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We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, –0.02 mL/min/1.73 m2 [95% confidence interval (CI), –3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P

Abstract Osteoarthritis is a common chronic disease and major cause of disability and chronic pain in ageing populations. In this pathology, the entire joint is involved, and the regeneration of articular cartilage still remains one of the main challenges. Here, we investigated the molecular mechanisms underlying cartilage regeneration in young mice using a full-thickness cartilage injury (FTCI) model. FTCI-induced cartilage defects were created in the femoral trochlea of young and adult C57BL/6 mice. To identify key molecules and pathways involved in the early response to cartilage injury, we performed RNA sequencing (RNA-seq) analysis of cartilage RNA at 3 days after injury. Young mice showed superior cartilage regeneration compared to adult mice after cartilage injury. RNA-seq analysis revealed significant upregulation of genes associated with the immune response, particularly in the IFN-γ signaling pathway and qRT-PCR analysis showed macrophage polarization in the early phase of cartilage regeneration (3 days) in young mice after injury, which might promote the removal of damaged or necrotic cells and initiate cartilage regeneration in response to injury. IFN-γR1- and IFN-γ-deficient mice exhibited impaired cartilage regeneration following cartilage injury. DMM-induced and spontaneous OA phenotypes were exacerbated in IFN-γR1−/− mice than in wild-type mice. Our data support the hypothesis that IFN-γ signaling is necessary for cartilage regeneration, as well as for the amelioration of post-traumatic and age-induced OA.

Abstract Introduction This study compared the clinical characteristics and antimicrobial susceptibility of uncomplicated acute pyelonephritis (APN) caused by Escherichia coli and Klebsiella pneumoniae. Methods We retrospectively reviewed the medical records of patients with uncomplicated APNs caused by E. coli and K. pneumoniae admitted to Keimyung University Dongsan Hospital between February 2014 and December 2021. Results We enrolled 497 patients (372 with E. coli infection, 125 with K. pneumoniae infection). Male, healthcare-associated infection, solid tumors, liver cirrhosis, chronic renal disease, solid organ transplantation, and antibiotic usage within the last 3 months were more strongly associated with K. pneumoniae uncomplicated APNs than with E. coli. Bacteremia and fever occurred more frequently in E. coli uncomplicated APNs. Antimicrobial resistance rates to piperacillin/tazobactam and carbapenem were higher in K. pneumoniae. Antimicrobial resistance rates to aztreonam and ciprofloxacin were lower in K. pneumoniae. Thirty-day mortality was more observed in K. pneumoniae group in univariate analysis, but this difference was not observed after adjustment. Male sex, ultimately fatal disease in McCabe, and prior antibiotic use within 3 months were more associated with K. pneumoniae. Conclusions Male, underlying diseases, and prior antibiotic use was more associated with K. pneumoniae. Further study will be needed that microbiome of each situation and the related with the distribution of the strains.

Abstract Vascular inflammation and fibrosis are hallmarks of hypertension and contribute to the development of cardiovascular disease and cognitive impairment. However, current anti-hypertensive drugs do not treat the underlying tissue damage, such as inflammation-associated fibrosis. Human amnion epithelial cells have several properties amenable for treating vascular pathology. This study tested the effect of amnion epithelial cells on vascular pathology and cognitive impairment during hypertension. Male C57Bl6 mice (8–12 weeks) were administered vehicle (saline; n = 58) or angiotensin II (0.7 mg/kg/d, n = 56) subcutaneously for 14 d. After surgery, a subset of mice were injected with 106 amnion epithelial cells intravenously. Angiotensin II infusion increased systolic blood pressure, aortic pulse wave velocity, accumulation of aortic leukocytes, and aortic mRNA expression of collagen subtypes compared to vehicle-infused mice (n = 9–11, P

Abstract Background Lipid disorders are a potent risk factor for cardiovascular diseases. Moreover, the intake of dietary fatty acids has been closely related to blood lipid levels. Therefore, this cross-sectional study examined the associations between dietary patterns related to fatty acid intake and lipid disorders in Korean adults. Methods From the 2013–2019 Korea National Health and Nutrition Examination Surveys data, 8399 men and 11404 women (aged ≥ 19 years) were selected. Reduced rank regression was employed to identify dietary patterns from 26 food groups, aiming to explain the maximum variation in the intake of saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), omega-3 fatty acids, and the PUFA/SFA ratio. Associations of quintiles (Q) of dietary pattern scores with lipid disorders were examined using multiple logistic regression stratified by sex. Results Three dietary patterns were identified: dietary pattern 1 showed positive factor loadings for vegetable oils, seasonings, legumes, nuts, and fish; dietary pattern 2 was high in consumption of red meat, bread and snacks, and milk and dairy products; and dietary pattern 3 was rich in fish and milk and dairy products. In men, dietary pattern 3 was inversely associated with elevated triglycerides (Q5 vs. Q1: odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.69–0.97, P-trend = 0.008). In women, dietary pattern 2 was positively associated with elevated total cholesterol (OR = 1.31, 95% CI = 1.12–1.52, P-trend

Abstract Although osteoarthritis (OA) is regarded as a disease of the articular cartilage, recent research has demonstrated alterations in periarticular muscles that surround the affected joint. Here, we investigated changes in periarticular muscle during the progression of OA, as well as the cause-and-effect relationship between muscle weakness and OA, in a mouse model of OA by destabilization of the medial meniscus (DMM). Pathological phenotypes in the periarticular muscles were assessed in the early and late stages of OA by DMM. OA pathology and pain behavior in the mice after DMM induction were examined in response to periarticular muscle weakness induced by multiple rounds of barium chloride (BaCl2) injections. The examinations were also performed in myostatin knockout mice with strengthened muscle phenotypes by muscle hypertrophy. Morphological alterations in the tibialis anterior (TA) and quadriceps muscles in DMM mice included variations in muscle-fiber size, aberrant extracellular matrix (ECM) deposition, inflammatory cell infiltration, and decreased muscle mass. Periarticular muscle fibers isolated from DMM mice showed reductions in the number of satellite cells and myogenic capacity of primary myoblast, as well as proliferation. DMM + muscle injury mice also showed exacerbated joint degeneration compared to the DMM vehicles. Myostatin knockout mice were characterized by attenuated OA and the complete abrogation of pain behavior after DMM. Our results suggest an association between muscle weakness and OA progression and pain.

Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.

