ONH-VD outcomes and clinical variables were assessed. ONH-VDs at the inferotemporal ONH sectors corresponding to the CMvD location were significantly lower in eyes with compared to those without CMvD. Multivariable linear regression analyses indicated that a lower inferotemporal ONH-VD was independently associated with CMvD presence and a greater CMvD angular extent (both P

Lupus miliaris disseminatus faciei (LMDF) and granulomatous rosacea are 2 distinct inflammatory dermatoses with overlapping clinical features: reddish-yellow papular eruptions localized on the central face. Consequently, LMDF can easily be misdiagnosed as granulomatous rosacea or vice versa. Because delayed treatment in LMDF may increase chances of permanent scar formation, accurate diagnosis is important. We therefore analyzed published literature and case studies to organize the essential features differentiating LMDF from granulomatous rosacea. In addition, we report each case of LMDF and granulomatous rosacea for direct comparison.

Background Migraine is a neurological, primary headache disorder affecting more than 1 billion people worldwide, with a multi-faceted burden that can significantly impact the everyday life of a patient, both during and between attacks. However, studies on patient awareness, burden, and clinical management of migraine in Korea are limited and outdated. The aim of this study was to comprehensively investigate the current difficulties and unmet needs that Korean patients with migraine encounter from their perspective. Methods A total of 207 patients with episodic or chronic migraine aged between 15 and 76 years, completed a survey designed to cover the following topics: diagnosis, understanding of the disease, treatment experience, disability, and quality of life. Patients were recruited by their neurologists from 11 specialized headache clinics in Korea and completed the survey between 22 July and 19 August 2019. Validated scales such as the Migraine Disability Assessment (MIDAS) questionnaire and Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) were used to assess levels of disability and quality of life, respectively, in patients. Results On average, it took 10.1 years from onset of symptoms to diagnosis and a mean of 3.9 hospitals were visited for treatment prior to the patient’s current hospital. There was a lack of understanding among respondents about migraine, with 55.6% believing that unilateral headache is a unique feature of migraine compared with other headache disorders. On average, high levels of disability and poor quality of life were reported by patients, as assessed by MIDAS and MSQv2.1, respectively, but only 23.7% had regularly taken preventive medication in the past. Overall satisfaction with previous doctor-patient relationships was reported by 29.5% of respondents, and satisfaction with preventive and acute medications by only 40.8% and 27.1% of the respondents, respectively. Conclusion Korean patients with migraine experience significant disability and reduced quality of life as a result of the disease and have clear unmet needs in terms of diagnosis, understanding of the disease, and disease management including treatment.

Background/Aims: Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy. Methods: Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 dia betes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes di agnosis to 2 years later. Results: We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several con founding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08). Conclusions: Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.

Even though mesenchymal stem cells (MSCs) are known for cartilage regeneration, their therapeutic efficacy needs to be enhanced. In the present study, we produced genome-edited silent information regulator 2 type 1 (Sirt1)-overexpressing MSCs, and evaluated their therapeutic potential in a damaged cartilage mouse liver fibrosis model. The Sirt1 gene was successfully inserted into a ‘safe harbor’ genomic locus in amniotic mesenchymal stem cells (AMMs), and the chondrogenic properties of the Sirt1 gene overexpressing AMMs (AMM/S) were characterized using quantitative PCR and histology. Therapeutic potentials were investigated in a collagen-induced arthritis (CIA) mouse model. Chondrocyte-differentiated AMM/S expressed cartilage-specific genes and were positive for Safranin O staining. Transplantation of AMM/S attenuated CIA progression and suppressed T helper (Th)-17 cell activation while increasing the Treg cell population in CIA mice. Pro-inflammatory factors, such as interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α were significantly decreased in AMM/S-injected joint tissues. In conclusion, genome-edited AMM/S may represent a safe and alternative therapeutic option for the treatment and repair of damaged cartilage, or in inflammatory joint arthritis.

PRECIS Choroidal microvasculature dropout (CMvD) is an independent predictor for overall and central visual field (VF) progression in open-angle glaucoma (OAG) eyes. PURPOSE The purpose of this study was to investigate the impact of CMvD identified by optical coherence tomography angiography (OCT-A) at baseline on subsequent VF progression in eyes with OAG. METHODS This retrospective observational study included 80 OAG eyes with CMvD [CMvD(+)] and without CMvD [(CMvD(-)] at baseline [40 of each matched for both age (10 y and below) and baseline VF severity (≤1 dB)]. The patients were followed regularly at 6-month intervals. VF progression was defined according to the Early Manifest Glaucoma Trial criteria. Associations of overall VF progression with baseline clinical factors, including the presence of CMvD and other variables, were analyzed by logistic regression with a generalized estimating equation in the entire OAG cohort. Linear mixed models were used to determine the differences in visual field mean sensitivity (VFMS) between the CMvD(+) and CMvD(-) groups globally and regionally at each follow-up point. RESULTS During a mean follow-up of 35.91±2.51 months, a significant difference was evident in the VF progression rate between the CMvD(-) and CMvD(+) groups (22.5% vs. 70%, P

