Background/Aims: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. Results: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. Conclusions Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Objectives: This study examined the factors associated with suicide risk among out-of-school youths (OSY) by analyzing their medical records retrospectively. Methods: The medical records of 280 OSYs who were admitted to the National Medical Center from January 2015 to December 2018 were examined. The demographic and clinical records, including behavioral problems, post-traumatic symptoms, harmful alcohol consumption, family functioning, and quality of life, were analyzed. Results: Among the 280 subjects, 80 (28.6%) were considered a high-risk suicidal group. The number of post-traumatic symptoms was found to be positively correlated, and the family functioning scores were negatively correlated with the increasing risk of suicide in the OSY based on the multiple regression analysis of the medical records. Conclusion The result of this study provides inputs for suicide prevention programs targeted at OSYs by identifying the risk and protective factors associated with suicide among the group.

Background: To evaluate workload in emergency rooms (ERs) among clinical specialties including neurology and investigate characteristics of neurological consultations in ER. Methods: A nationwide survey was conducted to evaluate the number of specialists, resident physicians/surgeons, and emergency consultations of each clinical specialty in Korean tertiary referral hospitals from 2018 to 2019. Characteristics of neurological emergency consultations during the same period were investigated in one of the hospitals that participated. Results: A total of 23 hospitals were included. Four irrelevant clinical specialties were excluded. The number of neurology specialists and resident physicians were 12.5/hospital (4.1% of all specialists) and 6.4/hospital (3.4% of all resident physicians/surgeons), respectively, while the mean numbers of specialists and resident physicians or surgeons per clinical specialty were 13.7/hospital and 8.6/hospital, respectively. Neurological consultations accounted for 11.0% of all ER consultations for severe patients (Korean Triage and Acuity Scale level 1-3). Annual ER consultations for severe patients per neurology specialist was 274.1, which was only second to pediatrics (290.0). Annual ER consultations for severe patients per resident physician was 406.6 which was 1.6 times higher than the second highest (internal medicine, 247.0). Frequent conditions for neurological ER consultation were dizziness (24.8%), motor weakness (23.9%), headache (10.6%), dysarthria (9.9%), and seizures (7.7%). Frequent primary diagnoses were cerebrovascular diseases (29.0%) and episodic and paroxysmal disorders (24.9%). Conclusions Workloads of neurology specialists for ER consultation were significantly heavy, and the workload of neurology resident physicians was the heaviest among all specialties. This should be considered in health care policies.

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin’s wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

Background: Because Korea is the fastest aging country, the stroke incidence is increasing rapidly. We investigate the trend of the number of patients with acute stroke in recent years and estimate the burden of the neurologist to treat the acute stroke patient visited the emergency department. Methods: We requested a questionnaire survey to all teaching hospitals on the number of hospital beds, the number of stroke patients who visited the emergency department, the number of stroke patients in charge of the neurologist, and the number of days on duty of residents from 2016 to 2019. Results: Of 69 teaching hospitals, 41 hospitals answered the survey. The average hospital beds per hospital were increased annually from 909 to 916. The average patients who visited the emergency department with stroke and were in charged to neurologists were rapidly increased from 799 to 867 per hospital. In particular, the number of patients with hyperacute cerebral infarction requiring the thrombolytic administration or mechanical thrombectomy were rapidly increased from 105 to 131. On the other hand, the average number of residents per hospital was decreased from 5.1 to 4.8. Therefore, the days on duty per resident were increased from 74 to 77. Conclusions The number of acute stroke patients, especially, hyperacute stroke required the rapid cooperation and high labor were increasing rapidly in recent years. However, because the number of residents were decreased, the burden was increasing. To improve the quality of acute stroke treatment, it is necessary to increase the number of residents.