Background Remote ischemic postconditioning (RIPoC) is induced by several cycles of brief, reversible, mechanical blood flow occlusion, and reperfusion of the distal organs thereby protecting target organs. We investigated if RIPoC ameliorated liver injury in a lipopolysaccharide (LPS)-induced endotoxemic rats. Methods Protocol 1) Rats were administered LPS and samples collected at 0, 2, 6, 12, and 18 h. 2) After RIPoC at 2, 6, and 12 h (L+2R+18H, L+6R+18H, and L+12R+18H), samples were analyzed at 18 h. 3) RIPoC was performed at 2 h, analysis samples at 6, 12, 18 h (L+2R+6H, L+2R+12H, L+2R+18H), and RIPoC at 6 h, analysis at 12 h (L+6R+12H). 4) Rats were assigned to a control group while in the RIPoC group, RIPoC was performed at 2, 6, 10, and 14 h, with samples analyzed at 18 h. Results Protocol 1) Liver enzyme, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB) levels increased while superoxide dismutase (SOD) levels decreased over time. 2) Liver enzyme and MDA levels were lower while SOD levels were higher in L+12R+18H and L+6R+18H groups when compared with L+2R+18H group. 3) Liver enzyme and MDA levels were lower while SOD levels were higher in L+2R+6H and L+6R+12H groups when compared with L+2R+12H and L+2R+18H groups. 4) Liver enzyme, MDA, TNF-α, and NF-κB levels were lower while SOD levels were higher in RIPoC group when compared with control group. Conclusions RIPoC attenuated liver injury in the LPS-induced sepsis model by modifying inflammatory and oxidative stress response for a limited period.

Abstract 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.

Abstract This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia ( 1) in a 5-point scoring system (0–4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949–0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Hypervirulent Klebsiella pneumoniae (KP) is defined according to hypermucoviscosity or various virulence factors and is clinically associated with community-acquired liver abscess (CLA). In this study, we investigated the clinical and microbiological characteristics of KP and significant factors associated with hypervirulence. The clinical characteristics, antimicrobial susceptibility, hypermucoviscosity, serotypes, hypervirulence-related genes, and biofilm formation of 414 KP isolates collected from the Keimyung University Dongsan Hospital between December 2013 and November 2015 were analyzed according to CLA. Significant risk factors for hypervirulent KP (HvKP) associated with CLA were investigated using logistic regression analysis. Notably, 155 (37.4%) isolates were hypermucoviscous, and 170 (41.1%) harbored aerobactin. CLA was present in 34 cases (8.2%). Epidemiology and treatment outcomes did not differ significantly between the CLA and non-CLA groups. The CLA group had significantly higher antibiotic susceptibility, K1/K2, rmpA, magA, allS, kfu, iutA, string test-positive result, and biofilm mass. Multivariate logistic regression revealed rmpA (OR, 5.67; 95% CI, 2.09–15.33; p = 0.001), magA (OR, 2.34; 95% CI, 1.01–5.40; p = 0.047), and biofilm mass >0.80 (OR, 2.13; 95% CI, 1.00–4.56; p = 0.050) as significant risk factors for CLA. rmpA was identified as the most significant risk factor for CLA among KP strains, implying that it is an important factor associated with HvKP.

Background/Aims To identify changes in symptoms and pulmonary sequelae in patients with coronavirus disease 2019 (COVID-19). Methods Patients with COVID-19 hospitalized at seven university hospitals in Korea between February 2020 and February 2021 were enrolled, provided they had ≥ 1 outpatient follow-up visit. Between January 11 and March 9, 2021 (study period), residual symptom investigations, chest computed tomography (CT) scans, pulmonary function tests (PFT), and neutralizing antibody tests (NAb) were performed at the outpatient visit (cross-sectional design). Additionally, data from patients who already had follow-up outpatient visits before the study period were collected retrospectively. Results Investigation of residual symptoms, chest CT scans, PFT, and NAb were performed in 84, 35, 31, and 27 patients, respectively. After 6 months, chest discomfort and dyspnea persisted in 26.7% (4/15) and 33.3% (5/15) patients, respectively, and 40.0% (6/15) and 26.7% (4/15) patients experienced financial loss and emotional distress, respectively. When the ratio of later CT score to previous ones was calculated for each patient between three different time intervals (1–14, 15–60, and 61–365 days), the median values were 0.65 (the second interval to the first), 0.39 (the third to the second), and 0.20 (the third to the first), indicating that CT score decreases with time. In the high-severity group, the ratio was lower than in the low-severity group. Conclusions In COVID-19 survivors, chest CT score recovers over time, but recovery is slower in severely ill patients. Subjects complained of various ongoing symptoms and socioeconomic problems for several months after recovery.

Background/Aims The aim of this study was to investigate long-term post-discontinuation outcomes in patients with rheumatoid arthritis (RA) who had been treated with tumor necrosis factor-α inhibitors (TNF-αi) which was then discontinued. Methods Sixty Korean patients with RA who participated in a 5-year GO-BEFORE and GO-FORWARD extension trials were included in this retrospective study. Golimumab was deliberately discontinued after the extension study (baseline). Patients were then followed by their rheumatologists. We reviewed their medical records for 2 years (max 28 months) following golimumab discontinuation. Patients were divided into a maintained benefit (MB) group and a loss-of-benefit (LB) group based on treatment pattern after golimumab discontinuation. The LB group included patients whose conventional disease-modifying antirheumatic drug(s) were stepped-up or added/switched (SC) and those who restarted biologic therapy (RB). Results The mean age of patients at baseline was 56.5 years and 55 (91.7%) were females. At the end of follow-up, 23 (38.3%) patients remained in the MB group. In the LB group, 75.7% and 24.3% were assigned into SC and RB subgroups, respectively. Fifty percent of patients lost MB after 23.3 months. Demographics and clinical variables at baseline were comparable between MB and LB groups except for age, C-reactive protein level, and corticosteroid use. Restarting biologic therapy was associated with swollen joint count (adjusted hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.01 to 3.55) and disease duration (adjusted HR, 1.12; 95% CI, 1.02 to 1.23) at baseline. Conclusions Treatment strategies after discontinuing TNF-αi are needed to better maintain disease control and quality of life of patients with RA.

Background/Aims Pulmonary toxicities of coronavirus disease 2019 (COVID-19) vaccination are exceedingly rare. However, there are a few reported cases after mRNA vaccination, especially from Asian countries. The purpose of this study was to report the clinical characteristics of patients with COVID-19 vaccine-related pneumonitis (CV-P) and to review cases reported in the literature. Methods We performed a prospective, observational case series analysis. Results Eleven patients with a median age of 80 years were enrolled. Ten patients developed CV-P after BNT162b2-mRNA vaccination and one after ChAdOx1 nCoV-19 vaccination. We identified various patterns of CV-P, including transient infiltration, life-threatening acute respiratory distress syndrome, and aggravation of underlying interstitial lung disease. Most patients showed favorable outcomes with good responses to corticosteroid therapy. Conclusions Identifying the mechanism of CV-P requires further investigation; however, radiological and laboratory findings in our case series support inflammatory dysregulation in the lung parenchyma after vaccination. Clinicians should consider CV-P in patients with atypical lung infiltration, no specific etiologies, and recent COVID-19 vaccination.

IntroductionHypervirulent Klebsiella pneumoniae (hvKp) has emerged as a clinically significant global pathogen in the last decade. However, the host immune responses of the macrophages during hvKp infection are largely unknown. In the present study, we aimed to compare the cytotoxic effects of hvKp and classical K. pneumoniae (cKp) in murine macrophages.ResultsWe found that the activation of caspase-1 -dependent pyroptosis was higher in cKp-infected macrophages compared with that in hvKp-infected macrophages. In Caspase-1 deficiency macrophages, pyroptosis diminished during infection. Both hvKp and cKp strains led to nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome formation and lysosomal cathepsin B activation, thus resulting in pyroptosis. Compared with the cKp strain, the hvKp strain inhibited these phenomena in murine macrophages.ConclusionHvKp infection resulted in different levels of pyroptosis via the activation of cathepsin B-NLRP3-caspase-1 in murine macrophages. Therefore, the manipulation of pyroptotic cell death is a potential target for host response during hvKp infection in macrophages.