Purpose To investigate whether progressive macular ganglion cell–inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thinning are predictive for detecting visual field (VF) progression in eyes with high myopia. Design Cohort study. Methods A total of 104 primary open-angle glaucoma (POAG) eyes with high myopia and 104 age- and VF severity-matched POAG eyes without high myopia (mean follow-up, 5.4 years) were included. High myopia was defined as a spherical equivalent 26.5 mm. Progressive GCIPL, RNFL, and VF deterioration were determined by Guided Progression Analysis (GPA) in optical coherence tomography and standard automated perimetry. The risk of VF progression was evaluated using Cox proportional hazard models. Results Highly myopic eyes with progressive GCIPL thinning had a significantly higher risk of developing VF progression after adjusting for the baseline intraocular pressure (HR 4.00; P = .001) or peak intraocular pressure (HR 3.11; P = .011) in the multivariable Cox proportional hazard model, whereas highly myopic eyes with progressive RNFL thinning were not significantly associated with VF progression. In eyes without high myopia, both progressive GCIPL (HR 4.67 or 3.62; P = .008 or .037, respectively) and RNFL (HR 6.60 or 3.97; P = .001 or .016, respectively) thinning were associated with a significantly higher risk of developing VF progression after adjusting for the baseline or peak intraocular pressure. Conclusions Monitoring macular GCIPL thickness was effective for predicting glaucoma progression regardless of the presence of high myopia

Background and Purpose Epidemiologic data suggest that cluster headache (CH) is significantly associated with cigarette smoking. The aim of this study was to determine differences in features between patients with a smoking history and those who are never-smokers, using data from a prospective multicenter registry. Methods Data used in this study were obtained from the Korean Cluster Headache Registry that collected data from consecutive patients diagnosed with CH. We compared clinical and demographic features between ever-smokers (current or former smokers) and never-smokers. Results This study enrolled 250 patients who were diagnosed with CH, of which 152 (60.8%) were ever-smokers and 98 (39.2%) were never-smokers. The age at CH onset was significantly lower in the never-smoker group than in the ever-smoker group [27.1±12.9 years vs. 30.6±10.9 years (mean±standard deviation), p=0.024]. Seasonal rhythmicity (58.1% vs. 44.7%, p=0.038) and triptan responsiveness (100% vs. 85.1%, p=0.001) were higher in never-smokers, while other clinical features such as pain severity, duration, attack frequency, and associated autonomic symptoms did not differ significantly between the groups. The male-to-female ratio was markedly higher in ever-smokers (29.4:1) than in never-smokers (1.7:1). Conclusions Most of the clinical features did not differ significantly between patients with a smoking history and never-smokers. However, the age at CH onset, sex ratio, and seasonal rhythmicity were significantly associated with smoking history.

PURPOSE To compare lamina cribrosa curvature (LCC) in pseudoexfoliation glaucoma (PXG) and primary open-angle glaucoma (POAG) and to elucidate the factors associated with LCC in both groups. DESIGN Retrospective, cross-sectional study. METHOD Forty eyes with PXG and visual field mean deviation-matched 40 eyes with POAG were included. Spectral domain optical coherence tomography enhanced depth imaging was used to acquire LC images. The LCC index (LCCI) was calculated as LCC depth/LCC width × 100. Calculated LCCI values were compared between the PXG and POAG groups. Logistic regression analysis was performed to investigate the factors related to the presence of PXG. Factors associated with LCCI were determined by uni- and multivariable linear regression analyses in both groups. RESULT Visual field mean deviation (-11.7 ± 9.7 dB vs -1.0 ± 8.5 dB, P = .731) and retinal nerve fiber thickness (647.4 ± 22.7 μm vs 68.3 ± 19.9 μm, P = .857) did not differ between the 2 groups. However, the mean (8.8 ± 2.9 in PXG, 6.6 ± 1.9 in POAG) and sectoral LCCIs assessed at 0, 30, 60, 90, and 120° were significantly greater in the PXG than in the POAG group (all, P < .05), but not at 150° (P = .113). Logistic regression analysis revealed that higher average LCCI (odds ratio [OR] = 1.509 [95% confidence interval 1.180-2.047], P = .003) and older age (OR = 1.074 [95% confidence interval 1.017-1.147], P = .019) were associated with the presence of PXG. IOP was associated with mean LCCI only in the POAG group (β = 0.150 [95% confidence interval 0.018-0.281], P = .027) while none of the factors showed association with LCCI in PXG. CONCLUSION PXG eyes had more steeply curved LC than POAG eyes with a similar level of glaucoma severity. The clinical implication(s) of steeper LCC in PXG should be investigated in a forthcoming study.