Objective: To analyze the computational fluid dynamics (CFD) of femoral artery pseudoaneurysm (FAP), identify a suitable location and timing for percutaneous thrombin injection (PTI) based on this analysis, and report our clinical experience with the procedure. Materials and Methods: CFD can be used to analyze the hemodynamics of the human body. An analysis using CFD recommended that the suitable location of the needle tip for PTI is at the center of the aneurysm sac and the optimal timing for starting PTI is during the early inflow phase of blood into the sac. Since 2011, seven patients (three male and four female; median age, 60 years [range, 43–75 years]) with FAP were treated with PTI based on the devised suitable location and time. Prior to the procedure, color Doppler ultrasonography was performed to determine the location and timing of the thrombin injection. Results: The technical success rate of the PTI was 100%. The amount of thrombin used for the procedure ranged from 200 IU to 1000 IU (median, 500 IU). None of the patients experienced any symptoms or signs of embolic complications during the procedure. Follow-up CT images did not reveal any embolism in the lower extremities and showed complete thrombosis of the pseudoaneurysm. Conclusion Based on our study of CFD, PTI administered centrally in the FAP during early inflow, as seen on color Doppler, can be an effective technique.

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin’s wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

BACKGROUND AND PURPOSE: Thrombectomy within 24 hours can improve outcomes in selected patients with a clinical-infarct mismatch. We devised an easy-to-use visual estimation tool that allows infarct volume estimation in centers with limited resources. METHODS: We identified 1,031 patients with cardioembolic or large-artery atherosclerosis infarction on diffusion-weighted images (DWIs) obtained before recanalization therapy and within 24 hours of onset, and occlusion of the internal carotid or middle cerebral artery. Acute DWIs were mapped onto a standard template and used to create visual reference maps with known lesion volumes, which were then used in a validation study (with 130 cases) against software estimates of infarct volume. RESULTS: The DWI reference map chart comprises 144 maps corresponding to 12 different infarct volumes (0.5, 1, 2, 3, 5, 7, 9, 11, 13, 15, 17, and 19 mL) in each of 12 template slices (Montreal Neurological Institute z-axis –15 to 51 mm). Infarct volume in a patient is estimated by selecting a slice with a similar infarct size at the corresponding z-axis level on the reference maps and then adding up over all slices. The method yielded good correlations to software volumetrics and was easily learned by both experienced and junior physicians, with approximately 1 to 2 minutes spent per case. The sensitivity, specificity, and accuracy for detecting threshold infarct volumes ( < 21, < 31, and < 51 mL) were very high (all about >90%). CONCLUSIONS: We developed easy-to-use reference maps that allow prompt and reliable visual estimation of infarct volumes for triaging patients to thrombectomy in acute stroke.
Atherosclerosis ; Cerebral Infarction ; Decision Making ; Diffusion Magnetic Resonance Imaging ; Humans ; Infarction ; Medical Staff, Hospital ; Methods ; Middle Cerebral Artery ; Sensitivity and Specificity ; Stroke ; Thrombectomy

PURPOSE: Many traumatic patients die from sepsis and multiple organ failure. Early recognition of post-traumatic sepsis in traumatic patients will help improve the prognosis. Recently, procalcitonin (PCT), macrophage migration inhibitory factor (MIF), and lactic acid have emerged as predictive factors. Our study aims to explore the significance of PCT, MIF and lactic acid as a predictor of posttraumatic-sepsis in trauma patients. METHODS: This study was conducted on prospective observational study patients who visited an emergency medical center in a university hospital from March 2014 to February 2016. We measured the white blood cells, c-reactive protein (CRP), lactic acid, PCT, and MIF with serum taken from the patient's blood within 1 hour of the occurrence of the trauma. The definition of post-traumatic sepsis was defined as being part of systemic inflammation response syndrome criteria with infections within a week. RESULTS: A total of 132 patients were analyzed, wherein 74 patients were included in the low injury severity score (ISS) group (ISS < 15) and 58 patients were included in the high ISS group (ISS ≥15). The mean PCT, MIF, and lactic acid levels were higher in the high ISS group (p < 0.05). Meanwhile, 38 patients were included in the early sepsis group and 94 patients were included in the non-sepsis group. The mean MIF levels were higher in the sepsis group than the non-sepsis group (p < 0.05) and there were no significant differences in the initial CRP, lactic acid, and PCT levels in these two groups. CONCLUSIONS MIF may be considered as a predictive factor for sepsis in trauma patients.