BackgroundThrombolytic agents such as tissue plasminogen activator (tPA) are the only drug class approved to treat ischemic stroke and are usually administered within 4.5 h. However, only ~20% of ischemic stroke patients are eligible to receive the therapy. We previously demonstrated that early intravenous administration of human amnion epithelial cells (hAECs) can limit brain inflammation and infarct growth in experimental stroke. Here, we have tested whether hAECs exert cerebroprotective effects in combination with tPA in mice.MethodsMale C57Bl/6 mice were subjected to middle cerebral artery occlusion for 60 min followed by reperfusion. Immediately following reperfusion, vehicle (saline, n = 31) or tPA (10 mg/kg; n = 73) was administered intravenously. After 30 min of reperfusion, tPA-treated mice were injected intravenously with either hAECs (1×106; n = 32) or vehicle (2% human serum albumin; n = 41). A further 15 sham-operated mice were treated with vehicle (n = 7) or tPA + vehicle (n = 8). Mice were designated to be euthanised at 3, 6 or 24 h post-stroke (n = 21, 31, and 52, respectively), and brains were collected to assess infarct volume, blood–brain barrier (BBB) disruption, intracerebral bleeding and inflammatory cell content.ResultsThere was no mortality within 6 h of stroke onset, but a high mortality occurred in tPA + saline-treated mice between 6 h and 24 h post-stroke in comparison to mice treated with tPA + hAECs (61% vs. 27%, p = 0.04). No mortality occurred within 24 h of sham surgery in mice treated with tPA + vehicle. We focused on early infarct expansion within 6 h of stroke and found that infarction was ~50% larger in tPA + saline- than in vehicle-treated mice (23 ± 3 mm3 vs. 15 ± 2 mm3, p = 0.02) but not in mice receiving tPA + hAECs (13 ± 2 mm3, p

Purpose: This study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea. Methods: Blood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010–2011. Results: A total of 300 and 346 isolates were identified in 2010–2011 and 2017–2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010–2011 and 2017–2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P

BackgroundImmune-evading severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical effectiveness of monoclonal antibody agents that exhibit decreased in vitro activity against SARS-CoV-2 variants needs to be elucidated.MethodsA nationwide, multicenter, retrospective cohort study was designed to evaluate the effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was prescribed in South Korea before and after the emergence of the delta variant, against which the in vitro activity of regdanvimab was decreased but present. Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease progression who were admitted within seven days of symptom onset were screened in four designated hospitals between December 2020 and September 2021. The primary outcomes, O2 requirements and progression to severe disease within 21 days of admission, were compared between the regdanvimab and supportive care groups, with a subgroup analysis of delta variant–confirmed patients.ResultsA total of 2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in the regdanvimab group than the supportive care group required O2 support (18.4% vs. 27.1%, P < 0.001) and progressed to severe disease (4.0% vs. 8.0%, P < 0.001). In the multivariable analysis, regdanvimab was significantly associated with a decreased risk for O2 support (HR 0.677, 95% CI 0.561–0.816) and progression to severe disease (HR 0.489, 95% CI 0.337–0.709). Among the 939 delta-confirmed patients, O2 support (21.5% vs. 23.5%, P = 0.526) and progression to severe disease (4.2% vs. 7.3%, P = 0.055) did not differ significantly between the regdanvimab and supportive care groups. In the multivariable analyses, regdanvimab treatment was not significantly associated with a decreased risk for O2 support (HR 0.963, 95% CI 0.697–1.329) or progression to severe disease (HR 0.665, 95% CI 0.349–1.268) in delta-confirmed group.ConclusionsRegdanvimab treatment effectively reduced progression to severe disease in the overall study population, but did not show significant effectiveness in the delta-confirmed patients. The effectiveness of dose increment of monoclonal antibody agents should be evaluated for variant strains exhibiting reduced susceptibility.

BackgroundWe proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.MethodsThe design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke.ResultsEight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload.ConclusionOur Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.Clinical trial registrationClinicalTrials.gov, identifier ACTRN12618000076279P.

Background/Aims We examined temporal trends in the rate of gout and seropositive rheumatoid arthritis (RA) hospital visits and healthcare costs in Korea. Methods We conducted a serial cross-sectional analysis of Korean national healthcare claims. We calculated the annual increase in hospital visits (emergency department [ED] visits, outpatient visits, and hospitalizations) and total healthcare costs per visit. Results From 2010 to 2017, the annual rates of ED visits, outpatient visits, and hospitalizations for gout increased from 6.28 to 21, from 638.38 to 1059.55, and from 12.37 to 15.6 per 100,000 persons, respectively. Before 2013, ED visits for gout were most common in patients over 70 years old, but they were most common in those aged between 30 and 49 years after 2013. The number of patients with ED visits, outpatient visits, and hospitalizations for RA from 2010 to 2017 increased from 1.25 to 1.87, from 219.04 to 307.49 and from 8.44 to 12.32 per 100,000 persons, respectively. However, there was no increase in the prevalence of ED visits for RA in any age group except for those older than 70 years. The cost per ED visit for gout significantly decreased from 496.3 to 273.6 US dollar during the study period. There was no significant change in the cost per ED visit for RA between 2010 and 2017. Conclusions There was a large increase in ED visits for gout during the study period. Further studies are needed to analyze the reason behind increased ED visits for gout and suggest ways on how to improve gout care.

Abstract Rapid outbreak of coronavirus disease 2019 (Covid-19) raised major concern regarding medical resource constraints. We constructed and validated a scoring system for early prediction of progression to severe pneumonia in patients with Covid-19. A total of 561 patients from a Covid-19 designated hospital in Daegu, South Korea were randomly divided into two cohorts: development cohort (N = 421) and validation cohort (N = 140). We used multivariate logistic regression to identify four independent risk predictors for progression to severe pneumonia and constructed a risk scoring system by giving each factor a number of scores corresponding to its regression coefficient. We calculated risk scores for each patient and defined two groups: low risk (0 to 8 points) and high risk (9 to 20 points). In the development cohort, the sensitivity and specificity were 83.8% and 78.9%. In the validation cohort, the sensitivity and specificity were 70.8% and 79.3%, respectively. The C-statistics was 0.884 (95% CI 0.833–0.934) in the development cohort and 0.828 (95% CI 0.733–0.923) in the validation cohort. This risk scoring system is useful to identify high-risk group for progression to severe pneumonia in Covid-19 patients and can prevent unnecessary overuse of medical care in limited-resource settings.