Introduction Incidence of microinvasive Breast cancer (DCISM) along with ductal carcinoma in situ is increasing due to mammographic screening. However, DCISM is not a common pathologic entity and surgical management of the axilla, overall treatment, and prognosis of this entity still remains unclear. Our study aims to determine whether sentinel lymph node biopsy (SLNB) is necessary for all DCISM patients and analyze the characteristics of lymph node-positive patients among DCISM patients to identify risk factors associated with lymph node metastasis. Materials and MethodsA total of 184,007 Breast cancer patients treated were registered in the Korean Breast Cancer Society Registry between 1978 to 2020. A retrospective review of the database was performed and the analysis includes diagnostic and clinic-pathologic characteristics such as positive lymph node and immunohistochemistry. A univariate analysis was carried out to determine associations between lymph node positivity and the clinical variables via Fisher’s exact test.ResultsOf the 184,007 patients, 2,556 (1.4%) breast cancer patients were classified as DCISM and 134 (5.2%) had at least one lymph node (node-positive), while 2,422 were node-negative patients. We found statistically significant results with hormone receptor status between node-positive and node-negative patients. Estrogen receptor (ER) and progesterone receptor (PR)-negative cases were associated with lower ORs (ER: OR=0.63, 95CI=0.43-0.92, P=0.016; PR: 0.67, 0.46-0.96, 0.026, respectively). A particularly interesting finding is that human epidermal growth factor receptor 2 (HER2)-negative cases were associated with higher OR (HER2: 2.03, 1.36-3.06, 0.001), suggesting hormone receptor status could be useful to identify potential lymph node metastases.ConclusionOur study suggests that we could omit axillary staging in DCISM patients, and consider optional SLNB in patients with ER, PR, and HER2 status with other overrepresented clinical entities such as palpable mass, BMI, and histologic grade.KeywordsMicroinvasive ductal carcinoma, Sentinel lymph node biopsy, lymph node metastasis Citation Format: Pill Sun Paik, Min Kyung Cho, Juneyoung Ahn, Chang Ik Yoon, Tae-Kyung Yoo, Woo-Chan Park. Risk factors for lymph node metastasis and the role of SLNB in microinvasive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-54.

Purpose Pathological complete response (pCR) predicts improved survival in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). However, the prognosis of patients with non-pCR remains unclear. The aim of this study was to evaluate the effect of radiological response pattern on breast cancer patients’ outcome. Method A total of 396 breast cancer patients who underwent neoadjuvant chemotherapy between 2010-2017 at Seoul St. Mary’s Hospital were retrospectively reviewed. Among them, patients who underwent 4-6 cycles of neoadjuvant chemotherapy and underwent response evaluation every 2 cycles using breast MRI were included for analysis. Early and late response ratio was calculated from breast MR images using the longest diameter of the main tumor. Early response ratio was calculated as post-2 cycle NAC / pre-NAC ratio. Late response ratio was calculated as post-4 cycle NC / post-2 cycle NAC ratio. Radiological response pattern was divided into three groups; fast-slow responder meaning early response ratio > late response ratio + 20%, slow-fast responder meaning late response ratio > early response ratio + 20% and constant responder meaning the difference between initial response ratio and later response ratio is lower than 20%. Survival analysis was done using the Kaplan-Meier method and multivariate analysis by Cox regression. Disease-free survival (DFS) was defined as locoregional recurrence, contralateral breast recurrence and distant metastasis. Result A total of 177 patients were included for analysis. Among them 19 (10.7%) patients were pCR, 122 (68.9%) patients had partial response, 29 (16.4%) patients had stable disease and 7 (4.0%) patients had progressive disease. Median follow-up period was 50 months (range, 3-112 months). Radiological response pattern was significantly associated with disease-free survival in univariate analysis (p=0.042). Fast-slow responders had significantly worse disease-free survival (DFS) in univariate analysis compared to slow-fast responders and constant responders (p=0.042, 5-year DFS 67.6%, 88.3% 67.6%). Radiological response pattern continued to be statistically significant by multivariable analysis (p=0.037). Conclusion Our results showed that fast-slow responders have worse survival compared to constant or slow-fast responders. Radiological response patterns may be useful to more accurately assess prognosis, especially when considering adjuvant chemotherapy. Citation Format: Juneyoung Ahn, Tae-kyung Yoo, Pill Sun Paik, Min Kyung Cho, Chang Ik Yoon, Woo Chan Park. Radiological response pattern predicts disease-free survival in breast cancer patients undergoing neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-45.

Background Despite the progress of advanced target therapeutic agents and immune checkpoint inhibitors, EGFR‐TKI resistance is still one of the biggest obstacles in treating lung cancer. Clinical studies with autophagy inhibitors are actively underway to overcome drug resistance. Methods We used PC9, PC9/GR, and HCC827/GR cell lines to evaluate the activation of autophagy and EGFR‐TKI resistance. Chloroquine was applied as an autophagic blocker and verteporfin was utilized as a YAP inhibitor. Results In this study, we tried to reveal the effect of autophagy adaptor p62 which is accumulated by autophagy inhibitor in EGFR‐TKI‐resistant lung adenocarcinoma. We identified that p62 has oncogenic functions that induce cell proliferation and invasion of EGFR‐TKI‐resistant lung adenocarcinoma. Interestingly, we found for the first time that YAP regulates p62 transcription through ERK, and YAP inhibition can suppress the expression of oncogenic p62. We also confirmed that the expressions of p62 and YAP have a positive correlation in EGFR‐mutant lung adenocarcinoma patients. To block cell survival via perturbing YAP‐p62 axis, we treated EGFR‐TKI‐resistant lung cancer cells with YAP inhibitor verteporfin. Remarkably, verteporfin effectively caused the death of EGFR‐TKI‐resistant lung cancer cells by decreasing the expressions of p62 with oncogenic function, YAP, and its target PD‐L1. So, the cumulative effect of oncogenic p62 should be considered when using autophagy inhibitors, especially drugs that act at the last stage of autophagy such as chloroquine and bafilomycin A1. Conclusion Finally, we suggest that targeting YAP‐p62 signaling axis can be useful to suppress the EGFR‐TKI‐resistant lung cancer. Therefore, drug repurposing of verteporfin for lung cancer treatment may be valuable to consider because it can inhibit critical targets: p62, YAP, and PD‐L1 at the same time., The accumulated p62 by autophagy inhibitor, chloroquine has oncogenic functions in EGFR‐TKI resistant lung adenocarcinoma. Hippo effector YAP regulates p62 transcription through ERK, and YAP inhibition significantly suppresses the expression of p62. We suggest that targeting YAP‐p62 signaling axis can be useful to overcome the EGFR‐TKI resistance in lung adenocarcinoma.

Maxillary nerve block is widely used for treating trigeminal neuralgia. Common complications of the procedure include bleeding and sensory abnormalities, but ophthalmic complications have been rarely reported. A 60-year-old woman underwent maxillary nerve block for refractory trigeminal neuralgia. Ten minutes after the procedure had ended, the patient reported double vision when she tried to turn the left eye outward. After examination, the patient was presumed to have diplopia due to the abducens nerve block. However, the symptom disappeared approximately 30 minutes later without any treatment. Thus, to prevent diplopia, the dose of local anesthetics should be reduced. Moreover, negative blood aspiration should be confirmed during the injection. To the best of our knowledge, this is the first case to report diplopia after maxillary nerve block without neurolysis through the lateral infrazygomatic approach.

Background In women, pregnancy is a period of relatively drastic hemodynamic change in a short period of time. Most pregnant women adapt well to these gradual hemodynamic changes. However, in women with congenital heart disease or other structural heart disease, adaptation to theses sudden hemodynamic changes is difficult, and heart failure or arrhythmia can get aggravated. This study shares our experiences on the outcomes of pregnancy in patients with structural heart disease. Methods From January 2007 to December 2016, we reviewed the medical records of all pregnant women with structural heart disease who received obstetric care at the Sejong General Hospital. Results During the study period, 103 pregnancies were observed in 79 women with structural heart disease. Of the 103 pregnancies, 55 were primiparous and 48 were multiparous. Echocardiography performed before pregnancy revealed that 52 patients had moderate to severe valvular regurgitation and 38 patients had moderate to severe valvular stenosis; 22 patients had mechanical valves and 5 patients had pulmonary hypertension. Overall, there were 9 maternal cardiac events, 7 obstetric events and 19 neonatal events. Pulmonary embolic events occurred only in 1 case; 77 deliveries were made, and 26 pregnancies did not last. Among 77 deliveries, 55 patients delivered by cesarean section (C/S) (71.43%). C/S in 16 of 55 patients was performed due to the maternal hemodynamic risk. Conclusions Overall complications associated with pregnancy in women with structural heart disease were very high at 28.16%. However, it is hoped that maternal and neonatal outcomes will be improved through careful observation and preparedness for anticipated complications.

Choroidal microvasculature dropout (CMvD) implies compromised optic nerve head perfusion in glaucoma patients. However, there are conflicting findings whether office-hour systemic blood pressure (BP) is related to the presence of CMvD. The present study investigated which systemic BP parameters, derived from 24-h ambulatory BP monitoring (ABPM), are associated with CMvD as assessed by optical coherence tomography angiography (OCT-A) in normal-tension glaucoma (NTG). This study included 88 eyes of 88 NTG patients who underwent 24-h ABPM and OCT-A imaging. Various systemic BP parameters associated with the presence of CMvD were evaluated using logistic regression analyses. CMvD was detected in 38 NTG eyes (43.2%). NTG eyes with CMvD had nighttime diastolic BP (DBP) dip of greater magnitude and longer duration than eyes without CMvD. In multivariate logistic regression, worse VF mean deviation (MD) (odds ratio [OR] 0.786; P = 0.001), greater nighttime DBP dip “%” (OR 1.051; P = 0.034), and higher daytime peak IOP (OR 1.459; P = 0.013) were significantly associated with the presence of CMvD. Based on our findings that the eyes with CMvD are closely associated with having nighttime DBP dip, NTG patients with CMvD should be recommended to undergo 24-h ABPM.