Abstract Background Inappropriate use of antibiotics not only increases antibiotic resistance as collateral damage but also increases clinical failure rates and medical costs. The purpose of this study was to determine the relationship between the appropriateness of antibiotic prescription and outcomes of community-acquired acute pyelonephritis (CA-APN). Methods A multicenter prospective cohort study was conducted at eight hospitals in Korea between September 2017 and August 2018. All hospitalized patients aged ≥ 19 years who were diagnosed with CA-APN on admission were recruited. The appropriateness of empirical and definitive antibiotics, as well as the appropriateness of antibiotic treatment duration and route of administration, was evaluated in accordance with the guideline and expert opinions. Clinical outcomes and medical costs were compared between patients who were administered antibiotics ‘appropriately’ and ‘inappropriately.’ Results A total of 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of them, 10 (2.5%) and 18 (5.7%) were administered ‘inappropriately’ empirical and definitive antibiotics, respectively. Of the 119 patients whose use of both empirical and definitive antibiotics was classified as ‘optimal,’ 57 (47.9%) received antibiotics over a longer duration than that recommended; 67 (56.3%) did not change to oral antibiotics on day 7 of hospitalization, even after stabilization of the clinical symptoms. Patients who were administered empirical antibiotics ‘appropriately’ had shorter hospitalization days (8 vs. 10 days, P = 0.001) and lower medical costs (2381.9 vs. 3235.9 USD, P = 0.002) than those who were administered them ‘inappropriately.’ Similar findings were observed for patients administered both empirical and definitive antibiotics ‘appropriately’ and those administered either empirical or definitive antibiotics ‘inappropriately’. Conclusions Appropriate use of antibiotics leads to better outcomes, including reduced hospitalization duration and medical costs.

Objectives Current healthcare reimbursement system is criticised for not adequately compensating physicians’ cognitive services. This study was performed to examine primary care physicians’ consultation fees in nine countries, relative to the national hourly minimum wage and to examine the correlations of the physician consultation fee with consultation length and other healthcare indices.Design and outcome measures Nine reference countries for which healthcare statistics are publicly available and outpatient consultation is compensated by fee-for-service payment were selected. A representative consultation fee was chosen to calculate the ratio of the consultation fee to the hourly minimum wage. The primary outcome was the correlation between the consultation fee/hourly minimum wage ratio and consultation length. In addition, the consultation fees were compared with fees for haemoglobin A1c tests and brain imaging. Pearson’s method was primarily used for correlation analysis.Results The mean representative consultation fee/hourly minimum wage ratio was 4.02 (median, 2.7; range, 0.80–10.36). The mean consultation length was 12.9 min (median, 14.7 min; range, 5–21.1 min). A significant correlation (r=0.79) was found between consultation length and the consultation fee/hourly minimum wage ratio. The ratio of consultation fee to hourly minimum wage was moderately negatively correlated with the annual number of physician visits, number of consultations per doctor and length of hospital stay. The brain CT fee/consultation fee ratio was moderately positively correlated with the number of CT units per 1 million population. In Japan and Korea, where the brain CT/consultation fee ratio was highest, the number of CT examinations per population was also highest.Conclusions The relationship of consultation fees to each country’s hourly minimum wage varied in nine reference countries; however, it was strongly correlated with consultation length. The imbalance in compensation for cognitive services might drive increased use of imaging tests in some countries.

Abstract Background Escherichia coli is among the most common uropathogens. Increased antibiotic resistance in Gram negative bacilli is global concern. Alternative therapeutic options including vaccines against uropathogenic E. coli (UPEC) have been developed. In this study, we compared the genotypic characteristics and antimicrobial susceptibility of UPEC according to phylogenetic groups. Methods We retrospectively reviewed the medical records of pyelonephritis patients with UPEC between February 2015 and June 2018. The study was conducted at a medical center in Korea. We compared the clinical and genotypic characteristics of UPEC according to phylogenetic groups. The phylogenetic groups and 29 virulence factors were identified using multiplex polymerase chain reaction. Results Phylogenetic group analysis revealed that most uropathogenic E. coli belonged to groups B2 and D: B2 (276, 77.7%), D (62, 17.5%), B1 (12, 3.4%), and A (5, 1.4%). Among the virulence factors, fyuA, fimH, traT, iutA, papG allele II, and papC were the most frequently observed. Phylogenetic group B2 was more closely related to virulence factors, including fimH, sfa/focED, focG, hlyA, cnf1, fyuA, and PAI, than group D. Groups B2 and D showed similar clinical presentations and complications. Group B2 had mostly healthcare-associated infections and antimicrobial resistance. Group D mostly had community-acquired infections. The K1 serotype was prevalent in group B2, and K5 was the most prevalent in group D. Conclusions Phylogenetic group B2 had more proportions and types of virulence factors than group D. Group B2 showed a high presentation of virulence factors related to adhesions and toxins. An increased presentation of antimicrobial resistance and healthcare-associated infections was also noted. Considering the genetic characteristics of UPEC, alternative therapeutic options targeting frequent virulence factors might be considered in addition to antibiotics.

ObjectiveTo assess the prevalence and relationship with vestibular function test results of positional preference in acute vestibular neuritis (VN).MethodsWe prospectively recruited 33 patients with VN during the acute phase. We assessed the severity of vertigo with a visual analog scale (VAS) and the degree of spontaneous nystagmus (SN) during sitting, the head rolling to the affected, and the healthy side. Patients performed other vestibular function tests, including ocular and cervical vestibular evoked myogenic potential (VEMP), on the same day or the next day of VNG testing.ResultsTwelve patients (12/33, 36%) with VN complained of more severe vertigo during lying on the affected side compared to the healthy side under visual fixation. Compared to patients without positional preference (without positional preference group), patients with positional preference (with positional preference group) showed a significantly higher VAS and maximal slow phase velocity (SPV) of SN at all positions except lying on the lesion side. However, there was no difference in the SPV gap between the two groups. 30% (10/33) of patients with VN complained of more severe vertigo while lying on the affected side compared to the healthy side without visual fixation. Maximal SPV of SN was not different between the two groups. There was no other significant difference in both canalith and otolith function test results between the two groups regardless of the visual fixation.ConclusionsOne-third of patients with acute VN had more severe vertigo while lying on the affected side than in the supine position. The positional preference was not directly related to the SN intensity or VEMP results. The positional preference might reflect the otolith damage in the setting of activation of the sustained otolith system, not the transient otolithic system.

Abstract Background The influence of the sympathetic nervous system (SNS) on metabolism of bone and cartilage expressing β-adrenergic receptors (AR) was suggested. Here, we investigated whether the SNS functions as a modulator of cartilage metabolism induced by interleukin-1beta (IL-1β). Methods Human articular chondrocytes and articular cartilage were collected from patients with osteoarthritis (OA). Chondrocyte monolayer and cartilage explant culture were stimulated with IL-1β. The activity of β-ARs was modulated by an agonist, norepinephrine (NE), and antagonists, including propranolol, atenolol, nebivolol, and nadolol. Results The levels of β1-, β2-, and β3-AR in OA cartilage and IL-1β-treated chondrocytes were lower than normal cartilage and untreated cells. Treatment of chondrocytes with IL-1β and β-blockers, including propranolol, atenolol, nebivolol, and nadolol, for 6 h significantly upregulated IL-1β-induced expression of MMP-1, -3, and − 13, compared to chondrocytes treated with IL-1β alone, indicating that antagonism of β-AR confers catabolic signals. On the other hand, NE antagonized IL-1β-induced catabolic response. In addition, NE significantly inhibited IL-1β-induced release of glycosaminoglycan (GAG) from cartilage explant culture. In addition, β-AR activity significantly affected IL-1β-stimulated phosphorylation of JNK and ERK. These results indicate that β-AR signal is associated with cartilage metabolism. Conclusions Our findings showed that β-ARs is a regulator of cartilage catabolism induced with IL-1β.