Cytology from gastrointestinal (GI) cancers is frequently obtained from ascites and peritoneal washing fluids. Examination of ascites and peritoneal washing fluids from patients with GI cancers can help in the tumor staging and prognosis. Tumor-derived DNA in these cytology samples can be a target for next generation sequencing (NGS). Targeted NGS was evaluated in ascites and peritoneal washing samples obtained from 33 patients with GI cancers. These sequences were compared with those from tumor tissue samples, and correlated with cytopathologic findings of the ascites and peritoneal fluid samples. The correlation between fluid and tissue genotyping results was 25%, with a sensitivity of 21.43%. The volume of tumor contained within the fluid samples was low, ranging from ~0 to 10%. Importantly, the sensitivity of detection of somatic mutations in the fluid samples could be increased to 69.2% by assessing samples containing >2% tumor volume. Evaluation of cells from ascitic fluid showed the presence of KRAS, TP53, and CDH1 mutations in 33, 13, and 7%, respectively, of patients with pancreatic cancer, and the presence of KRAS, TP53, and APC mutations in 25, 12, and 13%, respectively, of patients with gastric cancer. Ascites of one of the latter patients acquired KRAS mutation, which was a novel mutation during metastasis. Targeted NGS of ascites and peritoneal washing fluid have clinical implications, as well as limitations, in patients with GI cancers. NGS-based cytology examination may expand cytomolecular practices in GI cancer patients.

Background: Whether hyperthyroidism is an independent risk factor for cardiovascular events remains controversial. We aimed to evaluate the association of overt and subclinical hyperthyroidism with the risk of ischemic heart disease (IHD), stroke, heart failure, and cardiovascular mortality.Methods: Studies regarding the association between hyperthyroidism and cardiovascular events were searched on PubMed and Embase databases. The cardiovascular disease (CVD) risk was classified as high and low, based on pre-existing diseases, including history of coronary, cerebral, or peripheral artery disease; heart failure; atrial fibrillation; diabetes mellitus; or chronic kidney disease.Results: Thirty-seven cohort studies were included in this meta-analysis. The pooled hazard ratio for subjects with overt hyperthyroidism compared with the control group was 1.11 (95% confidence interval [CI], 1.03 to 1.19) for IHD, 1.35 (95% CI, 1.03 to 1.75) for stroke, and 1.20 (95% CI, 1.00 to 1.46) for cardiovascular mortality. For subjects with subclinical hyperthyroidism, the pooled hazard ratio was 1.24 (95% CI, 1.07 to 1.45) for IHD, when compared with the control group. Subgroup analysis by CVD risk showed that the risk of stroke in overt hyperthyroidism was increased in the low CVD risk group; however, these association was not observed in the high CVD risk group. Similarly, the risk of IHD in subjects with subclinical hyperthyroidism was significantly increased in the low CVD risk group.Conclusion: Overt hyperthyroidism is associated with increased risk of IHD, stroke, and cardiovascular mortality, and subclinical hyperthyroidism is associated with increased risk of IHD. These associations were particularly observed in the low risk CVD group without underlying CVD.

Background and Objectives: Iodine is known to be an important factor in the occurrence of goiter, and South Korea is a region with sufficient iodine supplementation. In this regard, we checked the size change of thyroid nodules found by health check-up in Koreans and examined which risk factors influence the size change. Materials and Methods: A total 7753 subjects who underwent thyroid sonography two or more times were included. We defined that there was a change in the size of the nodule when the difference in diameter identified in the last ultrasound was more than 3 mm. Results: Thyroid nodules were decreased in 895 subjects (11.5%) and increased in 1041 subjects (13.5%). The rate of increased nodule was on an increasing trend according to the duration (annual percent change 2.6%, p＜0.001). In contrast, the rate of decreased nodule was unchanged. Predictive factors related to decrease of the nodule size were young age, male sex, larger initial nodule size and thyroiditis. Similarly, young age, larger initial nodule size and diffuse parenchymal abnormality were significant predictive factors for increased nodules. However, diffuse parenchymal abnormality was not a predictive factor when we analyzed only thyroid nodules larger than 1 cm. Conclusion: In our study, 11.5-13.5% of benign thyroid nodules were increased or decreased during median 27 months of follow-up in iodine sufficient condition. Young age, larger initial size and diffuse parenchymal abnormality were common predictive factor affecting both the increase and decrease of thyroid nodules.

Background: Fontan-associated liver disease (FALD) is a hepatic disorder caused by hemodynamic changes and systemic venous congestion following the Fontan procedure. FALD includes liver cirrhosis and hepatocellular carcinoma (HCC), both of which may require liver transplantation (LT). However, the Fontan circulation, characterized by elevated central venous pressure and reduced cardiac output, is a challenging issue for surgeons and anesthesiologists.Case: We report a living-donor LT for the treatment of HCC. The patient was a 24-year-old male who underwent the Fontan procedure for pulmonary atresia and right ventricle hypoplasia. We focused on maintaining enough blood volume for cardiac output without causing pulmonary edema, as the patient is not well adapted to changes in volume. Owing to a multidisciplinary approach, the surgery was successfully performed without fatal adverse events.Conclusions: To our knowledge, this is the first case of isolated LT in a recipient who became an adult after having undergone the Fontan procedure.

Background/aims To investigate the correlation between optical coherence tomography angiography (OCTA) characteristics and visual outcomes in patients with acute and chronic nonarteritic anterior ischemic optic neuropathy (NAION). Methods We retrospectively reviewed clinical data and OCTA images of 26 eyes of 26 patients who had been diagnosed with unilateral NAION. OCTA images were acquired from 17 eyes at the acute stage and from 21 eyes at the chronic stage of NAION. We analyzed the peripapillary vessel density (VD) and macular VD in various layers of the retina and choroid for all images. Possible correlations between the OCTA parameters and visual outcomes were investigated. Results Among the OCTA parameters for the acute stage of NAION, the temporal peripapillary VD was found to be positively correlated with final visual acuity and visual field with statistical significance (P = 0.039 and 0.009, respectively). In the chronic stage of NAION, both peripapillary and superficial macular VDs were positively correlated with visual outcomes. The nasal perifoveal VD in the superficial capillary plexus (SCP) also had a significant correlation with final visual acuity for both acute and chronic stages (the Spearman correlation coefficient = 0.565 and 0.685, respectively). Conclusions In patients with NAION, significant correlations were found between OCTA parameters and visual outcomes. The temporal peripapillary VD measured during the acute stage was a significant predictor of final visual outcomes. The decreased nasal perifoveal VD in the SCP was strongly associated with poor visual prognosis.

Auranofin is a gold complex used as an anti-rheumatic agent and may act as a potent anticancer drug against breast tumors. Trametinib is a specific mitogen-activated protein kinase inhibitor, approved for the treatment of metastatic melanoma. The aim of this study was to examine the synergistic effects of auranofin and trametinib on apoptosis in MCF-7 human breast cancer cells. The combination treatment inhibited cancer cell proliferation and induced cell cycle arrest at the sub-G1 phase and apoptosis via poly (ADP-ribose) polymerase cleavage and caspase-3/7 activation. It is noteworthy that this treatment significantly increased p38 mitogen-activated protein kinase (MAPK) phosphorylation to induce mitochondrial stress, subsequently promoting cancer cell apoptosis through release of apoptosis-inducing factor. Further data demonstrated that combined treatment significantly induced increase in nuclear translocation of AIF. These results indicated that activation of the p38 MAPK signaling pathway and mitochondrial apoptosis may contribute to the synergistic consequences in MCF-7 cells. Collectively, our data demonstrated that combined treatment with auranofin and trametinib exhibited synergistic breast cancer cell death and this combination might be utilized as a novel therapeutic strategy for breast cancer.

Background Previous studies have reported notable differences in demographic and clinical features of cluster headache between Western and Asian populations, including lower prevalence of the chronic type and in women. Recently, prodromal symptoms of migraine and pre-attack symptoms of cluster headache have drawn attention regarding their potential pathophysiological implications and pre-emptive treatment. However, pre-attack symptoms of cluster headache have not been studied in the Asian population. Methods A total of 136 patients with cluster headache (21 first-onset, 110 episodic, and five chronic cases) were recruited in this multi-center study between October 2018 and December 2019. We evaluated the characteristics of pre-attack symptoms in a current bout using a structured questionnaire. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with presence of pre-attack symptoms. Results Pre-attack symptoms were reported in 71.3% of our patients with cluster headache. When present, pre-attack symptoms occurred at a median of 20 minutes (range 1–120) before the attack. The prevalence of local and painful, local and painless sensory, autonomic, and general symptoms was 58.8%, 14.7%, 11.0%, and 30.1%, respectively. Multivariable logistic regression analysis revealed that higher number of bouts was associated with higher prevalence of pre-attack symptoms (OR = 1.464, p = 0.044). Conclusions Pre-attack symptoms were frequently observed in Korean patients with cluster headache, which was consistent with previous Western studies.

Lactobacillus reuteri NK33 (NK33) and Bifidobacterium adolescentis NK98 (NK98) alleviate immobilization stress-induced depression. To understand the gut microbiota-mediated mechanisms of NK33 and NK98 against depression, we examined their effects on Escherichia coli K1 (K1)-induced depression and gut dysbiosis in mice. NK33, NK98, and their mixtures (1:1, 4:1, and 9:1) mitigated K1-induced depression and colitis. NK33 and NK98 additively or synergistically increased BDNF+/NeuN+ cell population and suppressed NF-κB action in the hippocampus. They alleviated gut dysbiosis by reducing the Proteobacteria population and increasing the Clostridia population. These results suggest that NK33 and NK98 may alleviate depression and colitis by ameliorating gut dysbiosis.