Abstract We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients’ blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.

Abstract Tonicity-responsive enhancer-binding protein (TonEBP; nuclear factor of activated T cells 5) is a transcription factor that responds to changes in osmolality. However, recent studies have shown that it also modulates immune responses under inflammatory conditions independently of hyperosmolality. Fibronectin fragments (FN-fs), which are abundant in the synovial fluid of patients with osteoarthritis (OA), induce expression of matrix metalloproteinases (MMPs) via the toll-like receptor-2 (TLR-2) signaling pathway. In this study we examined whether TonEBP is involved in 29-kDa FN-f-induced expression of MMPs. The expression of TonEBP was significantly higher in human osteoarthritis compared with normal cartilage samples. 29-kDa FN-f affected the expression of MMPs 1, 3, and 13 via TonEBP, and expression and nuclear accumulation of TonEBP were induced by activation of the phospholipase C/NF-κB/MAPK signaling pathway and, in particular, modulated by TLR-2. In addition, 29-kDa FN-f induced the expression of osmoregulatory genes, including Tau-T, SMIT, and AR, as well as voltage-dependent calcium channels via the TonEBP/TLR-2 signaling pathway. These results show that 29-kDa FN-f upregulates MMPs in chondrocytes via the TLR-2/TonEBP signaling pathway.

Background/Aims To explore the associations between body composition and pain, disease activity, and disability in rheumatoid arthritis (RA). Methods The study enrolled 335 patients with RA and underwent body composition measurement with an InBody analyzer. The associations of body mass index (BMI), body fat mass, and skeletal muscle mass with disease activity score in 28 joints (DAS28), an index derived to measure the subjective component of DAS28 (DAS28-P), a pain visual analogue scale (VAS), and disability measured with the health assessment questionnaire (HAQ) were explored. Obesity was defined as BMI ≥ 25 kg/m2. Results The median (interquartile range) disease duration was 6 years (3.5 to 9) and the mean DAS28 score was 3.6 ± 1.1. The mean BMI was 23.6 ± 3.6 kg/m2 and 109 patients (32.5%) were obese. Compared with non-obese patients, obese patients had a higher C-reactive protein (1.68 mg/dL vs. < 0.1 mg/dL, p = 0.013), higher pain VAS score (40 vs. 35, p = 0.031), and higher DAS28-erythrocyte sedimentation rate score (3.75 ± 1.18 vs. 3.46 ± 1.11, p = 0.031). In multivariate regression analysis, the DAS28 score in females was positively associated with the current steroid dose, body fat mass, and HAQ score, while the HAQ score in females was associated with older age, DAS28, lower skeletal muscle mass, and higher body fat/skeletal muscle ratio. In the multivariate regression analysis, the DAS28-P score in females was positively associated with body fat/skeletal muscle ratio and HAQ. Conclusions Body composition, such as the body fat mass and body fat/skeletal muscle ratio, is significantly associated with disease activity and disability in female RA patients.

Background/Aims It is difficult to reach a social agreement on the appropriate level of compensation for professionals. This study was performed to examine the physician fee embedded in the relative value unit (RVU) system in comparison with the Korean hourly minimum wage. Methods The Health Insurance Service Price and the Korean Classification of Procedural Terminology were used to obtain the hourly wages of physicians for designated health care services. In addition, the physician fee schedule at the United States Centers for Medicare and Medicaid Services and the Organisation for Economic Co-operation and Development (OECD) report on minimal wage were used. Health care service fees were selected based on laboratory, pathology, imaging, and procedure codes as well as examination fees. For calculation of physician labor costs per hour, physician workload × conversion factor was divided by the time involved. To calculate the proportion of physician labor fee in the total fee, the physician workload RVU for each service fee was divided by the total RVU. Results A total of 27 physician fee codes were selected. Compared to the Korean hourly minimum wage in 2015, the average physician wages were greater by 2.80-fold for primary care and by 3.05-fold for tertiary care. The mean proportion of physician labor cost in the total cost was 0.19, which was significantly lower than that of corresponding procedures in the United States RVU (mean, 0.48). Conclusions The average Korean physician wages compared to the hourly minimum wage were disproportionately low compared to the USA and other reference OECD countries.

Objectives: Two Coronavirus Disease 2019 (COVID-19) outbreaks simultaneously occurred at a church and a long-term care facility in Daegu, South Korea. This study aimed to investigate the epidemiological characteristics of COVID-19 and factors related to severe outcomes. Methods: We enrolled all inpatients diagnosed with COVID-19 between February 21 and April 2, 2020, in Daegu Dongsan Hospital. We analyzed their clinical and demographic data, laboratory parameters, radiological findings, symptoms, and treatment outcomes. Results: Of 694 patients, severe cases accounted for 19.7% (137 patients). No severe case was observed among patients aged ≤19 years. Hypertension was the most common comorbidity (27%), and cough was the most common symptom (59%). Asymptomatic patients accounted for 14.4% of cases. Lymphopenia, lactate dehydrogenase, C-reactive protein, and albumin were associated with severe outcomes. The first outbreak was mostly associated with younger age groups, and asymptomatic patients mostly showed mild progression. In the second outbreak involving a long-term care facility, both the number of severe patients and the mortality rate were higher. Conclusions: The overall mortality in Daegu was low, which might have resulted from large scale mass screening to detect patients and starting appropriate treatment, including hospitalization for severe cases, and quarantine for asymptomatic patients.

Abstract Background To investigate the frequency of pain among subjects with advanced radiographic knee osteoarthritis (OA) defined as Kellgren–Lawrence (KL) grade 4 and clinical features associated with pain. Methods Subjects from the Hallym Aging Study (HAS), the Korean National Health and Nutrition Examination Survey (KNHANES), and the Osteoarthritis Initiative (OAI) were included. Participants were asked knee-specific questions regarding the presence of knee pain. Clinical characteristics associated with the presence of pain were evaluated with multivariable logistic regression analysis. Results The study population consisted of 504, 10,152 and 4796 subjects from HAS, KNHANES, and OAI, respectively. KL grade 4 OA was identified in 9.3, 7.6, and 11.5% of subjects, while pain was absent in 23.5, 31.2, and 5.9% of subjects in KL grade 4 knee OA, respectively. After multivariable analysis, female gender showed a significant association with pain in the KNHANES group, while in the OAI group, younger age did. Advanced knee OA patients without pain did not differ from non-OA subjects in most items of SF-12 in both Korean and OAI subjects. Total WOMAC score was not significantly different between non-OA and advanced knee OA subjects without pain in the OAI. Conclusions Our study showed that a considerable number of subjects with KL grade 4 OA did not report pain. In patients whose pain arises from causes other than structural damage of the joint, therapeutic decision based on knee X-ray would lead to suboptimal result. In addition, treatment options focusing solely on cartilage engineering, should be viewed with caution.

BackgroundCoronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes.MethodsWe conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group.ResultsCompared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease.ConclusionDM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

Cryopreservation is used for blastocyst preservation of most mammalian embryos and is an important technique for breeding. We aimed to compare the efficiency of the cryopreservation method using the standard Cryotop device and the ReproCarrier device, a domestic product manufactured in Korea. The efficacy of the two devices was analyzed based on the survival rate, intracellular levels of reactive oxygen species (ROS), and apoptosis of the vitrified bovine blastocysts. The survival rates of the vitrified-warmed blastocysts were similar between the ReproCarrier group (58.4 ± 17.7%) and Cryotop group (59.9 ± 14.1%). Intracellular ROS levels and apoptotic index were determined by DCFDA staining and TUNEL assay. Changes in intracellular ROS levels, number of total nuclei, and cellular apoptosis of vitrified blastocysts after cryopreservation were not significantly different between the two groups. These results indicate that the ReproCarrier device method is as effective as the standard Cryotop method for vitrification of bovine blastocysts in vitro.

ObjectiveTo evaluate clinical effectiveness of regdanvimab, a monoclonal antibody agent for treating coronavirus 2019 (COVID-19).MethodsA retrospective cohort study was conducted at two general hospitals during the study period of December 2020 to May 2021. Mild COVID-19 patients with risk factors for disease progression admitted to the hospitals within seven days of symptom onset were enrolled and followed until discharge or referral. Multivariate analyses for disease progression were conducted in the total and propensity score (PS)-matched cohorts.ResultsA total of 778 mild COVID-19 patients were included and classified as the regdanvimab (n = 234) and supportive care (n = 544) groups. Significantly fewer patients required O2 supplementation via nasal prong in the regdanvimab group (8.1%) than in the supportive care group (18.4%, P < 0.001). The decreased risk for O2 support by regdanvimab treatment was noticed in the multivariate analysis of the total cohort (HR 0.570, 95% CI 0.343–0.946, P = 0.030), but it was not statistically significant in the PS-matched cohort (P = 0.057). Progression to severe disease was also significantly lower in the regdanvimab group (2.1%) than in the supportive care group (9.6%, P < 0.001). The significantly reduced risk for progression to severe disease by regdanvimab treatment was observed in the analysis of both the total cohort (HR 0.262, 95% CI 0.103–0.667, P = 0.005) and PS-matched cohort (HR 0.176, 95% CI 0.060–0.516, P = 0.002). Potential risk factors for progression were investigated in the supportive care group and SpO2 < 97% and CRP elevation >1.5 mg/dL were common risk factors for O2 support and progression to severe disease. Among the patients with any of these factors, regdanvimab treatment was associated with decreased risk for progression to severe disease with slightly lower HR (HR 0.202, 95% CI 0.062–0.657, P = 0.008) than that of the total cohort.ConclusionRegdanvimab treatment was associated with a decreased risk of progression to severe disease.

This study examined the physical properties of polytrimethylene terephthalate (PTT)/Tencel/cotton air vortex yarns and the wear comfort of their knitted fabrics for high emotional garments. In fine yarn count, the initial modulus of the air vortex yarn was similar to the ring yarn because of the elastic property of the PTT fibers in the yarns. In particular, the thermal shrinkage of the air vortex yarns was higher than that of the ring yarns because of the sensible thermal shrinkage of the PTT fibers, which resulted in higher relaxation shrinkage of the air vortex knitted fabric than those of ring and compact knitted fabrics. On the basis of the wear comfort, the air vortex yarns are compatible with winter textile goods. The pilling of the air vortex knitted fabric was superior to that of the ring and compact yarns. The tactile hand of the air vortex yarn knitted fabrics was stiffer than that of the ring and compact yarn knitted fabrics. However, the harsh tactile hand of the air vortex knitted fabric was estimated to improve in the thinner fabrics by the low elastic modulus of fine yarn because of the PTT fibers in the air vortex yarns.

Abstract. Background:. Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction. To distinguish MSA-P from IPD when the symptoms are relatively mild, we investigated the usefulness of the quantitative fractionalized autonomic indexes and evaluated the correlations of autonomic test indexes and functional status. Methods:. Thirty-six patients with parkinsonism (22 with IPD and 14 with MSA-P) in Soonchunhyang University Bucheon Hospital from February 2014 to June 2015 were prospectively enrolled in the study. We compared fractionalized autonomic indexes and composite autonomic scoring scale between patients with IPD and MSA-P with Hoehn and Yahr (H&Y) score ≤3. Parasympathetic indexes included expiratory/inspiratory ratio during deep breathing, Valsalva ratio (VR), and regression slope of systolic blood pressure (BP) in early phase II (vagal baroreflex sensitivity) during Valsalva maneuver. Sympathetic adrenergic indexes were pressure recovery time (PRT) and adrenergic baroreflex sensitivity (BRSa) (BP decrement associated with phase 3 divided by the PRT), sympathetic index 1, sympathetic index 3, early phase II mean BP drop, and pulse pressure reduction rate. Additionally, we compared the unified multiple system atrophy rating scale (UMSARS) and H&Y scores and the autonomic indexes in all patients. Results:. PRT was significantly different between the IPD and MSA-P groups (P = 0.004) despite the similar BP drop during tilt. Cut-off value of PRT was 5.5 s (sensitivity, 71.4%; specificity, 72.7%). VR (r = −0.455, P = 0.009) and BRSa (r = −0.356, P = 0.036) demonstrated a significant correlation with UMSARS and H&Y scores. Conclusions:. Among the cardiovascular autonomic indexes, PRT can be a useful parameter in differentiating the early stage of MSA-P from that of IPD. Moreover, VR, and BRSa may be the optimal indexes in determining functional symptom severity.

Background/Aims To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX) Methods The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks. Results Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile. Conclusions TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.

Abstract Background To evaluate the long-term efficacy, safety and immunogenicity of continuing LBEC0101; the etanercept (ETN) biosimilar; or switching from the ETN reference product (RP) to LBEC0101 in patients with rheumatoid arthritis (RA). Methods This multicentre, single-arm, open-label extension study enrolled patients who had completed a 52-week randomised, double-blind, parallel phase III trial of LBEC0101 vs ETN-RP. Patients treated with ETN-RP during the randomised controlled trial switched to LBEC0101; those treated with LBEC0101 continued to receive LBEC0101 in this study. LBEC0101 (50 mg) was administered subcutaneously once per week for 48 weeks with a stable dose of methotrexate. Efficacy, safety and immunogenicity of LBEC0101 were assessed up to week 100. Results A total of 148 patients entered this extension study (70 in the maintenance group and 78 in the switch group). The 28-joint disease activity scores (DAS28)-erythrocyte sedimentation rate (ESR) were maintained in both groups from week 52 to week 100 (from 3.068 to 3.103 in the maintenance group vs. from 3.161 to 3.079 in the switch group). ACR response rates at week 100 for the maintenance vs. switch groups were 79.7% vs. 83.3% for ACR20, 65.2% vs. 66.7% for ACR50 and 44.9% vs. 42.3% for ACR70. The incidence of adverse events and the proportion of patients with newly developed antidrug antibodies were similar in the maintenance and switch groups (70.0% and 70.5%, 1.4% and 1.3%, respectively). Conclusions Administration of LBEC0101 showed sustained efficacy and acceptable safety in patients with RA after continued therapy or after switching from ETN-RP to LBEC0101. Trial registration ClinicalTrials.gov, NCT02715908. Registered 22 March 2016.