Objective To examine the influences of depression and anxiety on headache‐related disability in people with episodic migraine or chronic migraine. Background Depression and anxiety are common comorbidities in people with migraine, especially among those with chronic migraine. Methods This cross‐sectional analysis of data from the longitudinal, internet‐based Chronic Migraine Epidemiology and Outcomes Study assessed sociodemographic and headache features, and headache‐related disability (Migraine Disability Assessment Scale). Four groups were defined based on scores from validated screeners for depression (9‐item Patient Health Questionnaire) and anxiety (7‐item Generalized Anxiety Disorder Scale): depression alone, anxiety alone, both, or neither. Results Respondents (N = 16,788) were predominantly women (74.4% [12,494/16,788]) and white (84.0% [14,044/16,788]); mean age was 41 years. Depression was more likely in persons with chronic migraine vs episodic migraine (56.6% [836/1476] vs 30.0% [4589/15,312]; P

PurposeThe purpose of this investigation is to gain insight into parents' perceptions of benefits vs burdens (value) of educational and healthcare service received for their child with ASD. Parents are the main integrators of long-term educational and healthcare service for their child with ASD.Design/methodology/approachDesign/methodology/approach included (1) a sentiment analysis of discussion forum posts from an autism message board using a rule-based sentiment analysis tool that is specifically attuned to sentiments expressed in social media and (2) a qualitative content analysis of one-on-one interviews with parents of children diagnosed with ASD, complemented with interviews with experienced educators and clinicians.FindingsFindings reveal the link between customized service integration and long-term benefits. Both parents and service providers emphasize the need to integrate healthcare and educational service to create holistic long-term care for a child with ASD. Parents highlight the benefits of varied services, but availability or cost are burdens if the service is not publicly provided, or covered by insurance. Service providers' lack of experience with ASD and people's ignorance of the challenges of ASD are burdens.Practical implicationsEnsuring health outcomes for a child with ASD requires an integrated service system and long-term, customer-centric service process because the scope of service covers the child's entire childhood. Customized educational and healthcare service must be allocated and budgeted early in order to reach the goal of a satisfactory service output for each child.Originality/valueThis is the first service research to focus on parents' challenges with obtaining services for their child with ASD. This paper provides service researchers and managers insight into parents' perceptions of educational and healthcare service value (i.e. benefits vs. burdens) received for their child with ASD. These insights into customer-centric perceptions of value may be useful to research and may help service providers to innovate and provide integrated service directly to parents, or indirectly to service providers, who serve children with ASD.

Background: This study aimed to assess the effects of sarcopenia and A Body Shape Index (ABSI) on cardiovascular disease (CVD) risk according to obesity phenotypes. Methods: We used data from the National Health and Nutrition Examination Survey 1999 to 2012. A total of 25,270 adults were included and classified into the following groups: metabolically healthy normal weight (MHNW), metabolically healthy over weight/obese (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). Sarcopenia was defined as the appendicular skeletal mass index

A close association has been reported between depression and migraine. However, information concerning the impacts of migraine on the clinical presentation and prevalence of depression in a population-based study is currently limited.Data from the Korean Headache-Sleep Study, a nationwide survey about headache and sleep for adults aged 19-69 years were used. Depression was defined when Patient Health Questionnaire-9 score ≥ 10.Of 2,695 participants who included in this study, 116 (4.3%), 143 (5.3%), and 1130 (41.9%) had depression, migraine, and non-migraine headache, respectively. Migraine (24/116 [20.5%] vs. 119/2579 [4.7%], p 0.001) and non-migraine headache (67/116 [58.1%] vs. 1063/2579 [41.3%], p 0.001) was more prevalent in the group of participants with depression than among participants without depression. Among participants with depression, there was no statistically differences in total Patient Health Questionnaire-9 (PHQ-9) scores among migraine, non-migraine headache, and non-headache groups (median with interquartile range, 12.0 [10.2-18.0] vs. 13.0 [11.0-16.0] vs. 12.0 [10.0-15.2], p = 0.514). Among subcomponent scores of PHQ-9, all subcomponent scores did not significantly differ by headache status except feeling tired or having little energy scores (non-migraine headache 2.0 [2.0-3.0] vs. non-headache 2.0 [1.0-2.0], p = 0.010).Diagnosis of depression based on PHQ-9 questionnaire and small sample size in subgroup analyses.Participants with depression exhibit an increased risk of migraine and non-migraine headache compared with participants without depression. Among participants with depression, the severity of depression did not significantly differ on the basis of headache status.

To determine whether eyes with open-angle glaucoma (OAG) and a localized choroidal microvasculature dropout (MvD) are associated with a greater degree of generalized choroidal vascular insufficiency within the β-parapapillary atrophy (β-PPA) than OAG eyes without MvD.Retrospective cross-sectional study.This study included 100 OAG eyes with visual field (VF) loss confined to a single hemifield (50 with and 50 without MvD, matched for age [≤10 years ols], axial length [≤1 mm], and VF severity [≤1 dB]), as well as 50 healthy eyes. Using optical coherence tomography angiography, parapapillary choroidal vessel density (pCVD) was measured on en-face images of choroidal maps within the entire β-PPA after excluding the MvD area and hemi-sectors of the β-PPA. pCVDs were compared among the 3 groups. The relationships between pCVD outcomes and various clinical variables were assessed. Logistical regression analyses were performed to determine the clinical factors associated with the presence of MvD in eyes with OAG.pCVDs corresponding to the VF-intact hemi-sectors and the entire β-PPA, excluding the MvD area, were significantly lower in eyes with MvD than in matched sectors of eyes without MvD. Multivariate linear regression analysis showed that the presence of MvD and greater MvD angular extent were independently associated with lower global pCVD in OAG eyes (all P.05). Logistic regression analyses showed that lower pCVD was the only factor significantly associated with the presence of MvD.Localized MvD was a strong predictor of generalized pCVD loss within the β-PPA in OAG eyes.