ObjectivesThis study proposes a method for classifying three types of resting membrane potential signals obtained as images through diagnostic needle electromyography (EMG) using TensorFlow-Slim and Python to implement an artificial-intelligence-based image recognition scheme.MethodsWaveform images of an abnormal resting membrane potential generated by diagnostic needle EMG were classified into three types—positive sharp waves (PSW), fibrillations (Fibs), and Others—using the TensorFlow-Slim image classification model library. A total of 4,015 raw waveform data instances were reviewed, with 8,576 waveform images subsequently collected for training. Images were learned repeatedly through a convolutional neural network. Each selected waveform image was classified into one of the aforementioned categories according to the learned results.ResultsThe classification model, Inception v4, was used to divide waveform images into three categories (accuracy = 93.8%, precision = 99.5%, recall = 90.8%). This was done by applying the pretrained Inception v4 model to a fine-tuning method. The image recognition model was created for training using various types of image-based medical data.ConclusionsThe TensorFlow-Slim library can be used to train and recognize image data, such as EMG waveforms, through simple coding rather than by applying TensorFlow. It is expected that a convolutional neural network can be applied to image data such as the waveforms of electrophysiological signals in a body based on this study.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS.MethodsA retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests.ResultsOverall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score 5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005).ConclusionsAfter steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score

The safety of healthcare workers (HCWs) against severe acute respiratory syndrome virus 2 (SARS-CoV-2) transmission is an important aspect of managing the coronavirus disease 2019 (COVID-19) pandemic. In the South Korea, highly stringent infection prevention and control (IPC) guidelines are implemented, and reports of healthcare-associated SARS-CoV-2 transmission among HCWs are limited. However, subclinical infections may have been missed by the current symptom-based screening strategy. To evaluate the risk of undetected SARS-CoV-2 transmissions from COVID-19 patients to HCWs, we conducted a multicenter seroprevalence study after the first surge of the COVID-19 outbreak. A total of 432 HCWs were evaluated, comprising 309 HCWs designated to laboratory-confirmed COVID-19 patient care and 123 non-designated HCWs. Designated HCWs wore personal protective equipment including an N95 respirator, eye protection, hooded overalls, shoe covers, and inner and outer gloves. Use of a powered air-purifying respirator was recommended for aerosol-generating procedures or long-duration care activities. A high-sensitivity (99.1%) fluorescence immunoassay immunoglobulin G (IgG) kit was used as the initial screening test, and two enzyme-linked immunosorbent assay kits for total and IgG antibodies were used to confirm the test results. A microneutralization test was additionally performed to evaluate the neutralizing activity of positive specimens. Among the evaluated HCWs, none of the non-designated HCWs had a positive result, while one of the HCWs designated for COVID-19 patient care (1/309, 0.3%) was seropositive for SARS-CoV-2 with confirmed neutralizing activity (1:40). This finding suggests that subclinical seroconversion may occur among HCWs caring for COVID-19 patients, although the risk is low under strict IPC guidance.

Systemic administration of human amnion epithelial cells (hAECs) was recently shown to reduce neuropathology and improve functional recovery following ischemic stroke in both mice and marmosets. Given the significant neuropathological overlap between ischemic stroke and traumatic brain injury (TBI), we hypothesized that a similar hAEC treatment regime would also improve TBI outcomes. Male mice (12 weeks old, n ​= ​40) were given a sham injury or moderate severity TBI by controlled cortical impact. At 60 ​min post-injury, mice were given a single tail vein injection of either saline (vehicle) or 1 ​× ​106 hAECs suspended in saline. At 24 ​h post-injury, mice were assessed for locomotion and anxiety using an open field, and sensorimotor ability using a rotarod. At 48 ​h post-injury, brains were collected for analysis of immune cells via flow cytometry, or histological evaluation of lesion volume and hAEC penetration. To assess the impact of TBI and hAECs on lymphoid organs, spleen and thymus weights were determined. Treatment with hAECs did not prevent TBI-induced sensorimotor deficits at 24 ​h post-injury. hAECs were detected in the injured brain parenchyma; however, lesion volume was not altered by hAEC treatment. Robust increases in several leukocyte populations in the ipsilateral hemisphere of TBI mice were found when compared to sham mice at 48 ​h post-injury; however, hAEC treatment did not alter brain immune cell numbers. Both TBI and hAEC treatment were found to increase spleen weight. Taken together, these findings indicate that—unlike in ischemic stroke—treatment with hAEC was unable to prevent immune cell infiltration and sensorimotor deficits in the acute stages following controlled cortical impact in mice. Although further investigations are required, our data suggests that the lack of hAEC-induced neuroprotection in the current study may be explained by the differential splenic contributions to neuropathology between these brain injury models.

Although the lungs are major targets for COVID-19 invasion, other organs-such as the kidneys-are also affected. However, the renal complications of COVID-19 are not yet well explored. This study aimed to identify the incidence of acute kidney injury (AKI) in patients with COVID-19 and to evaluate its impact on patient outcomes. This retrospective study included 704 patients with COVID-19 who were hospitalized at two hospitals in Daegu, Korea from February 19 to March 31, 2020. AKI was defined according to the serum creatinine criteria in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The final date of follow-up was May 1, 2020. Of the 704 patients, 28 (4.0%) developed AKI. Of the 28 patients with AKI, 15 (53.6%) were found to have AKI stage 1, 3 (10.7%) had AKI stage 2, and 10 (35.7%) had AKI stage 3. Among these patients, 12 (42.9%) recovered from AKI. In the patients with AKI, the rates of admission to intensive care unit (ICU), administration of mechanical ventilator (MV), and in-hospital mortality were significantly higher than in patients without AKI. Multivariable analysis revealed that old age (Hazard ratio [HR] = 4.668, 95% confidence interval [CI] = 1.250-17.430, p = 0.022), high neutrophil-to-lymphocyte ratio (HR = 1.167, 95% CI = 1.078-1.264, p < 0.001), elevated creatinine kinase (HR = 1.002, 95% CI = 1.001-1.004, p = 0.007), and severe AKI (HR = 12.199, 95% CI = 4.235-35.141, p < 0.001) were independent risk factors for in-hospital mortality. The Kaplan-Meier curves showed that the cumulative survival rate was lowest in the AKI stage 3 group (p < 0.001). In conclusion, the incidence of AKI in patients with COVID-19 was 4.0%. Severe AKI was associated with in-hospital death.