Recent large-scale genome-wide association studies have identified common genetic variations that may contribute to the risk of amyotrophic lateral sclerosis (ALS). However, pinpointing the risk variants in noncoding regions and underlying biological mechanisms remains a major challenge. Here, we constructed a convolutional neural network model with a large-scale GWAS meta-analysis dataset to unravel functional noncoding variants associated with ALS based on their epigenetic features. After filtering and prioritizing of candidates, we fine-mapped two new risk variants, rs2370964 and rs3093720, on chromosome 3 and 17, respectively. Further analysis revealed that these polymorphisms are associated with the expression level of CX3CR1 and TNFAIP1, and affect the transcription factor binding sites for CTCF, NFATc1 and NR3C1. Our results may provide new insights for ALS pathogenesis, and the proposed research methodology can be applied for other complex diseases as well.

Objective:Here, we present an overview of how a tertiary hospital responded to maintain necessary activities and protect patients and staff from the coronavirus disease (COVID-19) outbreak.Methods:Gil Medical Center, a tertiary hospital in Incheon, has operated a special response team since January 21, 2020. All visitors were assessed for body temperature and respiratory symptoms, and screened for recent overseas travel. Suspected COVID-19 patients were taken to a screening clinic. All febrile patients with or without respiratory symptoms were taken to a respiratory safety clinic. An isolation ward, which consisted of 10 negative-pressure rooms, was used to treat confirmed cases. More than 120 beds were prepared for the outbreak, and patients with pneumonia were preemptively isolated.Results:By May 5, 480 960 visitors were assessed at the control station, 3350 patients visited the triage center, and 1794 were treated in the respiratory safety clinic. Seventeen confirmed cases were admitted to the negative isolation ward, and 350 patients with pneumonia were preemptively isolated. A total of 2977 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction tests were performed.Conclusions:While tertiary hospitals play an important role in treating both COVID-19 patients and non-COVID-19 patients, hospital staff have to protect themselves from unexpected in-hospital transmission. A multifaceted response must be undertaken to protect tertiary hospitals and their staff during the COVID-19 epidemic.

Background: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis.Objectives: To investigate the efficacy and safety of guselkumab in Korean patients.Methods: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively.Results: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p

PRECIS Substantial proportion of primary angle closure glaucoma (PACG) eyes showed glaucomatous worsening after successful lens extraction and intraocular pressure (IOP) control, which may suggest that an earlier intervention may be required to prevent PACG. PURPOSE The purpose of this study was to investigate the longitudinal clinical course of the primary angle closure (PAC) disease spectrum, including PAC, primary angle closure suspect (PACS), and PACG patients, who underwent lens extraction. METHODS This retrospective observational study included 77 eyes from patients with PACS, PAC, and PACG who underwent lens extraction and were followed up for >2 years after surgery. The mean, peak, and fluctuation of IOP were analyzed before and after lens extraction among groups. Visual field (VF) mean deviation was compared immediately after lens extraction and the final follow-up. Postoperative glaucoma progression determined by 3 criteria (optic disc/retinal nerve fiber layer photographs, optical coherent tomography, and VF) was compared among the 3 groups. RESULTS Seventeen PACS, 24 PAC, and 36 PACG eyes were included. The mean and peak IOP, and IOP fluctuation IOP were significantly reduced postoperatively in all groups. Postoperative VF mean deviation was significantly aggravated only in the PACG group (from -7.26 to -8.82 dB, P

Cellular senescence is a major barricade on the path of cancer development, yet proteins secreted from senescent cells exert complex and often discordant effects on subsequent cancer evolution. Somatic genome alternations driving the formation of nevi and melanoma are efficient inducers of cellular senescence. Melanocyte and melanoma cell senescence is likely to come into play as a key factor affecting the course of tumorigenesis and responsiveness to therapy; little mechanistic information has been generated, however, that substantiates this idea and facilitates its clinical translation. Here, we established and characterized a model of melanoma cell senescence in which pharmacologically induced DNA damage triggered divergent ATM kinase- and STING-dependent intracellular signaling cascades and resulted in cell cycle arrest, cytomorphologic remodeling, and drastic secretome changes. Targeted proteome profiling revealed that senescent melanoma cells in this model secreted a panoply of proteins shaping the tumor immune microenvironment. CRISPR-mediated genetic ablation of the p38α and IKKβ signaling modules downstream of the ATM kinase severed the link between DNA damage and this secretory phenotype without restoring proliferative capacity. A similar genetic dissection showed that loss of STING signaling prevented type I interferon induction in DNA-damaged melanoma cells but otherwise left the senescence-associated processes in our model intact. Actionable proteins secreted from senescent melanoma cells or involved in senescence-associated intracellular signaling hold potential as markers for melanoma characterization and targets for melanoma treatment.