Abstract Background Knee osteoarthritis (OA) is the most common form of arthritis affecting the elderly. Understanding the risk factors for knee OA has been derived from cross sectional studies. There have been few longitudinal studies of risk factors for knee OA among Asian populations. The purpose of this study was to evaluate the risk factors for knee OA in elderly Korean community residents. Methods This prospective, population-based study was conducted on residents over 50 years of age in Chuncheon who participated in the Hallym Aging Study. Standardized weight-bearing semi-flexed knee anteroposterior radiographs were obtained in 2007 and in 2010. Of 504 participants at baseline, 322 participants (male: female = 150:172) underwent follow-up knee radiographs. Radiographic knee OA was defined as Kellgren/Lawrence (K-L) grade of ≥ 2. Risk factors assessed at baseline were tested for their association with incidence, progression, and worsening of radiographic knee OA by logistic regression analysis. Results The median age of these participants at follow-up was 71 years (interquartile range 66–75 years). Incident OA was observed in 33 (10.2%) and progression of OA (defined as an increase of Kellgren-Lawrence (K-L) grade at follow-up, from grades 2 or 3 at baseline) in 43 (13.55%) participants. In multivariate logistic regression analysis, only females were significantly associated with the progression of radiographic knee OA (odds ratio [OR] = 4.41, 95% confidence interval [CI] 1.32–14.77). Conclusions In this 3-year longitudinal study, the yearly incidence and progression of knee OA was higher than those previously reported in Western populations.

Abstract Endothelial Per-Arnt-Sim domain protein-1/hypoxia-inducible factor-2α (EPAS-1/ HIF-2α) is a catabolic transcription factor that regulates osteoarthritis (OA)-related cartilage destruction. Here, we examined whether microRNA-365 (miR-365) affects interleukin (IL)-1β-induced expression of catabolic factors in chondrocytes via regulation of HIF-2α. MiR-365 levels were significantly decreased in human OA cartilage relative to normal cartilage. Overexpression of miR-365 significantly suppressed IL-1β-induced expression of HIF-2α in human articular chondrocytes. Pharmacological inhibition of various IL-1β-associated signaling pathways revealed mitogen-activated protein kinase and nuclear factor-κB as the primary pathways driving IL-1β-mediated decreases in miR-365 and subsequent increase in HIF-2α expression. Using a luciferase reporter assay encoding the 3′ untranslated region (UTR) of human HIF-2α mRNA, we showed that overexpression of miR-365 significantly suppressed IL-1β-induced up-regulation of HIF-2α. AGO2 RNA-immunoprecipitation (IP) assay demonstrated that miR-365 and HIF-2α mRNA were enriched in the AGO2-IP fraction in miR-365-transfected primary chondrocytes compared to miR-con-transfected cells, indicating that HIF-2α is a target of miR-365. Furthermore, miR-365 overexpression significantly suppressed IL-1β-induced expression of catabolic factors, including cyclooxygenase-2 and matrix metalloproteinase-1, -3 and -13, in chondrocytes. In pellet culture of primary chondrocytes miR-365 prevented IL-1β-stimulated extracellular matrix loss and matrix metalloproteinase-13 expression. MiR-365 regulates IL-1β-stimulated catabolic effects in human chondrocytes by modulating HIF-2α expression.

Abstract This study was designed to investigate the frequency and pattern of orthostatic symptoms during head-up tilt (HUT) in patients with orthostatic intolerance during daily life, and to identify the relationship between the orthostatic symptoms during HUT and autonomic parameters. We prospectively collected autonomic data from 464 patients with orthostatic symptoms. Adrenergic and cardiovagal function tests including HUT were performed. Based on HUT results, we divided patients into orthostatic hypotension (OH), postural tachycardia syndrome (POTS), or normal HUT groups. We also investigated orthostatic symptoms during HUT. Only 25% of the patients reported orthostatic symptoms during HUT and 75% were asymptomatic. Typical orthostatic symptoms such as orthostatic dizziness and blurred vision, and atypical symptoms like chest tightness and headache occurred in 86% and 66%, respectively. Patients with POTS had symptoms more frequently than patients with OH during HUT. There were no differences in degrees of BP or HR changes between symptomatic and asymptomatic groups within the OH and POTS groups. HUT fails to reproduce symptoms of orthostatic intolerance in the majority of patients. Clinicians need to be aware that most patients with OH are asymptomatic during HUT and patients with POTS are more likely to be symptomatic than patients with OH.

BackgroundThe optimal combination of anesthetic agent and technique may have an influence on long-term outcomes in cancer surgery. In vitro and in vivo studies suggest that propofol independently reduces migration of cancer cells and metastasis. Thus, the authors retrospectively examined the link between propofol-based total intravenous anesthesia (TIVA) and recurrence or overall survival in patients undergoing modified radical mastectomy (MRM).MethodsA retrospective analysis of the electronic database of all patients undergoing MRM for breast cancer between January 2007 and December 2008 was undertaken. Patients received either propofol-based TIVA (propofol group) or sevoflurane-based anesthesia (sevoflurane group). We analyzed prognostic factors of breast cancer and perioperative factors and compared recurrence-free survival and overall survival between propofol and sevoflurane groups.ResultsA total of 363 MRMs were carried out during the period of the trial; 325 cases were suitable for analysis (173 cases of propofol group, and 152 cases of sevoflurane group). There were insignificant differences between the groups in age, weight, height, histopathologic results, surgical time, or postoperative treatment (chemotherapy, hormonal therapy, and radiotherapy). The use of opioids during the perioperative period was greater in propofol group than in sevoflurane group. Overall survival was no difference between the two groups. Propofol group showed a lower rate of cancer recurrence (P = 0.037), with an estimated hazard ratio of 0.550 (95% CI 0.311–0.973).ConclusionsThis retrospective study provides the possibility that propofol-based TIVA for breast cancer surgery can reduce the risk of recurrence during the initial 5 years after MRM.

This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010–2011 and 2017–2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, prospectively. Data collected were compared with those from the previous study in 2010–2012, with the same design and participation from 11 hospitals. A total of 617 patients were enrolled and compared to 818 patients’ data collected in 2010–2011. Escherichia coli was the most common causative pathogen of CA-APN in both periods (87.3% vs. 86.5%, p = 0.680). E. coli isolates showed significantly higher antimicrobial resistance against fluoroquinolone (32.0% vs. 21.6%, p < 0.001), cefotaxime (33.6% vs. 8.3%, p < 0.001), and trimethoprim/sulfamethoxazole (37.5% vs. 29.2%, p = 0.013) in 2017–2018 than in 2010–2011. Total duration of antibiotic treatment increased from 16.55 ± 9.68 days in 2010–2011 to 19.12 ± 9.90 days in 2017–2018 (p < 0.001); the duration of carbapenem usage increased from 0.59 ± 2.87 days in 2010–2011 to 1.79 ± 4.89 days in 2010–2011 (p < 0.001). The median hospitalization was higher for patients in 2017–2018 than in 2010–2011 (9 vs. 7 days, p < 0.001). In conclusion, antimicrobial resistance of E. coli to almost all antibiotic classes, especially third generation cephalosporin, increased significantly in CA-APN in South Korea. Consequently, total duration of antibiotic treatment, including carbapenem usage, increased.